Pyridoxine, Vitamin B6 is a water-soluble B-complex vitamin necessary for the proper function of over 70 different enzymes that participate in amino acid metabolism, among other things. Vitamin B6 is also involved in carbohydrate and fat metabolism. Vitamin B6 is involved in the synthesis of neurotransmitters in the brain and nerve cells, and may support mental function (mood) and nerve conduction. It may also improve emotional outlook and mood through serotonin synthesis. It is necessary for hemoglobin synthesis and red blood cell growth, immune support (white blood cell development), and has been used for arthritis relief

Deficiency symptoms include a skin condition called seborrhea with dry, flaky lesions around the eyes, nose and mouth, as well as signs and symptoms in the mucous membranes, peripheral nerves and blood forming system. In severe deficiency, seizures may occur. Vitamin B6 needs are increased in those individuals consuming a high protein diet as well as in women taking oral contraceptives (birth control pills).

Vitamin B6 is important in the treatment of excess homocysteine and therefore the prevention of heart disease. It is necessary in the conversion of the amino acid tryptophan into niacin, and therefore is involved in lowering cholesterol. Because B6 plays a role in prostaglandin synthesis it may help regulate blood pressure, muscle and heart function and pain levels, and reduce symptoms of PMS (each of which is partially regulated by prostaglandins). Vitamin B6 supplements (in conjunction with folic acid) reduce plasma levels of homocysteine. Vitamin B6, combined with magnesium, appears to reduce oxalate excretion and decrease the occurrence of kidney stones. Vitamin B6 is often recommended as a treatment of the inflammation and nerve compression in carpal tunnel syndrome. It is also an accessory treatment for symptoms of autism, and for reversing some of the side effects of a strong cancer medication, flurouracil.

Dietary Sources: Poultry, fish, whole grains and bananas.

Dosage: The RDA for vitamin B6 is 2mg. The dosage for relieving PMS, carpel tunnel and treating kidney stones is 10-50 mg one to three times per day.

Side Effects: As a water-soluble B vitamin, B6 is generally very safe as a dietary supplement. Excessive intakes (2-6 grams acutely or 500 mg chronically) are associated with sensory neuropathy (loss of feeling in the extremities) - which may or may not be reversible.

(Source: www.supplementwatch.com)

Research Overview

Human and animal studies were reviewed for pyridoxine deficiency and the effects of therapeutic application of the vitamin.
Pyridoxine deficiency has been shown to contribute to:
1. Increased risks associated with cigarette smoking
2. Gestational diabetes
3. Intensification of psychotic behavior in schizophrenia
4. Depression
5. Fatigue
6. Confused mental state
7. Decrease in serotonin and melatonin function
8. Convulsions
9. Tremors

Pyridoxine supplementation has been shown to:
1. Be effective in suppressing lactation following stillbirths, abortion and death of child
2. Cure carpal tunnel syndrome and eliminate need for surgery
3. Inhibit pancreatic cancers when administered with folate
4. Decrease risk of gastric cancer
5. Decrease symptoms associated with some chemotherapy
6. Suppress herpes simplex virus development
7. Improve immune function
8. Increase levels of lymphocytes and monocytes
9. Protect against parasitic infection
10. Aid the synthesis of CoQ10
11. Prevent abnormal increase in the number of cells
12. Improve glucose tolerance
13. Lower blood glucose levels
14. Improve glucose metabolism in gestational diabetes
15. Relieve symptoms of depression associated with oral contraceptive use
16. Provide better control for diabetes when combined with insulin
17. Alleviate PMS symptoms of depression, irritability, tiredness
18. Block epileptic seizures
19. Prevent seizures caused by isoniazid (tuberculosis treatment) toxicity
20. Prevent psychosis caused by isoniazid
21. Decreases depression associated with celiac disease
22. Be an effective treatment for hyperkinetic syndrome
23. Potentially improve dyskinesias (involuntary muscle movement) in Parkinson’s disease
24. Improve drug-induced dyskinesias
25. Dilate blood vessels and therefore be effective against motion sickness
26. Prevent lymphocyte blood count reduction
27. Reduce psychological distress associated with grief
28. Diminish homocysteine levels in the blood thus reducing the risk of cardiovascular disease
29. Prevent the formation of kidney stones

Following are some important aspects of pyridoxine
1. Children with leukemia have low levels of pyridoxine
2. People with chronic uremia have low levels of pyridoxine
3. Elderly people with low incomes and health problems tend to have low levels of pyridoxine
4. Teenage girls tend to have low levels of pyridoxine
5. Carpal tunnel symptoms reappear if pyridoxine is discontinued

Vitamin B6 Abstracts (457)

J Am Coll Nutr. 1999 Dec;18(6):582-90. Intakes of vitamin C, vegetables and fruits: which schoolchildren are at risk?

Hampl JS, Taylor CA, Johnston CS.

Graduate Program in Human Nutrition, Arizona State University, Tempe 85287-2502, USA.

OBJECTIVE: The purpose of this study was to determine vitamin C intakes among American schoolchildren. We investigated the leading sources of vitamin C in children's diets, the leading vegetables and fruits consumed by children and differences in dietary intake associated with vitamin C consumption. METHODS: Data from 1,350 7- to 12-year-old and 908 13- to 18-year-old schoolchildren were obtained from the 1994-1996 Continuing Survey of Food Intakes by Individuals (CSFII). The children were stratified by age and gender and then split into three vitamin C consumption groups based upon two 24-hour recalls: low (0 to 30.0 mg), marginal (30.1 to 59.9 mg), and desirable (>60.0 mg). Data were analyzed by tabulation and by ANOVA followed by post hoc Scheffe's test. Outcome measures included food groups and energy-adjusted intakes of micro- and macronutrients. RESULTS: Among the 7- to 12-year-olds, 12% of boys and 13% of girls had mean vitamin C intakes that were less than 30 mg/day, and, among 13- to 18-year-olds, 14% of boys and 20% of girls had low vitamin C intakes. In addition to consuming significantly more vitamin C, children with desirable vitamin C intakes also consumed significantly more (p <0.001) energy-adjusted folate and vitamin B6; children with low vitamin C intakes tended to have significantly greater (p <0.001) energy-adjusted intakes of fat and saturated fat. Children with desirable vitamin C intakes consumed significantly more (p <0.006) high-vitamin C fruit juice, low-vitamin C vegetables and whole milk. Children with low vitamin C intakes on average consumed two daily servings of vegetables and fruits, of which less than 1/5 of a serving was citrus, while children with desirable vitamin C intakes consumed an average of one daily serving of citrus. CONCLUSIONS: A considerable number of children drastically under-consumed vitamin C and total vegetables and fruits. Overall, children with desirable vitamin C intakes had healthier diets, including more milk and vegetables, than did their peers with low vitamin C intakes. Health care professionals should continue to promote at least five daily servings of vegetables and fruits and should advise parents that at least one of these should be rich in vitamin C.

J Am Acad Nurse Pract. 2003 Jan;15(1):18-22.

Carpal tunnel syndrome: current theory, treatment, and the use of B6.

Holm G, Moody LE.

University of South Florida, USA. dr.g.holm@usfaccess.com

PURPOSE: To present the current state of the science of pathophysiology, assessment and treatment of carpal tunnel syndrome, including the use of pyridoxine (B6). DATA SOURCES: Selected research articles, texts, Websites, personal communications with experts, and the authors' own clinical experience. CONCLUSIONS: Much is yet to be learned about carpal tunnel syndrome. While the basic treatment of NSAIDs and nighttime splints seems universally accepted, much controversy remains. The use of vitamin B6 as a treatment is one such controversy requiring further investigation. IMPLICATIONS FOR PRACTICE: Current treatment for carpal tunnel syndrome should include NSAIDs, nighttime splinting, ergonomic workstation review, and vitamin B6 200 mg per day.

Eur J Clin Nutr. 2002 Nov;56(11):1087-93. Biochemical deficiency of pyridoxine does not affect interleukin-2 production of lymphocytes from patients with Sjogren's syndrome.

Tovar AR, Gomez E, Bourges H, Ortiz V, Kraus A, Torres N.

Department of Physiology of Nutrition, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico, Mexico. artovar@quetzal.innsz.mx

BACKGROUND: There is evidence that pyridoxine deficiency may alter the immune response. It is not known whether a deficiency of this vitamin is evident in subjects with primary Sjogren's syndrome (SS). OBJECTIVE: We studied whether subjects with primary SS showed a biochemical deficiency of pyridoxine, and if it is associated with abnormal production of interleukin-2 from lymphocytes stimulated in vitro with phytohemagglutinin (PHA). DESIGN: Two studies were conducted, (i) biochemical and nutritional assessments were performed in a cross-over study in subjects with primary SS, who were supplemented with 25 mg/day of pyridoxine or placebo for 3 months. After 1 month washout, they were supplemented for 3 months with placebo, (ii) patients with SS and matched controls received pyridoxine or placebo for 45 days, and a blood sample was obtained to study IL-2 production and expression in T-lymphocytes stimulated with PHA. RESULTS: Subjects with primary SS showed limited dietary intake of pyridoxine and biochemical deficiency of this vitamin assessed through the activation coefficient of the erythrocyte aspartate aminotransferase. The biochemical deficiency did not affect production nor mRNA expression of IL-2 from T-lymphocytes stimulated in vitro with PHA compared with the control group. Supplementation of subjects with primary SS with 25 mg/day with pyridoxine for 45 days did not produce any significant change as compared to those patients supplemented with placebo. CONCLUSIONS: Subjects with primary SS showed biochemical deficiency of pyridoxine, possibly due to limited intake of this vitamin which was corrected by supplementation with pyridoxine. However, IL-2 production and mRNA expression from stimulated lymphocytes were unaffected by supplementation, probably because the deficiency was not severe enough to affect the immune system. SPONSORSHIP: This work was supported by the National Council of Science and Technology (CONACYT), Mexico, grant no. 212226-5-0902PM.

J Trop Pediatr. 2002 Oct;48(5):303-6.

Pyridoxine-dependent seizures: long-term follow-up of two cases with clinical and MRI findings, and pyridoxine treatment.

Ulvi H, Mungen B, Yakinci C, Yoldas T.

Firat University Medical Faculty, Department of Neurology, Elazig, Turkey. hizirulvi@yahoo.com

Pyridoxine-dependency is a rare autosomal recessive disorder causing a severe seizure disorder of neonatal onset. There are a few reports including neuroimaging studies, such as cranial CT and MRI, and one report with longitudinal MRI findings in two cases with pyridoxine-dependent seizures (PDS). We report long-term follow-up of two siblngs with PDS in the light of clinical, EEG, CT and MRI findings, and pyridoxine treatment. The first patient, an 8-year-old female who had neonatal seizures, has sequential cranial CT and MRIs which are normal except for mega cistema magna thus far. She still has mild mental retardation, although the accurate diagnosis was made when she was 6 years old and pyridoxine treatment was initiated. The second patient, a 1-year-old female, who is the younger sibling of the first patient, presented with neonatal seizures and PDS was diagnosed immediately, with resulting pyridoxine treatment (10 mg/kg/day). She is now neurologically normal, seizure-free, and has sequential normal CT and MRIs. These patients show rather benign clinical courses

Seizure. 2002 Sep;11(6):381-3. Add-on treatment with pyridoxine and sulthiame in 12 infants with West syndrome: an open clinical study.

Debus OM, Kohring J, Fiedler B, Franssen M, Kurlemann G.

University Children's Hospital, Department of Neuropediatrics, Westfalische-Wilhelms-Universitat Munster, Albert-Schweitzer-Str. 33, D - 48149 Munster, Germany. debuso@uni-muenster.de

To investigate the effect of sulthiame (STM) in West syndrome (WS) an open, uncontrolled add-on study was undertaken during initial pyridoxine (PDX) therapy in 12 infants, two with idiopathic and ten with symptomatic WS. All patients were initially treated with PDX (150-300 mg x kg (-1)body weight day(-1) ). In seven patients (58%) seizures and hypsarrhythmia stopped during the week after introduction of STM (10 mg x kg (-1)body weight day (-1)). In one the positive effect was temporary. Five of the responders (42%) remained seizure-free and without hypsarrhythmia under STM monotherapy, while one developed complex partial seizures after 25 months. STM was most effective in idiopathic WS (2 /2). During treatment with STM medication no patient suffered side effects attributable to the substance. Further controlled studies are necessary to evaluate the benefit of this potentially effective treatment.

Alcohol Clin Exp Res. 2002 Mar;26(3):340-6. Metadoxine in acute alcohol intoxication: a double-blind, randomized, placebo-controlled study.

Shpilenya LS, Muzychenko AP, Gasbarrini G, Addolorato G.

Narcological County Dispensary, Vasyleostrovsky District 4.th, Line V. 0.2 3-2 5, St. Petersburg, Russia.

BACKGROUND: At present there are only intriguing and preliminary clinical results regarding the efficacy of metadoxine (pyridoxol L-2-pyrrolidone-5-carboxylate) in acute alcohol intoxication. The present study was planned with the aim of investigating the effectiveness of metadoxine in the management of patients affected by acute ethanol intoxication. METHODS: A double-blind, randomized, multicenter, placebo-controlled trial was carried out on 58 patients of both sexes with acute ethanol intoxication. Patients were treated with a single dose of 900-mg intravenous metadoxine (n = 29) or with placebo (n = 29). Patients were clinically and biochemically evaluated at 0.5, 1, 2, 3, 6, 9, and 12 hr after treatment. RESULTS: Treatment with metadoxine significantly decreased the half-life of ethanol in blood (from 6.70 +/- 1.84 to 5.41 +/- 1.99 hr; p < 0.013) and showed a faster rate of ethanol elimination. The effects on ethanol half-life in blood were accompanied by a faster onset of recovery from intoxication, defined as the time of the transition of blood ethanol levels to the immediately lower range defined by intoxication categories (in g/liter: 0 to 0.5, absent; 0.51 to 1.0, mild; 1.1 to 2.5, moderate; >2.5, severe). Thus the median time to onset of recovery was 0.95 hr with metadoxine and 2.34 hr with placebo (p = 0.013). The effects of treatment on blood alcohol levels were paralleled by a significant decrease in the rating of the toxic clinical symptomatology. At 2 hr the improvement of toxic symptoms (in percent of maximum possible) was 68 +/- 28 vs. 44 +/- 27% in controls (p < 0.002). CONCLUSIONS: In patients with acute ethanol intoxication metadoxine accelerated the elimination of ethanol from blood, which led to faster recovery from intoxication, and improved the behavioral toxic symptomatology. Metadoxine could be helpful in the management of acute ethanol intoxication.

J Child Neurol. 2002 Mar;17(3):222-4.

Pyridoxine-dependent seizures associated with hypophosphatasia in a newborn.

Nunes ML, Mugnol F, Bica I, Fiori RM.

Division of Neurology, Hospital Sao Lucas, PUCRS School of Medicine, Porto Alegre-RS, Brazil. nunes@pucrs.br

Pyridoxine dependency and congenital hypophosphatasia are unusual metabolic disorders. We report a female infant born from healthy consanguineous parents with shortening of limbs, detected during pregnancy by ultrasonography. Immediately after delivery, the baby was admitted to the neonatal intensive care unit because of respiratory distress. A bone radiograph showed hypomineralization of all bones, and serum alkaline phosphatase was very low (10 U/L). Within the first day of life, seizures (focal clonic and tonic) started. The seizures were refractory to phenobarbital and other antiepileptic drugs. The first electroencephalogram (EEG) showed a burst-suppression pattern. Pyridoxine was administered (50 mg/kg) and completely controlled the seizures. Antiepileptic drugs were discontinued, and a maintenance dose of pyridoxine (10 mg/day) was established. A postpyridoxine EEG revealed the disappearance of the burst-suppression pattern. The patient died at age 26 days. Pyridoxine-dependent seizures, when recognized early and treated, have a more favorable prognosis. However, hypophosphatasia detected at birth almost always has a lethal outcome.

Pediatr Neurol. 2002 Mar;26(3):181-5. Pyridoxine-dependent seizures: findings from recent studies pose new questions.

Gospe SM.

Division of Pediatric Neurology, Department of Neurology, University of Washington, and Children's Hospital and Regional Medical Center, Seattle, WA 98105, USA.

Pyridoxine-dependent seizures, although a rare clinical entity, have been recognized as an etiology of intractable seizures in neonates and infants for more than 45 years. Recent research has focused on the molecular and neurochemical aspects of this disorder, as well as the optimal treatment of the condition. This review discusses the clinical features and management of patients with pyridoxine-dependent seizures together with a new hypothesis suggesting that an abnormality of pyridoxine transport may underlie the pathophysiology of this autosomal-recessive disorder.

N Engl J Med. 2001 Nov 29;345(22):1593-600.

Comment in: • N Engl J Med. 2002 Apr 4;346(14):1093-5. • N Engl J Med. 2002 Apr 4;346(14):1093-5. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels.

Schnyder G, Roffi M, Pin R, Flammer Y, Lange H, Eberli FR, Meier B, Turi ZG, Hess OM.

Division of Cardiology, Swiss Cardiovascular Center Bern, University Hospital. g.schnyder@lycos.com

BACKGROUND: We have previously demonstrated an association between elevated total plasma homocysteine levels and restenosis after percutaneous coronary angioplasty. We designed this study to evaluate the effect of lowering plasma homocysteine levels on restenosis after coronary angioplasty. METHODS: A combination of folic acid (1 mg), vitamin B12 (400 microg), and pyridoxine (10 mg)--referred to as folate treatment--or placebo was administered to 205 patients (mean [+/-SD] age, 61+/-11 years) for six months after successful coronary angioplasty in a prospective, double-blind, randomized trial. The primary end point was restenosis within six months as assessed by quantitative coronary angiography. The secondary end point was a composite of major adverse cardiac events. RESULTS: Base-tine characteristics and initial angiographic results after coronary angioplasty were similar in the two study groups. Folate treatment significantly lowered plasma homocysteine levels from 11.1+/-4.3 to 7.2+/-2.4 micromol per liter (P<0.001). At follow-up, the minimal luminal diameter was significantly larger in the group assigned to folate treatment (1.72+/-0.76 vs. 1.45+/-0.88 mm, P=0.02), and the degree of stenosis was less severe (39.9+/-20.3 vs. 48.2+/-28.3 percent, P=0.01). The rate of restenosis was significantly lower in patients assigned to folate treatment (19.6 vs. 37.6 percent, P=0.01), as was the need for revascularization of the target lesion (10.8 vs. 22.3 percent, P=0.047). CONCLUSIONS: Treatment with a combination of folic acid, vitamin B12, and pyridoxine significantly reduces homocysteine levels and decreases the rate of restenosis and the need for revascularization of the target lesion after coronary angioplasty. This inexpensive treatment, which has minimal side effects, should be considered as adjunctive therapy for patients undergoing coronary angioplasty

Am J Psychiatry. 2001 Sep;158(9):1511-4. Vitamin B(6) in the treatment of tardive dyskinesia: a double-blind, placebo-controlled, crossover study.

Lerner V, Miodownik C, Kaptsan A, Cohen H, Matar M, Loewenthal U, Kotler M.

Division of Psychiatry, Ministry of Health Be'er Sheva Mental Health Center, Faculty of Health Sciences Ben-Gurion University of the Negev, Israel. lernervld@yahoo.com

OBJECTIVE: The authors' goal was to conduct a double-blind trial of vitamin B(6) in the treatment of tardive dyskinesia in patients with schizophrenia. METHOD: Fifteen inpatients with schizophrenia who met research diagnostic criteria for tardive dyskinesia were randomly assigned to treatment with either vitamin B(6) or placebo for 4 weeks in a double-blind crossover paradigm. The Extrapyramidal Symptom Rating Scale was used to assess patients weekly. RESULTS: Mean scores on the parkinsonism and dyskinetic movement subscales of the Extrapyramidal Symptom Rating Scale were significantly better in the third week of treatment with vitamin B(6) than during the placebo period. CONCLUSIONS: Vitamin B(6) appears to be effective in reducing symptoms of tardive dyskinesia.

J Heart Lung Transplant. 2001 Sep;20(9):964-9. Pyridoxine improves endothelial function in cardiac transplant recipients.

Miner SE, Cole DE, Evrovski J, Forrest Q, Hutchison S, Holmes K, Ross HJ.

Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

BACKGROUND: Endothelial dysfunction is common in cardiac transplant recipients and predicts the development of transplant coronary artery disease. Hyperhomocysteinemia is associated with endothelial dysfunction in the general population, is common in transplant recipients, and has been associated with transplant coronary artery disease. Thus therapy that decreases homocysteine concentrations might also improve endothelial function and decrease the risk of transplant coronary artery disease. Folate and pyridoxine are important cofactors in distinct aspects of homocysteine metabolism. The purpose of this study was to determine whether folate or pyridoxine supplementation improves endothelial function in cardiac transplant recipients. METHODS AND RESULTS: This was a double-blind, randomized, placebo-controlled trial. We assigned 31 transplant recipients to either pyridoxine (n = 11:100 mg/day), folate (n = 12:5 mg/day), or placebo (n = 8) for 10 weeks. Fasting and post-methionine-load (methionine 100 mg/kg orally) homocysteine concentrations were determined. Brachial artery flow-mediated dilatation was used as a measure of endothelial function. At follow-up, we noted no significant changes in homocysteine concentrations in any of the groups. However, pyridoxine supplementation was associated with a significant improvement in endothelial function (2.8 +/- 6.7 to 6.9 +/- 6.3, p = 0.05). No significant changes were seen in patients treated with folate or placebo. CONCLUSIONS: Pyridoxine, but not folate supplementation, significantly improves endothelial function in cardiac transplant recipients.

Vestn Oftalmol. 2001 Sep-Oct;117(5):37-40.

[Prognostic significance of local and systemic indicators of lipid peroxidation and antioxidant system in perforating wounds of the eyes and their time course during local antioxidant treatment]

[Article in Russian]

Arkhipova LT, Dolgova IG.

Lipid peroxidation parameters malonic dialdehyde (MDA) and dienic conjugates (DC) and antioxidant defense (AOD) values superoxide dismutase (SOD), catalase, alpha-tocopherol were measured in the blood neutrophils and lacrimal fluid of 66 patients on days 1-2, 7-8, 14-15, and 21-22 after perforating wound of first, second, third, and fourth degree of severity according to P, 1. Lebekhov and in repeated injury, and the time course of these parameters during local treatment with therapeutic films with emoxipin and emoxipin + piridoxine was evaluated. A stable increase of MDA and DC levels in blood neutrophils, decrease of catalase, SOD, and alpha-tocopherol levels in blood neutrophils, and decrease of catalase enzymes and SOD activities in the lacrimal fluid of injured eye starting from days 7-8 are prognostically unfavorable signs. These data prompt the use of local and systemic treatment with antioxidants (emoxipin, tocopherol, etc.) in perforating wounds starting from the first days after the injury. Good clinical and antioxidant effect was observed after treatment with ocular therapeutic films with emoxipin and piridoxine.

J Clin Pharmacol. 2001 Aug;41(8):842-5. The safety of higher than standard dose of doxylamine-pyridoxine (Diclectin) for nausea and vomiting of pregnancy.

Atanackovic G, Navioz Y, Moretti ME, Koren G.

Division of Clinical Pharmacology/Toxicology, Hospital for Sick Children, Toronto, Canada.

A delayed-release combination of doxylamine-pyridoxine (D-P) (Diclectin) is the only approved antiemetic medication for use in pregnancy in Canada. The standard recommended dose is up to 4 tablets a day, regardless of body weight or severity of symptoms. The objective of this study was to determine the incidence of adverse maternal and fetal effects and pregnancy outcome in 225 women taking Diclectin at the recommended (n = 123) or higher than recommended (n = 102) doses. In this observational, prospective study, one-third (33.6%) of women reported having adverse effects (sleepiness, tiredness, and/or drowsiness) temporally related to the medication. There was no association between the dose per kg and rates of reported maternal adverse effects with doses ranging from 0.1 mg/kg to 2.0 mg/kg (1-12 tablets). Nausea and vomiting of pregnancy (NVP) was reported as severe by the majority (75.8%) of women. Mean birth weight (BW) was 3,400 g and gestational age (GA) 39 weeks. Multivariate analysis revealed that only prepregnancy weight and GA predicted lower BW, not the dose of D-P or the severity of NVP. There were two pregnancies with major malformation, a finding that is consistent with the rates of birth defects in the general population. It was concluded that the higher than standard dose of Diclectin, when calculated per kg of body weight, does not affect either the incidence of maternal adverse effects or pregnancy outcome. If needed, Diclectin can be given at doses higher than 4 tablets/day to normalize for body weight or optimize efficacy.

J Nutr. 2001 Aug;131(8):2204-7. Vitamin B-6-supplemented diets compared with a low vitamin B-6 diet suppress azoxymethane-induced colon tumorigenesis in mice by reducing cell proliferation.

Komatsu SI, Watanabe H, Oka T, Tsuge H, Nii H, Kato N.

Faculty of Applied Biochemistry, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.

Male ICR mice were examined for the effect of vitamin B-6 [pyridoxine (PN) HCl] on azoxymethane-induced colon tumorigenesis. Mice were fed the diets containing 1, 7, 14 or 35 mg PN HCl/kg for 22 wk, and given a weekly injection of azoxymethane (5 mg/kg body) for the initial 10 wk. Compared with the 1 mg PN HCl/kg diet, 7, 14 and 35 mg PN HCl/kg diets significantly suppressed the incidence and number of colon tumors, colon cell proliferation and expressions of c-myc and c-fos proteins. For some variables, 14 and 35 mg PN HCl/kg diets were more effective than the 7 mg/kg diet. Supplemental vitamin B-6 had no influence on the number of colon apoptotic cells. The results suggest that elevating dietary vitamin B-6 suppresses colon tumorigenesis by reducing cell proliferation.

J Nutr. 2001 Jun;131(6):1777-86.

Erratum in: • J Nutr 2001 Aug;131(8):2224. Assessment of vitamin B-6 status in young women consuming a controlled diet containing four levels of vitamin B-6 provides an estimated average requirement and recommended dietary allowance.

Hansen CM, Shultz TD, Kwak HK, Memon HS, Leklem JE.

Department of Food Science and Human Nutrition, Washington State University, Pullman, WA 99164-6376, USA.

The Recommended Dietary Allowance (RDA) of vitamin B-6 for young women was recently reduced from 1.6 to 1.3 mg/d based on an adequate plasma pyridoxal phosphate (PLP) concentration of 20 nmol/L. To assess vitamin B-6 requirements and suggest recommendations for intake, seven healthy young women consumed a controlled diet providing 1.2 g protein/kg body weight for a 7-d adjustment period (1.0 mg vitamin B-6/d) and three successive 14-d experimental periods (1.5, 2.1 and 2.7 mg/d, respectively). Direct and indirect vitamin B-6 status indicators were measured in plasma, erythrocytes and urine. Indicators most strongly correlated with vitamin B-6 intake [i.e., plasma and erythrocyte PLP, urinary 4-pyridoxic acid (4-PA) and total vitamin B-6] were regressed on vitamin B-6 intake and the dietary vitamin B-6 to protein ratio. Inverse prediction using adequate and baseline values estimated vitamin B-6 requirement. Adequate values were determined for plasma PLP and urinary 4-PA from baseline values of 60 previous subjects, using the statistical method suggested by Sauberlich. The current study suggests a vitamin B-6 Estimated Average Requirement (EAR) for young women of 1.1 mg/d or 0.016 mg/g protein, and a RDA of 1.5 mg/d or 0.020 mg/g protein. When results from this study are combined with data from four other recent studies, the combined data predict an EAR of 1.2 mg/d or 0.015 mg/g protein, and a RDA of 1.7 mg/d or 0.018 mg/g protein. This study suggests that the current vitamin B-6 RDA may not be adequate.

Harefuah. 2001 May;140(5):369-73, 456.

[Antidepressive effect of pyridoxine (vitamin B6) in neuroleptic-treated schizophrenic patients with co-morbid minor depression--preliminary open-label trial]

[Article in Hebrew]

Shiloh R, Weizman A, Weizer N, Dorfman-Etrog P, Munitz H.

Geha Psychiatric Hospital, Felsenstein Medical Research Center, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel.

BACKGROUND: Minor depression is reported in 20-60% of schizophrenic patients during various stages of their disorders; impairing patients' compliance, response to treatment and worsening their overall prognosis. Various anti-depressive treatments have been proposed for such cases but response rates are usually poor. Pyridoxine (Vitamin B6) in essential for the proper metabolism of various neurotransmitters that are considered relevant to the pathophysiology of depression and/or schizophrenia and it has been reported beneficial in ameliorating depressive symptoms as part of major depression, premenstrual syndrome or 'Chinese restaurant syndrome'. We hypothesized that addition of pyridoxine to on-going neuroleptic treatment could improve minor depression in schizophrenic patients. METHOD: Nine schizophrenic patients with co-morbid minor depression participated in this study. All participants had a stable unchanged clinical state (changes in Brief Psychiatric Rating Scale (BPRS). Scale for the Assessment of Positive Symptoms (SAPS), and Scale for the Assessment of Negative symptoms (SANS) scores < 5%) and all were maintained on unchanged doses of anti-psychotic drugs for at least 4 consecutive weeks prior to initiation of the study. Participants received, open-label, pyridoxine 150 mg/day in addition to their anti-psychotic treatment for 4 consecutive weeks. Mental status was evaluated before, during, and at the end of 4 weeks of pyridoxine administration using the BPRS, SAPS, SANS and HAM-D. RESULTS: Two of the nine patients (22%), characterized by higher initial HAM-D and SANS scores, and by older age and longer duration of illness, experienced marked improvements in depressive symptoms (23% and 28% decrease in HAM-D scores) following 4 weeks of pyridoxine administration. In one of these two, the improvement in depressive symptoms was accompanied by a parallel decrease in SANS Scores. CONCLUSION: A subgroup of schizophrenic patients with comorbid minor depression may benefit from pyridoxine addition to their on-going anti-psychotic treatment.

Am J Epidemiol. 2001 Apr 1;153(7):688-94. Association of the B-vitamins pyridoxal 5'-phosphate (B(6)), B(12), and folate with lung cancer risk in older men.

Hartman TJ, Woodson K, Stolzenberg-Solomon R, Virtamo J, Selhub J, Barrett MJ, Albanes D.

Department of Nutrition, The Pennsylvania State University, University Park, PA, USA.

A nested case-control study was conducted within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort to test for associations between selected B-vitamins (folate, vitamin B(6), vitamin B(12)) and incident lung cancer. This trial was conducted in Finland between 1985 and 1993. Serum was analyzed for these nutrients and homocysteine among 300 lung cancer cases and matched controls (1:1). Odds ratios and 95% confidence intervals were determined in conditional and unconditional (controlling for the matching factors) logistic regression models, after adjusting for body mass index, years of smoking, and number of cigarettes smoked per day. No significant associations were seen between serum folate, vitamin B(12), or homocysteine and lung cancer risk. The authors found significantly lower risk of lung cancer among men who had higher serum vitamin B(6) levels. Compared with men with the lowest vitamin B(6) concentration, men in the fifth quintile had about one half of the risk of lung cancer (odds ratio = 0.51; 95% confidence interval: 0.23, 0.93; p-trend = 0.02). Adjusting for any of the other serum factors (folate, B(12), and homocysteine) either alone or jointly did not significantly alter these estimates. This is the first report from a prospectively conducted study to suggest a role for vitamin B(6) in lung cancer.

J Ren Nutr. 2001 Apr;11(2):67-72. Homocysteine lowering effect of different multivitamin preparations in patients with end-stage renal disease.

Dierkes J, Domrose U, Bosselmann KP, Neumann KH, Luley C.

Institute of Clinical Chemistry and Biochemistry, Magdeburg, Germany.

OBJECTIVE: Hyperhomocysteinemia occurs in nearly 100% of patients with end-stage renal disease (ESRD) and is associated with increased morbidity and mortality. Means to reduce elevated homocysteine concentrations is supplementation with folic acid, vitamin B6, and vitamin B12. However, doses of vitamins required for optimized treatment are subject of debate. Therefore, the effect of 2 different multivitamin preparations on the homocysteine concentrations in patients with ESRD were compared. DESIGN: Patients received 3 times per week either 2 tablets of preparation A (800 microg folic acid, 6 microg vitamin B12, 10 mg vitamin B6), 2 tablets of preparation B (160 microg folic acid, no vitamin B12, 10 mg vitamin B6), or placebo for a period of 12 weeks with control of total homocysteine (tHcy) levels at baseline, and at 4, 8, and 12 weeks. SETTING: The study was performed at the University Hospital of Magdeburg, Germany in patients with ESRD treated with chronic intermittent maintenance hemodialysis. RESULTS: Preparation A reduced the tHcy concentration significantly by nearly 50%, whereas preparation B did not change the tHcy concentration in comparison with placebo. However, tHcy was not normalized in the majority of patients receiving preparation A. CONCLUSION: The reduction of tHcy achieved by a multivitamin containing 800 microg folic acid was substantial and even higher than the reduction reported in supplementation studies using higher doses of folic acid alone. Nevertheless, hyperhomocysteinemia in ESRD patients appears relatively refractory to vitamin supplementation, in contrast with results obtained in healthy volunteers.

Wiad Lek. 2001;54(1-2):11-8.

[Evaluation of vitamin B6 and calcium pantothenate effectiveness on hair growth from clinical and trichographic aspects for treatment of diffuse alopecia in women]

[Article in Polish]

Brzezinska-Wcislo L.

Katedry i Kliniki Dermatologii Slaskiej Akademii Medycznej w Katowicach.

The aim of the study was the clinical and trichological examination (trichogram and hair loss evaluation) conducted comparatively before and after the treatment in 46 women between pubescence and 30 years of age who had symptoms of diffuse alopecia. Calcium pantothenate was administered twice a day orally in doses 100 mg for 4-5 months. Vitamin B6 was injected every day (i ampoule intramusculary) for the period of 20 to 30 days and repeated again after 6 month. On the basis of clinical and trichological studies it was revealed that vitamin B6 administered parenterally for a period of several weeks induces improvement in the hair condition in a number of women and it reduces the hair loss especially in alopecia of telogenic patomechanism. Whereas calcium pantothenate in feminine diffuse alopecia did not show clearly the positive effect.

Endocr Pract. 2000 Nov-Dec;6(6):435-41.

Hyperhomocysteinemia in type 2 diabetes mellitus: cardiovascular risk factors and effect of treatment with folic acid and pyridoxine.

Baliga BS, Reynolds T, Fink LM, Fonseca VA.

Department of Pathology, University of Arkansas for Medical Sciences and VA Medical Center, Little Rock, Arkansas, USA.

OBJECTIVE: To determine whether hyperhomocysteinemia (HH) exacerbates other cardiovascular risk factors and markers of coagulation and hemostasis in patients with type 2 diabetes mellitus (DM) and whether treatment of HH with vitamins will alter these risk factors. METHODS: We measured several cardiovascular risk factors and markers of coagulation and hemostasis in patients with type 2 DM with and without HH. We also treated patients with type 2 DM and coexistent HH with high doses of folic acid and pyridoxine to determine whether this treatment would lower plasma total homocysteine concentrations as well as correct other associated cardiovascular risk factors in this population. RESULTS: Plasma levels of plasminogen activator inhibitor type 1 and fibrinogen were significantly higher in all patients with DM in comparison with control subjects (P<0.01), whether they had HH or not. No significant difference was noted between the two groups of patients with DM. The presence of hypertension and microalbuminuria did not lead to a higher plasma total homocysteine. After treatment with folic acid, 15 mg daily, and pyridoxine, 600 mg daily, fasting (basal) plasma total homocysteine declined significantly in patients with DM from 12.3 +/- 2.9 micromol/L to 9.1 +/- 1.1 micromol/L (P<0.01). The peak post-methionine load plasma total homocysteine in the patients with DM decreased from 39.9 +/- 11.4 micromol/L to 30.4 +/- 6.5 micromol/L (P<0.05). Neither fasting nor peak plasma total homocysteine changed in normal subjects. None of the cardiovascular risk factors measured changed significantly with the vitamin treatment. CONCLUSION: The coexistence of type 2 DM and HH does not lead to an exacerbation of abnormalities in the measured variables of coagulation and hemostasis. Treatment with high doses of folic acid and pyridoxine lowers the plasma total homocysteine significantly but does not improve any of the associated cardiovascular risk factors that we measured. Long-term clinical trials should be conducted to determine whether high-dose vitamin treatment will diminish the increased morbidity and mortality associated with cardiovascular disease in patients with type 2 DM.

Nephrol Dial Transplant. 2000 Sep;15(9):1410-3. Vitamin B6 supplementation can improve peripheral polyneuropathy in patients with chronic renal failure on high-flux haemodialysis and human recombinant erythropoietin.

Okada H, Moriwaki K, Kanno Y, Sugahara S, Nakamoto H, Yoshizawa M, Suzuki H.

Department of Nephrology, Saitama Medical College, Irumagun, Saitama, Japan.

BACKGROUND: High-flux haemodialysis (HD) has recently been vigorously promoted as a novel standard, and it can indeed efficiently reduce the occurrence of most uraemic symptoms due to middle molecular toxins and/or underdialysis. However, some symptoms remain problematical, particularly peripheral polyneuropathy (PPN). One of the possible reasons for this is that the patients may have low concentrations of some nutrients, e.g. vitamin B(6), necessary for normal peripheral neuron function. METHODS: Predialysis serum pyridoxal-5'-phosphate (P5P) level was determined in 36 chronic HD patients who were undergoing high-flux HD and receiving human recombinant erythropoietin. Among them, 26 patients suffered from PPN. Prior to supplementation, these 26 patients were examined and their neurological symptoms were ranked according to our PPN symptom score. Vitamin B(6) (60 mg/day) was randomly prescribed to 14 of them, and vitamin B(12) (500 microg/day) was prescribed to the others. After 4 weeks, all the patients were re-examined. RESULTS: We found that predialysis serum P5P levels of HD patients with PPN were not significantly lower than those of matched HD patients without PPN. Nonetheless, it was demonstrated that supplementation with vitamin B(6) for 4 weeks significantly increased the predialysis level of P5P and dramatically attenuated PPN symptoms compared with initial symptoms. No improvement was observed in response to vitamin B(12) supplementation. CONCLUSION: This result suggests that although vitamin B(6) deficiency could not be demonstrated in patients with chronic renal failure on high-flux HD, vitamin B(6) supplementation was effective in improving PPN symptoms of various aetiologies, possibly because of vitamin B(6) resistance to PPN in these patients.

Pediatr Neurol. 2000 Sep;23(3):202-6. Long-term follow-up of vitamin B(6)-responsive West syndrome.

Ohtsuka Y, Ogino T, Asano T, Hattori J, Ohta H, Oka E.

Department of Child Neurology, Okayama University Medical School, Okayama, Japan.

We performed a clinical and electroencephalographic follow-up study on 25 patients with West syndrome that was responsive to vitamin B(6) (eight cryptogenic patients and 17 symptomatic patients) who were older than 3 years at the last follow-up. All cryptogenic patients and 13 symptomatic patients were seizure free at the last follow-up. All cryptogenic patients and seven symptomatic patients had intelligent quotient or developmental quotient scores of 75 or higher. The recurrence of clinical seizures was always associated with increases in epileptic discharges. We could successfully discontinue pyridoxal phosphate administration in four cryptogenic and four symptomatic patients who were 1 year, 8 months to 24 years old.

Crit Care Med. 2000 Jun;28(6):2116-8. Pyridoxine therapy in a patient with severe hydrazine sulfate toxicity.

Nagappan R, Riddell T.

Intensive Care Unit, Whangarei Hospital, New Zealand.

OBJECTIVE: To report hydrazine sulfate as a cause of severe encephalopathy and to report its response to high-dose pyridoxine therapy. DESIGN: Case report. SETTING: An adult six-bed medical/surgical intensive care unit of a general hospital. PATIENT: One patient who developed severe encephalopathy after hydrazine sulfate. INTERVENTION: 5 g i.v. pyridoxine. MEASUREMENTS AND MAIN RESULTS: After 180 mg/day for 2 wks followed by 360 mg/day of hydrazine sulfate ingestion, our patient suffered severe encephalopathy. He received mechanical ventilation with attendant supportive measures and high-dose pyridoxine. The patient's encephalopathy resolved 24 hrs after receiving pyridoxine. CONCLUSION: Severe encephalopathy could result from hydrazine sulfate toxicity. High-dose pyridoxine is an effective treatment to reverse this encephalopathy.

J Child Neurol. 2000 Jun;15(6):424-8.

Current therapy for West syndrome in Japan.

Ito M, Seki T, Takuma Y.

Department of Pediatrics, Shiga Medical Center for Children, Tokyo, Japan. m-ito@qa2.so-net.ne.jp

We sent questionnaires concerning the current therapy for West syndrome to 208 institutions at which pediatric care members of the Japan Epilepsy Society were working. Of these, 129 (62%) institutions responded. Vitamin B6 was the preferred first-line drug, followed by the combination of vitamin B6 and valproate or monotherapy with valproate. Corticotropin was the third choice among the drugs. The dosage of corticotropin was lower than previously reported. The treatment of West syndrome is not well established at present and further research is needed to improve the therapeutic protocol.

Med Hypotheses. 2000 May;54(5):808-13. Prenatal high-dose pyridoxine may prevent hypertension and syndrome X in-utero by protecting the fetus from excess glucocorticoid activity.

McCarty MF.

Pantox Laboratories, San Diego, California, USA.

The increased risk for hypertension, insulin resistance syndrome, and coronary events associated with small-for-gestational-age birth, has plausibly been attributed to excessive prenatal exposure to glucocorticoids; this may up-regulate glucocorticoid activity throughout life by permanently decreasing expression of hippocampal glucocorticoid receptors crucial for feedback control of cortisol secretion. Since pyridoxal phosphate is a safe physiological antagonist of glucocorticoid activity, it is proposed that prenatal supplementation with high-dose pyridoxine may counteract the adverse impact of glucocorticoids on fetal growth, as well as on subsequent cardiovascular risk. Copyright 2000 Harcourt Publishers Ltd.

Med Hypotheses. 2000 May;54(5):803-7. High-dose pyridoxine as an 'anti-stress' strategy.

McCarty MF.

Pantox Laboratories, San Diego, California, USA.

Pyridoxine nutritional status has a significant and selective modulatory impact on central production of both serotonin and GABA - neurotransmitters which control depression, pain perception, and anxiety - owing to the fact that the decarboxylases which produce these neurotransmitters have a relatively low affinity for pyridoxal phosphate (PLP). Pyridoxine deficiency leads to increased sympathetic outflow and hypertension in rodents, possibly reflecting decreased central production of these neurotransmitters; conversely, supplemental pyridoxine lowers blood pressure in many animal models of hypertension, and there is preliminary evidence for antihypertensive activity in humans as well. Additionally, physiological levels of PLP interact with glucocorticoid receptors to down-regulate their activity. Thus, high-dose pyridoxine, by amplifying tissue levels of PLP, may be expected to have a favorable impact on certain dysphoric mental states, while diminishing sympathetic output and acting peripherally to blunt the physiological impact of corticosteroids. In light of growing evidence that chronic dysphoria, particularly when accompanied by hopelessness or cynicism, has a major negative impact on morbidity and mortality from a wide range of disorders, high intakes of pyridoxine may have the potential to improve prognosis in many individuals. With respect to cardiovascular health, reduction of homocysteine levels should contribute to this benefit. These predictions are consistent with recent epidemiology correlating plasma PLP levels with risk for vascular events and overall survival. Copyright 2000 Harcourt Publishers Ltd.

Neth J Med. 2000 Apr;56(4):138-46. Normohomocysteinaemia and vitamin-treated hyperhomocysteinaemia are associated with similar risks of cardiovascular events in patients with premature atherothrombotic cerebrovascular disease. A prospective cohort study.

Vermeulen EG, Rauwerda JA, Erix P, de Jong SC, Twisk JW, Jakobs C, Witjes RJ, Stehouwer CD.

Department of Surgery, Vascular Surgical Unit, University Hospital "Vrije Universiteit", PO Box 7057, 1007 MB, Amsterdam, The Netherlands. egj.vermeulen@azvu.nl

BACKGROUND: Mild hyperhomocysteinaemia (HHC) is associated with an increased risk of premature atherothrombotic cerebrovascular disease. We investigated the clinical efficacy with regard to the incidence of cardiovascular events of treatment of mild HHC with vitamin B(6) plus folic acid. METHODS: We studied 224 consecutive patients with clinically manifest atherothrombotic cerebrovascular disease with onset before the age of 56. Follow-up was obtained in 203 (90.6%) patients. At baseline, 52 (25.6%) were hyperhomocysteinaemic after methionine loading and started treatment with vitamin B(6) (250 mg) plus folic acid (5 mg); 151 (74.4%) were normohomocysteinaemic (reference group). RESULTS: During follow-up (median 57 months), 31 (20.5%) of the normo- and 11 (21.2%) of the hyperhomocysteinaemic patients had a new cardiovascular event. The crude incidence rate per person-year for any cardiovascular event was similar in both groups (0.043 [CI, 0.029-0.057] in the normo- vs. 0.045 [CI, 0.021-0. 069] in the hyperhomocysteinaemic group). Multivariate Cox-regression analyses showed that hypertension and cholesterol levels were associated with an increased risk of new cardiovascular events in the total group [relative risk [RR] (yes vs. no), 7.4 (3. 4-16.0) and RR (per 1 mmol/l), 1.9 (CI, 1.4-2.7)]. The adjusted RR for new cardiovascular events in the hyper- as compared to the normohomocysteinaemic patients was 0.96 (CI, 0.48-1.92). CONCLUSION: These data are consistent with a protective effect of treatment with vitamin B(6) plus folic acid in patients with premature atherothrombotic cerebrovascular disease and post-methionine HHC.

J Womens Health Gend Based Med. 2000 Mar;9(2):131-9. A synergistic effect of a daily supplement for 1 month of 200 mg magnesium plus 50 mg vitamin B6 for the relief of anxiety-related premenstrual symptoms: a randomized, double-blind, crossover study.

De Souza MC, Walker AF, Robinson PA, Bolland K.

Department of Food Science and Technology, The University of Reading, United Kingdom.

To investigate single and combined effects of daily dietary supplementation with 50 mg of vitamin B6 and 200 mg magnesium (as MgO) for one cycle for the relief of mild premenstrual symptoms, a randomized, double-blind, placebo-controlled, crossover design was used. Forty-four women with an average age of 32 years took part in the study. Each woman was randomly assigned, according to a Latin square design, to take consecutively all four of the following treatments daily for one menstrual cycle: (1) 200 mg Mg, (2) 50 mg vitamin B6, (3) 200 mg Mg + 50 mg vitamin B6 and (4) placebo. Throughout the study, each volunteer kept a daily record of symptoms using a 5-point ordinal scale in a menstrual diary of 30 symptoms. Symptoms were grouped into six categories: anxiety, craving, depression, hydration, other, and total. Urinary magnesium output for 24 hours was estimated using the Mg/creatinine concentration ratio. ANOVA showed no overall difference between individual treatments, but predefined treatment comparisons using factorial contrasts in ANOVA showed a significant effect of 200 mg/day Mg + 50 mg/day vitamin B6 on reducing anxiety-related premenstrual symptoms (nervous tension, mood swings, irritability, or anxiety) (p = 0.040). Urinary Mg output was not affected by treatment. A small synergistic effect of a daily dietary supplementation with a combination of Mg + vitamin B6 in the reduction of mild premenstrual anxiety-related symptoms was demonstrated during treatment of 44 women for one menstrual cycle. In view of the modest effect found, further studies are needed before making general recommendations for the treatment of premenstrual symptoms. The study indicated that absorption from MgO was poor and daily supplementation for longer than 1 month is necessary for tissue repletion.

Lancet. 2000 Feb 12;355(9203):517-22.

Comment in: • Lancet. 2000 Feb 12;355(9203):511-2. • Lancet. 2000 Jun 24;355(9222):2249; author reply 2250. Effect of homocysteine-lowering treatment with folic acid plus vitamin B6 on progression of subclinical atherosclerosis: a randomised, placebo-controlled trial.

Vermeulen EG, Stehouwer CD, Twisk JW, van den Berg M, de Jong SC, Mackaay AJ, van Campen CM, Visser FC, Jakobs CA, Bulterjis EJ, Rauwerda JA.

Department of General Surgery, University Hospital and Institute for Cardiovascular Research Vrije Universiteit, Amsterdam, The Netherlands.

BACKGROUND: A high plasma homocysteine concentration is associated with increased risk of atherothrombotic disease. We investigated the effects of homocysteine-lowering treatment (folic acid plus vitamin B6) on markers of subclinical atherosclerosis among healthy siblings of patients with premature atherothrombotic disease. METHODS: We did a randomised, placebo-controlled trial among 158 healthy siblings of 167 patients with premature atherothrombotic disease. 80 were assigned placebo and 78 were assigned 5 mg folic acid and 250 mg vitamin B6 daily for 2 years. The primary endpoint was the development or progression of subclinical atherosclerosis as estimated from exercise electrocardiography, the ankle-brachial pressure index, and carotid and femoral ultrasonography. FINDINGS: Ten participants in the treatment group, and 14 in the placebo group dropped out. Vitamin treatment, compared with placebo, was associated with a decrease in fasting homocysteine concentration (from 14.7 to 7.4 micromol/L vs from 14.7 to 12.0 micromol/L), and in postmethionine homocysteine concentration (from 64.9 to 34.9 micromol/L vs from 64.8 to 50.3 micromol/L). It was also associated with a decreased rate of abnormal exercise electrocardiography tests (odds ratio 0.40 [0.17-0.93]; p=0.035). There was no apparent effect of vitamin treatment on ankle-brachial pressure indices (0.87 [0.56-1.33]), or on carotid and peripheral-arterial outcome variables (1.02 [0.26-4.05] and 0.86 [0.47-1.59], respectively). INTERPRETATION: Homocysteine-lowering treatment with folic acid plus vitamin B6 in healthy siblings of patients with premature atherothrombotic disease is associated with a decreased occurrence of abnormal exercise electrocardiography tests, which is consistent with a decreased risk of atherosclerotic coronary events.

Med Clin (Barc). 2000 Jan 15;114(1):7-12. [Lowering high levels of fasting total homocysteine with folic acid and vitamins B in patients with venous thromboembolism: relationship between response and the C677T methylenetetrahydrofolate reductase (MTHRF) genotype]

[Article in Spanish]

Gonzalez Ordonez AJ, Medina Rodriguez JM, Fernandez Alvarez CR, Sanchez Garcia J, Fernandez Carreira JM, Alvarez Martinez MV, Coto Garcia E.

Servicio de Hematologia, Hospital San Agustin, Aviles. jagonzalez@medynet.com

BACKGROUND: High levels of plasma total homocysteine (tHcy) are involved in arterial or venous occlusive diseases. It essentially depends on the nutritional status of folic acid (FA) and vitamins B12 or B6, but also on the methylenetetrahydrofolate reductase (MTHFR) enzymatic activity. We aim to evaluate the response of the hyperhomocysteinemia (HHcy) to a standard schedule of vitamin supplementation, according with the MTHFR genotype. PATIENTS AND METHODS: 227 patients, diagnosed with venous thromboembolism (VTE) were analysed for tHcy (in fasting conditions), and for the MTHFR-C677T gene polymorphism. When the tHcy exceeded the cut-off point (men = 16, women = 15 mumol/l), the patients were supplemented with a dose equivalent to 1 mg FA, 0.2 mg B12 and 100 mg of B6, daily by 6 weeks. Afterwards they were reanalysed and the reduction was stratified by MTHFR genotype, looking for any difference in the response. RESULTS: The mean fasting tHcy was 12.3 mumol/l (SD = 8). The 51 hyperhomocysteinemic patients (22%) were older (65.1 y) than the normal ones (55.0 y) (p = 0.0001). The treatment was carried out properly in 46 patients (90%). The pre-treatment mean Hcy was 23.2 (SD = 10.5) mumol/l, and it was reduced to 13.0 (SD = 5.9) (p = 0.0001) (mean reduction = 42.1%). By genotype, the C/C reduced from 21.0 to 13.2 mumol/l (37%) (n = 18), the C/T from 25.0 to 12.6 mumol/l (46%) (n = 24), and the abnormal homozygotes T/T from 22.7 to 14.5 mumol/l (39%) (n = 4), although no statistical significant differences were found. In 80% of cases (37/46), tHcy values normalised. A negative correlation (r = -0.471) (p = 0.005) was observed between age and response. CONCLUSIONS: The FA/B6/B12 based therapy reduces in a simple, quick and effective way (> 40% in 6 weeks) the pathologic tHcy levels on a VTE population and this is not influenced by the MTHFR genotype. As HHcy seems related with recurrences of venous thrombosis, we could speculate if it would be useful to analyse routinely the tHcy, attempting reduction in selected cases.

Arch Tierernahr. 2000;53(3):227-39.

Effects of vitamin B6 supplementation in rats during lactation on vitamin B6 concentration and transaminase activities in the offspring.

Roth-Maier DA, Kettler SI, Benedikt J, Kirchgessner M.

Institute of Nutritional Sciences, Technical University Munich, Freising-Weihenstephan, Germany. Roth-Maier@weihenstephan.de

The aim of the present investigation was to study the effect of a varying maternal vitamin B6 supplementation during lactation period on vitamin B6 levels in blood, liver and total body, and on the activity of two transaminase enzymes in the offspring. Therefore, eighty female Sprague-Dawley rats were fed a semi-synthetic diet (0.2 mg vitamin B6 per kg) which was supplemented during gravidity with 5 mg vitamin B6 per kg diet. During the following lactation period the rats were assigned to one of 10 vitamin B6 treatment groups (supplementation of 0, 3, 6, 9, 12, 15, 18, 36, 360, 3600 mg vitamin B6 per kg diet). At day 14 of lactation the pubs of all dams were decapitated and blood, liver, and carcass were used for analysis of vitamin B6 concentration, activities of two transaminases, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in plasma, erythrocytes, and liver, and of haematological parameters. While the liver and total body wet weights as well as the haematological parameters (red blood cells, haemoglobin concentration, hematocrit, middle corpuscular cell volume, middle corpuscular haemoglobin, middle corpuscular haemoglobin concentration) did not differ within the experimental groups, the present data clearly show that in blood, liver and total body of the offspring exists a slight dose-response relationship between the maternal dietary vitamin B6 supplementation and the vitamin B6 concentration. Concerning the activities of the transaminases a dietary supplementation above 3 mg vitamin B6 per kg diet had no influence on the AST and ALT activities in offspring plasma. In the erythrocytes no statistical significant influence of the vitamin B6 supplementation during lactation on the activities of AST and ALT was found. The activities of ALT and AST in liver were not consistently altered by the vitamin B6 supplementation of the dams during lactation. In conclusion these results indicate that a minimal maternal dietary vitamin B6 supply of 3.1 mg per kg diet is necessary with regard to health and development of their offspring. But not all of the analysed parameters as the liver and total body weights, the activities of AST and ALT in the erythrocytes, and the haematological parameters were influenced by a deficient maternal dietary vitamin B6 supply.

J Anim Sci. 2000 Jan;78(1):88-93. Added dietary pyridoxine, but not thiamin, improves weanling pig growth performance.

Woodworth JC, Goodband RD, Nelssen JL, Tokach MD, Musser RE.

Department of Animal Sciences and Industry, Kansas State University, Manhattan 66506-0210, USA.

We conducted two trials to determine the effects of added dietary pyridoxine (vitamin B6) or thiamin (vitamin B1) on growth performance of weanling pigs. In Exp. 1, weanling pigs (n = 180, initially 5.55 +/- .84 kg, and 21 +/- 2 d of age) were fed either a control diet (no added pyridoxine or thiamin) or the control diet with added thiamin (2.8 or 5.5 mg/kg) from thiamin mononitrate or pyridoxine (3.9 or 7.7 mg/kg) from pyridoxine HC1. These five diets were fed in meal form in two phases (d0 to 14 and 14 to 35 after weaning), with identical vitamin concentrations in both phases. From d 0 to 14 after weaning, pigs fed added pyridoxine had increased (quadratic, P < .05) ADG and ADFI; pigs fed 3.9 mg/kg of added pyridoxine had the greatest improvement. From d 14 to 35 and 0 to 35, ADG and ADFI increased (linear P = .06) for pigs fed increasing pyridoxine. Growth performance was not improved by added thiamin. In Exp. 2, weanling pigs (n = 216, initially 6.08 +/- 1.13 kg, and 21 +/- 2 d of age) were fed a control diet or the control diet with 1.1, 2.2, 3.3, 4.4, or 5.5 mg/kg of added pyridoxine from pyridoxine HCl. From d 0 to 14 after weaning, increasing pyridoxine increased (quadratic, P < .05) ADG and ADFI; pigs fed 3.3 mg/kg of added pyridoxine had the greatest ADG and ADFI. Break-point analysis suggested a requirement estimate of 3.3 and 3.0 mg/kg of added pyridoxine to maximize ADG and ADFI, respectively. From d 14 to 35 or 0 to 35, increasing pyridoxine had no effect (P > .10) on pig growth performance. These results suggest that adding 3.3 mg/kg of pyridoxine (7.1 to 7.9 mg/kg of total pyridoxine) to diets fed from d 0 to 14 after weaning can improve pig growth performance.

Am J Cardiol. 1999 Dec 1;84(11):1359-61, A8. Effect of short-term vitamin (folic acid, vitamins B6 and B12) administration on endothelial dysfunction induced by post-methionine load hyperhomocysteinemia.

Chao CL, Chien KL, Lee YT.

Department of Internal Medicine (Cardiology), National Taiwan University Hospital, Taipei. clchao@ha.mc.ntu.edu.tw

This study showed that short-term vitamin administration effectively reduced post-methionine load homocysteine levels and thereby ameliorated endothelium-dependent flow-mediated vasodilation in 16 healthy adults. Post-methionine load homocysteine levels decreased from 22.7+/-3.8 to 17.0+/-2.1 micromol/L (p <0.001), and flow-mediated vasodilation after methionine load increased from 8.6+/-3.6% to 13.8+/-2.9% (p <0.001) after vitamin administration.

Kidney Int. 1999 Dec;56(6):2292-6. Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous folinic acid and pyridoxine therapy.

Touam M, Zingraff J, Jungers P, Chadefaux-Vekemans B, Drueke T, Massy ZA.

Division of Nephrology, INSERM U507, and Biochemistry B Laboratory, Necker Hospital, Paris, France.

Effective correction of hyperhomocysteinemia in hemodialysis patients by intravenous folinic acid and pyridoxine therapy. BACKGROUND: Folic acid supplementation is only partially efficacious in correcting moderate elevation of plasma total homocysteine (tHcy) concentrations observed in hemodialysis (HD) patients. Experimental and clinical data have suggested that this partial efficacy may be due to impairment of folic acid metabolism to 5-methyltetrahydrofolate (MTHF) and of MTHF transmembrane transport as well. To bypass these difficulties, we assessed the efficacy of intravenous (i.v.) folinic acid, a ready precursor of MTHF, on reducing plasma tHcy concentrations in HD patients. METHODS: In a cohort of 37 patients on intermittent HD treatment, plasma tHcy concentrations were determined before and during i.v. supplementation of folinic acid (50 mg once per week), together with i.v. pyridoxine (250 mg 3 times per week), to prevent vitamin deficiency, particularly in those treated by recombinant erythropoietin. RESULTS: Folinic acid and pyridoxine i.v. supplementation was given for 11.2 +/- 2.45 months (range 7.5 to 17 months). The mean plasma tHcy levels decreased significantly from 37. 3 +/- 5.8 microM at baseline to 12.3 +/- 5.4 microM on folinic acid treatment (P < 0.001). Moreover, 29 of the 37 patients (78%) had normal plasma tHcy levels at the end of follow-up (that is, <14.1 microM, mean 9.8 microM, range 6.2 to 13 microM). No adverse effects attributable to folinic acid treatment were observed during this time. CONCLUSIONS: Intravenous folinic acid therapy (50 mg) once per week associated with pyridoxine supplementation appears to be an effective and safe strategy to normalize plasma tHcy levels in the majority of chronic HD patients.

Am J Clin Nutr. 1999 Nov;70(5):881-7. Increased dietary micronutrients decrease serum homocysteine concentrations in patients at high risk of cardiovascular disease.

Chait A, Malinow MR, Nevin DN, Morris CD, Eastgard RL, Kris-Etherton P, Pi-Sunyer FX, Oparil S, Resnick LM, Stern JS, Haynes RB, Hatton DC, Metz JA, Clark S, McMahon M, Holcomb S, Reusser ME, Snyder GW, McCarron DA.

Division of Metabolism, Department of Medicine, University of Washington, Seattle, USA.

BACKGROUND: Elevated blood homocysteine is a risk factor for cardiovascular disease. A 5-micromol/L increase is associated with an approximately 70% increase in relative risk of cardiovascular disease in adults. For patients with established risk factors, this risk is likely even greater. OBJECTIVE: Effects of increased dietary folate and recommended intakes of vitamins B-12 and B-6 on serum total homocysteine (tHcy) were assessed in individuals at high risk of cardiovascular disease. DESIGN: This trial was conducted at 10 medical research centers in the United States and Canada and included 491 adults with hypertension, dyslipidemia, type 2 diabetes, or a combination thereof. Participants were randomly assigned to follow a prepared meal plan (PMP; n = 244) or a self-selected diet (SSD; n = 247) for 10 wk, which were matched for macronutrient content. The PMP was fortified to provide >/=100% of the recommended dietary allowances for 23 micronutrients, including folate. RESULTS: Mean folate intakes at 10 wk were 601 +/- 143 microgram/d with the PMP and 270 +/- 107 microgram/d with the SSD. With the PMP, serum tHcy concentrations fell from 10.8 +/- 5.8 to 9.3 +/- 4.9 micromol/L (P < 0.0001) between weeks 0 and 10 and the change was associated with increased intakes of folate, vitamin B-12, and vitamin B-6 and with increased serum and red blood cell folate and serum vitamin B-12 concentrations. tHcy concentrations did not change significantly with the SSD. CONCLUSIONS: The PMP resulted in increased intakes and serum concentrations of folate and vitamin B-12. These changes were associated with reduced serum tHcy concentrations in persons at high risk of cardiovascular disease.

Arch Dis Child. 1999 Nov;81(5):431-3. Epidemiology of pyridoxine dependent and pyridoxine responsive seizures in the UK.

Baxter P.

Ryegate Centre, Sheffield Children's Hospital, Tapton Crescent, Sheffield S10 5DD, UK. p.s.baxter@sheffield.ac.uk

OBJECTIVE: To study the epidemiology of pyridoxine dependent seizures and other forms of pyridoxine responsive seizures. DESIGN: Monthly notifications to the British Paediatric Surveillance Unit over two years. Questionnaire follow up. SETTING: UK and the Republic of Ireland. PATIENTS: Children aged 15 years or younger whose seizures respond to pyridoxine. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Numbers of children with definite, probable, and possible pyridoxine dependent seizures or other seizures responsive to pyridoxine. RESULTS: Point prevalence and birth incidence: 1/687 000 and 1/783 000, respectively (definite and probable cases); 1/317 000 and 1/157 000, respectively (all types of pyridoxine responsiveness). NOTIFICATIONS: Pyridoxine dependency: 14 definite, 9 probable, and 10 possible cases; neonatal seizures not meeting case definitions: 7; infantile spasms: 5. Eight of 18 families of definite/probable cases had 2 affected siblings. Just over a third had atypical presentations and just under a third had features and/or initial diagnoses of birth asphyxia and neonatal hypoxic ischaemic encephalopathy. CONCLUSIONS: Pyridoxine dependency is rare. Atypical presentations are relatively frequent. A trial of pyridoxine is justified in all cases of early onset intractable seizures or status epilepticus, whatever the suspected cause.

Med Pregl. 1999 Nov-Dec;52(11-12):501-4.

[A case report of pyridoxine-responsive homocystinuria]

[Article in Croatian]

Milosevic-Tosic M, Borota J, Katanic D, Vlaski J.

Institut medicinskih sluzbi, Zavod za biohemiju, Medicinski fakultet, Novi Sad.

INTRODUCTION: Homocystinuria is a rare, congenital, autosomal-recessive, metabolic disease biochemically characterized by homocysteinemia and homocystinuria and by multi-system clinical disorders. It is a biochemical abnormality of methionine metabolism caused either by transulfuration pathway disorders or by disorders of homocysteine remethilation into methionine and as such it can be a result of numerous specific and different genetic lesions. CASE REPORT: Homocystinuria is most commonly caused by deficiency of cystationine beta synthetase enzyme which catalyses the synthesis of cystathionine from homocysteine and serine in the methinione pathway. This results in accumulation of homocysteine and methionine in plasma and leads to excretion of excessive urinary homocysteine. Depending on specific property of the mutant enzyme molecule some patients respond to very high doses of pyridoxine with decreases of methionine and homocystine and some not. Pyridoxine responsiveness is based on the presence of small residual activity of cystathionine beta synthetase which is not present in nonresponsive patients. Homocystinuria due to cystathionine beta-synthase (CBS) deficiency is characterized by numerous different clinical abnormalities, but changes in four organ systems are dominant (eye, skeletal, central nervous and vascular system). CASE DESCRIPTION: Six years ago a six year-old boy was admitted to the hospital with vision problems. Ophthalmologic examination revealed a lens dislocation and because of many stigmates the child was sent to endocrinologist. The child had a marfanoid stature, with pectus carinatum and genu valgum, ataxic gait with motoric discoordination, muscle tone which ranged from hypotonia to hypertonia of extrapvramidal type and low intellectual abilities. A simple cyanide-nitroprusside test of patient's urine was positive suggesting homocystinuria. The diagnosis was established after plasma and urine amino acid analysis by HPLC. Concentration of homocystine and methionine were 52 mumol/l and 57 mumol/l in plasma and 249 mumol/du and 55 mumol/du in urine, respectively. After four months of treatment with pyridoxine there were not any significant changes in plasma homocysteine and methionine, but at the same time decrease in urine of these two amino acids were more than 2.5 times higher. This confirms that the patient has a pyridoxine-responsive type of homocystinuria and the dose was increased to 60 mg/day and 600 mg/day. This results in further decline of homocysteine and methionine in plasma and urine which persists up to now (for six years).

J Child Neurol. 1999 Oct;14(10):687-90.

Pyridoxine-dependent seizures in an older child.

Yoshikawa H, Abe T, Oda Y.

Department of Pediatrics, Niigata City General Hospital, Niigata, Japan. yos@seagreen.ocn.ne.jp

The case of a 12-year-old girl with pyridoxine-dependent seizures is reported. She developed status epilepticus just after birth and ordinary antiepileptic drugs were administered without effect. Her seizures ceased only on the administration of pyridoxine. Status epilepticus associated with the withdrawal of pyridoxine occurred three times, and ceased only after the renewed administration of pyridoxine. She now has mental retardation and mild spastic diplegia. The reported cases of pyridoxine-dependent seizures usually have been neonates and infants. Older patients were not fully investigated, and so we have reviewed these cases of pyridoxine-dependent seizures. As known previously, pediatricians should not forget that pyridoxine should be continued for life.

Mol Cell Biochem. 1999 Oct;200(1-2):155-62.

Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats.

Vasdev S, Ford CA, Parai S, Longerich L, Gadag V.

Department of Medicine, Health Sciences Centre, Memorial University of Newfoundland, St. John's, Canada.

In spontaneously hypertensive rats (SHRs) excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels, increasing cytosolic free calcium and blood pressure. N-acetyl cysteine normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes. It is known that dietary vitamin B6 supplementation can increase the level of endogenous cysteine. Our objective was to investigate whether a dietary supplementation of vitamin B6 can prevent hypertension and associated changes in SHRs. Starting at 7 weeks of age, animals were divided into three groups of six animals each. Animals in WKY-control group and SHR-control group were given a normal vitamin B6 diet; and SHR-vitamin B6 group, a high vitamin B6 diet (20 times the recommended dietary intake; RDA) for the next 14 weeks. After 14 weeks, systolic blood pressure, platelet [Ca2+]i and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls compared to WKY controls. These animals also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin B6 supplementation attenuated the increase in systolic blood pressure, tissue aldehyde conjugates and associated changes. These results further support the hypothesis that aldehydes are involved in increased systolic blood pressure in SHRs and suggest that vitamin B6 supplementation may be an effective antihypertensive.

Thromb Res. 1999 Sep 15;95(6):281-8. Treatment of hyperhomocysteinemia with folic acid and vitamins B12 and B6 attenuates thrombin generation.

Undas A, Domagala TB, Jankowski M, Szczeklik A.

Department of Medicine, University School of Medicine, Cracow, Poland.

The effect of homocysteine-lowering treatment on thrombin generation was investigated in 17 subjects with hyperhomocysteinemia (aged 22-60 years), 11 of whom had symptomatic atherosclerotic vascular disease. All subjects had fasting total homocysteine levels above 16 micromol/L. The formation of thrombin was assessed by measuring thrombin-antithrombin III complexes and prothrombin fragment 1+2 in peripheral venous blood and in the bleeding time blood collected at 30-second intervals from skin incisions on a forearm. All the tests were performed before and after an 8-week treatment with folic acid p.o. 5 mg/day, vitamin B6 p.o. 300 mg/day, and vitamin B12 i.m. 1000 microg given on a weekly basis. Following the 8-week therapy, the median plasma homocysteine concentration became significantly reduced from 20 to 10 micromol/L, while plasma levels of fibrinogen, prothrombin, and antithrombin III as well as activity of protein C, S, and factor VII showed no changes. Vitamin treatment was associated with a significant fall in thrombin-antithrombin III complexes and prothrombin fragment 1+2 concentrations in peripheral venous blood. Bleeding time became prolonged by about 60 seconds. At sites of hemostatic plug formation, plasma concentrations of both thrombin markers significantly decreased. Compared with pretreatment values, significantly less thrombin was produced during the first 3 minutes of bleeding after homocysteine-lowering therapy. In subjects with hyperhomocysteinemia a reduction of plasma fasting homocysteine concentration by folic acid and vitamins B12 and B6 administration is associated with attenuation of thrombin generation both in peripheral blood and at sites of hemostatic plug formation.

J Nutr Sci Vitaminol (Tokyo). 1999 Aug;45(4):449-58.

Adequacy of maternal pyridoxine supplementation during pregnancy in relation to the vitamin B6 status and growth of neonates at birth.

Chang SJ.

Department of Biology, National Cheng Kung University, Tainan, Taiwan. sjchang@mail.ncku.edu.tw

To evaluate the adequacy of maternal pyridoxine supplementation during pregnancy for both maternal and neonatal status at birth, vitamin B6 status, assessed by plasma pyridoxal phosphate (PLP), pyridoxal (PL) and total aldehyde vitamer (PLP + PL) concentrations, and the growth of neonates, including weight, length, head and chest circumferences, were examined for 209 neonates whose mothers were supplemented with 0, 1, 2 or 3 mg pyridoxine.HCl (PN.HCl)/d during pregnancy. Maternal PN.HCl supplementations were positively correlated to both maternal (r = 0.62) and cord (r = 0.78) plasma PLP concentrations (p < 0.0001). Mothers supplemented with 2 or 3 mg/d PN.HCl had significantly higher plasma concentrations of PLP and total B6 aldehyde vitamer in maternal and cord blood compared with those receiving 0 or 1 mg PN.HCl/d. A growth benefit for neonates whose mothers had maternal and cord plasma PLP concentrations > or = 40 nM was revealed by the maternal supplementation of 2 mg PN.HCl/d during pregnancy. Thus, in healthy pregnant women, according to our study, a daily supplement of 2 mg PN.HCl provides the adequacy of maternal and neonatal vitamin B6 status and the satisfactory growth of neonates at birth.

Rinsho Ketsueki. 1999 Aug;40(8):667-72.

[An infant case of sideroblastic anemia that responded to oral pyridoxine]

[Article in Japanese]

Kudo K, Ito M, Horibe K, Iwase K, Kojima S.

Department of Pediatrics, Nagoya University School of Medicine.

An 8-month-old boy was admitted because of paleness. Laboratory studies disclosed microcytic and hypochromic anemia: red blood cell count 156 x 10(4)/microliter, hemoglobin 3.5 g/dl, mean cell volume 66 fl, and reticulocytes 0.5/1000. Serum iron was 433 micrograms/dl and exocrine pancreatic dysfunction was not observed. Examination of bone marrow revealed prominent erythroid hyperplasia; 18% of the erythroblasts were distinct ringed sideroblasts. Electron microscopic studies found intramitochondrial iron deposits in the erythroblasts. The patient was given a diagnosis of sideroblastic anemia and responded to oral pyridoxine (50 mg/day) with an immediate increase of reticulocytes to 97/1000, resulting in an improved hemoglobin concentration. He has maintained remission for more than 1 year following discontinuation of pyridoxine, which was administered for 2 months. Congenital sideroblastic anemia is relatively rare and mostly occurs in males, suggesting an X-linked recessive mode of inheritance. Recently, X-linked sideroblastic anemia has been shown to be caused by missense mutations in the delta-aminolevulinic acid synthase (ALAS) gene. A point mutation in exon 5 of the ALAS gene was found in this patient. Iron-deficiency anemia is the most common hematologic disease of infancy and childhood, resulting from lack of sufficient iron for synthesis of hemoglobin. It is therefore mandatory to differentiate sideroblastic anemia from iron-deficiency anemia and other common anemias.

Clin Neuropharmacol. 1999 Jul-Aug;22(4):241-3.

Vitamin B6 in treatment of tardive dyskinesia: a preliminary case series study.

Lerner V, Kaptsan A, Miodownik C, Kotler M.

Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

Tardive dyskinesia (TD) remains a significant problem for patients and physicians. Several reports have suggested that vitamin B6 (pyridoxine) can be helpful in the treatment of some neuroleptic-induced movement disorders, including parkinsonism and TD. This report presents the results of a preliminary study of five patients with TD who underwent a four week open-label clinical trial of vitamin B6 (100 mg/d) in addition to their regular medications. The severity of the involuntary movements was assessed using the Abnormal Involuntary Movement Scale (AIMS), Barnes Akathisia Rating Scale (BARS) and the Simpson-Angus Scale (SAS). The patients' clinical status was assessed with the Brief Psychiatric Rating Scale (BPRS). With the addition of vitamin B6 to their treatment, four patients had clinically significant (greater than 30%) improvement on the measures of involuntary movement and, in three cases, there was also clinically significant improvement on the BPRS. None of the patients had side effects attributable to vitamin B6. The results suggest that vitamin B6 may alleviate TD, but it will need to be further tested in controlled double-blind trials.

J Intern Med. 1999 Jul;246(1):87-96. Normohomocysteinaemia and vitamin-treated hyperhomocysteinaemia are associated with similar risks of cardiovascular events in patients with premature peripheral arterial occlusive disease. A prospective cohort study.

de Jong SC, Stehouwer CD, van den Berg M, Geurts TW, Bouter LM, Rauwerda JA.

Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands.

OBJECTIVES: Mild hyperhomocysteinaemia (HHC), fasting or after methionine loading, is associated with an increased risk and severity of atherosclerotic vascular disease. Post-methionine and fasting HHC are responsive to treatment with vitamin B, and folic acid. We performed a prospective cohort study amongst normohomocysteinaemic and vitamin-treated (vitamin B6, 250 mg plus folic acid, 5 mg daily) hyperhomocysteinaemic patients with premature peripheral arterial occlusive disease and assessed the incidence of cardiovascular events. DESIGN: We studied 273 consecutive patients with clinically manifest peripheral arterial occlusive disease with onset before the age of 56, 79 (28.9%) of whom had postmethionine HHC. Follow-up was obtained in 232 (85'%o) patients. At baseline, 70 (30')/) were hyperhomocysteinaemic after methionine loading and started treatment with vitamin B, and folic acid; 162 (70%) were normohomocysteinaemic (reference group). RESULTS: During the follow-up period (median 20, range 1-63 months), 48 (29.6%) and 23 (32.9%) of the normo- and the hyperhomocysteinaemic patients, respectively, had a new cardiovascular event. Most (75%) involved the peripheral arterial system. The crude incidence rate for any cardiovascular event was 0.16 (95% CI, 0.12-0.21) per person per year in the normohomocysteinaemic and 0.16 (95% CI, 0.09-0.22) per person per year in the hyperhomocysteinaemic group. Multivariate Cox regression analyses showed that higher plasma homocysteine levels were associated with an increased risk of new cardiovascular events in the normohomocysteinaemic patients (relative risk [RR] per 1 micromol L(-1), 1.17 [CI, 1.05-1.30] for fasting and 1.06 [CI, 1.01-1.12] for postmethionine levels), but not in the hyperhomocysteinaemic (vitamin-treated) patients. The adjusted RR for new cardiovascular events in the hyper- as compared to the normohomocysteinaemic patients was 0.76 (CI, 0.33-1.74). CONCLUSIONS: These data are consistent with a protective effect of treatment with vitamin B6 and folic acid in patients with premature peripheral arterial occlusive disease and postmethionine HHC. Double-blind randomized trials are necessary to confirm this.

Cancer Epidemiol Biomarkers Prev. 1999 Jun;8(6):513-8. Methylenetetrahydrofolate reductase, diet, and risk of colon cancer.

Slattery ML, Potter JD, Samowitz W, Schaffer D, Leppert M.

University of Utah Medical School, Salt Lake City 84108, USA.

Individuals with different forms of the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, carriers of the C677T mutation versus wild type, show differences in enzyme levels; these differences have been hypothesized to be related to DNA methylation and, perhaps, to the nucleotide pool size. Using data from an incident case-control study, we evaluated the combined effect of dietary intake of folate, methionine, vitamin B6, vitamin B12, and alcohol and various forms of the MTHFR gene on risk of colon cancer. Individuals homozygous for the variant form of the MTHFR gene (TT) had a slightly lower risk of colon cancer than did individuals who were wild type [CC, odds ratio (OR) = 0.8, 95% confidence interval (CI) = 0.6-1.1 for men; and OR = 0.9, 95% CI = 0.6-1.2 for women]. High levels of intake of folate, vitamin B6, and vitamin B12 were associated with a 30-40% reduction in risk of colon cancer among those with the TT relative to those with low levels of intake who were CC genotype. Associations were stronger for proximal tumors, in which high levels of intake of these nutrients were associated with a halving of risk among those with the TT genotype. The inverse association with high levels of these nutrients in those with the TT genotype was stronger among those diagnosed at an older age. Although imprecise, the inverse association with the low-risk diet that was high in folate and methionine and without alcohol was observed for both the TT genotype (OR = 0.4 95% CI = 0.1-0.9) and the CC/CT genotype (OR = 0.6, 95% CI = 0.4-1.0), but this association was not seen with the high-risk diet for either the TT or CC/CT genotype. Although associations were generally weak, these findings suggest that those with differing MTHFR genotypes may have different susceptibilities to colon cancer, based on dietary consumption of folate, vitamin B6, and vitamin B12.

J Am Soc Nephrol. 1999 Jun;10(6):1287-96. Effects of high-dose folic acid and pyridoxine on plasma and erythrocyte sulfur amino acids in hemodialysis patients.

Suliman ME, Divino Filho JC, Barany P, Anderstam B, Lindholm B, Bergstrom J.

Department of Clinical Science, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden.

In this investigation, sulfur amino acids (sAA) and sulfhydryls were determined in the plasma and erythrocytes (RBC) of 10 uremic patients on regular hemodialysis (HD) treatment and 10 healthy subjects, before and after supplementation with 15 mg/d of folic acid and 200 mg/d of pyridoxine for 4 wk. The basal total plasma concentrations of homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cys-Gly), gamma-glutamylcysteine (gamma-Glu-Cys), glutathione (GSH), and free cysteinesulfinic acid (CSA) were significantly higher in HD patients when compared to healthy subjects, whereas methionine (Met) and taurine (Tau) concentrations were the same in the two groups. HD patients showed significantly higher RBC levels of Hcy and Cys-Gly, whereas the RBC concentrations of Met, Cys, Tau, and GSH were not different from those in the healthy subjects. The plasma concentrations of sAA and sulfhydryls differed compared with RBC levels in the healthy subjects and HD patients. In both groups, supplementation with high doses of folic acid and pyridoxine reduced the plasma Hcy concentration. In addition, increased plasma concentrations of Cys-Gly and GSH were found in the HD patients and of CSA in the healthy subjects. After vitamin supplementation, the RBC concentrations of Hcy, Cys, and GSH increased and that of Tau decreased in healthy subjects. The only significant finding in RBC of HD patients was an increase in GSH levels after supplementation. This study shows several RBC and plasma sAA and sulfhydryl abnormalities in HD patients, which confirms earlier findings that RBC and plasma pools play independent roles in interorgan amino acid transport and metabolism. Moreover, high-dose supplementation with folic acid and pyridoxine significantly reduced Hcy levels, but did not restore the sAA and sulfhydryl abnormalities to normal levels. The increase that was observed in GSH after vitamin supplementation may have a beneficial effect in improving blood antioxidant status in uremic patients. Finally, the findings of elevated plasma Cys levels correlating to the elevated plasma Hcy levels in the presence of elevated plasma CSA levels, both before and after vitamin supplementation, led to the hypothesis that a block in decarboxylation of CSA is linked to hyperhomocysteinemia in end-stage renal failure.

J Am Soc Nephrol. 1999 Jun;10(6):1287-96. Effects of high-dose folic acid and pyridoxine on plasma and erythrocyte sulfur amino acids in hemodialysis patients.

Suliman ME, Divino Filho JC, Barany P, Anderstam B, Lindholm B, Bergstrom J.

Department of Clinical Science, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden.

In this investigation, sulfur amino acids (sAA) and sulfhydryls were determined in the plasma and erythrocytes (RBC) of 10 uremic patients on regular hemodialysis (HD) treatment and 10 healthy subjects, before and after supplementation with 15 mg/d of folic acid and 200 mg/d of pyridoxine for 4 wk. The basal total plasma concentrations of homocysteine (Hcy), cysteine (Cys), cysteinylglycine (Cys-Gly), gamma-glutamylcysteine (gamma-Glu-Cys), glutathione (GSH), and free cysteinesulfinic acid (CSA) were significantly higher in HD patients when compared to healthy subjects, whereas methionine (Met) and taurine (Tau) concentrations were the same in the two groups. HD patients showed significantly higher RBC levels of Hcy and Cys-Gly, whereas the RBC concentrations of Met, Cys, Tau, and GSH were not different from those in the healthy subjects. The plasma concentrations of sAA and sulfhydryls differed compared with RBC levels in the healthy subjects and HD patients. In both groups, supplementation with high doses of folic acid and pyridoxine reduced the plasma Hcy concentration. In addition, increased plasma concentrations of Cys-Gly and GSH were found in the HD patients and of CSA in the healthy subjects. After vitamin supplementation, the RBC concentrations of Hcy, Cys, and GSH increased and that of Tau decreased in healthy subjects. The only significant finding in RBC of HD patients was an increase in GSH levels after supplementation. This study shows several RBC and plasma sAA and sulfhydryl abnormalities in HD patients, which confirms earlier findings that RBC and plasma pools play independent roles in interorgan amino acid transport and metabolism. Moreover, high-dose supplementation with folic acid and pyridoxine significantly reduced Hcy levels, but did not restore the sAA and sulfhydryl abnormalities to normal levels. The increase that was observed in GSH after vitamin supplementation may have a beneficial effect in improving blood antioxidant status in uremic patients. Finally, the findings of elevated plasma Cys levels correlating to the elevated plasma Hcy levels in the presence of elevated plasma CSA levels, both before and after vitamin supplementation, led to the hypothesis that a block in decarboxylation of CSA is linked to hyperhomocysteinemia in end-stage renal failure.

BMJ. 1999 May 22;318(7195):1375-81.

Comment in: • ACP J Club. 1999 Nov-Dec;131(3):60. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review.

Wyatt KM, Dimmock PW, Jones PW, Shaughn O'Brien PM.

Academic Department of Obstetrics and Gynaecology, North Staffordshire Hospital, Stoke on Trent ST4 6QG.

OBJECTIVE: To evaluate the efficacy of vitamin B-6 in the treatment of premenstrual syndrome. DESIGN: Systematic review of published and unpublished randomised placebo controlled trials of the effectiveness of vitamin B-6 in the management of premenstrual syndrome. SUBJECTS: Nine published trials representing 940 patients with premenstrual syndrome. MAIN OUTCOME MEASURES: Proportion of women whose overall premenstrual symptoms showed an improvement over placebo. A secondary analysis was performed on the proportion of women whose premenstrual depressive symptoms showed an improvement over placebo. RESULTS: Odds ratio relative to placebo for an improvement in overall premenstrual symptoms was 2.32 (95% confidence interval 1.95 to 2.54). Odds ratio relative to placebo for an improvement in depressive symptoms was 1.69 (1.39 to 2.06) from four trials representing 541 patients. CONCLUSION: Conclusions are limited by the low quality of most of the trials included. Results suggest that doses of vitamin B-6 up to 100 mg/day are likely to be of benefit in treating premenstrual symptoms and premenstrual depression.

Can J Cardiol. 1999 Apr;15 Suppl B:31B-34B.

Homocyst(e)ine, vitamins and genetic interactions in vascular disease.

Malinow MR.

Oregon Health Sciences University, Portland, Oregon, USA. malinowr@ohsu.edu

Blood homocyst(e)ine levels are an important, independent and frequent risk factor for clinical atherosclerosis and venous thrombosis. Folic acid, vitamins B6 and B12, renal and thyroid functions, certain medications and certain genotypes are known to modulate plasma homocyst(e)ine levels. Intake of B vitamins through diet, supplementation and fortified foods effectively reduces homocyst(e)ine concentration and thus may reduce the risk of cardiovascular disease. This is true even in individuals who are genetically predisposed to hyperhomocyst(e)inemia. Randomized clinical trials are needed to investigate these effects further.

J Am Soc Nephrol. 1999 Apr;10(4):840-5. Intake of vitamins B6 and C and the risk of kidney stones in women.

Curhan GC, Willett WC, Speizer FE, Stampfer MJ.

Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA. gary.curhan@channing.harvard.edu

Urinary oxalate is an important determinant of calcium oxalate kidney stone formation. High doses of vitamin B6 may decrease oxalate production, whereas vitamin C can be metabolized to oxalate. This study was conducted to examine the association between the intakes of vitamins B6 and C and risk of kidney stone formation in women. The relation between the intake of vitamins B6 and C and the risk of symptomatic kidney stones were prospectively studied in a cohort of 85,557 women with no history of kidney stones. Semiquantitative food-frequency questionnaires were used to assess vitamin consumption from both foods and supplements. A total of 1078 incident cases of kidney stones was documented during the 14-yr follow-up period. A high intake of vitamin B6 was inversely associated with risk of stone formation. After adjusting for other dietary factors, the relative risk of incident stone formation for women in the highest category of B6 intake (> or =40 mg/d) compared with the lowest category (<3 mg/d) was 0.66 (95% confidence interval, 0.44 to 0.98). In contrast, vitamin C intake was not associated with risk. The multivariate relative risk for women in the highest category of vitamin C intake (> or =1500 mg/d) compared with the lowest category (<250 mg/d) was 1.06 (95% confidence interval, 0.69 to 1.64). Large doses of vitamin B6 may reduce the risk of kidney stone formation in women. Routine restriction of vitamin C to prevent stone formation appears unwarranted.

Nutr Metab Cardiovasc Dis. 1999 Apr;9(2):55-63.

Dietary vitamin B6 supplementation prevents ethanol-induced hypertension in rats.

Vasdev S, Wadhawan S, Ford CA, Parai S, Longerich L, Gadag V.

Department of Medicine, Memorial University of Newfoundland, St. John's, Canada.

BACKGROUND AND AIMS: All known pathways of ethanol metabolism result in the production of acetaldehyde, a highly reactive compound. Acetaldehyde has been shown to deplete vitamin B6 in chronic alcoholics. It also binds with sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing vascular cytosolic free calcium, peripheral vascular resistance and blood pressure. The aldehyde-binding thiol compound, N-acetyl cysteine, attenuates elevated blood pressure and associated adverse changes in ethanol-induced hypertensive rats. Vitamin B6 supplementation increases the level of endogenous cysteine. Aim of this work was thus to investigate whether a dietary supplementation of vitamin B6 can prevent ethanol-induced hypertension and associated changes in Wistar-Kyoto (WKY) rats. METHODS AND RESULTS: Starting at 7 weeks of age, WKY rats were divided into three groups of six animals each. The control group received a normal vitamin B6 diet (regular chow) and normal drinking water, the ethanol group, the same diet plus 1% ethanol in the drinking water, and the ethanol + vitamin B6 group a high vitamin B6 diet (20 times normal diet) and 1% ethanol in the drinking water. After 14 weeks, systolic blood pressure, platelet [Ca2+]i and kidney and aortic aldehyde conjugate levels were significantly higher in the ethanol group. These rats also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Dietary vitamin B6 supplementation prevented these changes. CONCLUSIONS: Dietary vitamin B6 supplementation prevented ethanol-induced hypertension and associated changes in WKY rats by normalizing tissue aldehyde conjugate levels.

Am J Cardiol. 1999 Mar 15;83(6):821-5. Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B6 and B12.

Lobo A, Naso A, Arheart K, Kruger WD, Abou-Ghazala T, Alsous F, Nahlawi M, Gupta A, Moustapha A, van Lente F, Jacobsen DW, Robinson K.

Department of Cardiology, The Cleveland Clinic Foundation, Ohio 44195, USA.

An increased plasma homocysteine concentration is a risk factor for atherosclerosis. Folic acid lowers homocysteine but the optimal dose in patients with coronary artery disease (CAD) is unclear. This placebo-controlled, single-blind, dose-ranging study evaluates the effect of low-dose folic acid on homocysteine levels in 95 patients aged 61 +/- 11 years (mean +/- SD) with documented CAD. Patients in each group were given either placebo or 1 of 3 daily supplements of folic acid (400 microg, 1 mg, or 5 mg) for 3 months. Each active treatment arm also received 500 microg vitamin B12 and 12.5 mg vitamin B6. Total plasma homocysteine levels were measured after 30 and 90 days. Folic acid 400 microg reduced homocysteine levels from 13.8 +/- 8.8 to 9.6 +/- 2.0 micromol/L at 90 days (p = 0.001). On 1- and 5-mg folic acid, levels decreased from 13.0 +/- 6.4 to 9.8 +/- 4.0 micromol/L (p = 0.001) and from 14.8 +/- 6.9 to 9.7 +/- 3.3 micromol/L (p < 0.001), respectively. The decrease was similar in all treatment groups. There was no significant change with placebo. Although the sample size is small, these findings suggest that daily administration of 400 microg/day folic acid combined with vitamin B12 and vitamin B6 may be equivalent to higher doses in reducing homocysteine levels in patients with CAD.

Treat News. 1999 Mar 5;(No 314):7-8.

Neuropathy: nutritional prevention/treatment suggested.

James JS.

AIDS: A simple regimen of calcium, magnesium, and vitamin B6 appears to prevent and treat peripheral neuropathy, a side effect of some drugs used to combat AIDS. Although the treatment has not been proven effective, anecdotal reports indicate that it works, and has few risks. Doctors can also use certain prescription drugs to alleviate the discomfort associated with neuropathy. In cases of severe neuropathy, doses of drugs may be reduced or stopped to prevent lasting nerve damage. Patients contemplating this regimen should know that significant overdoses of vitamin B6 can actually cause neuropathy.

Atherosclerosis. 1999 Mar;143(1):177-83. Combination of low-dose folic acid and pyridoxine for treatment of hyperhomocysteinaemia in patients with premature arterial disease and their relatives.

van der Griend R, Haas FJ, Biesma DH, Duran M, Meuwissen OJ, Banga JD.

Department of Internal Medicine, Sint Antonius Hospital, Nieuwegein, The Netherlands. r.griend@digd.azu.nl

Hyperhomocysteinaemia is an independent risk factor for atherosclerotic disease and venous thrombosis. The optimal homocysteine-lowering vitamin dose and target total homocysteine (tHcy) concentration are currently unknown. We prospectively studied the homocysteine-lowering effect after 8 weeks low-dose combination of folic acid (0.5 mg) and pyridoxine (100 mg) in 49 hyperhomocysteinaemic persons (33 patients with documented premature arterial disease and 16 of their first-degree relatives). Hyperhomocysteinaemia was in both sexes defined as fasting tHcy concentration > 12 micromol/l and/or post-methionine load tHcy concentration > 38 micromol/l. Low-dose vitamin therapy significantly reduced fasting tHcy concentration (median 13.9 to 9.3 micromol/l, reduction 32% (95% CI: 27-37%)) and post-load tHcy concentration (median 55.2 to 36.5 micromol/l, reduction 30% (95% CI: 25-35%)). Fasting tHcy reduction was similar in women and men, as well as in patients and relatives. Post-load tHcy reduction was significantly less in men compared to women (P = 0.04) and in relatives compared to patients (P = 0.03). Although low-dose combination of folic acid and pyridoxine results in a substantial reduction of tHcy concentrations (30-32%) in subjects with hyperhomocysteinaemia, the normalisation percentage to predefined criteria was less impressive (49%).

Br J Nutr. 1999 Mar;81(3):191-201.

Comment in: • Br J Nutr. 1999 Mar;81(3):175-6. Plasma pyridoxal phosphate and pyridoxic acid and their relationship to plasma homocysteine in a representative sample of British men and women aged 65 years and over.

Bates CJ, Pentieva KD, Prentice A, Mansoor MA, Finch S.

MRC Human Nutrition Research, Cambridge, UK. Chris.Bates@mrc-hnr.cam.ac.uk

Concentrations of pyridoxal phosphate and pyridoxic acid were measured in fasting plasma samples from British men and women aged 65 years and over, participating in a National Diet and Nutrition Survey during 1994-5, selected to be representative of the population of mainland Britain. In this population, the concentration of pyridoxal phosphate declined, whereas pyridoxic acid rose, with increasing age and frailty; however, both status indicators were strongly and directly (with a positive coefficient) correlated with estimates of vitamin B6 intake. This was little affected by the inclusion of food energy and protein intakes in the model. Forty-eight percent of the participants living in the community and 75% of those living in institutions had plasma pyridoxal phosphate concentrations below a range considered normal from other studies. In a univariate regression model, plasma pyridoxal phosphate concentrations were inversely correlated with plasma homocysteine concentrations, consistent with the hypothesis that vitamin B6 status may influence plasma homocysteine levels, and hence vascular disease risk. However, this relationship was partly attenuated in a multiple regression model including age, sex, domicile and biochemical status indices, including those of folate and vitamin B12. There was evidence that plasma pyridoxal phosphate was sensitive to metabolic conditions associated with inflammation and the acute-phase reaction, and that plasma pyridoxic acid was sensitive to renal function. Thus, neither index is an ideal predictor of vitamin B6 status in older people, unless these confounding factors are allowed for. Since poor vitamin B6 status may have health implications, e.g. for immune function, cognition, and for essential intermediary metabolic pathways in older people, it needs to be investigated as a possible public health problem.

60: Marks J. Vitamin B-6. Many have found relief from disorders for which no effective treatment exists. BMJ. 1999 Feb 13;318(7181):463. No abstract available. PMID: 9974473

Zh Nevrol Psikhiatr Im S S Korsakova. 1999;99(1):37-41.

[Cerebrolysin and magnesium-B6 in the treatment of side effects of psychotropic drugs]

[Article in Russian]

Panteleeva GP, Bondar' VV, Krasnikova NI, Raiushkin VA.

51 patients were observed. Schizophrenia was diagnosed in 31 patients and endogenous depression in 20 cases. All the patients had extrapyramidal and somato-vegetative side effects of neuroleptics and antidepressive drugs, and were resistant to conventional corrective therapy for at least a period of 3 weeks. In addition to current treatment of both basic disease and adverse effects, cerebrolysin was administered (5-10 ml i.v./dr, during 28 days) and magme B6 (20-30 ml per os during 21 days). By the treatment end-point either moderate or marked reduction of extrapyramidal disorders (according to ESRS) was observed in 74.4% of patients treated by cerebrolysin and in 72.2% treated by magne B6; somato-vegetative adverse effects reduced (by SARS) in 85.8% and in 83.8% respectively. Both drugs showed equally high efficacy against hyperkinetic and cardiovascular side effects (symptoms relief was in 59-62% and 65-69%, respectively). Cerebrolysin is more preferable in cases of side vegetative events, dysomnia and dysuria; magne B6 was more effective in correction of akineto-hypertonic and hyperkinetic-hypertonic syndromes as well as in cholinolytic side effects.

Alcohol Alcohol. 1998 Nov-Dec;33(6):631-8. Benfotiamine in treatment of alcoholic polyneuropathy: an 8-week randomized controlled study (BAP I Study).

Woelk H, Lehrl S, Bitsch R, Kopcke W.

Psychiatrisches Krankenhaus, Giessen, Germany.

A three-armed, randomized, multicentre, placebo-controlled double-blind study was used to examine the efficacy of benfotiamine vs a combination containing benfotiamine and vitamins B6 and B12 in out-patients with severe symptoms of alcoholic polyneuropathy (Benfotiamine in treatment of Alcoholic Polyneuropathy, BAP I). The study period was 8 weeks and 84 patients fulfilled all the prerequisite criteria and completed the study as planned. Benfotiamine led to significant improvement of alcoholic polyneuropathy. Vibration perception (measured at the tip of the great toe) significantly improved in the course of the study, as did motor function. and the overall score reflecting the entire range of symptoms of alcoholic polyneuropathy. A tendency toward improvement was evident for pain and co-ordination; no therapy-specific adverse effects were seen.

Biochim Biophys Acta. 1998 Aug 24;1381(3):351-4.

Effect of pyridoxine and insulin administration on brain glutamate dehydrogenase activity and blood glucose control in streptozotocin-induced diabetic rats.

Nair AR, Biju MP, Paulose CS.

Molecular Neurobiology and Cell Biology Unit, Department of Biotechnology, Cochin University of Science and Technology, Cochin 682 022, India.

Blood glucose level and kinetic parameters of glutamate dehydrogenase (GDH) were measured in the cerebellum, brain stem and cerebral cortex of control, insulin treated, pyridoxine treated, pyridoxine and insulin treated and untreated streptozotocin-diabetic rats. The combined administration of insulin and pyridoxine was found to be better in controlling the hyperglycaemia. Insulin with pyridoxine treatment brought back the increased maximal velocity of GDH during diabetes to control state. Also, there was an increase in Michaelis-Menten constant. These results suggest that pyridoxine and insulin together serve a better control for diabetes. Copyright Elsevier Science B.V.

Am J Clin Nutr. 1998 Aug;68(2):389-95. Riboflavin and vitamin B-6 intakes and status and biochemical response to riboflavin supplementation in free-living elderly people.

Madigan SM, Tracey F, McNulty H, Eaton-Evans J, Coulter J, McCartney H, Strain JJ.

Human Nutrition Research Group, University of Ulster, Coleraine, Northern Ireland.

Free-living elderly people aged > or = 65 y were recruited to assess riboflavin and vitamin B-6 intakes and status and the effect of riboflavin supplementation on biochemical indicators of these 2 vitamins. The status of riboflavin (erythrocyte glutathione reductase activation coefficient; EGRAC) and vitamin B-6 (plasma pyridoxal-5'-phosphate; PLP) were determined in a total sample of 92 subjects, from whom dietary intake data were obtained by using the diet history method (n = 83). Although dietary intakes of both vitamins were considered to be adequate according to current reference values, abnormal EGRAC and plasma PLP values were identified in 49% and 38% of subjects, respectively, with 21% having suboptimal status for both nutrients. A subgroup of subjects from the initial sample (n = 45) was assigned in a double-blind manner to receive either 1.6 or 25 mg riboflavin or placebo daily for 12 wk. In those subjects with a baseline EGRAC or plasma PLP value falling outside the currently accepted threshold value for adequacy, low-dose riboflavin supplementation improved status of the limiting nutrient significantly (P<0.0001 and P = 0.020 for EGRAC and plasma PLP responses, respectively). We conclude that a high proportion of healthy elderly people may have suboptimal status for these nutrients despite apparently adequate dietary intakes. Furthermore, we showed that riboflavin supplementation at physiologic doses corrects biochemical abnormalities of not only EGRAC, but also plasma PLP, confirming the biochemical interdependency of these vitamins and suggesting that riboflavin is the limiting nutrient.

Am J Obstet Gynecol. 1998 Jul;179(1):135-9. Effects of folic acid and vitamin B6 supplementation on women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction.

Leeda M, Riyazi N, de Vries JI, Jakobs C, van Geijn HP, Dekker GA.

Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Free University Hospital, Amsterdam, The Netherlands.

OBJECTIVE: Our purpose was to assess the incidence of hyperhomocysteinemia in patients with a history of preeclampsia or fetal growth restriction, to evaluate the effects of vitamin supplementation on the methionine loading test, and to study the course of subsequent pregnancies in women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction. STUDY DESIGN: A total of 207 consecutive patients with a history of preeclampsia or fetal growth restriction was tested for hyperhomocysteinemia. Thirty-seven were found to be positive and were treated with folic acid and vitamin B6, and 27 had a second methionine loading test after vitamin supplementation. Fourteen patients became pregnant again while receiving vitamins and aspirin. RESULTS: All patients who underwent a methionine loading test after vitamin supplementation had a completely normalized methionine loading test. Of the 14 pregnancies in women receiving vitamins and aspirin, 7 were complicated by preeclampsia. Birth weights were 2867 +/- 648 g compared with 1088 +/- 570 g in the previous pregnancies. CONCLUSIONS: Vitamin B6 and folic acid correct the methionine loading test in patients with hyperhomocysteinemia. Perinatal outcome in patients with a history of preeclampsia or fetal growth restriction and hyperhomocysteinemia appears to be favorable.

Natl Med J India. 1998 Jul-Aug;11(4):171-2.

Effect of pyridoxine or riboflavin supplementation on plasma homocysteine levels in women with oral lesions.

Lakshmi AV, Ramalakshmi BA.

National Institute of Nutrition, Indian Council of Medical Research, Andhra Pradesh, India.

BACKGROUND: A moderate increase in plasma homocysteine level has been reported to be involved in neural tube defects, which can be prevented with folic acid supplementation. Folic acid, vitamins B6- and B12-dependent enzymes are required to metabolize homocysteine. A study in rats showed higher tissue homocysteine levels in riboflavin as well as pyridoxine deficiency. We studied the effect of treatment with pyridoxine or riboflavin on plasma total homocysteine concentration in women with clinical and biochemical deficiencies of riboflavin and pyridoxine. METHODS: Plasma total homocysteine concentrations were measured in 20 women with glossitis and angular stomatitis before and after supplementation with pyridoxine or riboflavin. RESULTS: Pyridoxine treatment significantly reduced plasma homocysteine concentration while riboflavin treatment did not have a significant effect. CONCLUSIONS: Plasma total homocysteine levels tended to be higher in women with clinical and biochemical deficiency of vitamin B6 and therapy with pyridoxine reduced its level significantly. Riboflavin supplementation did not have a significant impact on plasma homocysteine concentration in women with glossitis and angular stomatitis.

Res Exp Med (Berl). 1998 Jul;198(1):37-42. Vitamin supplementation during weight reduction--favourable effect on homocysteine metabolism.

Henning BF, Tepel M, Riezler R, Gillessen A, Doberauer C.

Med. Klinik I, Univ.-Klinik Marienhospital, Herne, Germany.

Moderately elevated homocysteine concentrations, reflecting deficiency of some nutritional factors required for homocysteine metabolism (folate, vitamin B-6, vitamin B-12) and/or less severe genetic defects, are common in the general population. Several studies have indicated the role of homocysteine as an independent risk factor for vascular disease. A pilot study published recently suggested that plasma homocysteine levels increase during weight reduction in slightly overweight, otherwise healthy subjects (group A). We examined a comparable group of 13 overweight subjects (group B) using a standardised caloric intake and defined vitamin supplementation (Medyn: folate 0.2 mg/ vitamin B-68.0 mg/ vitamin B-120.010 mg three times the day orally) to determine the effect of weight reduction on serum homocysteine levels and to compare the results with those of the pilot study. Mean body weight declined from 87.0 +/- 20.2 to 84.2 +/- 20.1 kg (P < 0.05) in group A and 85.7 +/- 11.3 to 82.5 +/- 9.9 kg (P = 0.049) in group B. Serum homocysteine levels rose from 7.9 +/- 2.0 to 8.7 +/- 2.3 mumol/l (P < 0.0001) in group A and decreased from 8.19 +/- 1.73 to 7.35 +/- 0.88 mumol/l (P = 0.0022) in group B. No correlation was found between the changes in body weight and in homocysteine levels (r = 0.02 in group A, r = 0.18 in group B). Additionally, no correlation was found between serum folate levels and changes in homocysteine levels (r = 0.03 in group A, r = 0.09 in group B). The results suggest that an adequate oral vitamin-supplementation protects against increased homocysteine production during weight reduction.

Clin Cancer Res. 1998 Jun;4(6):1567-71.

Efficacy of pyridoxine to ameliorate the cutaneous toxicity associated with doxorubicin containing pegylated (Stealth) liposomes: a randomized, double-blind clinical trial using a canine model.

Vail DM, Chun R, Thamm DH, Garrett LD, Cooley AJ, Obradovich JE.

Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison 53706, USA. vaild@svm.vetmed.wisc.edu

A cutaneous reaction termed palmar-plantar erythrodysesthesia (PPES) or hand-foot syndrome can be dose limiting for Doxil, a doxorubicin containing pegylated (Stealth) liposome. The objective of this study was to determine the ability of concomitant pyridoxine therapy to prevent the development of PPES during Doxil therapy. Forty-one dogs with non-Hodgkin's lymphoma were randomized in a double-blind fashion to receive either oral pyridoxine or placebo daily during Doxil chemotherapy (1.0 mg/kg, i.v., every 3 weeks for a total of five treatments). Cutaneous toxicity was determined by clinical and histological scoring. No difference was observed in remission rates (71.4 versus 75%) achieved between groups. The likelihood of developing serious PPES and having to decrease or discontinue Doxil therapy was 4.2 times (relative risk) greater in placebo group dogs than in pyridoxine group dogs (P = 0.032). Pyridoxine did not completely abrogate PPES; however, it occurred later and less dramatically than in placebo-treated dogs and resulted in fewer treatment delays or discontinuations, allowing a higher cumulative dose of Doxil to be received. Compared to the 5.0 mg/kg cumulative target dose, pyridoxine-treated dogs received a median cumulative dose of 4.7 mg/kg (mean, 4.1 mg/kg), and the placebo-treated dogs received a median of 2.75 mg/kg (mean, 2.9 mg/kg; P < 0.028). A trend (P = 0.084) toward prolongation of remission length was observed in dogs receiving pyridoxine, which was likely attributable to their ability to receive more Doxil without delay or discontinuation. We conclude that pyridoxine is effective in delaying the onset and severity of PPES in this canine model.

Am J Clin Nutr. 1998 May;67(5):858-66.

Erratum in: • Am J Clin Nutr 1998 Sep;68(3):758.

Comment in: • Am J Clin Nutr. 1999 Jun;69(6):1287-9. Effect of B-group vitamins and antioxidant vitamins on hyperhomocysteinemia: a double-blind, randomized, factorial-design, controlled trial.

Woodside JV, Yarnell JW, McMaster D, Young IS, Harmon DL, McCrum EE, Patterson CC, Gey KF, Whitehead AS, Evans A.

School of Clinical Medicine, The Queen's University of Belfast, United Kingdom. p9495754@qub.ac.uk

Mild hyperhomocysteinemia is accepted as a risk factor for premature cardiovascular disease. In a population with a high prevalence of cardiovascular disease, we screened a group of clinically healthy working men aged 30-49 y (n = 509) for plasma homocysteine and 5,10-methylene tetrahydrofolate reductase (MTHFR) genotype status. Those with mildly elevated homocysteine concentrations (> or = 8.34 micromol/L) were selected for intervention. In a randomized, factorial-design, controlled trial we assessed the effects of B-group vitamins and antioxidant vitamin supplementation on homocysteine concentrations. The 132 men were randomly assigned to one of four groups: supplementation with B-group vitamins alone (1 mg folic acid, 7.2 mg pyridoxine, and 0.02 mg cyanocobalamin), antioxidant vitamins alone (150 mg ascorbic acid, 67 mg RRR-alpha-tocopherol, and 9 mg beta-carotene), B-group vitamins with antioxidant vitamins, or placebo. Intervention was double-blind. A total of 101 men completed the 8-wk intervention. When homocysteine concentrations were analyzed by group, significant (P < 0.001) decreases (32.0% and 30.0%, respectively) were observed in both groups receiving B-group vitamins either with or without antioxidants. The effect of B-group vitamins alone over 8 wk was a reduction in homocysteine concentrations of 27.9% (95% CI: 22.0%, 33.3%; P < 0.001) whereas antioxidants alone produced a nonsignificant increase of 5.1% (95% CI: -2.8%, 13.6%; P = 0.21). There was no evidence of any interaction between the two groups of vitamins. The effect of B-group vitamin supplementation seemed to depend on MTHFR genotype. Supplementation with the B-group vitamins with or without antioxidants reduced homocysteine in the men with mildly elevated concentrations, and hence may be effective in reducing cardiovascular risk.

Neuromuscul Disord. 1998 May;8(3-4):210-2.

Effect of vitamin B6 supplementation in McArdle's disease: a strategic case study.

Phoenix J, Hopkins P, Bartram C, Beynon RJ, Quinlivan RC, Edwards RH.

Department of Biomolecular Science, UMIST, Manchester, UK.

A patient-blind study into the effect of a 10-week cessation of long-term vitamin B6 supplementation on B6 status and performance in McArdle's disease is reported. Muscle performance was assessed both subjectively and objectively by an ischaemic fatiguing protocol of the adductor pollicis muscle. Nine weeks after withdrawal of supplementation, vitamin B6 status had changed from adequacy to inadequacy and the force loss during the ischaemic fatiguing protocol had increased at all frequencies studied. The patient reported decreased exercise tolerance after 7 weeks and by the tenth week was experiencing an increase in muscle cramps. Vitamin B6 status and muscle performance may be linked in McArdle's disease and there is potential for enhancement of performance by B6 supplementation.

71: [No authors listed] Can J Cardiol. 1999 Apr;15 Suppl B:31B-34B.

Homocyst(e)ine, vitamins and genetic interactions in vascular disease.

Malinow MR.

Oregon Health Sciences University, Portland, Oregon, USA. malinowr@ohsu.edu

Blood homocyst(e)ine levels are an important, independent and frequent risk factor for clinical atherosclerosis and venous thrombosis. Folic acid, vitamins B6 and B12, renal and thyroid functions, certain medications and certain genotypes are known to modulate plasma homocyst(e)ine levels. Intake of B vitamins through diet, supplementation and fortified foods effectively reduces homocyst(e)ine concentration and thus may reduce the risk of cardiovascular disease. This is true even in individuals who are genetically predisposed to hyperhomocyst(e)inemia. Randomized clinical trials are needed to investigate these effects further. . Harv Health Lett. 1998 Apr;23(6):8. No abstract available. PMID: 9577258

72: den Heijer M, Brouwer IA, Bos GM, Blom HJ, van der Put NM, Spaans AP, Rosendaal FR, Thomas CM, Haak HL, Wijermans PW, Gerrits WB. Vitamin supplementation reduces blood homocysteine levels: a controlled trial in patients with venous thrombosis and healthy volunteers. Arterioscler Thromb Vasc Biol. 1998 Mar;18(3):356-61. PMID: 9514403

J Indian Med Assoc. 1998 Mar;96(3):82-3.

Assessment of efficacy of pyridoxine in control of radiation induced sickness.

Mahajan MK, Singh V.

Department of Radiotherapy, Christian Medical College, Ludhiana.

A randomised prospective study to evaluate the role of adjuvant administration of pyridoxine hydrochloride was carried out in 104 patients undergoing radiation therapy. In study group 52 patients received tablet pyridoxine (controlled release) 100 mg daily one hour before the radiation therapy, for a period of 7 days, while the control group was treated by irradiation alone. Reduced radiation induced sickness was observed in study group (32.6% versus 48.1%). Loss of appetite (0% versus 1.9%), nausea (11.5% versus 21.1%) and vomiting (21.1% versus 28.8%) were lower for pyridoxine treated patients than for control patients. The above observed reduction in radiation induced sickness was found to be statistically insignificant (p > 0.05). The present data also did not reveal a statistical correlation between integral dose and radiation sickness.

J Nephrol. 1998 Mar-Apr;11 Suppl 1:49-50. Pyridoxine-responsive PH1: treatment.

Toussaint C.

Departement medico-chirurgical de Nephrologie, Cliniques Universitaires de Bruxelles, Hopital Erasme, Belgium.

Owing to the rarity of PH, the efficacy of pyridoxine therapy has only been tested in very small series of patients. From two recent reports including 18 patients, 50% of patients would be unresponsive to pyridoxine whereas oxaluria would be normalized in 20% of patients and somewhat reduced-but not to normal level-in the remaining 30%. In a few aneodotical cases pyridoxine administration was reported to improve kidney function in patients with renal failure secondary to hyperoxaluria. It is reminded that megadoses of pyridoxine (0.5 to 6 g daily) may induce severe sensory neuropathy.

JAMA. 1998 Feb 4;279(5):359-64.

Comment in: • JAMA. 1998 Aug 5;280(5):417-8; author reply 418-9. • JAMA. 1998 Aug 5;280(5):417; author reply 418-9. • JAMA. 1998 Aug 5;280(5):418-9. • JAMA. 1998 Aug 5;280(5):418; author reply 418-9. • JAMA. 1998 Aug 5;280(5):418; author reply 418-9. • JAMA. 1998 Feb 4;279(5):392-3. Folate and vitamin B6 from diet and supplements in relation to risk of coronary heart disease among women.

Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, Hennekens C, Stampfer MJ.

Department of Epidemiology, Harvard School of Public Health, Boston, Mass 02115, USA. eric.rimm@channing.harvard.edu

CONTEXT: Hyperhomocysteinemia is caused by genetic and lifestyle influences, including low intakes of folate and vitamin B6. However, prospective data relating intake of these vitamins to risk of coronary heart disease (CHD) are not available. OBJECTIVE: To examine intakes of folate and vitamin B6 in relation to the incidence of nonfatal myocardial infarction (MI) and fatal CHD. DESIGN: Prospective cohort study. SETTING AND PATIENTS: In 1980, a total of 80082 women from the Nurses' Health Study with no previous history of cardiovascular disease, cancer, hypercholesterolemia, or diabetes completed a detailed food frequency questionnaire from which we derived usual intake of folate and vitamin B6. MAIN OUTCOME MEASURE: Nonfatal MI and fatal CHD confirmed by World Health Organization criteria. RESULTS: During 14 years of follow-up, we documented 658 incident cases of nonfatal MI and 281 cases of fatal CHD. After controlling for cardiovascular risk factors, including smoking and hypertension and intake of alcohol, fiber, vitamin E, and saturated, polyunsaturated, and trans fat, the relative risks (RRs) of CHD between extreme quintiles were 0.69 (95% confidence interval [CI], 0.55-0.87) for folate (median intake, 696 microg/d vs 158 microg/d) and 0.67 (95% CI, 0.53-0.85) for vitamin B6 (median intake, 4.6 mg/d vs 1.1 mg/d). Controlling for the same variables, the RR was 0.55 (95% CI, 0.41-0.74) among women in the highest quintile of both folate and vitamin B6 intake compared with the opposite extreme. Risk of CHD was reduced among women who regularly used multiple vitamins (RR=0.76; 95% CI, 0.65-0.90), the major source of folate and vitamin B6, and after excluding multiple vitamin users, among those with higher dietary intakes of folate and vitamin B6. In a subgroup analysis, compared with nondrinkers, the inverse association between a high-folate diet and CHD was strongest among women who consumed up to 1 alcoholic beverage per day (RR =0.69; 95% CI, 0.49-0.97) or more than 1 drink per day (RR=0.27; 95% CI, 0.13-0.58). CONCLUSION: These results suggest that intake of folate and vitamin B6 above the current recommended dietary allowance may be important in the primary prevention of CHD among women.

Am J Clin Nutr. 1998 Feb;67(2):208-20. Vitamin B-6 requirement and status assessment of young women fed a high-protein diet with various levels of vitamin B-6.

Huang YC, Chen W, Evans MA, Mitchell ME, Shultz TD.

Department of Food Science and Human Nutrition, Washington State University, Pullman 99164-6376, USA.

The vitamin B-6 requirement of young women consuming a constant high-protein diet (1.55 g/kg body wt) and the effect of various ratios of vitamin B-6 to protein on this requirement were studied. Eight women were fed a lactoovovegetarian basal diet containing 0.45 mg vitamin B-6 (2.66 micromol as pyridoxine) and 30 micromol carnitine for 92 d. The protocol consisted of successive baseline adjustment (9 d), depletion (27 d), and repletion (two 21-d and then one 14-d) periods. Vitamin B-6 intakes were 1.60, 0.45, 1.26, 1.66, and 2.06 mg, resulting in ratios of vitamin B-6 (in mg) to protein (in g) for the five periods of 0.016, 0.005, 0.013, 0.017, and 0.021, respectively. Direct and indirect as well as short- and long-term vitamin B-6 status measures were assessed weekly. Regression analysis revealed that the amount of dietary vitamin B-6 required to normalize urinary 4-pyridoxic acid, plasma pyridoxal-P, erythrocyte pyridoxal-P and pyridoxal, and erythrocyte alanine and aspartate aminotransferase activity coefficients to predepletion baseline values was 1.94 mg vitamin B-6/d (0.019 mg vitamin B-6/g protein). This study suggests that the current vitamin B-6 recommended dietary allowance of 1.6 mg/d based on 0.016 mg/g protein is not an adequate intake and may require reevaluation.

Int J Vitam Nutr Res. 1998;68(2):98-103.

Folic acid and Vitamin B6 supplementation and plasma homocysteine concentrations in healthy young women.

Dierkes J, Kroesen M, Pietrzik K.

Dept. of Pathophysiology of Human Nutrition, University of Bonn., Germany.

Elevated plasma homocysteine levels are a risk factor for atherosclerotic disease. Elevated fasting plasma homocysteine concentrations can be reduced by vitamin supplementation with folic acid, vitamin B6 and vitamin B12, but the effect of nutritive amounts of single vitamins on homocysteine plasma levels within the normal range is not known. This study was performed to investigate the effect of folic acid supplementation (400 micrograms/d) on fasting plasma homocysteine levels in healthy young women, in comparison to vitamin B6 (2 mg/d) or a combination of both vitamins. Healthy young women with normal homocysteine levels were supplemented for four weeks either with folic acid, vitamin B6 or the combination. The combination of folic acid and vitamin B6 reduced plasma homocysteine by 17%. Supplementation with folic acid reduced plasma homocysteine levels by 11.5%. The effect of folic acid and vitamin B6 was not significantly different from the effect of folic acid alone. Vitamin B6 had no effect on plasma homocysteine concentrations. Results show that homocysteine levels within the normal range are lowered by low-dose vitamin supplementation including folic acid.

J Hepatol. 1998 Jan;28(1):54-60.

Comment in: • J Hepatol. 1999 Apr;30(4):739-40.

Metadoxine accelerates fatty liver recovery in alcoholic patients: results of a randomized double-blind, placebo-control trial. Spanish Group for the Study of Alcoholic Fatty Liver.

Caballeria J, Pares A, Bru C, Mercader J, Garcia Plaza A, Caballeria L, Clemente G, Rodrigo L, Rodes J.

Liver Unit, Hospital Clinic i Provincial, University of Barcelona, Spain. rovira@medicina.ub.es

BACKGROUND/AIMS: Our aim was to investigate the effectiveness of metadoxine (pyridoxol L, 2 pyrrolidone-5-carboxylate) in the treatment of alcoholic fatty liver. METHODS: A double-blind randomized multicenter trial involving 136 chronic active alcoholic patients diagnosed with fatty liver by clinical, biochemical and ultrasonographic criteria was performed. Patients were treated with 1500 mg/day of metadoxine (n = 69) or placebo (n = 67) for 3 months. Patients were clinically and biochemically evaluated every month. Ultrasonography was performed before and after treatment. RESULTS: At the end of the study there was a significant improvement in the liver function tests in both groups. However, the changes were more rapid and greater in patients treated with metadoxine, in whom significant changes in serum levels of bilirubin, aminotransferases and gammaglutamyl transpeptidase were already observed after 1 month of treatment, and normalization of these parameters was observed at the end. After treatment, the percentage of patients with ultrasonographic signs of steatosis was significantly lower in the metadoxine group (28% vs 70%, p < 0.01) and the degree of steatosis was also lower in this group. Sixteen patients treated with metadoxine and 15 with placebo continued drinking. Alcohol intake was lower than initially, and similar in both groups. In the metadoxine group, the biochemical changes were similar in both the abstinent and the nonabstinent patients. In contrast, in the placebo group the improvement in the liver function tests was significantly higher in abstinents. Among patients who continued drinking, the prevalence (45% vs 92%, p < 0.05) and the degree of steatosis were also significantly lower in patients treated with metadoxine. CONCLUSIONS: In patients with alcoholic fatty liver, metadoxine accelerates the normalization of liver function tests and the ultrasonographic changes, even in those who do not completely abstain from alcohol intake. Thus, metadoxine could be useful in the treatment of the early stages of alcoholic liver disease.

J Psychopharmacol. 1998;12(2):220-1.

High-dose vitamin E plus vitamin B6 treatment of risperidone-related neuroleptic malignant syndrome.

Dursun SM, Oluboka OJ, Devarajan S, Kutcher SP.

Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada. sdursun@is.dal.ca

We present a case of a 74-year-old patient with schizoaffective disorder, who developed risperidone-related neuroleptic malignant syndrome. This patient responded satisfactorily to the supportive management and vit E plus vit B6.

Urol Int. 1998;60(2):105-7. Magnesium hydrogen carbonate natural mineral water enriched with K(+)-citrate and vitamin B6 improves urinary abnormalities in patients with calcium oxalate nephrolithiasis.

Bren A, Kmetec A, Kveder R, Kaplan-Pavlovcic S.

Department of Nephrology, University Medical Center, Ljubljana, Slovenia. Andrej.Bren@mf.uni-lj.si

The influence of drinking magnesium hydrogen carbonate natural mineral water enriched with potassium citrate on urinary metabolic abnormalities was prospectively studied in 27 patients with recurrent calcium oxalate nephrolithiasis. The mean 24-hour urinary pH shifted from 6.34 to 6.93 (p < 0.01), the mean urinary magnesium/urinary creatinine ratio rose from 0.47 to 0.67 (p < 0.01), the mean urinary citrate/urinary creatinine ratio increased from 0.26 to 0.35 (p NS), and the mean 24-hour urinary calcium decreased from 7.98 to 6.05 mmol (p < 0.05). The effects of magnesium hydrogen carbonate natural mineral water enriched with potassium citrate were found to be favorable on urinary calcium, urinary magnesium/urinary creatinine ratio and urinary pH in patients with calcium oxalate nephrolithiasis.

Zh Nevrol Psikhiatr Im S S Korsakova. 1998;98(9):30-2.

[Diabetic polyneuropathy treatment by milgamma-100 preparation]

[Article in Russian]

Sadekov RA, Danilov AB, Vein AM.

Efficiency of Milgamma-100 preparation (100 mg of benfothiamine + 100 mg of pyridoxin) was studied in treatment of diabetic polyneuropathy in 14 patients with diabetes mellitus type II (1 dragee 3 times a day, within 6 weeks). After the course of treatment the intensity of pains was decreased according to visual analogous scale on the average from 8.2 to 2.3 scores, the indices of vibratory sensitivity improved significantly as well as the data of cardiovascular tests characterizing parasympathetic control of heart rhythm. Meanwhile latent periods of the evoked sympathetic potentials on arms and legs which were initially lengthened became significantly shorter. A clear-cut tendency was also found to increasing conduction rate for excitation through the motor nerves. The treatment resulted in the improvement of the condition in 93% of the cases. The conclusion was made about efficiency and safety of Milgamma-100 preparation application in therapy of patients with diabetic polyneuropathy.

J Intern Med. 1997 Jul;242(1):79-81.

Pyridoxin-responsive anaemia in a patient with a history of polycythaemia vera.

Van Gameren II, Wijnja L, Louwes H, de Wolf JT.

Department of Internal Medicine, Martini Hospital, van Swietenlaan, The Netherlands.

Pancytopenia in the course of polycythaemia vera (PV) following the proliferative and stable phase, ultimately leads to a spent phase characterized by extensive marrow fibrosis. We describe a patient with a history of PV and pancytopenia caused by myelodysplasia, before a genuine end stage myelofibrosis had occurred. The related anaemia was responsive to pyridoxin.

Pediatr Neurol. 1997 Jul;17(1):54-7. Randomized, controlled trial of high-dose intravenous pyridoxine in the treatment of recurrent seizures in children.

Jiao FY, Gao DY, Takuma Y, Wu S, Liu ZY, Zhang XK, Lieu NS, Ge ZL, Chui W, Li HR, Cao YM, Bai AN, Liu SB.

Department of Pediatrics, Shaanxi Provincial People's Hospital, Xian, P.R. China.

To determine the efficacy of pyridoxine in treating seizures, 90 infants and children with recurrent convulsions primarily due to acute infectious diseases were enrolled in the present study. Forty patients were treated with high-dose pyridoxine (30 or 50 mg/kg/day) by intravenous infusion, and 50 subjects served as controls. Antiepileptic drugs and other therapies were similar in the two groups except for pyridoxine. Clinical efficacy criteria were based on the frequency of convulsions per day and on the duration of individual seizures after therapy was initiated. The results indicated that total response rates in the pyridoxine group and control group were 92.5% and 64%, respectively (chi-square = 14.68, P < .001). After initiation of therapy, seizures resolved after 2.4 +/- 1.4 days in the pyridoxine group and after 3.7 +/- 2.0 days in the control group (t = 3.67, P < .001). No adverse effects of pyridoxine were apparent during the observation period. We conclude that pyridoxine is an effective, safe, well-tolerated, and relatively inexpensive adjunct to routine antiepileptic drugs for treatment of recurrent seizures in children.

J Nutr. 1997 Jun;127(6):1219-28. Chronic exercise affects vitamin B-6 metabolism but not requirement of growing rats.

Hadj-Saad F, Lhuissier M, Guilland JC.

Laboratoire de Physiologie, Faculte de Medecine, Dijon, France.

The effect of chronic exercise (forced swimming) on vitamin B-6 status and metabolism was studied in growing male rats fed deficient (0 mg pyridoxine-HCl/kg), suboptimal (2 mg pyridoxine-HCl/kg) or control (7 mg pyridoxine-HCl/kg) diets for 9 wk. Sedentary rats were fed the same diets. Body weight gain was lower in deficient rats than in both other dietary groups. Sedentary rats were heavier than trained rats of all diet groups. Erythrocyte aspartate aminotransferase, urinary 4-pyridoxic acid excretion, blood (plasma and erythrocytes) and tissue B-6 vitamers were measured. Urinary 4-pyridoxic acid, plasma pyridoxal 5'-phosphate and erythrocyte aspartate aminotransferase values of exercised and sedentary rats responded to changes in dietary pyridoxine but were not different from one another. After 9 wk of vitamin B-6 depletion, tissue concentrations of pyridoxal 5'-phosphate and pyridoxamine 5;5'-phosphate were 41-66% and 26-49% lower, respectively, in the deficient groups than in the control groups. Larger percentage differences occurred in plasma than in tissues (95 vs. 22-66%). In liver, pyridoxal 5'-phosphate concentrations were lower, whereas pyridoxal concentrations were higher in trained than in sedentary rats. In gastrocnemius muscle, pyridoxal 5'-phosphate, pyridoxamine 5'-phosphate and total vitamin B-6 concentrations were higher in trained than in sedentary rats. Concentrations of vitamin B-6 compounds in heart, kidneys, brain and adrenals were not affected by training. On the basis of the vitamin B-6-dependent variables measured in this study, we conclude that prolonged exercise affects the metabolism of vitamin B-6, but does not increase the vitamin B-6 requirement in growing rats.

Ann Epidemiol. 1997 May;7(4):285-93. Vitamin intake: a possible determinant of plasma homocyst(e)ine among middle-aged adults.

Shimakawa T, Nieto FJ, Malinow MR, Chambless LE, Schreiner PJ, Szklo M.

Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, MD, USA.

PURPOSE: Many epidemiologic studies have identified elevated plasma homocyst(e)ine as a risk factor for atherosclerosis and thromboembolic disease. To examined the relationship between vitamin intakes and plasma homocyst(e)ine, we analyzed dietary intake data from a case-control study of 322 middle-aged individuals with atherosclerosis in the carotid artery and 318 control subjects without evidence of this disease. METHODS: All of these individuals were selected from a probability sample of 15,800 men and women who participated in the Atherosclerosis Risk in Communities (ARIC) Study. RESULTS: Plasma homocyst(e)ine was inversely associated with intakes of folate, vitamin B6, and vitamin B12 (controls only for this vitamin)--the three key vitamins in homocyst(e)ine metabolism. Among nonusers of vitamin supplement products, on average each tertile increase in intake of these vitamins was associated with 0.4 to 0.7 mumol/L decrease in plasma homocyst(e)ine. An inverse association of plasma homocyst(e)ine was also found with thiamin, riboflavin, calcium, phosphorus, and iron. Methionine and protein intake did not show any significant association with plasma homocyst(e)ine. CONCLUSIONS: In almost all analyses, cases and controls showed similar associations between dietary variables and plasma homocyst(e)ine. Plasma homocyst(e)ine among users of vitamin supplement products was 1.5 mumol/L lower than that among nonusers. Further studies to examine possible causal relationships among vitamin intake, plasma homocyst(e)ine, and cardiovascular disease are needed.

86: Kurlemann G, Deufel T, Schuierer G. Pyridoxine--responsive West syndrome and gamma-aminobutyric acid. Eur J Pediatr. 1997 Feb;156(2):158-9. No abstract available. PMID: 9039527

87: Ray M, Kumar L, Prasad R. Homocystinuria with early thromboembolic episodes and rapid response to high dose pyridoxine. Indian Pediatr. 1997 Jan;34(1):67-9. No abstract available. PMID: 9251284

88: Salhany JM, Stevenson M. Hypothesis: potential utility of pyridoxal 5'-phosphate (vitamin B6) and levamisole in immune modulation and HIV-1 infection. AIDS Patient Care STDS. 1996 Dec;10(6):353-6. Review. No abstract available. PMID: 11361551

Fortschr Med. 1996 Nov 20;114(32):439-43.

[Medicamentous therapy of alcoholic polyneuropathy. Randomized double-blind study comparing 2 vitamin B preparations and a nucleotide preparation]

[Article in German]

Kretschmar C, Kaumeier S, Haase W.

III. Psychiatrische Klinik, Klinik fur Suchtkrankheiten, Schwerin.

In a randomized double-blind study involving 303 patients with alcoholic polyneuropathy the efficacy and tolerability of the combinations thiamine/pyridoxine, benfotiamine/pyridoxine, and the nucleotides of cytidine and uridine administered orally for 21 days were compared. Pain and paraesthesia, measured on a visual 10-cm-long analogue scale, as also pallaesthesia and the strength of the dorsiflexion and plantar flexors of the foot, clearly improved in all treatment groups. Clinically relevant differences in efficacy were not observed. All the drugs tested were well tolerated.

Eur J Oral Sci. 1996 Oct-Dec;104(5-6):583-8.

Prevention of etretinate-induced craniofacial malformations by vitamin B6 in the rat.

Jacobsson C, Granstrom G.

Department of Pedodontics, University of Gothenburg, Sweden.

The preventive effect of vitamin B6 on etretinate-induced malformations in pregnant Sprague-Dawley rats was studied. The etretinate-induced malformation was produced by intraperitoneal administration of 10 mg/kg etretinate at embryonal day 8.5. Vitamin B6 was administered as intramuscular injections at embryonal day 7.5 and 8.5. Vitamin B6 reduced the number and severity of facial clefts, micrognatia, meningocele, microtia and blood vessel anomalies. It is suggested that vitamin B6 induces suppressive effects on etretinate-induced teratogenesis when administered before or at the same time as the teratogen.

Z Ernahrungswiss. 1996 Sep;35(3):273-81.

[The effect of different vitamin B6 supplies on the vitamin B6 status (pyridoxine, pyridoxal and pyridoxamine) of the liver and the body of lactating rats]

[Article in German]

Benedikt J, Roth-Maier DA, Kirchgessner M.

Institut fur Ernahrungsphysiologie, Technische Universitat Munchen, Freising-Weihenstephan.

Eighty female Sprague-Dawley rats were fed a semisynthetic diet during gravidity which was supplemented with 5 mg vitamin B6 per kg diet. The daily food intake was 14 g. During the following lactation the rats were assigned to one of 10 vitamin B6 treatment groups (0, 3, 6, 9, 12, 15, 18, 36, 360 and 3,600 mg per kg diet). The feed was given ad libitum. At day 14 of lactation the rats were decapitated. Parameters for determination of the vitamin B6 status were concentration of pyridoxine, pyridoxal and pyridoxamine in liver and body analyzed by using HPLC. Body was defined without the gastroenteral tract that was divided into carcass (extrahepatic compartments without liver) and total body (extrahepatic compartments plus liver). The mean weight of liver was 13 g with a dry mass of 33%; there was no difference between the treatment groups. The vitamin B6 concentration was lowest in rats fed 0 mg vitamin B6/kg diet (5 micrograms/g fresh matter, FM) and highest in the rats fed 3600 mg vitamin B6/kg diet (10.9 micrograms/g FM). The total vitamin B6 consisted on the average of 38% pyridoxal and 62% pyridoxamine. This was only changed significantly at the highest supplementation level, where 20% pyridoxine were detected instead of pyridoxamine. The mean weight of carcass averaged 212 g at a dry matter content of 31%. The vitamin B6 concentration ranged in the treatment groups from 0 mg to 360 mg vitamin B6/kg diet between 2.1 micrograms/g FM and 2.8 micrograms/g FM. It was highest in the 3600 mg vitamin B6 treatment group at 7.5 micrograms/g FM. The total vitamin B6 consisted of 63% pyridoxal and 37% pyridoxamine. It was only significantly affected in the 3600 mg vitamin B6 treatment group, where also pyridoxine could be found in the amount of 56%. The results indicate that alimentary vitamin B6 supply had more influence on liver vitamin B6 concentration than on carcass concentration. Total body concentration is very similar carcass concentration, as 95% of vitamin B6 is located there. The suitability of the parameters by the evaluation of the vitamin B6 requirement was confirmed the comparison of two statistical methods. It is concluded that a vitamin B6 supply of 5 to 6 mg/kg diet is necessary to meet the requirements during lactation.

J Urol. 1996 Jun;155(6):1847-51.

A prospective study of the intake of vitamins C and B6, and the risk of kidney stones in men.

Curhan GC, Willett WC, Rimm EB, Stampfer MJ.

Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

PURPOSE: The association between the intake of vitamins C and B6, and kidney stone formation was examined. MATERIALS AND METHODS: We conducted a prospective study of the relationship between the intake of vitamins C and B6 and the risk of symptomatic kidney stones in a cohort of 45,251 men 40 to 75 years old with no history of kidney calculi. Vitamin intake from foods and supplements was assessed using a semiquantitative food frequency questionnaire completed in 1986. RESULTS: During 6 years of followup 751 incident cases of kidney stones were documented. Neither vitamin C nor vitamin B6 intake was significantly associated with the risk of stone formation. For vitamin C the age-adjusted relative risk for men consuming 1,500 mg. daily or more compared to less than 250 mg. daily was 0.78 (95% confidence interval 0.54 to 1.11). For vitamin B6 the age-adjusted relative risk for men consuming 40 mg. daily or more compared to less than 3 mg. daily was 0.91 (95% confidence interval 0.64 to 1.31). After adjusting for other potential stone risk factors the relative risks did not change significantly. CONCLUSIONS: These data do not support an association between a high daily intake of vitamin C or vitamin B6 and the risk of stone formation, even when consumed in large doses.

Exp Clin Endocrinol Diabetes. 1996;104(4):311-6.

A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy.

Stracke H, Lindemann A, Federlin K.

Third Medical Department, University of Giessen, Germany.

In a double-blind, randomized, controlled study, the effectiveness of treatment with a combination of Benfotiamine (an Allithiamine, a lipid-soluble derivative of vitamin B1 with high bioavailability) plus vitamin B6/B12 on objective parameters of neuropathy was studied over a period of 12 weeks on 24 diabetic patients with diabetic polyneuropathy. The results showed a significant improvement (p = 0.006) of nerve conduction velocity in the peroneal nerve and a statistical trend toward improvement of the vibration perception threshold. Long-term observation of 9 patients with verum over a period of 9 months support the results. Therapy-specific adverse effects were not seen. The results of this double-blind investigation, of the long-term observation and of the reports in the literature support the contention that the neurotropic benfotiamine-vitamin B combination represents a starting point in the treatment of diabetic polyneuropathy.

J Gerontol A Biol Sci Med Sci. 1996 Jan;51(1):B100-7.

Dietary intakes of energy and water-soluble vitamins in different categories of aging.

van der Wielen RP, de Wild GM, de Groot LC, Hoefnagels WH, van Staveren WA.

Department of Human Nutrition, Wageningen Agricultural University, The Netherlands.

The dietary intakes of energy and the vitamins thiamin, riboflavin, B6, and C were assessed in four groups of elderly people, using the same modified dietary history method. The groups consisted of female nursing home residents (n = 40), people at admission to a nursing home (n = 21), free-living elderly people with a sedentary life style (n = 120), and physically active free-living elderly people (n = 66). Mean energy intake varied from 6.5 +/- 1.2 Megajoule (MJ)/day (nursing home residents) to 8.8 +/- 2.2 MJ/day (physically very active persons) in females and from 8.8 +/- 2.5 MJ/day (admission to nursing home) to 10.1 +/- 2.3 MJ/day (physically very active persons) in males. Dietary intakes of the selected vitamins were below the minimum requirements in almost half of the nursing home residents. However, the relative contribution of the various food groups to the dietary intake of these vitamins was similar in the four groups of elderly people. Stimulation of physical activity to increase energy requirements and use of foods with a high nutrient density may result in an improvement of dietary adequacy.

Am J Obstet Gynecol. 1995 Sep;173(3 Pt 1):881-4. Pyridoxine for nausea and vomiting of pregnancy: a randomized, double-blind, placebo-controlled trial.

Vutyavanich T, Wongtra-ngan S, Ruangsri R.

Department of Obstetrics and Gynecology, Faculty of Medicine, Chiang Mai University, Thailand.

OBJECTIVE: Our purpose was to determine the effectiveness of pyridoxine for nausea and vomiting of pregnancy. STUDY DESIGN: During an 11-month period 342 women who first attended Chiang Mai University Hospital antenatal clinic at < or = 17 weeks' gestation were randomized to received either oral pyridoxine hydrochloride, 30 mg per day, or placebo in a double-blind fashion. Patients graded the severity of their nausea by a visual analog scale and recorded the number of vomiting episodes over the previous 24 hours before treatment and again during 5 consecutive days on treatment. RESULTS: There was a significant decrease in the mean of posttherapy minus baseline nausea scores in the pyridoxine compared with that in the placebo group (t test, p = 0.0008). There was also a greater reduction in the mean number of vomiting episodes, but the differences did not reach statistical significance (p = 0.0552). CONCLUSION: Pyridoxine is effective in relieving the severity of nausea in early pregnancy.

Ned Tijdschr Geneeskd. 1995 Aug 19;139(33):1694-7.

[Pyridoxine-dependent epilepsy in an infant]

[Article in Dutch]

van Waarde WM, Tummers RF, Bosschaart AN, Hageman G.

Medisch Spectrum Twente, Enschede.

A newborn girl with seizures was, after repeated conventional anticonvulsive treatment, cured by pyridoxine administration. Pyridoxine-dependent seizures are an uncommon disease with autosomal-recessive heredity and a variable clinical picture. The prognosis may be favourable when diagnosis is made early. Confusion with perinatal asphyxia, and initial good response to usual anticonvulsive treatment can lead to delay in diagnosis.

Res Commun Mol Pathol Pharmacol. 1995 Aug;89(2):208-20.

Prevention of myocardial infarction by vitamin B6.

Ellis JM, McCully KS.

Titus County Memorial Hospital, Mt. Pleasant, Texas 75455, USA.

Vitamin B6 is effective in the treatment of carpal tunnel syndrome and related disorders in patients with vitamin B6 deficiency. Hyperhomocysteinemia, a risk factor for atherosclerosis, is associated with deficiencies of vitamin B6, folate, and cobalamin. Patients who were given vitamin B6 for carpal tunnel syndrome and other degenerative diseases were found to have 27% of the risk of developing acute cardiac chest pain or myocardial infarction, compared with patients who had not taken vitamin B6. Among elderly patients of the author (JE) expiring at home, the average age at death from myocardial infarction was 8 years later in those who had taken vitamin B6, compared with those who had not taken vitamin B6. The preventive effect of vitamin B6 on progression of coronary heart disease may be related to increased formation of pyridoxal phosphate, the coenzyme that is required for catabolism of the atherogenic amino acid, homocysteine.

Vet Hum Toxicol. 1995 Aug;37(4):342-5.

Pyridoxine as therapy in theophylline-induced seizures.

Glenn GM, Krober MS, Kelly P, McCarty J, Weir M.

Walter Reed Army Institute of Research, Washington, DC, USA.

Theophylline-induced seizures have significant morbidity and mortality and are difficult to treat. Theophylline therapy for asthma has been observed to depress plasma pyridoxal 5'-phosphate (PLP) levels which may decrease gamma-aminobutyric acid (GABA) synthesis and thereby contribute to seizures. We hypothesized that treatment with pyridoxine might prove beneficial in theophylline-induced seizures. One hundred thirty-nine mice were injected with 250 mg theophylline/kg ip and 89 mice were injected with 250-750 mg pyridoxine/kg ip as treatment. Decreased rates of seizure (42 vs 70%, p < 0.002) and death (29 vs 56%, p < 0.002) were observed. Six New Zealand White rabbits were given 115 mg theophylline/kg iv over 50 min followed by treatment with an iv bolus of 115 mg pyridoxine/kg, with subsequent continuous drip infusion of 230 mg/kg over 50 min. Serum theophylline levels and plasma PLP levels showed significant negative correlation prior to pyridoxine infusion with a mean peak theophylline level of 182 micrograms/ml and a mean low PLP level of 64 nM/L. Electroencephalogram (EEG) tracings were obtained before infusions, during theophylline infusion and during pyridoxine infusion. All 6 rabbits developed abnormal EEGs during theophylline infusion and all 6 rabbit EEG patterns returned to baseline during treatment with pyridoxine. These findings suggest that pyridoxine may partially reverse theophylline-induced central nervous system toxicity.

Lancet. 1995 Jul 8;346(8967):85-9.

Comment in: • Lancet. 1995 Sep 2;346(8975):635.

Effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin concentrations.

Naurath HJ, Joosten E, Riezler R, Stabler SP, Allen RH, Lindenbaum J.

Department of Geriatric Medicine, University Witten-Heddecke, Velbert, Germany.

In a prospective, multicentre, double-blind controlled study, the effect of an intramuscular vitamin supplement containing 1 mg vitamin B12, 1.1 mg folate, and 5 mg vitamin B6 on serum concentrations of methylmalonic acid (MMA), homocysteine (HCYS), 2-methylcitric acid (2-MCA), and cystathionine (CYSTA) was compared with that of placebo in 175 elderly subjects living at home and 110 in hospital. Vitamin supplement and placebo were administered eight times over a 3-week period. Vitamin supplement but not placebo significantly reduced all four metabolite concentrations at the end of the study in both study groups. The maximum effects of treatment were usually seen within 5-12 days. Initially elevated metabolite concentrations returned to normal in a higher proportion of the vitamin than of the placebo group: 92% vs 20% for HYCS; 82% vs 20% for MMA; 62% vs 25% for 2-MCA; and 42% vs 25% for CYSTA. The response rate to vitamin supplements supports the notion that metabolic evidence of vitamin deficiency is common in the elderly, even in the presence of normal serum vitamin levels. Metabolite assays permit identification of elderly subjects who may benefit from vitamin supplements.

100: Lewis PJ. Pain in the hand and wrist. Pyridoxine supplements may help patients with carpal tunnel syndrome. BMJ. 1995 Jun 10;310(6993):1534. No abstract available. PMID: 7787619

Pediatrics. 1995 May;95(5):700-4.

Comment in: • Pediatrics. 1996 May;97(5):782. • Pediatrics. 1996 May;97(5):782-3.

Acute isoniazid neurotoxicity in an urban hospital.

Shah BR, Santucci K, Sinert R, Steiner P.

Department of Pediatrics, Children's Medical Center of Brooklyn, State University of New York 11203-2098, USA.

OBJECTIVES. To describe the presentation and treatment of acute isoniazid (INH) neurotoxicity appearing at an inner-city municipal hospital. DESIGN. Case series. PARTICIPANTS. Seven patients (eight patient visits) with an age range of 5 days to 14.9 years. RESULTS. At our institution, no children appeared with acute INH neurotoxicity in the period 1985 through 1990, whereas seven patients were treated from 1991 through 1993. This paralleled the rise in the number of children with tuberculous infection and disease seen at our institution, from an average 96 per year to 213 per year during these two time periods. All seven patients were receiving INH daily for tuberculosis (TB) prophylaxis. Accidental ingestion (five episodes) and suicidal attempts (three episodes) accounted for these visits. The total amount ingested range from 14.3 to 99.3 mg/kg (mean, 54 mg/kg). All but one patient presented with afebrile seizures. One patient presented twice with seizures. Acute INH neurotoxicity was not suspected on the first admission; however, when readmitted 4 weeks later with another seizure, the diagnosis of acute INH neurotoxicity was made. INTERVENTION. Intravenous pyridoxine was used in five episodes. Because it was not a stocked item in our pediatric emergency cart (as well as at another hospital, necessitating a transfer of a patient with refractory seizures to our hospital), the average delay was 5.8 hours (range, 1.3 to 13 hours) before it was given. Two patients with refractory seizures failed to respond to anticonvulsants, and their seizures were controlled only after parenteral pyridoxine. CONCLUSIONS. We have seen an increased incidence of acute INH neurotoxicity because of the resurgence of TB in New York City. Others as well may see a similar rise based on local trends in TB infection and disease. Acute INH toxicity should be suspected in children presenting with seizures with or without fever. In patients with a known access to INH, seizures should be considered to be caused by INH toxicity unless proved otherwise. Parenteral pyridoxine, the specific antidote for INH-induced refractory seizures, should be readily available in every emergency department in the areas similarly experiencing increasing trends of TB.

Am J Clin Nutr. 1995 Mar;61(3):571-6.

Pyridoxine supplementation protects mice from suppression of contact hypersensitivity induced by 2-acetyl-4-tetrahydroxybutylimidazole (THI), ultraviolet B radiation (280-320 nm), or cis-urocanic acid.

Reeve VE, Bosnic M, Boehm-Wilcox C, Cope RB.

Department of Veterinary Pathology, University of Sydney, Australia.

Evidence exists implicating the epidermal ultraviolet B (UVB) photoproduct cis-urocanic acid as an immunogenic mediator of the systemic suppression of T cell-mediated immunity by UVB exposure. Cis-urocanic acid appears to act via histamine receptor pathways, and histamine receptor antagonists and other imidazole ring compounds may modify its immune suppressing action. A component of the food coloring substance ammonia caramel, 2-acetyl-4-tetrahydroxybutylimidazole (THI), which is known to cause lymphopenia in rats, appears to suppress immunity by a similar pathway when the contact hypersensitivity reaction has been the immune function assay in mice. The induction of lymphopenia in rats by THI is inhibited by the vitamin pyridoxine. This study demonstrates that the suppression of contact hypersensitivity in mice by UVB radiation, cis-urocanic acid, or THI is strongly inhibited by supplemental pyridoxine, fed at 30 mg/kg diet, in comparison with the normal diet, which supplies 7 mg pyridoxine/kg diet. These results suggest that pyridoxine competes with cis-urocanic acid and THI for the same binding site or receptor, which we postulate to be a histamine-like T lymphocyte receptor, and that a role may exist for the control of photoimmunosuppression by this vitamin.

Am J Hum Genet. 1995 Mar;56(3):616-22.

Pyridoxine-responsive gyrate atrophy of the choroid and retina: clinical and biochemical correlates of the mutation A226V.

Michaud J, Thompson GN, Brody LC, Steel G, Obie C, Fontaine G, Schappert K, Keith CG, Valle D, Mitchell GA.

Service de genetique medicale, Hopital Ste-Justine, Montreal, Quebec, Canada.

We discovered the missense mutation, A226V, in the ornithine-delta-aminotransferase (OAT) genes of two unrelated patients with gyrate atrophy of the choroid and retina (GA). One patient, who was a compound for A226V and for the premature termination allele R398ter, showed a significant (P < .01) decrease in mean plasma ornithine levels, following pyridoxine supplementation with a constant protein intake: 826 +/- 128 microM (n = 5; no pyridoxine supplementation) versus 504 +/- 112 microM (n = 6; 500 mg pyridoxine/d) and 546 +/- 19 microM (n = 6; 1,000 mg pyridoxine/d). In extracts of fibroblasts from a second GA patient homozygous for A226V and from Chinese hamster ovary cells expressing an OAT-cDNA-containing A226V, we found that OAT activity increased from undetectable levels to approximately 10% of normal when the concentration of pyridoxal phosphate was increased from 50 to 600 microM. A226V is the fourth disease-causing pyridoxine-responsive human mutation to be reported.

Eur J Clin Invest. 1995 Mar;25(3):176-81.

Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease.

Van den Berg M, Boers GH, Franken DG, Blom HJ, Van Kamp GJ, Jakobs C, Rauwerda JA, Kluft C, Stehouwert CD.

Department of Vascular Surgery, Free University Hospital, Amsterdam, The Netherlands.

Hyperhomocysteinaemia, defined as an abnormally high plasma homocysteine concentration after an oral methionine load, is common in young (< or = 50 years) patients with peripheral arterial occlusive disease. It is thought to predispose to atherosclerosis by injuring the vascular endothelium. Treatment with pyridoxine and/or folic acid may lower plasma homocysteine levels. In mildly hyperhomocysteinaemic patients with peripheral arterial occlusive disease, we studied the effect of daily treatment with pyridoxine (250 mg) plus folic acid (5 mg) on homocysteine metabolism (i.e. plasma concentrations in the fasting state and after methionine loading, in 48 patients) and on endothelial function (in 18 patients). Endothelial function was estimated as the plasma concentrations of the endothelium-derived proteins, von Willebrand factor (vWF), thrombomodulin (TM), and tissue-type plasminogen activator (tPA). At baseline, fasting homocysteine levels were above normal in 24 of the 48 patients (50%); post-load levels, by definition, were above normal in 100% of patients. After 12 weeks of treatment, fasting and post-load levels were normal in 98 and 100% of patients, respectively. Endothelial function was assessed in 18 patients who completed 1 year of treatment. At baseline, median vWF (235%) and TM (57.1 ng mL-1) levels were above normal. At follow-up, vWF levels had decreased to 170% (P = 0.01) and TM levels had decreased to 49 ng mL-1 (P = 0.04). tPA levels were normal at baseline and did not change. Endothelial dysfunction is present in young patients with peripheral arterial occlusive disease and hyperhomocysteinaemia. Pyridoxine plus folic acid treatment normalizes homocysteine metabolism in virtually all patients, and appears to ameliorate endothelial dysfunction.

J Child Neurol. 1995 Mar;10(2):143-7.

Medical treatment of West syndrome in Japan.

Watanabe K.

Department of Pediatrics, Nagoya University School of Medicine, Japan.

Although corticotropin (ACTH) is still the most effective drug for the treatment of West syndrome, a variety of other treatment modalities have been tried because of corticotropin's frequent and sometimes serious side effects. A recent survey on the treatment of this devastating disorder by Japanese child neurologists disclosed different therapeutic approaches from those taken by American or European child neurologists. Most Japanese child neurologists use vitamin B6 as the first agent and corticotropin as the third or second drug. Moreover, the dosage of corticotropin used by them is considerably smaller. Therefore, the current status of medical treatment of West syndrome is reviewed, especially comparing Japan with other countries.

Ann Nutr Metab. 1995;39(5):285-90.

Effect of pyridoxine and magnesium on stress-induced gastric ulcers in mice selected for low or high blood magnesium levels.

Henrotte JG, Aymard N, Allix M, Boulu RG.

Institut de Chimie des Substances Naturelles, CNRS, Gif-sur-Yvette, France.

Gastric ulcers were induced by immobilization in adult female mice with genetically low (MGL) or high (MGH) blood magnesium levels, obtained by selective breeding at the CSAL-CNRS (Orleans, France). All animals, fed with the same standard diet rich in magnesium, were divided into four groups of 20 animals and injected subcutaneously every 2 days for 10 days with isotonic saline (group 1), pyridoxine chlorhydrate 1.11 mg/kg in saline (group 2), magnesium lactate 149 mg/kg in saline (group 3) or both pyridoxine and magnesium (group 4). Subsequently, animals were submitted to a complete fast and an immobilization stress for 17 h. Then, they were sacrificed and the gastric mucosa was dissected for ulcer count. Among the controls (group 1), the mean number of gastric ulcers per mouse was significantly larger in the MGL than in the MGH line (p = 0.0003). In the MGH line, no significant differences were observed between control and treated groups. In the MGL line, pyridoxine associated or not with magnesium (groups 2 and 4) significantly reduced the mean number of ulcers. Magnesium treatment alone (group 3) had little effect. These results can be compared with the greater vulnerability to stress previously observed in Swiss mice fed with a magnesium-deficient diet. However, in this latter group, the number of stress ulcers was reduced not only by pyridoxine but also by the sole magnesium treatment, contrary to our present findings in MGL mice.

Can J Public Health. 1995 Jan-Feb;86(1):66-70.

Measuring drug effectiveness by default: the case of Bendectin.

Neutel CI, Johansen HL.

Centre for Canadian Health Statistics, Ottawa.

In 1983, Bendectin was voluntarily removed from the market by Merrell Dow Pharmaceuticals Inc. because of the many product liability suits pending. Earlier, 10 to 25% of pregnancies were exposed to Bendectin and over the years the drug was used in as many as 33 million pregnancies. The scientific evidence available pointed to the safety of Bendectin. This article considers some of the effects of the withdrawal of the drug. In 1983, hospital admissions for excessive vomiting in pregnancy per thousand live births rose by 37% over 1980-82 ratios and by 50% in 1984. In the United States, hospitalization rose by similar amounts. A rough estimate of excess hospital costs over the years 1983-87 is $16 million for Canada and $73 million for the U.S. Such estimates do not take into consideration other costs, such as extra physician visits, increased absenteeism from work, and the effect on quality of life of the pregnant woman and her family. No decrease in rates of congenital malformations could be shown to offset this increased cost to society.

Int J Tissue React. 1995;17(1):15-20.

Effect of pyrrolidone carboxylate (PCA) and pyridoxine on liver metabolism during chronic ethanol intake in rats.

Calabrese V, Ragusa N, Rizza V.

Institute of Biological Chemistry, University of Catania School of Medicine, Italy.

Rats subjected to chronic ethanol intake for a period of 28 days showed significant elevation in blood ethanol levels, a marked decrease in hepatic reduced glutathione (GSH) content and a decrease in liver tryptophan pyrrolase (TPO) activity. A daily intraperitoneal injection of a combined solution of pyrrolidone carboxylate (PCA) and vitamin B6 (pyridoxine hydrochloride) (0.3 mmoles/kg) into ethanol-treated rats resulted in the blood ethanol levels becoming significantly reduced, while the hepatic GSH content and TPO activity were markedly elevated. Our results support the view that PCA and pyridoxine operate to restore the redox imbalance of the hepatocytes caused by chronic alcohol intake.

N Engl J Med. 1994 Dec 8;331(23):1553-8. Results of long-term treatment with orthophosphate and pyridoxine in patients with primary hyperoxaluria.

Milliner DS, Eickholt JT, Bergstralh EJ, Wilson DM, Smith LH.

Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905.

BACKGROUND. The prognosis for patients with primary hyperoxaluria has been ominous, with the expectation of renal failure, poor results with transplantation, and early death. METHODS. We studied the long-term effects of orthophosphate and pyridoxine therapy in 25 patients with primary hyperoxaluria who were treated for an average of 10 years (range, 0.3 to 26). Their mean age at the start of treatment was 12 years (median, 6; range, 0.5 to 32). We also studied the effect of orthophosphate and pyridoxine on urinary supersaturation with calcium oxalate, crystal inhibition using a seeded growth system, and crystal formation using scanning electron microscopy in 12 patients during three-day stays in the clinical research center. RESULTS. The mean (+/- SD) glomerular filtration rate at the start of treatment was 91 +/- 26 ml per minute per 1.73 m2. The median decline in glomerular filtration rates was 1.4 ml per minute per 1.73 m2 of body-surface area per year. The actuarial survival free of end-stage renal disease was 96, 89, 74, and 74 percent of 5, 10, 15, and 20 years, respectively. Treatment with orthophosphate and pyridoxine reduced urinary supersaturation with calcium oxalate from 8.3 +/- 3.0 to 2.1 +/- 1.7 kJ per mole at 38 degrees C (P < 0.001), increased the inhibition of calcium oxalate formation from 63 +/- 11 to 108 +/- 10 inhibitor units per 24 hours (P < 0.001), and improved the crystalluria score from 2.6 +/- 0.3 to 0.6 +/- 0.1 (P < 0.001). CONCLUSIONS. Treatment of patients with primary hyperoxaluria with orthophosphate and pyridoxine decreases urinary calcium oxalate crystallization and appears to preserve renal function.

J Vasc Surg. 1994 Dec;20(6):933-40. Combined vitamin B6 plus folic acid therapy in young patients with arteriosclerosis and hyperhomocysteinemia.

van den Berg M, Franken DG, Boers GH, Blom HJ, Jakobs C, Stehouwer CD, Rauwerda JA.

Department of Surgery, Free University Hospital, Amsterdam, The Netherlands.

PURPOSE: Hyperhomocysteinemia is associated with arteriosclerotic and thromboembolic events. The homocysteine-lowering effect of combined treatment with vitamin B6 plus folic acid has never been explored in a large group of patients with vascular disease. Therefore we studied the effects of at least 6 weeks treatment with these vitamins in 72 patients with cardiovascular disease and mild hyperhomocysteinemia (defined as an increase of the plasma homocysteine level after methionine loading greater than 97.5 percentile of age-matched control subjects but less than 200 mumol/L). METHODS: The existence of mild hyperhomocysteinemia was investigated in 309 consecutive patients under 50 years of age with peripheral arterial occlusive disease, cerebral arterial occlusive disease, or coronary artery occlusive disease. All patients with an abnormal loading test result were treated with vitamin B6, 250 mg daily, plus folic acid, 5 mg daily. After 6 weeks of treatment a second methionine loading test was performed to assess the homocysteine-lowering effect. RESULTS: Mild hyperhomocysteinemia was detected in 72 patients (23%), 33 (46%) of whom also had hyperhomocysteinemia when fasting. Treatment with vitamin B6 plus folic acid normalized the postload plasma homocysteine concentration in 66 of the 72 patients (92%), whereas fasting hyperhomocysteinemia was normalized in 30 of 33 (91%) patients. In six patients therapy failed to achieve normalization of the postload homocysteine levels. In three of these patients, the same treatment was continued for an additional 6 weeks, and in the remaining three patients betaine was added to the treatment regimen. After 6 weeks of additional treatment all six patients had normal postload plasma homocysteine concentrations. CONCLUSION: The prevalence of mild hyperhomocysteinemia in young patients with arterial occlusive disease is high. Simple and inexpensive therapy with vitamin B6 plus folic acid will normalize homocysteine metabolism, as assessed by the homocysteine plasma level after methionine loading, in virtually all these patients.

Neurology. 1994 Sep;44(9):1728-32.

Pyridoxine-responsive hyper-beta-alaninemia associated with Cohen's syndrome.

Higgins JJ, Kaneski CR, Bernardini I, Brady RO, Barton NW.

Clinical Neurogenetics Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892.

We report intermittent seizures, lethargy, and Cohen's syndrome in a 4-year-old girl with hyper-beta-alaninemia and a partial deficiency of beta-alanyl-alpha-ketoglutarate transaminase (AKT). To examine the role of beta-alanine (beta ALA) in cellular metabolism, we cultured her skin fibroblasts in medium containing increasing amounts of beta ALA. At concentrations of 10 to 25 mM, beta ALA caused more than a 50% reduction in the growth of her cells compared with normal control skin fibroblasts. The addition of 0.1 mM of pyridoxine to the culture medium abolished these toxic effects and increased her skin fibroblast AKT enzyme activity more than twofold. During a 2-year period of clinical observation, there were no further episodes of seizures or somnolence in our patient while she received oral pyridoxine therapy.

Pediatrics. 1994 Sep;94(3):318-21.

Glutamate in pyridoxine-dependent epilepsy: neurotoxic glutamate concentration in the cerebrospinal fluid and its normalization by pyridoxine.

Baumeister FA, Gsell W, Shin YS, Egger J.

Dr. v. Haunersches Kinderspital, Universitat Munchen, Germany.

BACKGROUND. Pyridoxine-dependent epilepsy is a rare autosomal recessive disorder. Untreated patients suffer from a progressive encephalopathy with mental retardation, intractable epilepsy, and progressive neurological signs and symptoms. Lifelong supplementation with vitamin B6 is the treatment of choice. However, despite early treatment, many patients develop mental retardation. OBJECTIVES. To assess the role of glutamate as an excitatory neurotransmitter and neurotoxin in pyridoxine-dependent epilepsy. METHODS. We examined cerebrospinal fluid (CSF) levels of glutamate, gamma-aminobutyric acid, and pyridoxal-5'-phosphate in a patient with pyridoxine dependency while on and off vitamin B6 treatment. RESULTS. Off vitamin B6 the glutamate level was two hundred times normal. An intermediate dose of vitamin B6 (5 mg/kg BW/day) caused normalization of the EEG and remission of the seizures, but the CSF glutamate concentration was still ten times normal. With a higher dose of pyridoxine (10 mg/kg BW/day) the CSF glutamic acid normalized. CONCLUSIONS. The results indicate that control of epilepsy might not suffice as the therapeutic aim in treating of pyridoxine dependency. In view of the evidence for the role of excitatory amino acids in destruction of CNS nerve cells, the optimal treatment must counteract the raised levels of CSF glutamate and the dosage of vitamin B6 must be adjusted accordingly. The development of mental retardation might theoretically be prevented by adjusting the dose of vitamin B6 to achieve not only remission of epilepsy but also normalization of CSF glutamate.

J Am Coll Nutr. 1994 Aug;13(4):383-91.

Combinations of low thiamin, riboflavin, vitamin B6 and vitamin C intake among Dutch adults. (Dutch Nutrition Surveillance System).

van der Beek EJ, Lowik MR, Hulshof KF, Kistemaker C.

Department of Human Nutrition, TNO Toxicology and Nutrition Institute, The Netherlands.

OBJECTIVE: Clustering of low vitamin intake may entail a greater functional and/or health risk than the summation of separate low intakes may suggest. Therefore, the prevalence of combined low thiamin, riboflavin, vitamin B6 and vitamin C intake in various adult sex-age groups in The Netherlands was estimated. METHODS: Nutritional risks were evaluated by comparing the calculated intakes with the recommendations for each vitamin. For this purpose the data of a subsample of 3353 adults of a nationwide food consumption survey were used, which had been collected in 1987-88 within the framework of the Dutch Nutrition Surveillance System. Food consumption data were obtained through 2-day dietary records. Respondents were segmented into tertiles based on their vitamin intake per 1000 kcal (4.2 MJ) to adjust for energy intake. RESULTS: As compared with the RDAs, mean overall intake was lowest for vitamin B6. Based on tertile analyses, the risk for inadequate intake was relatively high for vitamin C, small for riboflavin and intermediate for thiamin and vitamin B6. Low vitamin densities clustered somewhat since the prevalence of combined low intakes for all four vitamins was higher than expected from probability calculations. This interdependence was mainly the result of a higher consumption of alcoholic beverages and of other food products with a low vitamin density. CONCLUSION: In affluent societies nutritional risk assessment should not be based solely on single vitamins but should also be oriented at combined low intake levels.

Teratology. 1994 Jul;50(1):27-37.

Bendectin and birth defects: I. A meta-analysis of the epidemiologic studies.

McKeigue PM, Lamm SH, Linn S, Kutcher JS.

Consultants in Epidemiology and Occupational Health, Inc., Washington, DC 20007.

"Bendectin" (Doxylamine/Dicyclomine/Pyridoxine) was widely used for the treatment of nausea and vomiting of pregnancy until 1983, when production was discontinued in the face of lawsuits alleging that the drug caused congenital malformations. We have conducted a meta-analysis of the 16 cohort and 11 case-control studies that report birth defects from Bendectin-exposed pregnancies. This meta-analysis provides an estimate of the relative risk of malformation at birth in association with Bendectin exposure. The pooled estimate of the relative risk of any malformation at birth in association with exposure to Bendectin in the first trimester was 0.95 (95% Cl 0.88 to 1.04). Separate analyses were undertaken for cardiac defects, central nervous system defects, neural tube defects, limb reductions, oral clefts, and genital tract malformations. In these categories, the pooled estimates of relative risk ranged from 0.81 for oral clefts to 1.11 for limb reductions, with all 95% confidence intervals enclosing unity. With the exception of studies for oral clefts and for pyloric stenosis, tests for heterogeneity of association indicated for each table that all studies were estimating the same odds ratio. These studies, as a group, showed no difference in the risk of birth defects between those infants whose mothers had taken Bendectin during the first trimester of pregnancy and those infants whose mothers had not. It is unlikely that Bendectin exposure contributed to the prevalence of congenital malformations in the population.

Hum Exp Toxicol. 1994 May;13(5):321-3.

Intravenous pyridoxine in acute ethanol intoxication.

Mardel S, Phair I, O'Dwyer F, Henry JA.

Accident and Emergency Department, Aberdeen Royal Infirmary, UK.

Intravenous pyridoxine was evaluated as an agent for the reversal of ethanol-induced central nervous depression in a randomised double blind controlled study of 108 patients presenting with a clinical diagnosis of acute ethanol intoxication to two accident and emergency departments. Level of consciousness, measured by a modified Glasgow coma scale, showed no significant change after a single 1 g dose of intravenous pyridoxine when compared to controls given saline. The mean fall in blood alcohol concentration after one hour was 33 mg dl-1 (7.2 mmol l-1) in both groups suggesting that pyridoxine has no antidotal action and no short term effect on the rate of metabolism of ethanol.

Urol Res. 1994;22(3):161-5.

Effect of combined supplementation of magnesium oxide and pyridoxine in calcium-oxalate stone formers.

Rattan V, Sidhu H, Vaidyanathan S, Thind SK, Nath R.

Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

A combined supplement of magnesium oxide (300 mg/day) and pyridoxine.HCl (10 mg/day) was given p.o. to 16 recurrent calcium oxalate (CaOx) stone formers, and its therapeutic efficacy was biochemically evaluated by measuring various parameters of blood (Na, K, Mg, urea, creatinine, calcium, phosphate, uric acid, alanine transaminase, aspartate transaminase and alkaline phosphatase) and urine (volume, pH, creatinine, Na, K, Mg, uric acid, calcium, phosphate, oxalate and citrate) at 0, 30, 60, 90 and 120 days of treatment. Serum Mg significantly (P < 0.01) increased after 30 days of treatment and remained constant thereafter while other blood parameters were unaltered. Combined treatment led to a significant increase in the urinary excretion of Mg and citrate over pretreatment values while oxalate excretion showed a gradual and significant decline during the therapy. The results confirmed the efficacy of MgO-pyridoxine supplementation in terms of changes in urinary excretion of lithogenic and inhibitory components, leading to a significant (P < 0.01) decrease in CaOx risk index from 0.09 +/- 0.04 at 0 day to 0.05 +/- 0.02 after 120 days of treatment.

Clin Investig. 1993 Dec;71(12):993-8.

Hyperhomocysteinemia and the response to vitamin supplementation.

Ubbink JB, van der Merwe A, Vermaak WJ, Delport R.

Department of Chemical Pathology, Faculty of Medicine, University of Pretoria.

The long-term vitamin requirements of men (n = 22) with moderate hyperhomocysteinemia (plasma total homocysteine concentration > 16.3 mumol/l) were investigated over a period of 48 weeks. An initial 6-week period of vitamin supplementation (1.0 mg folic acid, 10 mg pyridoxine, 0.05 mg cyanocobalamin) reduced plasma homocysteine levels 54.7% (P < 0.001). However, 18 weeks after vitamin therapy was discontinued, only seven participants (subgroup A) still had plasma homocysteine levels of 16.3 mumol/l or lower. The remainder of the participants (subgroup B) required a second 6-week period of vitamin therapy to normalize the elevated plasma homocysteine levels. Substitution of vitamin supplementation by dietary guidelines to increase folate intake from food products failed to maintain normal plasma homocysteine levels in participants from subgroup B. Long-term vitamin supplementation may be required in some individuals to prevent hyperhomocysteinemia.

Clin Nephrol. 1993 Oct;40(4):236-40.

The effect of high-dose pyridoxine and folic acid supplementation on serum lipid and plasma homocysteine concentrations in dialysis patients.

Arnadottir M, Brattstrom L, Simonsen O, Thysell H, Hultberg B, Andersson A, Nilsson-Ehle P.

Department of Nephrology, University Hospital, Lund, Sweden.

Pyridoxine and folic acid supplementation in dialysis patients is a matter of debate. This study was performed to estimate the effects of pharmacologic doses of these vitamins on serum lipid and plasma homocysteine concentrations, which are known to be high in dialysis patients. Both hemodialysis and continuous ambulatory peritoneal dialysis patients were included in the study. Pyridoxine supplementation had a mild but significant cholesterol-lowering effect (7%). Folic acid supplementation significantly lowered plasma homocysteine concentrations by a mean of 30%. There was a strong, inverse correlation between blood folate and plasma homocysteine concentrations. These results indicate that daily supplementation with pyridoxine 300 mg and folic acid 5 mg has a beneficial effect on the cardiovascular risk profile in dialysis patients.

Nippon Jinzo Gakkai Shi. 1993 Aug;35(8):975-80.

Effects of high-dose vitamin B6 therapy on microcytic and hypochromic anemia in hemodialysis patients.

Toriyama T, Matsuo S, Fukatsu A, Takahashi H, Sato K, Mimuro N, Kawahara H.

Department of Internal Medicine, Nagoya Kyoritsu Hospital, Japan.

In an attempt to treat hemodialysis patients suffering from microscopic and hypochromic anemia (MHA) and who are either sufficient or deficient in serum ferritin level, we investigated the effects of oral administration of vitamin B6 (VB6). Twenty-six patients with MHA undergoing long-term stable hemodialysis treatment were divided into three groups. There was no significant difference in the serum VB6 levels in these patients as compared with normal subjects before the study. Patients in group I, whose serum ferritin levels were normal, were orally administered 180mg of VB6 every day for 20 weeks. Patients in groups II and III, whose serum ferritin levels were far below normal (due to suspected iron deficiency anemia), were either administered iron alone (intravenous administration of 40mg of iron for 12 consecutive dialysis treatments, for 4 weeks--group II) or both iron and VB6 (group III). There was significant improvement in the hematocrit, mean corpsular volume (MCV), and mean corpsular hemoglobin (MCH) in group I patients supporting the contention that this group of patients had pyridoxine responsive anemia (PRA). The number of sideroblasts in bone marrow in these patients, however, was significantly low when compared to that of the normal subjects. In addition, the combined therapy with iron and VB6 led to the longer-sustained improvement in hematocrit in patients with suspected iron deficiency anemia (group III) when compared to those treated with iron alone (group II).(ABSTRACT TRUNCATED AT 250 WORDS)

An Esp Pediatr. 1993 Jul;39(1):37-41.

[Homocystinuria: effectiveness of the treatment with pyridoxine, folic acid, and betaine]

[Article in Spanish]

Montero Brens C, Dalmau Serra J, Cabello Tomas ML, Garcia Gomez AM, Rodes Monegal M, Vilaseca Busca A.

Departamento de Pediatria, Hospital Infantil La Fe, Valencia.

We present the results achieved with vitamin (pyridoxine and folic acid) and betaine (trimethyl-glycine) treatment of three patients with homocystinuria. Cases 1 and 2 were detected by having clinical findings suggestive of the disease (ocular and orthopedic alterations) and case 3 was diagnosed after a family metabolic screening was done. All presented a positive Brand's test and an abnormal elevation of plasma and urine homocysteine, as well as high methionine and low cystine levels in the plasma. Initially, when pyridoxine (600 mg/d) and folic acid (10 mg/d) were given for one month, a partial fall in the homocysteine levels was observed in cases 2 and 3, but not in case 1. When betaine was added (6 g/d), homocysteine disappeared from the plasma after the first month in cases 2 and 3, but only after the third month in case 1. Case 1 also showed a moderate clinical improvement in behavior and school performance. The treatment was maintained for two years in case 1, and for one year in cases 2 and 3. After betaine therapy, no disturbances were observed in the hepatic, renal and bone marrow functions, nor were there any clinically relevant ill-effects. These findings show that betaine offers a therapeutic alternative in the treatment of this disease, independent of the patient's response to pyridoxine.

Epilepsia. 1993 Jul-Aug;34(4):757-63.

Treatment of infantile spasms with high-dosage vitamin B6.

Pietz J, Benninger C, Schafer H, Sontheimer D, Mittermaier G, Rating D.

Department of Child Neurology, University of Heidelberg, Federal Republic of Germany.

High-dose vitamin B6 (pyridoxine-HCl, 300 mg/kg/day orally) was introduced as the initial treatment of recently manifested infantile spasms in 17 children (13 symptomatic cases with identified brain lesion and 4 cryptogenic cases). 5 of 17 children (2 cryptogenic, 2 with severe pre/perinatal brain damage and one with Sturge-Weber syndrome) were classified as responders to high-dose vitamin B6. In all 5 cases the response to vitamin B6 occurred within the first 2 weeks of treatment and within 4 weeks all patients were free of seizures. Two patients developed other seizures (partial seizures, etiologically unclear blinking attacks), but no relapse of infantile spasms was observed among the five responders to vitamin B6. No serious adverse reactions were noted. Side effects were mainly gastrointestinal symptoms, which were reversible after reduction of the dosage. Considering the life-threatening side effects of treatment with ACTH/corticosteroids or valproate, a controlled clinical trial with high-dose vitamin B6 would appear justified to either prove or disprove efficacy.

Harefuah. 1993 May 16;124(10):616-8, 667.

[Pyridoxine for severe metabolic acidosis and seizures due to isoniazid overdose]

[Article in Hebrew]

Adler M, Girsh-Solomonovich Z, Raikhlin-Eisenkraft B.

Intensive Care Unit, Wolfson Medical Center, Holon.

A 15-year-old girl took 3 g of isoniazid (15 tablets) in a suicide attempt and was brought unconscious to the emergency room. She was in respiratory failure, with seizures that could not be stopped with diazepam. Severe metabolic acidosis with normal serum lactate developed (pH 6.85), but did not improve after infusion of bicarbonate. Intravenous administration of pyridoxine led to prompt cessation of the seizures and to gradual improvement of acid-base status. She recovered consciousness after several hours and was discharged a week later.

Biull Eksp Biol Med. 1993 May;115(5):479-81.

[Effect of low doses of emoxipine and pyridoxine hydrochloride on the status of patients with cataract and glaucoma]

[Article in Russian]

Ianovskaia NP, Shtol'ko VN, Burlakova EB.

It has been shown that eyes instillation of pyridoxine hydrochloride low doses during 20 days affects the vision and tonographic characteristics of patients with glaucoma and earlier stage of cataract. Light eyes have been shown to be more sensitive to treatment than dark ones. From 10 to 40 min after emoxipin or pyridoxine hydrochloride low doses instillation, some pupil constriction has been registered. The data obtained suggest that low doses of this substances affect eyes cholinoreactive structures and may be useful for treatment glaucoma and early stage cataract.

Clin Ter. 1993 Mar;142(3):243-50.

[Therapeutic use of metadoxine in chronic alcoholism. Double blind study of patients in a department of general medicine]

[Article in Italian]

Rizzo A, Breda A, Moretto F, Pace M, Dotta C, Gelso E, Sanzuol F, Tossani C.

Divisione Medica, USL 12, Ospedale di Valdobbiadene (TV).

Sixty patients, recognized as chronic alcoholics on the grounds of the case history and with a score above 11 of the Munich Alcoholism Test (MALT) have been treated with metadoxine or placebo for thirty days according to a double blind randomized design. In the group treated with active drug there has been a significant reduction higher than in the controls of the scores relating to the abstinence symptomatology, in particular regarding the neuropsychic residual symptomatology (anxiety, depression, insomnia) after the first week of treatment, a reduced requirement of benzodiazepines and/or neuroleptics, and a significant decrement higher than in the controls of the score of MALT at the end of treatment. Furthermore, metadoxine seems to make easy the maintenance of abstinence, at least at short term.

Magnes Res. 1993 Mar;6(1):11-9.

Audiogenic seizures in magnesium-deficient mice: effects of magnesium pyrrolidone-2-carboxylate, magnesium acetyltaurinate, magnesium chloride and vitamin B-6.

Bac P, Herrenknecht C, Binet P, Durlach J.

S.D.R.M. Hopital Saint-Vincent de Paul, Paris, France.

Magnesium deficiency in mice causes and increases audiogenic seizures. This effect was reversed by oral administration of magnesium acetyltaurinate (ATaMg), magnesium pyrrolidone-2-carboxylate (PCMH), MgCl2. When treatment was discontinued, audiogenic seizures recurred only in the groups treated with PCMH or MgCl2. Following intraperitoneal administration of AtaMg, the mice were protected against audiogenic seizures after 4 h and this protection persisted for up to 72 h after the treatment. With the other magnesium salts (PCMH and MgCl2) maximum protection occurred by 6 h after the injection, but after that time the number of seizures increased sharply. Intraperitoneal taurine alone only reduced the severity of the audiogenic seizures. The length of treatment needed to inhibit audiogenic seizures was reduced by treatment with a combination of vitamin B-6 (a magnesium fixing agent) and PCMH or MgCl2. However this combination of vitamin B-6 and magnesium salts did not prevent the recurrence of audiogenic seizures, which was only achieved by ATaMg. The results suggest that audiogenic seizures in magnesium-deficient mice form a model of magnesium depletion. This depletion is completely inhibited by the combination of an inhibitory neurotransmitter (taurine) and magnesium, in the form of magnesium acetyltaurinate.

J Am Coll Nutr. 1993 Feb;12(1):73-6.

Brief communication: effect of pharmacologic doses of vitamin B6 on carpal tunnel syndrome, electroencephalographic results, and pain.

Bernstein AL, Dinesen JS.

Department of Neurology, Kaiser Permanente Medical Center, Hayward, CA 94545.

The role of vitamin B6 as a therapeutic agent in the treatment of carpal tunnel syndrome was examined by monitoring both the standard clinical and electrophysiological parameters for entrapment neuropathy at the wrist. Electroencephalogram (EEG) studies were done in an attempt to identify patients most likely to benefit from B6 treatment. EEGs did not prove useful as predictors of clinical response to vitamin B6. Our patients, however, did not show any abnormalities prior to treatment, and no changes occurred during the treatment period. Motor latency, while the most common screening test for carpal tunnel syndrome, was not significantly changed during the course of treatment. It did not prove to be a useful test for monitoring clinical effectiveness of the treatment. Parameters showing the greatest changes were pain scores and sensory latency, which most closely paralleled clinical assessments. Pain scores, more than any other parameters, were improved in these patients following vitamin B6 treatment. Vitamin B6 has been shown to change pain thresholds in clinical and laboratory studies. This may be the basis of the significant improvement in pain scores when electrophysiologic data showed only mild improvement. This study suggests that vitamin B6 deficiency may not be a cause of carpal tunnel syndrome in spite of the observed therapeutic effect, without toxicity, of vitamin B6 treatment.

Am J Hypertens. 1993 Jan;6(1):33-40.

Comment in: • Am J Hypertens. 1993 Jan;6(1):89-90.

Defective 3,4-dihydroxyphenylalanine decarboxylation to dopamine in hydralazine-treated hypertensive patients may be pyridoxine remediable.

Shigetomi S, Kuchel O.

Clinical Research Institute of Montreal, Quebec, Canada.

The previously observed defective dopamine (DA) generation from 3,4-dihydroxyphenylalanine (DOPA) can also be seen in patients treated for many years by hydralazine. This may be due to a hydralazine-induced depletion of pyridoxine, an essential coenzyme of the aromatic L-amino acid decarboxylase (LAAD). Eleven hydralazine-treated stable essential hypertensive (EH) patients, initially found to have a defect in the DOPA decarboxylation to DA, tested by a single DOPA administration (500 mg, orally), were retested by the same test 4 days after pyridoxine pretreatment (100 mg/day) for data on blood pressure (BP), pulse rate, and renal and plasma catecholamines and their metabolites, as well as plasma atrial natriuretic factor (ANF), cyclic GMP (cGMP), plasma renin activity (PRA), and plasma aldosterone (PA). Initially, hydralazine-treated stable EH patients manifested, following DOPA administration, lower DOPA decarboxylation to DA than control subjects. Pyridoxine pretreatment accelerated DA generation from exogenous DOPA and attenuated the DOPA-induced increases in plasma and urinary DOPA and its metabolite 3-O-methyl-DOPA, but accentuated the increase in free DA and its main metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), while BP, ANF, cGMP, PRA, and PA remained unaffected. The DOPA-induced increments of urinary DA were, in contrast to plasma DA changes, blunted by pyridoxine pretreatment. The attenuation of the sodium excretion by pyridoxine pretreatment exceeded that of the DA excretion, suggesting that pyridoxine suppressed a natriuretic factor, other than ANF, or activated a sodium-retaining factor, other than renin or aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Probl Tuberk. 1993;(6):42-5.

[The use of preparations of methazid combined with riboflavin and pyridoxine for the correction of methazid-induced metabolic disorders of the B-group vitamins in rats]

[Article in Russian]

Kovalenko TA, Kodentsova VM, Sokol'nikov AA, Iakushina LM, Kharitonchik LA, Sonin BV, Stroev EA.

It was established that 10-day administration of suppository methazide (20 mg per 100 g b. w.) induces B2 vitamin deficiency indicated by relevant hepatic and plasmic values. In vitamin B2 deficiency methazide-induced changes in vitamin B6 metabolism are less marked in rats provided with riboflavin. Use of suppository methazide in combination with riboflavin (100 micrograms per animal which is a recommended daily dose) prevents B2 deficiency. It is recommended daily use combinations of methazide with riboflavin or piridoxin in essential daily consumption doses to treat patients with alimentary vitamin B2 and B6 deficiencies. This will not only prevent side effects of methazide, but also help to overcome deficiency of the above vitamins.

129: Adachi K, Katsuki T. [A case of acquired primary sideroblastic anemia treated with vitamin B6] Nippon Naika Gakkai Zasshi. 1992 Dec 10;81(12):2007-9. Japanese. No abstract available. PMID: 1289451

130: de' Clari F. The paradoxical anticonvulsive and awakening effect of high-dose pyridoxine treatment for isoniazid intoxication. Arch Intern Med. 1992 Nov;152(11):2346-7. No abstract available. PMID: 1290558

J Am Diet Assoc. 1992 Nov;92(11):1372-5.

Consumption of a dehydrated ration for 31 days at moderate altitudes: status of zinc, copper, and vitamin B-6.

Deuster PA, Gallagher KL, Singh A, Reynolds RD.

Department of Military Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.

Intake of energy zinc, copper, and vitamin B-6 and indexes of zinc, copper and vitamin B-6 status were determined for eight men who consumed a high-carbohydrate dehydrated ration for 31 days of high activity at moderate altitudes (2,400 to 4,300 m). Data were collected 2 months before exposure (PRE), four times during the month at moderate altitudes (ALT), and 1 month after return (RET). Mean (+/- standard error) energy intake was 2,725 +/- 215, 3,430 +/- 79, and 3,370 +/- 215 kcal/day during PRE, ALT, and RET, respectively. Zinc and copper intakes averaged 10.6 +/- 1.6 and 1.0 +/- 0.1 mg/day during PRE and increased significantly to 16.9 +/- 0.7 and 3.5 +/- 0.1 mg/day during ALT; zinc and copper intakes were 15.5 +/- 1.6 and 1.9 +/- 0.3 mg/day for RET, respectively. Similarly, vitamin B-6 intake was significantly higher during ALT (PRE = 2.2 +/- 0.5 mg/day; ALT = 4.2 +/- 0.4 mg/day; and RET = 2.6 +/- 0.4 mg/day) as compared with PRE and RET. No significant changes were noted for plasma zinc, copper, or their related proteins or plasma or erythrocyte pyridoxal-5'-phosphate. Finally, no changes in urinary excretion of zinc were observed. The results indicate that dehydrated rations provide zinc, copper, and vitamin B-6 in amounts above the Recommended Dietary Allowances. Such diets may be consumed for at least 1 month without compromising status for these nutrients.

Fortschr Med. 1992 Oct 20;110(29):544-8.

[Therapy of neuropathies with a vitamin B combination. Symptomatic treatment of painful diseases of the peripheral nervous system with a combination preparation of thiamine, pyridoxine and cyanocobalamin]

[Article in German]

Eckert M, Schejbal P.

St. Marienhospital, Lunen.

STUDY DESIGN: In an open, multicentric observational study involving 234 doctors in private practice, the evolution of symptoms and the tolerability of a vitamin B preparation (Neurotrat forte) used as treatment in 1,149 patients with polyneuropathy, neuralgia, radiculopathy and neuritis associated with pain and paresthesias, were observed. The form of administration (ampoules, dragees), dosage and duration of treatment were left to the individual care-providing physician. The target symptoms evaluated were intensity of pain, muscle weakness affecting the legs, and paresthesia. RESULTS: Under treatment, there was a clear improvement in these symptoms. At a second examination approximately three weeks after initiation of treatment, a positive effect on pain in particular was observed in 69% of the cases. Similar observations were also made for paresthesias and muscular weakness in the legs.

Vopr Med Khim. 1992 Sep-Oct;38(5):36-40.

[Use of vitamins in allergic illnesses in children]

[Article in Russian]

Balabolkin II, Gordeeva GF, Fuseva ED, Dzhunelov AB, Kalugina OL, Khamidova MM.

Therapeutic efficacy of vitamins B6, P and E was studied in children with allergic diseases. Bronchial asthma and atopic dermatitis were treated more effectively if maximal doses of vitamin B6 were used. Quercetin was found to be useful for treatment of children with pollinosis in order to correct impairments in metabolism of lymphocyte membrane lipids. Only slight efficacy of vitamin E was detected in atopic dermatitis of children.

J Am Coll Nutr. 1992 Jun;11(3):272-82.

Thiamin and vitamin B6 intakes and erythrocyte transketolase and aminotransferase activities in morbidly obese females before and after gastroplasty.

Turkki PR, Ingerman L, Schroeder LA, Chung RS, Chen M, Russo-Mcgraw MA, Dearlove J.

Dept. of Nutrition and Food Management, Syracuse University, NY 13244-1250.

To assess the need for postoperative vitamin supplements, intakes and nutritional status of thiamin (B1) and vitamin B6 were studied in 18 female gastroplasty patients who received a placebo or different levels of supplemental vitamins. Postoperative erythrocyte transketolase basal (BA) and thiamin pyrophosphate-stimulated (SA) activities and activity coefficients (AC) correlated significantly with B1 intake. Despite a decrease in apotransketolase, low thiamin intakes were associated with increased AC values during the first 3 months. With return to low B1 intakes following repletion during month 4, the AC values remained normal with low total activities. Both alanine (EALT) and aspartate (EAST) aminotransferase apoenzyme levels declined and AC values increased significantly during the first 3 months. Although the EALT-indices were more sensitive to changes in B6 intake than the EAST-indices, the EASTBA and SA correlated most consistently with the intake. Postoperative dietary intakes of both vitamins were inadequate for maintenance of normal activities of these erythrocyte enzymes. Although B1 intake of greater than or equal to 1.0 mg/day was adequate for maintenance of normal thiamin status in most subjects of this study, supplementation with greater than or equal to 1.5 mg/day is prudent even though it may not prevent the early postoperative loss of apotransketolase. Vitamin B6 intake at the current recommended dietary allowance (1.6 mg) was not adequate to maintain coenzyme saturation of the erythrocyte aminotransferases. Marginal intake of other nutrients may have affected the utilization of both thiamin and vitamin B6.

Onderstepoort J Vet Res. 1992 Jun;59(2):111-8.

Experimental Albizia versicolor poisoning in sheep and its successful treatment with pyridoxine hydrochloride.

Gummow B, Bastianello SS, Labuschagne L, Erasmus GL.

Department of Infectious Diseases, Faculty of Veterinary Science, Onderstepoort.

Five sheep developed severe nervous signs after being drenched with Albizia versicolor pod-material. Four of these sheep were treated with pyridoxine hydrochloride (a vitamin B6) when the symptoms of toxicity became life-threatening. All the treated sheep recovered dramatically and completely after treatment while the untreated one died 2 h after receiving pod-material. A therapeutic dose of 20-25 mg pyridoxine hydrochloride/kg body mass given twice with an 8 h interval is the recommended treatment regimen. The route of administration will depend on the severity of symptoms. Chemical pathology and post-mortem findings are discussed.

Ann Nutr Metab. 1992;36(5-6):313-7.

Effect of pyridoxine on mice gastric ulcers and brain catecholamines after an immobilization stress.

Henrotte JG, Franck G, Santarromana M, Nakib S, Dauchy F, Boulu RG.

CNRS, Faculty of Pharmacy, Paris, France.

Fifty adult female Swiss albino mice were injected with either 1.11 mg/kg body weight pyridoxine or saline, subsequently they were all submitted to an immobilization stress with a complete fast for 17 h. At the end of this period, the animals were sacrificed, the gastric mucosa was dissected for ulcer count, and brain noradrenaline, dopamine and serotonin were determined by liquid chromatography. In addition, 26 nonstressed mice were used as controls, 16 of them being fed at libitum and 10 submitted to the same fasting period as the first two groups. In the stressed animals, the average number of gastric ulcers per mouse was twice as large in the saline-treated group than in the pyridoxine-treated group (p < 0.05). With a single exception, no ulcer was found in the non stressed controls. Brain norepinephrine content was almost identical in fasting controls and in stressed mice treated with pyridoxine; in the stressed animals treated with saline, the average norepinephrine content was higher by 15% and in the fed controls lower by 11% than in the two preceding groups. Pyridoxine treatment entailed a very significant reduction (p < 0.002) of norepinephrine variability, mainly due to the absence of high values (> or = 750 ng/g of fresh brain) which occurred only in the saline-treated group. Similar results were yielded for brain dopamine. No variations were observed for brain serotonin. These results suggest the antistress effect of pyridoxine.

Int Urol Nephrol. 1992;24(4):453-7.

Vitamin B6 requirements in chronic renal failure.

Mydlik M, Derzsiova K, Guman M, Hrehorovsky M.

4th Department of Medicine, University Hospital, Kosice.

According to our results the long-term daily oral supplementation of 6 mg vitamin B6 was sufficient for prevention of vitamin B6 deficiency in chronic renal failure, regular dialysis treatment and CAPD groups of patients. Haemodialysis and charcoal haemoperfusion have led to non-significant decrease of erythrocyte vitamin B6. A favourable effect was found of daily oral administration of 50 mg pyridoxine on electrophoretic mobility of peripheral blood lymphocytes and cellular immunity.

J Child Neurol. 1992 Jan;7(1):24-8.

Pyridoxine-dependent seizures: report of a case with atypical clinical features and abnormal MRI scans.

Tanaka R, Okumura M, Arima J, Yamakura S, Momoi T.

Department of Pediatrics, Wakayama Red Cross Hospital, Japan.

A Japanese girl with atypical pyridoxine-dependent seizures is reported. Until 9 months of age the seizures had been controlled by conventional anticonvulsants. The initial administration of pyridoxine was followed by a collapse; the suppression-burst pattern changed to an almost flat pattern in the EEG. T1- and T2-weighted magnetic resonance imaging (MRI) scans showed poor differentiation between white and gray matter, and T2-weighted MRI scans showed periventricular hyperintensity areas adjacent to the posterior horns of lateral ventricles. The findings in this patient indicate that pyridoxine should be given to infants with intractable epilepsy, regardless of the response to anticonvulsants, and that resuscitation facilities should be available during such a trial.

139: Marangella M, Vitale C, Petrarulo M, Cosseddu D, Gallo L, Linari F. Pathogenesis of severe hyperoxalaemia in Crohn's disease-related renal failure on maintenance haemodialysis: successful management with pyridoxine. Nephrol Dial Transplant. 1992;7(9):960-4. No abstract available. PMID: 1328946

Pharmacol Res. 1992 Jan;25(1):87-93.

Pyridoxol L,2-pyrrolidon-5 carboxylate prevents active fibroplasia in CCl4-treated rats.

Annoni G, Contu L, Tronci MA, Caputo A, Arosio B.

Istituto di Medicina Interna, Universita degli Studi di Milano, Italy.

In the present study we evaluated the protective activity of pyridoxol L,2-pyrrolidon-5 carboxylate (metadoxine) against CCl4 intoxication in rats, especially in relation to liver fibrosis. After 6 consecutive weeks of CCl4 treatment, the animals developed liver fibrosis and inflammation as revealed by histological analysis which also included semiquantitative scoring of these features. In addition the serum levels of the immunoreactive prolyl hydroxylase (SIRPH), an enzyme involved in the hydroxylation of the procollagen molecule, were significantly higher (44.2 +/- 16.3 micrograms/ml; P less than 0.005) in this group of animals than in controls (26.1 +/- 8.06). On the contrary, animals treated with CCl4 + metadoxine (200 mg/kg i.p.) had less severe liver fibrosis and normal SIRPH levels (21.5 +/- 14.6). These data suggest that metadoxine may be an effective pharmacological tool for preventing the progression of liver disease in rats exposed to CCl4 to cirrhosis.

141: Cash JM, Zawada ET Jr. Isoniazid overdose. Successful treatment with pyridoxine and hemodialysis. West J Med. 1991 Dec;155(6):644-6. No abstract available. PMID: 1812641

J Nutr. 1991 Nov;121(11):1738-45.

Pyridoxal-5'-phosphate and pyridoxal biokinetics in male Wistar rats fed graded levels of vitamin B-6.

Bode W, van den Berg H.

TNO-CIVO Toxicology and Nutrition Institute Zeist, Department of Clinical Biochemistry, The Netherlands.

Biokinetic parameters of plasma pyridoxal-5'-phosphate (PLP) and pyridoxal (PL) disposition were studied in male Wistar rats (age 8 mo) fed a purified diet containing less than 0.5, approximately 3 or approximately 6 mg pyridoxine.HCl/kg diet from weaning, with animals fed the 6 mg/kg diet serving as the control group. Basal plasma PLP concentration was lower in both the less than 0.5 and 3 mg/kg diet groups than in control animals (98 +/- 12, 314 +/- 40 and 514 +/- 56 nmol/L, respectively). Basal plasma PL concentration was lower in the less than 0.5 mg/kg diet group only [60 nmol/L (measured in pooled samples), 190 +/- 73 and 235 +/- 63 nmol/L for less than 0.5, 3 and 6 mg/kg diet groups, respectively]. In both the less than 0.5 and 3 mg/kg diet groups, PLP clearance was lower than in control rats (0.158 +/- 0.025, 0.131 +/- 0.040 and 0.240 +/- 0.051 L.h-1.kg body weight-1, respectively). In the less than 0.5 mg/kg diet group, PLP synthesis was more efficient than in control animals (34.7 +/- 9.3, 12.1 +/- 2.5 and 16.7 +/- 11.4% for less than 0.5, 3 and 6 mg/kg diet groups, respectively). In both the less than 0.5 and 3 mg/kg diet groups, volume of distribution of PLP as well as of PL was larger than in controls. It is concluded that B-6 vitamer metabolism is influenced by vitamin B-6 status. The metabolic pathway involved (PLP synthesis and/or PLP degradation) was observed to depend on degree of vitamin B-6 deficiency.

Arch Dis Child. 1991 Sep;66(9):1081-2.

No sensory neuropathy during pyridoxine treatment in homocystinuria.

Mpofu C, Alani SM, Whitehouse C, Fowler B, Wraith JE.

Willink Biochemical Genetics Unit, Royal Manchester Children's Hospital.

Seventeen patients with cystathionine synthase deficiency homocystinuria were examined clinically and neurophysiologically for evidence of sensory neuropathy. All had received high dose pyridoxine (vitamin B-6) for many years. Absence of neurological disturbance in all cases suggests long term treatment with pyridoxine in the dosages used in homocystinuric patients is not harmful.

Biochem Biophys Res Commun. 1991 Aug 30;179(1):615-9.

A deficiency of vitamin B6 is a plausible molecular basis of the retinopathy of patients with diabetes mellitus.

Ellis JM, Folkers K, Minadeo M, VanBuskirk R, Xia LJ, Tamagawa H.

Department of Medicine, Titus County Hospital, Mt. Pleasant, Texas.

Eighteen patients with diabetes mellitus, some of whom had variously retinopathy, pregnancy, and the carpal tunnel syndrome, and were variously treated with steroids and vitamin B6, have been overviewed for periods of 8 months to 28 years. We have established an association of a deficiency of vitamin B6 with diabetes by monitoring the specific activity of the erythrocyte glutamic oxaloacetic transaminase and again by the association with the carpal tunnel syndrome (C.T.S.). It has been known for a decade that C.T.S. is caused by a B6 deficiency. The absence of retinopathy in vitamin B6-treated diabetic patients over periods of 8 months - 28 years appears monumental. These observations are like discovery and constitute a basis for a new protocol to establish the apparent relationship of a deficiency of vitamin B6 as a molecular cause of diabetic neuropathy. Blindness and vision are so important that the strength or weakness of the observations are not important; the conduct of a new protocol is important.

J Nutr. 1991 Jul;121(7):1062-74.

Vitamin B-6 requirements of elderly men and women.

Ribaya-Mercado JD, Russell RM, Sahyoun N, Morrow FD, Gershoff SN.

U.S. Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111.

The vitamin B-6 requirements of 12 men and women over 60 y old were studied. The protocol consisted of a 5-d baseline period and four experimental periods during which the subjects successively received 0.003, 0.015, 0.0225 and 0.03375 mg of vitamin B-6/(kg body wt.d). Dietary protein was 1.2 or 0.8 g/(kg body wt.d). At 5- or 6-d intervals, xanthurenic acid (XA) after a 5-g L-tryptophan load and 4-pyridoxic acid (4-PA) in 24-h urine, erythrocyte aspartate aminotransferase activity coefficient (EAST-AC) and plasma pyridoxal-5'-phosphate (PLP) were measured. These measurements were abnormal during vitamin B-6 depletion but returned to normal during repletion. Men who ingested approximately 120 g protein/d required 1.96 +/- 0.11 mg of vitamin B-6 to normalize XA; women who ingested 78 g protein/d required 1.90 +/- 0.18 mg of vitamin B-6 to normalize XA. To attain normal levels of EAST-AC and 4-PA in men, 2.88 +/- 0.17 mg of vitamin B-6 were needed; to normalize PLP, 1.96 +/- 0.11 mg of vitamin B-6 were required. Women required 1.90 +/- 0.18 mg or more of vitamin B-6 to normalize these measurements. Vitamin B-6 requirements were not decreased in two of three subjects who ingested 54 g of protein daily. Thus, vitamin B-6 requirements of elderly men and women are about 1.96 and 1.90 mg/d, respectively.

Obstet Gynecol. 1991 Jul;78(1):33-6.

Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized, double-blind placebo-controlled study.

Sahakian V, Rouse D, Sipes S, Rose N, Niebyl J.

Department of Obstetrics and Gynecology, University of Iowa College of Medicine, Iowa City.

Fifty-nine women completed a randomized, double-blind placebo-controlled study of pyridoxine hydrochloride (vitamin B6) for the treatment of nausea and vomiting of pregnancy. Thirty-one patients received vitamin B6, 25-mg tablets orally every 8 hours for 72 hours, and 28 patients received placebo in the same regimen. Patients were categorized according to the presence of vomiting: severe nausea (score greater than 7) or mild to moderate nausea (score of 7 or less). The severity of nausea (as graded on a visual analogue scale of 1-10 cm) and the number of patients with vomiting over a 72-hour period were used to evaluate response to therapy. Twelve of 31 patients in the vitamin B6 group had a pre-treatment nausea score greater than 7 (severe) (mean 8.2 +/- 0.8), as did ten of 28 patients in the placebo group (mean 8.7 +/- 0.9) (not significant). Following therapy, there was a significant difference in the mean "difference in nausea" score (ie, baseline - post-therapy nausea) between patients with severe nausea receiving vitamin B6 (mean 4.3 +/- 2.1) and placebo (mean 1.8 +/- 2.2) (P less than .01). In patients with mild to moderate nausea and in the group as a whole, no significant difference between treatment and placebo was observed. Fifteen of 31 vitamin B6-treated patients had vomiting before therapy, compared with ten of 28 in the placebo group (not significant). At the completion of 3 days of therapy, only eight of 31 patients in the vitamin B6 group had any vomiting, compared with 15 of 28 patients in the placebo group (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Biol Psychiatry. 1991 May 1;29(9):931-41.

Niacin and vitamin B6 in mental functioning: a review of controlled trials in humans.

Kleijnen J, Knipschild P.

Department of Epidemiology/Health Care Research, University of Limburg, The Netherlands.

Fifty-three controlled trials of the effects of niacin, vitamin B6, and multivitamins on mental functions are reviewed. The results are interpreted with emphasis on the methodological quality of the trials. It turns out that virtually all trials show serious short-comings: in the number of participants, the presentation of baseline characteristics and outcomes, and the description of changes in concomitant treatments. Only in autistic children are some positive results are found with very high dosages of vitamin B6 combined with magnesium, but further evidence is needed before more definitive conclusions can be drawn. For many other indications (hyperactive children, children with Down's syndrome, IQ changes in healthy schoolchildren, schizophrenia, psychological functions in healthy adults and geriatric patients) there is no adequate support from controlled trials in favor of vitamin supplementation.

Eur J Pediatr. 1991 May;150(7):452-5.

Pyridoxine-dependent seizures, clinical and therapeutic aspects.

Haenggeli CA, Girardin E, Paunier L.

Department of Paediatrics, Hopital Cantonal Universitaire, Geneva, Switzerland.

Pyridoxine-dependency is a rare autosomal recessive disorder causing a severe seizure disorder of prenatal or neonatal onset, psychomotor retardation and death in untreated patients. Treatment requires life-long supplementation with pyridoxine (vitamin B6). The underlying defect is unknown, and there is no biological marker for the disease. Clinical diagnosis is often delayed and severe neurological sequelae are common. This article summarizes both clinical and therapeutic aspects.

Paediatr Indones. 1991 May-Jun;31(5-6):165-9.

The influence of pyridoxin in the treatment of tetanus neonatorum.

Dianto, Mustadjab I.

Department of Child Health, Gunung Wenang Hospital Medical School, Sam Ratulangi University, Manado.

During a 2-year-period (1988-1990) 31 patients with tetanus neonatorum were recruited for this study. The patients were divided into 2 groups: The first group (15 patients) was treated with ATS injection, oral metronidazole and amoxycillin, and diazepam suppositoria. The second group (16 patients) was treated with the same regimen, as the first group plus pyridoxin injection 100 mg on the first day followed by 25 mg orally on the next days. There was no statistical difference in the two groups concerning the gestation period, sex, severity of the disease (p greater than 0.05), place of delivery (all at home) and mode of delivery delivered by traditional midwife/dukun). The mortality of the first group (without pyridoxin) was 60% and the second (with pyridoxin) 37.5% (p less than 0.05).

Electroencephalogr Clin Neurophysiol. 1991 Mar;78(3):215-21.

Pyridoxine-dependent epilepsy: EEG investigations and long-term follow-up.

Mikati MA, Trevathan E, Krishnamoorthy KS, Lombroso CT.

Department of Neurology, Children's Hospital, Boston, MA 02115.

The EEG features and clinical correlates were investigated before, directly after, and on long-term follow-up after initiation of pyridoxine therapy in 6 patients with B6-dependent epilepsy. At each phase, the EEG provided important diagnostic and prognostic information. Pre-B6 3 neonates manifested a unique EEG pattern of generalized bursts of 1-4 Hz sharp and slow activity. This pattern has not been previously described in neonates with B6 dependency and in this age group appears to be highly suggestive of the diagnosis. Five patients experienced an apparent initial response to traditional antiepileptics. The parenteral pyridoxine test, performed in all 5, and repeated in 3, proved to be a highly reliable and reproducible diagnostic test. After 50-100 mg of B6 there was cessation of clinical seizures within minutes and of paroxysmal discharges within hours. On long-term follow-up (3-28 years) all 6 patients were seizure free on B6 (10-100 mg/day) monotherapy. Recurrences of seizures and of specific sequential EEG changes (background slowing, photoparoxysmal response, spontaneous discharges, stimulus-induced myoclonus, generalized seizures) occurred upon B6 withdrawal. Long-term prognosis correlated with the EEG. Two patients had persistently abnormal EEG backgrounds and were moderately to severely retarded, while 4 had normal EEGs with normal or near normal development.

Pediatr Neurol. 1991 Mar-Apr;7(2):91-6.

Vitamin B6 and valproic acid in treatment of infantile spasms.

Ito M, Okuno T, Hattori H, Fujii T, Mikawa H.

Department of Pediatrics, Shimane Medical University, Izumo, Japan.

Twenty patients with infantile spasms were treated with high doses of vitamin b6, valproic acid, or both. Three of 13 patients (23%) treated initially with high doses of vitamin B6 demonstrated a definite reduction in seizures; 2 patients had no improvement on electroencephalography. Vitamin B6 therapy alone was continued in a single patient (8%) who remained seizure-free during the 15-month follow-up period. Initial treatment with vitamin B6 and valproic acid improved the electroencephalogram significantly more (P less than 0.05) than initial vitamin B6 treatment alone. The group which had valproic acid added to vitamin B6 therapy had significantly fewer seizures (P less than 0.05) and better electroencephalograms (P less than 0.01) than did the group treated initially with vitamin B6 alone. There were no significant differences among the group treated initially with vitamin B6, the group treated initially with valproic acid, and the group in which valproic acid was substituted for vitamin B6. ACTH was more effective in abolishing seizures than was valproic acid or vitamin B6 and valproic acid. ACTH had an excellent effect on seizures in 86% of patients who did not respond well to vitamin B6, valproic acid, or both; however, many of these patients had later recurrence of infantile spasms. The combination of vitamin B6 and valproic acid is effective and safe in the treatment of infantile spasms.

Am J Pediatr Hematol Oncol. 1991 Fall;13(3):345-50.

Sideroblastic anemia showing unique response to pyridoxine.

Murakami R, Takumi T, Gouji J, Nakamura H, Kondou M.

Department of Pediatrics, Kobe University School of Medicine, Japan.

We treated and followed up for 6 years a patient with pyridoxine-responsive sideroblastic anemia. The patient was a boy age 1 year and 9 months, who was diagnosed on the basis of peripheral red cell morphology and an increased number of sideroblasts in the bone marrow. Bone marrow erythroblasts showed a marked reduction of delta-aminolevulinic acid synthase (ALA-S) activity. The response of the patient to pyridoxine and its active form, pyridoxal phosphate, was unique. After the first course of pyridoxal phosphate therapy (300 to 500 mg/day i.v. for 4 days), all hematological data were restored to normal and remained normal for 29 months without the further administration of pyridoxal phosphate. The second course of pyridoxal phosphate therapy (500 mg/day i.v. for 2 days) was effective for 6 months. The third, fourth, and fifth courses of the therapy consisted of daily oral pyridoxine hydrochloride at a dose of 180 mg/day for 4 to 6 weeks, and the respective periods of hematological remission were 7, 12, and greater than 18 months. These observations suggest the presence of a complicated ALA-S activating or inactivating system, or both, in our patient.

Int J Clin Pharmacol Res. 1991;11(1):35-40.

Alcoholic abstinence syndrome: short-term treatment with metadoxine.

Bono G, Sinforiani E, Merlo P, Belloni G, Soldati M, Gelso E.

Third Department of Neurology, Intituto Ricovero e Cura a Carattesre Scientifico (IRCCS) C. Mondino, University of Pavia, Italy.

The effects of metadoxine (pyrrolidone carboxylate of pyridoxine), a compound with central benzodiazepine-like properties, were evaluated in two groups of chronic alcoholics (inpatients) presenting a mild withdrawal syndrome. According to a double-blind study design 20 patients received metadoxine 900 mg twice daily eluted in 500 ml of saline infusion, while 20 (the control group) were given 500 ml of saline infusion twice daily with equivalent doses of pyridoxine (40 mg/die) every morning over a 10-day period. The results indicate that metadoxine treatment was able to control alcohol abstinence, thus allowing a reduction in the needs for standard benzodiazepine therapy. The central activity of gamma-aminobutyric acid of this compound might play a crucial role in the clinical effects demonstrated.

Cancer. 1990 Dec 1;66(11):2421-8.

Abnormal vitamin B6 status in childhood leukemia.

Pais RC, Vanous E, Hollins B, Faraj BA, Davis R, Camp VM, Ragab AH.

Department of Pediatrics (Division of Hematology/Oncology), Emory University School of Medicine, Atlanta, GA 30322.

Vitamin B6 is involved in many biological processes of potential relevance to carcinogenesis and tumor growth, including DNA synthesis and maintenance of immunocompetence, yet very little information exists on B6 nutritional status in childhood leukemia. Using a radioenzymatic assay, the authors measured plasma pyridoxal 5'-phosphate (PLP), the biologically active form of B6, in 11 newly diagnosed untreated children with leukemia and 11 age-matched controls. The children with leukemia had significantly lower PLP levels than the controls. In 26 additional leukemia patients and 26 additional controls, a high-performance liquid chromatography assay also demonstrated lower plasma PLP levels in childhood leukemia compared with controls. These differences were significant for both acute lymphoblastic leukemia (ALL) and for acute nonlymphoblastic leukemia (ANLL). The PLP values did not correlate with indices of leukemia cell burden, but did correlate with reported B6 intake, suggesting that illness-related diet changes are at least partially responsible for the low PLP levels. Before any chemotherapy, overall nutritional status was suboptimal in 53% of ALL cases and 57% of ANLL cases. Newly diagnosed children with leukemia have suboptimal overall nutrition as well as suboptimal vitamin B6 status.

J Indian Med Assoc. 1990 Dec;88(12):336-7.

An antilactogenic effect of pyridoxine.

Gupta T, Sharma R.

Department of Obstetrics and Gynaecology, Indira Gandhi Medical College, Shimla.

The efficacy of pyridoxine in suppression of lactation was studied. Patients under study included the cases of stillbirths, neonatal deaths and second trimester abortions. The clinical response was good in 80%, fair in 14% and poor in 6% of cases. Administration of pyridoxine only was associated with a rapid and trouble-free suppression of lactation in 94% of cases.

No To Hattatsu. 1990 Sep;22(5):501-6.

[Chronological change of EEG findings in a case of pyridoxine dependency seizures]

[Article in Japanese]

Koga R, Otani K, Abe J, Futagi Y, Takeuchi T, Yabuuchi H.

Department of Pediatric Neurology, Osaka Medical Center.

A patient of pyridoxine dependent seizures was reported. He was born at 34 weeks' gestation and weighted 2,760 g. Apgar scores were 6 and 9 at 1 and 5 minutes, respectively. He showed the first seizure 2 hours after his birth. Phenobarbital, phenytoin, sodium valproate, diazepam and clonazepam were not effective. Pyridoxal phosphate (50 mg) was given intravenously, resulting in suppression of convulsions. However, muscle tonus was severely depressed. In EEG, a discontinuous pattern was found in quiet and indeterminate sleep on the 2nd day of life. At 5th week multifocal spikes were found, and the discontinuous pattern persisted. Ictal discharges at 13th week showed generalized, continuous, irregular and high voltage slow waves with multifocal spikes. At 27th week of life, high voltage slow waves disappeared and multifocal spike discharges decreased. At 2 years and 10 months of age, the patient was suffering from athetotic cerebral palsy and severe mental retardation. Pyridoxal phosphate at the doses of 35-40 mg/kg/day had been administered. Irritability sometimes occurred and additional 50 mg of pyridoxal phosphate controlled this irritability effectively.

Arch Intern Med. 1990 Aug;150(8):1751-3.

Comment in: • Arch Intern Med. 1992 Nov;152(11):2346-7.

Reversal of prolonged isoniazid-induced coma by pyridoxine.

Brent J, Vo N, Kulig K, Rumack BH.

Rocky Mountain Poison and Drug Center, Denver General Hospital, CO 80204.

Isoniazid overdose is known to result in the rapid onset of seizures, metabolic acidosis, and prolonged obtundation. Pyridoxine has been reported to be effective in treating isoniazid-induced seizures. We report three cases of obtundation secondary to isoniazid overdose that was immediately reversed by intravenous pyridoxine. In two of these cases, status seizures were stopped by intravenous pyridoxine administration, but the patients remained comatose for prolonged periods. The comas were immediately reversed by the administration of additional pyridoxine. In the third case, the patient's lethargy was treated by intravenous pyridoxine on presentation and was followed by immediate awakening. Pyridoxine is effective in treating not only isoniazid-induced seizures, but also the mental status changes associated with this overdose. The dose required to induce awakening may be higher than that required to control seizures.

Int J Neurosci. 1990 Jun;52(3-4):225-32.

Pyridoxine improves drug-induced parkinsonism and psychosis in a schizophrenic patient.

Sandyk R, Pardeshi R.

Department of Psychiatry College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, NY 10032.

Drug-induced Parkinsonism is a common serious side-effect of neuroleptic therapy. In cases of irreversible drug-induced Parkinsonism, pharmacological management is notoriously difficult. A schizophrenic patient with severe neuroleptic-induced Parkinsonism and Tardive Dyskinesia is presented in whom administration of pyridoxine (vitamin B6) (100 mg/d) resulted in dramatic and persistent attenuation of the movement disorders as well as reduction of psychotic behavior. Since pyridoxine deficiency is associated with marked reduction of cerebral serotonin concentrations and pineal melatonin production in rats, the effects of pyridoxine on the movement disorder and psychosis may have been mediated largely by enhancing serotonin and melatonin functions. An additional effect of excess pyridoxine administration on GABA and dopamine activity cannot be excluded. Pyridoxine has been reported to attenuate the severity of levodopa-induced dyskinesias in patients with Parkinson's disease and it is suggested that pyridoxine supplementation should be considered in psychiatric patients with drug-induced movement disorders including persistent Parkinsonism. An underlying pyridoxine deficiency in these patients may exacerbate the psychotic behavior and additionally, potentially increase the risk of drug-induced movement disorders.

J Am Diet Assoc. 1990 Jun;90(6):830-4.

Contribution of various food groups to dietary vitamin B-6 intake in free-living, low-income elderly persons.

Manore MM, Vaughan LA, Lehman WR.

Department of Family Resources, Arizona State University, Tempe 85287-2502.

Elderly persons are reported to have low dietary intakes of vitamin B-6. Knowing which foods are the primary contributors of dietary vitamin B-6 may be useful to health professionals working to improve the nutritional status of the elderly. Therefore, we examined the contribution of five food groups--flesh foods (including all meat/fish/poultry), grains/cereals, legumes/nuts, fruits/vegetables, and dairy products/eggs--to dietary vitamin B-6 intake in 198 free-living elderly persons aged 60 years or older. Subjects were primarily Caucasian, low-income non-smokers; their mean age was 72 years. Mean dietary vitamin B-6 intake, determined from 3-day diet records, was 1.6 +/- 0.6 mg/day. The fruit/vegetable group was the largest dietary contributor of vitamin B-6 (0.69 mg/day). Flesh foods and cereals/grains contributed equally to the vitamin B-6 intake (0.35 and 0.34 mg/day, respectively). The lowest contributors were dairy products/eggs and legumes/nuts. Approximately 96% of the vitamin B-6 intake could be accounted for by the five food groups. Twenty percent of the population (no. = 39) consumed less than 66% of the Recommended Dietary Allowance (RDA) for vitamin B-6; their vitamin B-6 intake from fruits/vegetables and grains/cereals was 0.36 and 0.10 mg/day, respectively. Individuals with vitamin B-6 intakes greater than or equal to 100% of the RDA (no. = 69) consumed greater amounts of fruits/vegetables (primarily bananas) and grains/cereals (primarily breakfast cereal) than did persons who consumed less than 66% of the RDA for vitamin B-6; their vitamin B-6 intake from fruits/vegetables and grains/cereals was 0.98 and 0.55 mg/day, respectively. In the elderly population studied, plant foods were the major dietary contributors of vitamin B-6.

Onderstepoort J Vet Res. 1990 Jun;57(2):109-14.

Pyridoxine (a vitamin B6) and its derivative pyridoxal as treatment for Albizia versicolor poisoning in guinea-pigs.

Gummow B, Erasmus GL.

Veterinary Research Institute, Onderstepoort.

In the course of three experiments it was established that all the toxic effects of a lethal dose of Albizia versicolor pods (greater than 4.5 g/kg) in guinea-pigs could be countered by concurrent subcutaneous injection of pyridoxine (10 mg/kg). This treatment was also successful once severe symptoms had set in. Pyridoxal, on the other hand, was found to be ineffective as a therapeutic agent. The fact that pyridoxal does not counter the action of the toxin indicates an atypical site of action by the toxin as regards the normal pathways which require vitamin B6 as a co-factor.

Pract Odontol. 1990 Jun;11(6):41-7.

Final results of a dental caries clinical trial using heat killed lactic bacteria (Streptococci and Lactobacilli) orally.

Bayona-Gonzalez A, Lopez-Camara V, Gomez-Castellanos A.

National University of Mexico (UNAM), Mexico City.

The results of a dental caries clinical trial in 245 seven-year-old children are reported. Chewable tablets of two different types were prepared: A) Containing pyridoxine (Vit. B6) and heat-killed lactic bacteria. B) Placebo tablets with pyridoxine only. They were randomly given once a week for 16 weeks to experimental and control groups respectively. Four evaluation surveys were conducted during 24 months of follow up, using the "Decay, Missing, Filled, Surfaces" index (DMFS) for the clinical evaluation of the permanent teeth. A consistent reduction in the incidence of dental caries in the experimental group was observed in all 4 surveys. After 2 years of follow up a 42% reduction in the incidence rate of dental caries was observed in the experimental group compared to the control group. Summary tables and discussion of the clinical evaluation surveys are given. The potential use of these clinical findings as support for a future dental caries vaccine evaluation project is proposed.

Atherosclerosis. 1990 Feb;81(1):51-60.

Impaired homocysteine metabolism in early-onset cerebral and peripheral occlusive arterial disease. Effects of pyridoxine and folic acid treatment.

Brattstrom L, Israelsson B, Norrving B, Bergqvist D, Thorne J, Hultberg B, Hamfelt A.

Department of Neurology, University Hospital, University of Lund, Sweden.

Severe homocysteinemia due to genetic defects either of pyridoxal 5-phosphate (PLP)-dependent cystathionine beta-synthase (CBS) or of enzymes in vitamin B12 and folate metabolism is associated with very early-onset vascular disease. Therefore, we studied homocysteine metabolism in 72 patients presenting before the age of 55 years with occlusive arterial disease of cerebral, carotid, or aorto-iliac vessels. Twenty patients (28%) had basal homocysteinemia; and 26 patients (36%) had abnormal increases of plasma homocysteine after peroral methionine loading, which exceeded the highest value for 46 comparable controls and was within the range for 20 obligate heterozygotes for homocystinuria due to CBS deficiency. Basal plasma homocysteine content was strongly and negatively correlated to vitamin B12 and folate concentrations. Plasma PLP was depressed in most patients but there was no correlation between PLP and homocysteine values. In 20 patients, treatment with pyridoxine hydrochloride (240 mg/day) and folic acid (10 mg/day) reduced fasting homocysteine after 4 weeks by a mean of 53%, and methionine response by a mean of 39%. These data show that a substantial proportion of patients with early-onset vascular disease have impaired homocysteine metabolism, which may contribute to vascular disease, and that the impaired metabolism can be improved easily and without side effects.

Invest New Drugs. 1990 Feb;8(1):57-63.

Pyridoxine therapy for palmar-plantar erythrodysesthesia associated with continuous 5-fluorouracil infusion.

Fabian CJ, Molina R, Slavik M, Dahlberg S, Giri S, Stephens R.

University of Kansas Medical Center, Division of Clinical Oncology, Kansas City 66102.

The limiting toxicity of low dose continuous infusion 5-fluorouracil (200-300 mg/m2/day) is often palmar-plantar erythrodysesthesia (PPE). PPE developed in 16/25 patients (exact 95% confidence interval of 42%-82%) with metastatic colon cancer enrolled in a phase II trial. In this trial, 5-FU was given continuously at a dose of 200 mg/m2/day until toxicity or progressive disease forced discontinuation. The first signs of the syndrome developed at a median of 2 months following infusion initiation and, unless treatment was interrupted, became progressively worse. The incidence of moderate to severe PPE was 71% in the 14 previously untreated patients (exact 95% confidence intervals of 42-92%). Seventy-eight percent of the responders in the no prior treatment group developed PPE. The incidence of moderate to severe PPE was only 27% in the 11 previously treated patients (exact 95% confidence intervals of 6-61%). The higher incidence of PPE in the previously untreated patients probably resulted from a longer total infusion time (median = 7.3 months) than the previously treated (median = 4.5 months). The longer infusion time in turn was a result of the higher response rates (64 vs 18%) in the previously untreated versus treated groups. Five previously untreated patients who developed PPE received 50 or 150 mg of pyridoxine/day when moderate PPE changes were noted. Reversal of PPE without interruption of the 5-FU was seen in 4/5 patients. Four of these patients who received pyridoxine had responded to 5-FU treatment. No adverse affect of pyridoxine on clinical response was noted.(ABSTRACT TRUNCATED AT 250 WORDS)

J Am Acad Dermatol. 1990 Feb;22(2 Pt 2):340-2.

Relief of the photosensitivity of erythropoietic protoporphyria by pyridoxine.

Ross JB, Moss MA.

Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.

Twenty-five years ago the use of pyridoxine was described for the treatment of photosensitivity eruptions. We report two cases of erythropoietic protoporphyria, which were only moderately responsive to beta-carotene and sunscreens, whereas the use of pyridoxine has been associated with a marked reduction in photosensitivity without evidence of adverse effects. Regarding the mechanism of action, we can only speculate that pyridoxine could be mediated by increased endogenous nicotinamide production. We believe that our results warrant therapeutic trial of oral pyridoxine in patients with unrelieved photosensitivity as a result of erythropoietic protoporphyria.

165: Folkers K, Ellis J. Successful therapy with vitamin B6 and vitamin B2 of the carpal tunnel syndrome and need for determination of the RDAs for vitamins B6 and B2 for disease states. Ann N Y Acad Sci. 1990;585:295-301. No abstract available. PMID: 2192614

J Nutr. 1989 Dec;119(12):1940-8.

Response of B-6 vitamers in plasma, erythrocytes and tissues to vitamin B-6 depletion and repletion in the rat.

Sampson DA, O'Connor DK.

Western Human Nutrition Research Center, U.S. Department of Agriculture, Presidio of San Francisco, CA 94129.

We determined the response patterns of B-6 vitamers in blood and tissues to vitamin B-6 depletion and repletion. B-6 vitamers were measured in plasma, erythrocytes, liver, muscle, kidney, heart, brain, spleen and lung by reverse-phase high performance liquid chromatography in male rats pair-fed control or vitamin B-6-deficient diets for 2 or 4 wk, or for 4 wk followed by 1 wk of repletion with the control diet (n = 4/group). Food intake (15.6 +/- 0.3 g/d, mean +/- SEM; n = 28) and body weight (190 +/- 2 and 290 +/- 5 g at wk 0 and 5, respectively; n = 28) of control groups were not different from those of deficient groups throughout the study. After 2 wk of vitamin B-6 depletion, tissue concentrations of pyridoxal phosphate (PLP) and pyridoxamine phosphate (PMP) were about 50% and 10-40% lower, respectively, in the deficient than in the control group (except for spleen PMP); in plasma and erythrocytes, PLP and pyridoxal concentrations were about 90% lower in the deficient group. Differences in vitamer concentrations between control and deficient groups were not larger after 4 wk of depletion than after 2 wk. Vitamer concentrations in plasma, erythrocytes and all tissues returned to control levels after 1 wk of repletion with the control diet. These results demonstrate that B-6 vitamers in blood and tissues of the rat respond quickly and reversibly to changes in dietary vitamin B-6, with larger percentage changes occurring in plasma and erythrocytes than in tissues.

Farmakol Toksikol. 1989 Nov-Dec;52(6):43-6.

[The effect of pyridoxine on the cerebral hemodynamics in vestibular disorders]

[Article in Russian]

Skoromnyi NA.

By means of hydrogen clearance on conscious rabbits with implanted platinum electrodes it was established that pyridoxine (1 and 10 mg/kg) used against the background of sea sickness decreased the dilatational reaction of the cerebral vessels occurring during the stimulation of the vestibular apparatus, reduced the blood supply to the cerebral hemispheres with insignificant changes of oxygen tension in the cortical structures, relieved acidosis and hypoxemia developing during sickness in the orthostatic position, increased oxygenation of the arterial blood without influencing significantly pathomorphological shifts in the brain tissue.

Food Chem Toxicol. 1989 Oct;27(10):627-30.

Effect of oral and parenteral administration of B6 vitamers on the lymphopenia produced by feeding ammonia caramel or 2-acetyl-4(5)-(1,2,3,4-tetrahydroxy)butylimidazole to rats.

Gobin SJ, Paine AJ.

DHSS Department of Toxicology, St Bartholomew's Hospital Medical College, London, England.

The ability of B6 vitamers to prevent the lymphopenic effects of ammonia caramel fed to rats has been evaluated. Diets containing 10 ppm pyridoxine or pyridoxal prevented the lymphopenia produced in rats consuming an 8% (w/v) solution of ammonia caramel, whereas the dietary content of pyridoxamine needed to be increased to 20 ppm to have the same effect. In contrast to the results of the enteral administration of the individual B6 vitamers, pyridoxamine was found to be the most effective vitamer in preventing the ammonia caramel-induced lymphopenia when administered parenterally. However, all the nutritionally active forms of vitamin B6 were able to prevent the depression of the peripheral blood lymphocyte count, which resulted from ingestion of ammonia caramel by rats. The proposal that oral administration of pyridoxine may prevent the intestinal absorption of the lymphopenic constituent of ammonia caramel, 2-acetyl-4(5)-(1,2,3,4-tetrahydroxy)butylimidazole (THI), is discredited, since THI was found to reduce the lymphocyte count after parenteral administration in rats fed 0.04 ppm pyridoxone in the diet and that increased amounts of dietary pyridoxine (10 ppm) could still prevent this effect. These findings further emphasise the important relationship between dietary vitamin B6 content and the lymphopenic effects of ammonia caramel/THI in the rat.

J R Coll Gen Pract. 1989 Sep;39(326):364-8.

Pyridoxine (vitamin B6) and the premenstrual syndrome: a randomized crossover trial.

Doll H, Brown S, Thurston A, Vessey M.

Department of Community Medicine and General Practice, Oxford.

A randomized double-blind crossover trial was conducted to study the effects of pyridoxine (vitamin B6) at a dose of 50 mg per day on symptoms characteristic of the premenstrual syndrome. Sixty three women aged 18-49 years, identified by means of a general practice based survey of menstrual patterns in the community, entered the trial. All of the women had noticed moderate to severe premenstrual symptoms during the previous year. The women kept a daily menstrual diary which graded the severity of nine individual symptoms from zero to three. After completing a diary for an initial month the women were randomized to receive either drug or placebo for three months, after which the treatments were crossed over for a further three months. Thirty two women completed the full seven months of the study. In these women a significant beneficial effect (P less than 0.05) of pyridoxine was observed on emotional type symptoms (depression, irritability and tiredness). No significant effect was observed on premenstrual symptoms of any other type.

PIP: Researchers initiated a randomized double blind crossover trial as part of a community based postal survey of menstrual patterns of 68 women in England. Each woman jotted down daily the severity of symptoms (e.g., depression, headache, etc.). After this 1st study cycle and being randomly assigned to the pyridoxine or placebo group, they either took 50 mg/day of pyridoxine or placebo tablets for 3 months. At the end of 3 months, they followed the other treatment. 37 women completed 6 months and only 32 completed the full 7 months. The results of the study show pyridoxine to significantly affect emotional type symptoms (depression, irritability, and tiredness [p.05]), but not somatic (headache, breast discomfort, swollen abdomen, swollen hands or feet) or menstrual (stomach cramps, backache, other) symptoms. Women who took oral contraceptives (OCs) had nonsignificant higher adjusted premenstrual symptom scores, particularly for emotional type symptoms, during both pyridoxine and placebo months that did those who did not take OCs. This study was complicated by a placebo effect. It revealed a significant decrease in the level of all symptom scores from the 1st month to the 4th month by a mean of 57% (p=.001) when the women took the placebo initially. Emotional type symptoms decreased by 69% (p.05), somatic type by 52% (p.05), and menstrual type nonsignificantly by 15%. On the other hand, when women took the placebo after taking pyridoxine for a month, the combined level of all symptom scores only increased 37% on average (nonsignificant). Based on the results of this study, pyridoxine appears to alleviate premenstrual depression. Further research is needed to confirm the results of this and other similar studies.

Am J Clin Nutr. 1989 Aug;50(2):391-9.

Dose-response relationships regarding vitamin B-6 in elderly people: a nationwide nutritional survey (Dutch Nutritional Surveillance System).

Lowik MR, van den Berg H, Westenbrink S, Wedel M, Schrijver J, Ockhuizen T.

TNO-CIVO Toxicology and Nutrition Institute, Department of Human Nutrition, Zeist, The Netherlands.

The dietary intake and biochemical status of vitamin B-6 in 476 apparently healthy Dutch elderly people (aged 65-79 y), who were not using drugs known to affect vitamin B-6 metabolism, were evaluated. Intake of vitamin B-6 per gram protein was related to biochemical data, namely plasma pyridoxal 5'-phosphate (PLP) and cofactor stimulation of aspartate aminotransferase in erythrocytes (AST-AC). Based on a cutoff point of 2.02 for AST-AC, approximately 9% of the elderly people not using vitamin B-6 supplements had a marginal vitamin B-6 status. About 7% were using vitamin B-6 supplements. Dietary intake of vitamin B-6 per gram protein was negatively related to AST-AC. Vitamin B-6 intakes per gram protein higher than 0.020 mg were necessary to ensure an AST-AC value less than 2.02. At high PLP values AST-AC hardly varied. The results seem to indicate a higher requirement of vitamin B-6 in elderly people than in younger adults.

Am J Clin Nutr. 1989 Aug;50(2):339-45.

Plasma pyridoxal 5'-phosphate concentration and dietary vitamin B-6 intake in free-living, low-income elderly people.

Manore MM, Vaughan LA, Carroll SS, Leklem JE.

Department of Family Resources and Human Development, Arizona State University, Tempe 85287-2502.

Free-living, elderly persons (aged greater than or equal to 60 y, n = 198) were recruited to determine the effects of age, sex, health status, dietary vitamin B-6 intakes, and B-6 supplement use on plasma pyridoxal 5'-phosphate (PLP). Vitamin B-6 intakes were determined from 3-d diet records; supplementation was based on self-reported brand and frequency data. Fasting blood samples were analyzed for PLP. Subjects were primarily low-income Caucasians. There was no linear relationship between dietary vitamin B-6 intake, age, sex or health status, and PLP while accounting for supplemental vitamin B-6 use. PLP, however, was negatively correlated with age (p less than 0.001) in individuals with PLP values between 32 and 90 nmol/L. Vitamin B-6 status was low (PLP less than 32 nmol/L) in 32% of this elderly population (n = 198) and could be attributed to low dietary vitamin B-6 intakes and/or the presence of health problems reported to alter vitamin B-6 status. This research suggests that low vitamin B-6 status is prevalent in low-income, elderly persons, especially those with multiple health problems.

Teratology. 1989 Aug;40(2):151-5.

Erratum in: • Teratology 1990 Feb;41(2):250-1.

Bendectin and human congenital malformations.

Shiono PH, Klebanoff MA.

National Institute of Child Health and Human Development, Prevention Research Program, Bethesda, Maryland 20892.

The relationship between Bendectin exposure during the first trimester of pregnancy and the occurrence of congenital malformations was prospectively studied in 31,564 newborns registered in the Northern California Kaiser Permanente Birth Defects Study. The odds ratio for any major malformation and Bendectin use was 1.0 (95% confidence interval 0.8-1.4). There were 58 categories of congenital malformations; three of them were statistically associated with Bendectin exposure (microcephaly--odds ratio = 5.3, 95% confidence interval = 1.8-15.6; congenital cataract--odds ratio = 5.3, 95% confidence interval = 1.2-24.3; lung malformations (ICD-8 codes 484.4-484.8)--odds ratio = 4.6, 95% confidence interval = 1.9-10.9). This is exactly the number of associations that would be expected by chance. An independent study (the Collaborative Perinatal Project) was used to determine whether vomiting during pregnancy in the absence of Bendectin use was associated with these three malformations. Two of the three (microcephaly and cataract) had strong positive associations with vomiting in the absence of Bendectin use. We conclude that there is no increase in the overall rate of major malformations after exposure to Bendectin and that the three associations found between Bendectin and individual malformations are unlikely to be causal.

Clin Ter. 1989 Jul 31;130(2):115-22.

[Metadoxine in alcohol-related pathology]

[Article in Italian]

Santoni S, Corradini P, Zocchi M, Camarri F.

Metadoxine is an active drug for treatment of acute and chronic alcohol intoxication, affecting both liver and brain function. The authors reviewed the international pharmacological and clinical literature on the drug which shows the potential usefulness of metadoxine in the treatment of alcohol-induced diseases. The case report concerns the results in 20 chronic alcoholics, admitted to the hospital for acute alcohol intake treated with metadoxine (one 500 mg tablet twice daily). Biohumoral hepatopathy parameters and clinical parameters of neuropsychic behaviour were examined simultaneously. Compared with a control group of patients undergoing traditional therapy (sedative and multi-vitamin drugs), metadoxine showed a significant improvement of the values of gamma-GT, GPT, blood ammonia, blood alcohol and of neuropsychic and behavioural parameters such as agitation, tremor, asterixis, sopor and depression. No side-effects or unfavourable reactions occurred during metadoxine treatment, which confirms the safety of this molecule.

Diabetes. 1989 Jul;38(7):881-6.

Erythrocyte O2 transport and metabolism and effects of vitamin B6 therapy in type II diabetes mellitus.

Solomon LR, Cohen K.

Department of Medicine, Veterans Administration Medical Center, West Haven, CT 06516.

The effects of vitamin B6 on erythrocyte metabolism, erythrocyte hemoglobin O2 affinity (P50), and nonenzymatic glycosylation were studied in 15 Caucasian men with type II (non-insulin-dependent) diabetes mellitus. A control group of 13 healthy Caucasian men was also evaluated. Before treatment, diabetic subjects had low mean cell hemoglobin concentration values and increases in both erythrocyte 2,3-diphosphoglycerate (2,3-DPG) levels and erythrocyte hexokinase activities. Although all three of these changes are associated with a decrease in hemoglobin O2 (Hb-O2) affinity, P50 values were normal in diabetic subjects. Moreover, P50 values normalized to pH 7.4 (P50(7.4] were inversely related to the level of glycosylated hemoglobin (HbA1c). Both erythrocyte 2,3-DPG and erythrocyte ATP were also inversely related to HbA1c. Vitamin B6 nutriture, as determined by erythrocyte aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities, was normal in all diabetic subjects before vitamin B6 therapy. Nonetheless, HbA1c levels decreased after 6 wk of treatment with 150 mg/day pyridoxine and increased again during placebo administration. These changes were not explained by changes in fasting blood glucose. Pyridoxine therapy also decreased P50(7.4) values and increased erythrocyte AST and ALT activities but had no effect on 2,3-DPG, ATP, or the activities of hexokinase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase. These observations suggest that 1) nonenzymatic glycosylation may play a role in regulating both erythrocyte metabolism and Hb-O2 affinity in diabetic subjects, and 2) vitamin B6 therapy may modify nonenzymatic glycosylation of hemoglobin in this population.

Hepatology. 1989 Apr;9(4):582-8. Vitamin B6 repletion in cirrhosis with oral pyridoxine: failure to improve amino acid metabolism.

Henderson JM, Scott SS, Merrill AH, Hollins B, Kutner MH.

Department of Surgery, Emory University School of Medicine, Atlanta, Georgia 30322.

This study evaluated the effect of daily oral pyridoxine supplementation in patients with cirrhosis. Eight subjects were treated with 25 mg of pyridoxine for 28 days. Before and after the supplementation period, B6 status was assessed by measuring fasting plasma vitamer levels and response to a 25 mg oral pyridoxine load. In addition, a 24-hr urine collection was analyzed during each load study for B6 metabolites. The data indicated that supplementation achieved repletion of peripheral B6 stores, as evidenced by: (i) a significant (p less than 0.005) rise in fasting plasma pyridoxal phosphate after supplementation (mean +/- S.D. = 56.8 +/- 30.5 nmoles per liter) as compared to initial levels (17.0 +/- 17.8 nmoles per liter); (ii) a higher (p less than 0.05) percentage excretion of the pyridoxine load as urinary 4-pyridoxic acid (31.0 +/- 9.3%) compared to the initial load (19.6 +/- 5.8%), and (iii) a postsupplementation area under the plasma concentration vs. time curve for pyridoxal phosphate (377 +/- 529 nmoles.hr per liter), which was decreased (p less than 0.005) from the presupplementation value (934 +/- 756 nmoles.hr per liter). The postsupplementation fasting plasma pyridoxal phosphate concentrations were within the normal range. The consequences of B6 repletion on amino acid metabolism were measured by oral protein loads (n = 4) or oral methionine loads (n = 4). No significant changes were observed for methionine or any other amino acid in regard to plasma fasting concentration, peak concentration or AUC. Although the vitamin B6 deficiency of cirrhosis was corrected by daily oral pyridoxine supplementation, there was apparently no improvement in the deranged amino acid metabolism.

Klin Wochenschr. 1989 Jan 4;67(1):38-41.

Carpal tunnel syndrome and vitamin B6.

Laso Guzman FJ, Gonzalez-Buitrago JM, de Arriba F, Mateos F, Moyano JC, Lopez-Alburquerque T.

Departamento de Medicina, Hospital Clinico Universitario, Salamanca, Spain.

Twelve patients with carpal tunnel syndrome were studied. Clinical and electrophysiological data were obtained and an estimation of vitamin B6 (pyridoxine) status by an assay of erythrocyte aspartate aminotransferase and coenzyme stimulation assay were done. None of the patients was found to have vitamin B6 deficiency. Patients were treated with 150 mg of pyridoxine daily for 3 months. Erythrocyte aspartate aminotransferase increased significantly (p less than 0.001) in all the patients. In 6 patients there were clinical and electrophysiological improvement and erythrocyte aspartate aminotransferase increased more than in the other 6 patients. The data obtained appear to indicate that although vitamin B6 deficiency is not common in carpal tunnel syndrome patients, pyridoxine supplementation can be recommended as adjuvant treatment in those patients undergoing surgery.

Cesk Neurol Neurochir. 1989 Jan;52(1):28-31.

[Administration of high doses of B6 in age-related epileptic encephalopathies]

[Article in Czech]

Zouhar A, Slapal R.

The authors present an account on 14 patients with markedly pharmaco-resistant age-conditioned epileptic encephalopathies (4 x West's syndrome, 5 x Lennox-Gastaut's syndrome and 5 x an intermediate stage of the two), treated with large doses of vitamin B6 (Pyridoxin Spofa). The mean age at the onset of therapy was 2.5 years (0.5-6 years). In addition to hitherto unsuccessful medication, the patients were given at first five-day treatment of vitamin B6 50-100 mg/day by the i.m. route, and then 200-300 mg/day orally. A marked clinical effect was recorded in five children, in another five it was less marked and usually only transient. Only in four patients the seizures were not affected, incl. three times in Lennox-Gastaut's syndrome. The EEG changes correlated with the clinical course. The authors recommend to attempt early administration of large doses of vitamin B6 in refractory age-conditioned epilepsies in the first three years of life.

Haemostasis. 1989;19 Suppl 1:24-8.

Lowered antithrombin III activity and other clotting changes in homocystinuria: effects of a pyridoxine-folate regimen.

Palareti G, Coccheri S.

Department of Angiology and Blood Coagulation, University Hospital S. Orsola, Bologna, Italy.

Few studies have dealt with blood-clotting changes in patients affected by homocystinuria. The aim of this contribution is to briefly review studies published so far on the topic and report the results of our investigation performed in 3 patients. At baseline we found reduced antithrombin III and factor VII levels in all the patients, in line with the results of other authors, and other slight and less constant changes such as lowered factor X activity and protein C antigen, and increased beta-thromboglobulin levels. During pyridoxine and folate treatment, antithrombin III activity rapidly returned to normal; factor VII increased and beta-thromboglobulin decreased. These blood-clotting abnormalities may play a role in the thrombotic tendency associated with homocystinuria. Their nature is still uncertain, but the improvement observed during active metabolic treatment suggests that the defect in amino acid transsulfuration of homocystinuria may directly affect synthesis or activity of some clotting factors.

Vopr Onkol. 1989;35(1):34-8.

[Anticarcinogenic action of vitamins PP and B6 in the natulan initiation of malignant growth in mice]

[Article in Russian]

Draudin-Krylenko VA, Bukin IuV, Nikonova TV.

Parenteral administration of vitamins PP and B6 at the initiation stage of natulan-induced carcinogenesis was shown to significantly inhibit formation of lung adenomas. The preventive effect was found to depend on treatment schedule. Biochemical aspects of anticarcinogenic action of the vitamins require special investigation.

Br J Clin Pract. 1988 Nov;42(11):448-52.

Pyridoxine in the treatment of premenstrual syndrome: a retrospective survey in 630 patients.

Brush MG, Bennett T, Hansen K.

We present a survey summarising the retrospective reports of the therapeutic effect of pyridoxine (vitamin B6) in 630 women suffering from premenstrual syndrome (PMS) who attended a PMS clinic during the period 1976-1983. The daily doses of pyridoxine hydrochloride varied from 40 to 100 mg early in the study and from 120 to 200 mg in the later period of the investigations. The response to treatment was recorded as good (no significant residual complaints) in 40 per cent or more of patients taking 100-150 mg pyridoxine daily and in 60 per cent of patients treated with 160-200 mg daily. Together with partial response (useful benefit but still some significant complaints), the positive effect of the treatment increased to 65-68 per cent and 70-88 per cent respectively. No symptoms consistent with a diagnosis of peripheral neuropathy were reported.

J Surg Oncol. 1988 Apr;37(4):269-71.

Pyridoxine: a potential local antidote for Mitomycin-C extravasation.

Rentschler R, Wilbur D.

Department of Internal Medicine, Loma Linda University Medical Center, California 92350.

Two cases are presented which suggest that pyridoxine injected into a Mitomycin-C extravasation site may slow or prevent necrosis, and may decrease the pain associated with the chronic ulceration of extravasation.

Arzneimittelforschung. 1988 Mar;38(3):396-9.

[Antivertiginous action of vitamin B 6 on experimental minocycline-induced vertigo in man]

[Article in German]

Claussen CF, Claussen E.

Neurootologie, Universitats-HNO-Klinik Wurzburg.

By means of a former investigation it has been proved equilibriometrically that the application of 7 X 100 mg minocycline may induce a central equilibrium dysregulation of the brainstem type. It was the purpose of this study to further assure that the minocycline induced brainstem vertigo is due to a destabilization of a supervisory gamma-aminobutyric acid (GABA)ergic loop from the archeocerebellum upon the pontomedullary vestibular regulating pathways. As it is pharmacologically known that pyridoxine is essential for the synthesis of GABA, an inhibitory CNS neurotransmitter, 2 separate double blind trials on 20 healthy young persons each were carried out after the intake of 7 X 100 mg minocycline during 3 days with and without 7 X 40 mg pyridoxine simultaneously. These trials were checked against an additional placebo or initial non drug investigation. In all the 40 test persons it could be proved that the amount of vertigo and nausea symptoms was increased significantly due to the application of minocycline only. However, when combining minocycline with vitamin B 6, the vertigo and nausea symptoms as well as the nystagmus signs from the monaural and the binaural vestibular ocular tests as well as the vestibular spinal signs from the craniocorpography recordings of the stepping and the standing procedures were remarkably reduced. There were no statistical differences between the initial or placebo trials versus the trials with a combination of minocycline with vitamin B 6. The same holds for the vestibular vegetative reactions, measured by the simultaneous electrocardiography during the vestibular tests. All the equilibriometric tests applied showed a significant destabilization under the influence of a pure minocycline loading.(ABSTRACT TRUNCATED AT 250 WORDS)

Arq Cent Estud Curso Odontol. 1988 Jan-1989 Dec;25-26(1-2):28-34.

[Tooth extraction wound healing after administration of vitamin B6 (pyridoxine). Histological study in rats]

[Article in Portuguese]

de Lucia MB, Martinelli C.

Male rats with 250 grs of weight were injected daily with 0.1 ml of B6 vitamin by peritoneal (way paths). The animal were sacrificed at three, seven, 10, 15 and 21 day after the upper incisor extraction. Its hemimaxila were retired and fixed in 10% formalin and after had been embedded in paraffin sections were cut with 6 micrometers pick. The analysis of the sections stained by hematoxylin and eosin when compared with the controls showed that: 1) the blood clot and fibrin net are substituted more rapidly by the granulation tissue; 2) granulation tissue is more plentiful, early and mature; 3) the bone tissue is more plentiful and mature.

Eksp Onkol. 1988;10(2):17-9.

[Protective action of nicotinamide and pyridoxine on the initiation stage of carcinogenesis induced in mice by procarbazine]

[Article in Russian]

Nikonova TV, Draudin-Krylenko VA, Bukin IuV, Turusov VS.

It is shown that at the initiating stage of procarbazine carcinogenesis in F1 female mice the parenteral administration of nicotinamide or pyridoxine results in a significant decrease in the lung adenoma rate from 77% to 18 or 46%, respectively. Pyridoxal, pyridoxal-5'-phosphate and L-penicillamine did not influence the lung adenoma frequency.

Int J Vitam Nutr Res. 1988;58(1):73-7.

Vitamin B6 status of Finnish elderly. Comparison with Dutch younger adults and elderly. The effect of supplementation.

Tolonen M, Schrijver J, Westermarck T, Halme M, Tuominen SE, Frilander A, Keinonen M, Sarna S.

University of Helsinki, Finland.

About 25% of Finnish and Dutch elderly appeared to be more or less deficient in vitamin B6 as compared to younger adults. Deficiency was observed at the cellular (PLP, EGOT and alpha-EGOT) as well as at the plasma level (PLP). The benefit of a one-year daily supplementation with 2 mg of pyridoxine-HCl was investigated at the biochemical and psychological level as compared to a placebo group. After one year, none of the supplemented elderly was deficient in biochemical terms. At the psychological level and at the level of general well-being, the elderly supplemented with vitamin B6 showed slight improvements. However, for the psychological variables significant correlations with the vitamin B6 parameters were not observed. Plasma fatty acids (e.g. gamma-linolenic acid) showed no correlation with the vitamin B6 status.

Int Urol Nephrol. 1988;20(4):353-9.

Control of hyperoxaluria with large doses of pyridoxine in patients with kidney stones.

Mitwalli A, Ayiomamitis A, Grass L, Oreopoulos DG.

Department of Medicine, Toronto Western Hospital, University of Toronto, Canada.

Pyridoxine in doses of 250-500 mg daily by mouth was administered to 12 patients suffering from recurrent calcium oxalate renal calculi and idiopathic hyperoxaluria. This therapy decreased urinary oxalate excretion significantly (p less than 0.025) during up to 18 months of treatment. In that period eight patients showed no evidence of active stone disease; three showed slight increase in the size of their old stone(s) and one patient formed one new stone. None of these patients developed any significant complications of the therapy. These findings support the view that pyridoxine in pharmacological doses is useful in the control of elevated urinary oxalate excretion in patients with recurrent renal oxalate calculi.

Nephrol Dial Transplant. 1988;3(1):28-32.

Oxalate metabolism in end-stage renal disease: the effect of ascorbic acid and pyridoxine.

Morgan SH, Maher ER, Purkiss P, Watts RW, Curtis JR.

Division of Inherited Metabolic Diseases, MRC Clinical Research Centre, Harrow, UK.

Oxalate metabolism was studied in ten patients with end-stage renal disease. No patient with primary hyperoxaluria was included in this study. Five patients were on regular haemodialysis and five patients were on chronic ambulatory peritoneal dialysis (CAPD). Oxalate metabolism was assessed by measurement of plasma oxalate concentration (POx), oxalate metabolic pool size (OxMP), tissue oxalate accumulation rate (TOxA), oxalate production rate (OxPR) and dialysis clearance of oxalate (DCOx). These observations were made on three separate occasions in each of the ten patients: initially when the patients were taking a routine ascorbic acid supplement of 100 mg per day; then after a period of 1 month with no ascorbic acid supplement; and then finally after a further period of 1 month's treatment with pyridoxine 800 mg daily. The values for POx, OxMP and TOxA were significantly increased in all ten patients and in the range observed in some patients with type I primary hyperoxaluria. There was no significant difference between immediate prehaemodialysis POx and the POx in the CAPD patients. The DCOx was very much greater during haemodialysis (mean 85 ml/min) than during CAPD (mean 8 ml/min). The acute fall in POx during haemodialysis was greater than 50% of the immediate pre-haemodialysis concentration. Ascorbic acid in a dose of 100 mg/day had no significant effect on the parameters of oxalate metabolism studied. Pyridoxine in a dose of 800 mg/day produced a significant fall in POx in both haemodialysis and CAPD patients.

188: Konstantinova OV, Chudnovskaia MV, Ianenko EK, Korolev VV. [Use of magnesium oxide and vitamin B6 for the prevention of oxalate urolithiasis] Urol Nefrol (Mosk). 1987 Nov-Dec;(6):12-5. Russian. No abstract available. PMID: 3438942

Biochem Med Metab Biol. 1987 Aug;38(1):1-8.

Biochemical studies on bilharzial and nonbilharzial hyperoxaluria: effect of pyridoxine and allopurinol treatment.

el-Habet AE, el-Sewedy SM, el-Sharaky A, Gaafar NK, Abdel-Rafee A, Hamoud F.

Department of Biochemistry, Alexandria University, Egypt.

The urinary excretion levels of oxalic acid, calcium, kynurenic, and xanthurenic acids and serum pyridoxal and pyridoxal phosphate concentrations were determined for nonbilharzial and bilharzial hyperoxaluric patients with or without urinary stones. The effects of pyridoxine and allopurinol treatment were also studied. The different groups studied showed elevated levels of urinary oxalic acid, calcium, kynurenic, and xanthurenic acids as well as decreases in serum pyridoxal and pyridoxal phosphate concentrations. These data indicate that nonbilharzial hyperoxaluric patients suffer from dietary B6 deficiency, whereas bilharzial hyperoxaluric patients may suffer from impaired pyridoxine phosphokinase activity. Pyridoxine supplementation is recommended for the treatment of nonbilharzial hyperoxaluric patients. Allopurinol may be the proper drug in the treatment of oxaluria and stone formation or of bilharzial patients.

South Med J. 1987 Jul;80(7):882-4.

Treatment of carpal tunnel syndrome with vitamin B6.

Ellis JM.

In my practice, vitamin B6 (pyridoxine) therapy (100 to 200 mg daily for 12 weeks) has proved curative for a large percentage of patients having carpal tunnel syndrome (CTS). Laboratory determination of the vitamin B6 status has been useful in diagnosing deficiency and in making decisions relative to surgery. This paper directs particular attention to prevention of CTS during pregnancy and discusses changes in symptoms during the course of treatment of CTS with vitamin B6.

J Natl Cancer Inst. 1987 May;78(5):951-9.

Suppression of tumor growth and enhancement of immune status with high levels of dietary vitamin B6 in BALB/c mice.

Gridley DS, Stickney DR, Nutter RL, Slater JM, Shultz TD.

Effects of dietary vitamin B6 at levels ranging from deficiency to megadoses on the development of herpes simplex virus type 2-transformed (H238) cell-induced tumors and on in vitro responses relating to cell-mediated immunity were examined. Male BALB/cByJ mice (n = 260), 5 weeks of age, were fed 20% casein diets containing pyridoxine (PN) at 0.2, 1.2 for the control diet, 7.7, or 74.3 mg/kg diet for 4-11 weeks. After 4 weeks of dietary treatment, 120 of the mice received an injection of H238 cells; mice without H238 injection served as controls. At 4, 8, and 11 weeks, animals from each group were euthanized and blood and spleen samples obtained. Mice fed 0.2 mg PN developed mild deficiency symptoms and gained significantly less weight than those fed 1.2-, 7.7-, and 74.3-mg PN diets. Thirteen to 16 days after tumor cell injection, primary tumor incidence was lowest in mice fed 74.3 mg PN; later, incidence among groups was similar. Mice fed 1.2 mg PN had the largest primary tumor volume, the highest incidence of lung metastases, and the greatest number of metastatic nodules per animal at 7 weeks post injection. Overall, lower tumor volumes were found in animals fed 7.7 and 74.3 mg PN (14 and 32% less than the tumor volume for those fed 1.2 mg PN, respectively); mice fed 0.2 mg PN had the lowest tumor volume. Blood and spleen lymphoproliferative response to stimulation by phytohemagglutinin or concanavalin A generally tended to be higher in mice fed 7.7 and 74.3 mg PN as compared to that in animals fed either 0.2 or 1.2 mg PN. However, decreased mitogen-stimulated responsiveness was observed in all animals with progressive tumor growth. Tumor growth also resulted in splenomegaly and increased thymic atrophy. Significant negative relationships between tumor volume and tumor pyridoxal 5-phosphate (PLP) concentrations were observed for 1.2-, 7.7-, and 74.3-mg PN diet groups. These data suggest that high dietary intake of vitamin B6 may have suppressed tumor development by either immune enhancement or PLP growth regulation of this tumor.

Am J Med Genet. 1987 Apr;26(4):959-69.

Psychiatric manifestations of homocystinuria due to cystathionine beta-synthase deficiency: prevalence, natural history, and relationship to neurologic impairment and vitamin B6-responsiveness.

Abbott MH, Folstein SE, Abbey H, Pyeritz RE.

Homocystinuria commonly affects the central nervous system (CNS), primarily as mental retardation, seizures, and stroke. Case reports have long suggested a predisposition to schizophrenia, but no careful study of predisposition to psychiatric illness has been performed. Accordingly, we evaluated 63 persons with homocystinuria due to cystathionine beta-synthase deficiency for psychiatric disturbance, intelligence, evidence of other CNS problems, and responsiveness to vitamin B6. The overall rate of clinically significant psychiatric disorders was 51%, predominated by four diagnostic categories: episodic depression (10%), chronic disorders of behavior (17%), chronic obsessive-compulsive disorder (5%), and personality disorders (19%). The average IQ was 80 +/- 27 (1 SD); and an IQ of less than or equal to 79 was two-thirds more common among vitamin B6-nonresponsive patients compared to vitamin B6-responsive patients. Aggressive behavior and other disorders of conduct were particularly common among patients with mental retardation and among vitamin B6-nonresponsive patients.

Epilepsy Res. 1987 Mar;1(2):152-4.

Disappearance of neonatal seizures and low CSF GABA levels after treatment with vitamin B6.

Kurlemann G, Loscher W, Dominick HC, Palm GD.

Department of Pediatrics, University of Munster, F.R.G.

In an infant with neonatal seizures, CSF GABA levels were determined before and after treatment with vitamin B6. Before onset of treatment, the level of GABA in CSF was very low (13 pmol/ml). Injection of vitamin B6 blocked the seizures immediately. When GABA level in CSF was again analysed after continued treatment with vitamin B6, a value of 127 pmol/ml was determined, which is within the normal concentration range in children. The data substantiate previous findings in brain tissue from a patient with vitamin B6-dependent seizures, and strongly indicate that impairment of central GABAergic activity was the cause of the seizures.

Plast Reconstr Surg. 1987 Mar;79(3):456-62.

Carpal tunnel syndrome and vitamin B6.

Kasdan ML, Janes C.

We reviewed 1075 patients presenting over a 12-year period with symptoms of carpal tunnel syndrome. A total of 994 had a final diagnosis of carpal tunnel syndrome. There were 444 male and 550 female patients with a mean age of 42 years. Three-hundred and ninety-five related symptoms to their job. Surgery was performed in 27 percent of the total diagnosed cases with approximately 97 percent relief of symptoms. Satisfactory alleviation of symptoms was obtained in 14.3 percent of patients treated conservatively prior to 1980, with one or a combination of splinting anti-inflammatory agents, job or activity change, and steroid injections. In 1980, vitamin B6 (pyridoxine) was added as a method of conservative treatment. Satisfactory improvement was obtained in 68 percent of 494 patients treated with a controlled dosage (100 mg b.i.d.). While our findings were not the result of a controlled scientific study, we feel they suggest that regulated use of vitamin B6 may be helpful in treating many cases of carpal tunnel syndrome.

195: Wolf E. Vitamin therapy helps fight CTS. Occup Health Saf. 1987 Feb;56(2):67. No abstract available. PMID: 3822321

J Child Neurol. 1987 Jan;2(1):38-40.

Pyridoxine dependency seizures: report of a case with unusual features.

Pettit RE.

Pyridoxine dependency is a rare cause of neonatal seizures. Newborns with this disorder are often hyperirritable and fail to respond to the usual anticonvulsants. The diagnosis is established by cessation of seizures after the administration of parenteral pyridoxine. Reported is a case of pyridoxine dependency that illustrates several problems in management. The amount of pyridoxine required to control seizures is variable and may exceed 100 mg per day. The electroencephalogram (EEG) may not change significantly during the initiation of therapy. During intercurrent illnesses, parenteral pyridoxine may need to be given. Additional pyridoxine may be needed even when the EEG is normal. Treatment should continue indefinitely.

J Fr Ophtalmol. 1987;10(1):35-40.

[Monobloc lamellar autokeratoplasty (MLAK) and corneal cicatrization. Apropos of a comparative trial in a control group and a group treated with a L-cystine and pyridoxine hydrochloride combination]

[Article in French]

Rivaud C, Negrel AD.

In pterygium cure, one piece lamellar corneo-conjunctival autokeratoplasty allows to perform a reproducible corneal injury in human clinic, and thus, to study the epithelial healing. The authors describe a comparative test on 2 groups of 18 subjects each, receiving in this blind study, either classical post-operative treatment (witness group), or in addition to this treatment: L-Cystine and Pyridoxine Chlorhydrate. Two tests are analysed: the duration of epithelial healing in one day (negative fluorescein test) and post operative "well being" (estimated on the intensity of photophobia, tears and pain). Statistical analysis (non parameter tests) display a significant difference in favor of the group treated by Cystine B 6.

Schweiz Med Wochenschr. 1986 Dec 13;116(50):1783-6.

[Pyridoxine can normalize oxaluria in idiopathic renal lithiasis]

[Article in French]

Jaeger P, Portmann L, Jacquet AF, Burckhardt P.

Pyridoxine (vitamin B6), given to patients with primary hyperoxaluria of type I, generally leads to a decrease in urinary excretion of oxalate owing to stimulation of conversion of glyoxylate to glycine instead of oxalate. It is not known, however, whether pyridoxine would equally influence hyperoxalurias of other origins, e.g. idiopathic or enteric. Two groups of patients were therefore given pyridoxine orally for 2 months (300 mg/d). Group 1 consisted of 10 idiopathic stone formers with mild hyperoxaluria of unknown origin. Group 2 consisted of 4 patients with enteric hyperoxaluria after intestinal bypass surgery. As a mean, enteric hyperoxaluria was not influenced by vitamin B6, which suggests that this disorder is the consequence of intestinal hyperabsorption of oxalate rather than of glyoxylate. In contrast, idiopathic hyperoxaluria was influenced by vitamin B6: urinary excretion of oxalate decreased in 8 patients out of 10 and became normal in 7. However, two patients did not respond to pyridoxine; both had concomitant severe hyperuricosuria (greater than 1 g/24 h), an observation suggesting that in these cases hyperoxaluria was of dietary origin. Four of the patients whose urinary excretion of oxalate became normal while on pyridoxine were followed up for 8 to 36 months after treatment: in all of them oxaluria remained normal. One whose oxaluria had returned to the upper normal limit was retreated after 2 years and again displayed a fall in urinary oxalate. It is concluded that pyridoxine given to idiopathic hyperoxalurics may correct the disorder, as in primary hyperoxaluria of type I; this is not the case in enteric hyperoxaluria. The mechanisms governing this sensitivity to vitamin B6 remain to be clarified.

J Pediatr. 1986 Dec;109(6):1001-6.

Blood coagulation changes in homocystinuria: effects of pyridoxine and other specific therapy.

Palareti G, Salardi S, Piazzi S, Legnani C, Poggi M, Grauso F, Caniato A, Coccheri S, Cacciari E.

The aim of this study was to investigate the blood coagulation changes in three patients with homocystinuria, in baseline condition and during therapy. At baseline, antithrombin III activity and factor VII levels were reduced in all three patients; antithrombin III protein and protein C antigen were also slightly lowered in one patient, and factor X in another. beta-Thromboglobulin, a measure of platelet activation, was increased in one case. During pyridoxine treatment, antithrombin III activity was rapidly restored to normal; factor VII increased and beta-thromboglobulin decreased. These data suggest that, in addition to platelet activation, abnormalities of blood clotting, and particularly reduction of antithrombin III, may play a role in the thrombotic tendency associated with homocystinuria. The nature of these clotting alterations is still uncertain, but their improvement during active metabolic treatment suggests that the defect in amino acid transsulfuration of homocystinuria may directly affect synthesis or activity of some liver-dependent clotting factors.

Toxicol Lett. 1986 Dec;34(2-3):129-39.

Safety of pyridoxine--a review of human and animal studies.

Cohen M, Bendich A.

A literature review was conducted on adverse effects associated with administration of high oral doses of pyridoxine (vitamin B6) to animals and man. The human data suggest that doses of pyridoxine greater than 500 mg/day for prolonged periods of time can result in sensory nerve damage. Doses less than 500 mg/day appear to be safe on the basis of literature reports where the compound was administered for periods ranging from 6 months to 6 years.

201: Jerez E, Rapado A. [Therapeutic effect of pyridoxine and succinimide in the treatment of a patient with primary hyperoxaluria] Arch Esp Urol. 1986 May;39(4):279-82. Spanish. No abstract available. PMID: 3740976

Neuropediatrics. 1986 Feb;17(1):7-10.

High dose B6 treatment in infantile spasms.

Blennow G, Starck L.

A total dose of 0.2-0.4 g.kg-1 pyridoxine stopped infantile spasms with hypsarrhythmia in three infants within five to six days. The case histories are presented and the results briefly discussed.

Pediatrics. 1985 Nov;76(5):769-73.

Nutritionally relevant supplementation of vitamin B6 in lactating women: effect on plasma prolactin.

Andon MB, Howard MP, Moser PB, Reynolds RD.

Pharmacologic doses of vitamin B6 administered to lactating women have been reported to suppress plasma prolactin. As a result, some physicians have recommended restriction of vitamin B6 intake for lactating women. In the present investigation, 20 lactating women were given supplemental doses of vitamin B6, 0.5 to 4.0 mg/d, beginning 24 hours after delivery. Plasma prolactin, plasma pyridoxal phosphate, and breast milk total vitamin B6 concentrations were determined during the first 9 months postpartum. Women receiving the supplement of 4.0 mg compared with 0.5 mg of vitamin B6 per day had significantly higher plasma pyridoxal phosphate (P less than .01) and breast milk total vitamin B6 concentrations (P less than .05) beginning at 1 month postpartum and continuing through the duration of the study. Plasma prolactin concentrations were not significantly different between the two groups. The percentage of all women, regardless of treatment, in whom lactation persisted at 1 and 2 weeks and 1, 3, 6, and 9 months were 100%, 100%, 100%, 90%, 80%, and 65%, respectively. All women who ceased to lactate during the study reported doing so by choice. Nutritionally relevant doses of vitamin B6 elevated plasma pyridoxal phosphate and breast milk total vitamin B6 concentrations of lactating women without reducing plasma prolactin concentration or halting lactation.

Vopr Pitan. 1985 Sep-Oct;(5):43-5.

[Action of pyridoxine on lipid metabolism in carbon disulfide-poisoned rats]

[Article in Russian]

Petrova S.

The author studied the influence of pyridoxine (8 mg/kg bw) on upset lipid metabolism in rats exposed to carbon disulfide (30 mg/m3) inhalation over 90 days. The content of total lipids, total esterified and free cholesterol, free fatty acids, phospholipids, triglycerides and beta-lipoproteins was measured in serum on days 15, 30 and 90 since exposure. Carbon disulfide alone caused a reduction in the level of some lipid groups on day 15, whereas on days 30 and 90 it provokes an elevation of the content of total fats and all lipid groups under study. Administration of pyridoxine alone brought about a decrease in lipid characteristics. The combined use of the vitamin and carbon disulfide made these characteristics return to normal. Pyridoxine is a possible active factor in the prophylaxis of atherosclerotic lesions in carbon disulfide poisoning.

Clin Sci (Lond). 1985 Jul;69(1):87-90.

The effect of pyridoxine on oxalate dynamics in three cases of primary hyperoxaluria (with glycollic aciduria).

Watts RW, Veall N, Purkiss P, Mansell MA, Haywood EF.

We have measured glomerular filtration rate (GFR), extracellular fluid volume (ECF), oxalate distribution volume (OxDV), plasma oxalate concentration (POx.), plasma total clearance of oxalate (PCOx.), oxalate metabolic pool size [(OxDV) X (POx.)], renal clearance of oxalate (RCOx.), oxalate excretion, tissue clearance of oxalate (TCOx.) and tissue oxalate accumulation rate [(TOx.A) = (TCOx.) X (POx.)] in three patients with type I primary hyperoxaluria (hyperoxaluria with hyperglycollic aciduria) when they were taking pyridoxine and after discontinuation of the vitamin. Seven days after stopping pyridoxine the plasma oxalate concentration, oxalate metabolic pool size and the urinary excretion of oxalate had all increased between seven- and eight-fold in two of the patients. The third patient showed no changes on stopping pyridoxine. These results support the view that pyridoxine acts by reducing oxalate biosynthesis in some patients with type I primary hyperoxaluria. The possible biochemical basis for this effect is discussed.

Postgrad Med. 1985 May 15;77(7):32-7.

Premenstrual syndrome. Tactics for intervention.

Havens C.

Premenstrual syndrome (PMS) is a very common disorder. It is diagnosed by excluding other disorders, including psychopathology, and with use of a menstrual diary. Although the cause of PMS remains unknown, treatment is usually effective. For the majority of patients, reassurance, dietary changes, and regular exercise are all that is necessary. If this is ineffective, vitamin B6 and, if indicated, vitamin E or zinc sulfate should be added to the regimen. If therapy still is not effective, a diuretic (preferably spironolactone [Aldactone]) or natural progesterone should be added. This may also be done during the three to six months required for dietary therapy to achieve maximum effectiveness. Diuretics are less expensive, easier to use, and easier to obtain than natural progesterone, which is not widely available. If oral contraceptives are desirable for the patient, progestin-dominant pills may be tried instead of a diuretic or natural progesterone. For those patients whose symptoms are resistant to all of the aforementioned therapy, bromocriptine (Parlodel) or danazol (Danocrine) can be added to the regimen; these drugs, however, should be prescribed only by practitioners experienced in their use.

Biol Psychiatry. 1985 May;20(5):467-78.

Vitamin B6, magnesium, and combined B6-Mg: therapeutic effects in childhood autism.

Martineau J, Barthelemy C, Garreau B, Lelord G.

This article reports the behavioral, biochemical, and electrophysiological effects of four therapeutic crossed-sequential double-blind trials with 60 autistic children: Trial A--vitamin B6 plus magnesium/magnesium; Trial B--vitamin B6 plus magnesium; Trial C--magnesium; and Trial D--vitamin B6. Therapeutic effects were controlled using behavior rating scales, urinary excretion of homovanillic acid (HVA), and evoked potential (EP) recordings. The behavioral improvement observed with the combination vitamin B6-magnesium was associated with significant modifications of both biochemical and electrophysiological parameters: the urinary HVA excretion decreased, and EP amplitude and morphology seemed to be normalized. These changes were not observed when either vitamin B6 or magnesium was administered alone.

N Engl J Med. 1985 Apr 11;312(15):953-7.

Response to a physiologic dose of pyridoxine in type I primary hyperoxaluria.

Yendt ER, Cohanim M.

We measured urinary oxalate and glycolate excretion before and during pyridoxine administration (2 to 200 mg per day) in four patients with primary hyperoxaluria. In two patients with type I primary hyperoxaluria, urinary oxalate and glycolate excretion fell markedly in response to a physiologic dose of pyridoxine of 2 mg per day and became completely normal when the dose was increased to 25 mg per day. In the other two patients, who had a different type of primary hyperoxaluria (normal urinary glycolate excretion), there was no response to 2 mg of pyridoxine per day. In one of these patients, doses of 25 and 50 mg per day were also ineffective, but a moderate reduction in oxalate excretion took place with 200 mg per day; in the other patient there was a moderate reduction in oxalate excretion with 25 mg of pyridoxine per day. Our findings suggest that the degree of hyperoxaluria in this disorder may be only slight or moderate if the patient has been ingesting a pyridoxine-rich diet or multivitamin tablets containing small amounts of pyridoxine. Our results also suggest that smaller doses of pyridoxine than those heretofore employed should be tried in patients with primary hyperoxaluria.

Am J Clin Nutr. 1985 Apr;41(4):684-8.

Depressed plasma pyridoxal phosphate concentrations in adult asthmatics.

Reynolds RD, Natta CL.

In 15 adult patients with bronchial asthma, plasma and erythrocyte pyridoxal phosphate (PLP) concentrations were significantly lower than in 16 controls (P less than 0.0001 and P less than 0.005, respectively). Oral supplementation of seven asthmatics with 50 mg pyridoxine as pyridoxine X HC1 twice daily failed to produce a sustained elevation of PLP in either the plasma or erythrocytes. However, all subjects reported a dramatic decrease in frequency and severity of wheezing or asthmatic attacks while taking the supplement. The reasons for the failure of a uniform elevation in plasma and erythrocyte PLP concentration and for the apparent beneficial effects of pyridoxine supplementation on the asthmatic symptoms of the patients are unknown at present.

Biull Eksp Biol Med. 1985 Apr;99(4):430-1.

[Liver and blood enzyme spectra of rats with model anthracosis based on feeding a diet with additional amounts of methionine and pyridoxine]

[Article in Russian]

Pichkhadze GM.

The data obtained during studies of the enzymic spectrum of the liver and blood of rats with experimental anthracosis fed the diet containing additional quota of methionine and pyridoxine are presented. It was established that introduction of additional quota of methionine and pyridoxine in the animals' diet with an optimal fat content reduced the negative manifestations on the part of the enzymic systems of the liver and blood characteristic of experimental anthracosis and thus promoted retardation of fibrous process in the lungs. Additional introduction into the diet of rats with experimental anthracosis of methionine alone appeared ineffective.

Ann Neurol. 1985 Feb;17(2):117-20.

Atypical presentations of pyridoxine-dependent seizures: a treatable cause of intractable epilepsy in infants.

Goutieres F, Aicardi J.

We report on 3 patients with atypical pyridoxine-dependent seizures. Each had either late onset of convulsions (2 cases) or seizure-free intervals of up to several months' duration in the absence of pyridoxine supplementation. The findings, taken together with those in 9 previously reported cases, indicate that a trial of pyridoxine should be performed in all seizure disorders with onset before 18 months of age, regardless of type.

Acta Obstet Gynecol Scand. 1985;64(8):667-70.

No effect of vitamin B-6 against premenstrual tension. A controlled clinical study.

Hagen I, Nesheim BI, Tuntland T.

Vitamin B-6 100 mg given daily throughout the menstrual cycle was compared with placebo in a randomized, double-blind crossover trial in 34 women who suffered from premenstrual tension. Vitamin B-6 was no better than placebo. There was a substantial period effect, as the women evidenced a considerable preference for the second drug they received, irrespective of whether this was vitamin B-6 or placebo. Blood magnesium was measured; no significant difference was found between the 34 women with premenstrual tension and 10 healthy women without such complaints. Vitamin B-6 caused a small but statistically significant rise in blood magnesium level. In the individual patients, no correlation was found between changes in blood magnesium and premenstrual symptoms.

J Am Diet Assoc. 1985 Jan;85(1):46-9.

Vitamin B-6 status of southern adolescent girls.

Driskell JA, Clark AJ, Bazzarre TL, Chopin LF, McCoy H, Kenney MA, Moak SW.

The vitamin B-6 status of 583 white and black adolescent girls living in Alabama, Arkansas, North Carolina, Oklahoma, and Virginia was assessed using the parameters coenzyme stimulation of erythrocyte alanine aminotransferase activities and dietary intakes of the vitamin. The sample included 382 white and 201 black girls who were 12, 14, or 16 years of age; the sample was also divided into low, medium, and high per capita income groups. The height and weight measurements of the subjects were within normal ranges. The mean estimated daily vitamin B-6 intake of the girls from food sources was 1.20 mg daily, as indicated by evaluation of data obtained via two nonsequential 24-hour food recalls; about half of the subjects reported consuming less than 66% of the Recommended Dietary Allowance for the vitamin. Approximately 20% of the girls had marginal vitamin B-6 status and 13%, deficient status, as indicated by coenzyme stimulation values. Coenzyme stimulation and dietary values of the race, age, and income groups were similar. Vitamin B-6 inadequacy appears to be fairly prevalent among white and black southern adolescent girls.

Int Med Res. 1985;13(3):174-9.

Controlled trial of pyridoxine in the premenstrual syndrome.

Williams MJ, Harris RI, Dean BC.

A total of 617 patients diagnosed by their general practitioner, according to set criteria, as having premenstrual symptoms were treated in general practice for three menstrual cycles with either pyridoxine or placebo. Treatment was randomized and administered blind. In the 434 patients analyzed, an improvement was found in 7 of the 9 symptoms assessed for both treatments, but the differences between treatments did not reach conventional significance levels. However, improvement as measured by global assessment after three cycles was significantly greater in the patients treated with pyridoxine (p less than 0.02).

Cutis. 1984 Nov;34(5):481-3.

Lupus vulgaris responding to double antituberculous therapy.

Heller GL, Pavlidakey GP, Hashimoto K, Greenberg M, Rosenberg M.

A patient with a 3 by 4 cm ulcerated lesion on the nose and upper lip in whom previous antibiotics and antifungal treatments for a "mixed infection" were of no avail is presented. Her history revealed that she has had pulmonary and pharyngeal tuberculosis and subsequently scrofuloderma of cervical lymph nodes. She eventually responded well to isoniazid, rifampin, and pyridoxine therapy.

Proc Natl Acad Sci U S A. 1984 Nov;81(22):7076-8.

Enzymology of the response of the carpal tunnel syndrome to riboflavin and to combined riboflavin and pyridoxine.

Folkers K, Wolaniuk A, Vadhanavikit S.

Differential enzymic analyses of the erythrocyte glutamic-oxaloacetic transaminase and the erythrocyte glutathione reductase of a patient with a 3-yr history of the carpal tunnel syndrome (CTS) revealed high deficiencies of both vitamin B-6 and riboflavin as based on approximately equal to 30% levels of the specific activities of these enzymes. Riboflavin for 5 months caused nearly complete disappearance of the CTS and caused no change in the specific activity of erythrocyte glutamic-oxaloacetic transaminase. Combined riboflavin and pyridoxine treatment increased (P less than 0.001) the specific activities of erythrocyte glutathione reductase and erythrocyte glutamic-oxaloacetic transaminase to normal levels with total disappearance of the CTS. Objectively, the strength of pinch of both hands increased (P less than 0.001) on treatment with riboflavin and further increased (P less than 0.001) on the combined treatment. For the first time, a significant riboflavin deficiency has been found to be related to CTS. Riboflavin therapy was effective biochemically, subjectively, and objectively, and riboflavin and pyridoxine were even more effective when concomitantly administered.

J Nutr. 1984 May;114(5):977-88.

Effect of maternal pyridoxine X HCl supplementation on the vitamin B-6 status of mother and infant and on pregnancy outcome.

Schuster K, Bailey LB, Mahan CS.

The effect of maternal pyridoxine X HCl (PN-HCl) supplementation on the vitamin B-6 status of pregnant women and their infants at birth and on pregnancy outcome was investigated. Volunteer subjects were randomly assigned a daily vitamin B-6 supplement containing 0, 2.6, 5, 7.5, 10, 15 or 20 mg of PN-HCl in a double-blind study. The mean dietary vitamin B-6 intake of the group was 1.43 +/- 1.28 mg/day as estimated from 24-hour dietary recalls. Maternal plasma pyridoxal 5'-phosphate (PLP) levels were positively correlated with vitamin B-6 supplementation at 30 weeks gestation (r = 0.55, P less than 0.0005) and at delivery (r = 0.54, P less than 0.01). Cord plasma PLP levels reached a maximum when maternal PN-HCl supplementation was 7.5 mg and greater. Supplemental PN-HCl at the 7.5-mg level was required to prevent a decrease in maternal plasma PLP at delivery. Apgar scores at 1 minute after birth were higher (P less than 0.05) for infants whose mothers took 7.5 mg or more supplemental PN-HCl than for infants of mothers who took 5 mg or less. These findings indicate that a vitamin B-6 intake between 5.5 and 7.6 mg/day (diet plus supplement as pyridoxine equivalents) was required to maintain maternal plasma PLP levels at term at a level comparable to initial values.

218: Koutsky J, Hladovec J, Prerovsky I, Dvorak V, Novotny A, Herzmann J. [Prevention of the prothrombotic effects of oral contraceptives with vitamin B6] Cesk Gynekol. 1984 Mar;49(2):98-103. Czech. No abstract available. PMID: 6705067

219: Kridl J, Zvara V, Revusova V, Gratzlova J, Ondrus B. [Inhibition of calcium oxalate urolithiasis with pyridoxine and magnesium in an experiment] Bratisl Lek Listy. 1984 Jan;81(1):21-8. Slovak. No abstract available. PMID: 6692164

Int J Vitam Nutr Res. 1984;54(2-3):185-93.

Evaluation of pyridoxine intake and pyridoxine status among aged institutionalised people.

Guilland JC, Bereksi-Reguig B, Lequeu B, Moreau D, Klepping J, Richard D.

The vitamin B6 status of 60 institutionalised elderly subjects (group A: 31 men, mean age = 77 yr and 29 women, mean age = 84 yr) and 41 healthy young adults (group B or control group: 18 men, mean age = 30 yr and 23 women, mean age = 27 yr) was evaluated using erythrocyte aspartate aminotransferase activity coefficient (alpha EGOT) and plasma pyridoxal phosphate (PLP) level (vitamin B6-deficient subjects = alpha greater than 2.0 and PLP less than 80 nmol/l). The kilocalorie, protein and pyridoxine intakes were also estimated. Regarding calories and protein, the diets may be generally considered satisfactory in respect to the French 1981 RDA. The mean dietary intake of vitamin B6 was less than 2 mg/day in all groups. Ninety per cent of the aged, 80 per cent of females in group B in contrast to 56 per cent of males in group B consumed less than their individual vitamin B6 requirements as determined by a probability method. As the incidence of vitamin B6 biochemical deficiency was much higher in the group A (71% for males and 86% for females) than in the control group (11% for males and 30% for females), it is concluded that the high incidence of biochemical vitamin B6 deficiency noted in the aged appeared more relevant from an altered metabolism of the vitamin than from a too low energy intake. Supplements with high doses of vitamin B6 to aged subjects caused a significant decrease in alpha EGOT and a significant increase in PLP levels.

Nephron. 1984;38(1):9-16.

Immunologic abnormalities in hemodialysis patients: improvement after pyridoxine therapy.

Casciato DA, McAdam LP, Kopple JD, Bluestone R, Goldberg LS, Clements PJ, Knutson DW.

8 male patients undergoing maintenance hemodialysis were studied to determine the effect of administering supplements of pyridoxine hydrochloride, 50 mg/day for 3-5 weeks, on tests of immune function. In the 3 patients who initially had abnormal nitroblue tetrazolium reduction tests, the values returned to normal with therapy (p less than 0.05). The generation of chemotactic factors from plasma was defective in all evaluated patients and improved after pyridoxine therapy in 4 of 5 patients (p less than 0.01). The lymphocyte subpopulations changed with a rise in the populations of null cells after supplementation with pyridoxine. In addition, lymphocyte transformation in response to mitogens improved in the 3 patients who initially showed low values in these assays. The improvements occurred with pyridoxine therapy even though some patients who responded had no evidence for vitamin B6 deficiency before therapy, as indicated by a normal erythrocyte glumatic-pyruvic transaminase index. We conclude that several parameters of immune function are improved with pyridoxine supplementation. Studies are necessary to establish the minimum daily intake of pyridoxine which will maintain improved values of these tests of immune function in hemodialysis patients.

Pediatr Pharmacol (New York). 1984;4(3):199-202.

Acute isoniazid intoxication: reversal of CNS symptoms with large doses of pyridoxine.

Brown A, Mallett M, Fiser D, Arnold WC.

Acute toxicity from ingestion of isoniazid (INH) is manifested by coma and seizures unresponsive to conventional therapy. Though small doses of pyridoxine can reverse the seizure activity of acute isoniazid toxicity, large doses of pyridoxine (B6) are needed to completely reverse the symptoms. A case report is presented demonstrating the need for large doses of pyridoxine to reverse the symptoms of isoniazid intoxication and the literature of isoniazid toxicity in the pediatric age group is reviewed.

223: Brooks SC, D'Angelo L, Chalmeta A, Ahern G, Judson JH. An unusual schizophrenic illness responsive to pyridoxine HCl (B6) subsequent to phenothiazine and butyrophenone toxicities. Biol Psychiatry. 1983 Nov;18(11):1321-8. No abstract available. PMID: 6652165

Int J Radiat Oncol Biol Phys. 1983 Oct;9(10):1513-9.

Misonidazole neurotoxicity in mice decreased by administration with pyridoxine.

Eifel PJ, Brown DM, Lee WW, Brown JM.

A series of toxicological and pharmacological experiments was performed to test the hypothesis that alterations of pyridoxine (Vitamin B6) metabolism may play an important role in the development of misonidazole (MISO) neurotoxicity. The formation of a Schiff's base between the final reduction product of MISO, 2-amino MISO (NH2-MISO), and pyridoxal-HCl in ethanol was demonstrated. Mice receiving daily intraperitoneal injections of MISO suffered significantly less toxicity (as determined by survival, weight gain and neurological tests) when large doses of pyridoxine-HCl (PYR) were delivered concomitantly, and consequently were able to tolerate administration of more than twice as many MISO injections. PYR did not alter the pharmacokinetics of MISO, either when given simultaneously or when given by multiple repeated daily injections prior to MISO. The administration of PYR also did not alter the radiosensitization by MISO in an in vivo-in vitro cloning assay with the EMT6 tumor in BALB/c mice. If depletion or altered metabolism of pyridoxine by reduced metabolites is also responsible for the neurotoxic effects of nitroimidazoles in humans, then concomitant administration of pyridoxine (in doses greater than the molar quantity of NH2-MISO formed) should inhibit the development of such symptoms and allow administration of larger doses of MISO than are currently clinically employable.

Arch Dis Child. 1983 Jun;58(6):415-8.

Pyridoxine dependent seizures--a wider clinical spectrum.

Bankier A, Turner M, Hopkins IJ.

We report 4 infants with pyridoxine dependent seizures who had clinical features that led to diagnostic uncertainty. Their clinical course was unusual in 1 or more of the following: later onset of initial seizures; a seizure free period after taking of anticonvulsants, but before taking of pyridoxine; a long remission after withdrawal of pyridoxine; and atypical seizure type. This report illustrates a broader range of clinical features and highlights the need to consider the diagnosis of pyridoxine dependent seizures in any infant with intractable epilepsy, regardless of the pattern of seizures and the response to anticonvulsant medications. In such a case, 100 mg intravenous pyridoxine should be given and, if a definite clinical response is established, oral pyridoxine should be continued indefinitely.

Ann Emerg Med. 1983 May;12(5):303-5.

Isoniazid overdose treated with high-dose pyridoxine.

Yarbrough BE, Wood JP.

Large doses of pyridoxine recently have been shown to prevent the seizures and acidosis caused by ingestion of more than two to three grams of isoniazid. We present three cases of massive isoniazid ingestion, producing seizures and acidosis, that were treated successfully by administration of one gram of pyridoxine intravenously for each gram of isoniazid ingested.

Scand J Gastroenterol. 1983 Mar;18(2):299-304.

Reversal of psychopathology in adult coeliac disease with the aid of pyridoxine (vitamin B6).

Hallert C, Astrom J, Walan A.

Signs of mental depression are typical in adults presenting with coeliac disease. The response to treatment was evaluated in 12 consecutive patients by means of the Minnesota Multiphasic Personality Inventory (MMPI), with surgical patients serving as controls. The coeliacs reported no change in depressive symptoms after 1 year's gluten withdrawal despite evidence of improvement in the small intestine. When retested after 3 years, however, after 6 months of 80 mg/day of oral pyridoxine (vitamin B6) therapy, they showed a fall in the score of scale 2 ('depression') from 70 to 56 (p less than 0.01), which became normalized like other pretreatment abnormalities in the MMPI. Cholecystectomy in the control subjects produced no alterations in the MMPI profile. The results indicate a causal relationship between adult coeliac disease and concomitant depressive symptoms which seems to implicate metabolic effects from pyridoxine deficiency influencing central mechanisms regulating mood.

Ann Neurol. 1983 Jan;13(1):103-4.

Pyridoxine-dependency seizure: report of a rare presentation.

Krishnamoorthy KS.

A child developed minor motor seizures at the age of 14 months accompanied by an abnormal electroencephalogram showing single spikes and polyspikes over the vertex and frontocentral regions. Seizures continued until the age of 22 months despite administration of several standard anticonvulsants. At age 22 months, pyridoxine, 75 mg daily, was initiated and anticonvulsants were discontinued. Both the seizures and the electroencephalographic abnormality have disappeared over the ensuing 20 months with pyridoxine therapy.

Proc Eur Dial Transplant Assoc. 1983;19:308-12.

Reduction of elevated plasma oxalic acid by pyridoxine therapy in patients on RDT.

Balcke P, Schmidt P, Zazgornik J, Kopsa H.

In eight chronic haemodialysed patients with secondary hyperoxalaemia due to renal insufficiency vitamin B6, an important co-enzyme in oxalic acid metabolism, was administered. Mean plasma oxalic acid values decreased from 149.5 +/- 67.0 mmol/L to 99.0 +/- 36.4 mmol/L within two weeks and to 93.8 +/- 33.1 mmol/L after four weeks of pyridoxine treatment (p less than 0.01, p less than 0.01). The mean reduction was 46 per cent (32.0 to 56.1). Patients with high pre-values of plasma oxalic acid had the most pronounced decrease. In order to prevent calcium oxalate deposition a reduction of plasma oxalic acid in patients on RDT seems to be an important goal in long term haemodialysis treatment.

Proc Eur Dial Transplant Assoc. 1983;20:417-21.

Pyridoxine therapy in patients with renal calcium oxalate calculi.

Balcke P, Schmidt P, Zazgornik J, Kopsa H, Minar E.

In 12 patients with idiopathic calcium oxalate calculi pyridoxine was administered. Within six weeks mean daily oxalic acid excretion decreased from 480 +/- 122 mumol to 336 +/- 83 mumol. Glycolic acid excretion fell from 208 +/- 51 mumol to 153 +/- 26 mumol (normal range: oxalic acid 228-412 mumol/day, glycolic acid 130-290 mumol/day). The reduction of oxalic acid excretion seems to be beneficial in prevention of idiopathic calcium oxalate calculi.

Acta Ophthalmol (Copenh). 1982 Dec;60(6):894-906.

Homocystinuria treated with pyridoxine.

Blika S, Saunte E, Lunde H, Gjessing LR, Ringvold A.

Four cases of homocystinuria with lens luxation have been examined. As judged from the plasma amino acid pattern, they all responded well on pyridoxine treatment. Two of them discontinued the treatment on their own, and one of these died at the age of 17 years. The lens luxation progressed in one case despite adequate treatment. Scanning electron microscopy of one lens revealed partly broken zonules, abnormal zonular attachment, and a spongy appearance of the capsule proper. Hoping that adequate treatment will reduce more serious complications such as thromboembolism in these patients, it is concluded that an early diagnosis largely depends on the ophthalmologist, who should perform the silver-nitroprusside test, specific for homocystinuria, in all patients with non traumatic lens luxation.

Proc Natl Acad Sci U S A. 1982 Dec;79(23):7494-8.

Response of vitamin B-6 deficiency and the carpal tunnel syndrome to pyridoxine.

Ellis JM, Folkers K, Levy M, Shizukuishi S, Lewandowski J, Nishii S, Schubert HA, Ulrich R.

The specific activities and percentage deficiencies of the glutamic oxaloacetic transaminase of erythrocytes (EGOT) were determined for patients with carpal tunnel syndrome (CTS) diagnosed by clinical examination and electrical conduction data; the EGOT data revealed a severe deficiency of vitamin B-6. After double-blind treatment with pyridoxine and placebo, two physicians identified those receiving pyridoxine (clinically improved) and those receiving placebo (did not improve) without error, P less than 0.0078. Correcting a deficiency of the coenzyme at receptors of existing molecules of the apoenzyme appears to take place within days; correction of the deficiency in the number of molecules of the transaminase takes place over 10-12 weeks. The clinical response, appraised by the diminution of the symptoms of CTS, was correlated only with the restored levels of the transaminase which presumably results from a translational long-term increase in the number of molecules of EGOT by a mechanism activated by correcting a deficiency of pyridoxal 5'-phosphate. Apparent Km values of EGOT were identical for groups of patients with CTS and others without CTS but with identical specific activities, indicating that CTS is a primary deficiency of vitamin B-6 rather than one of a dependency state. Clinical improvement of the syndrome with pyridoxine therapy may frequently obviate hand surgery.

Drug Intell Clin Pharm. 1982 Nov;16(11):876-7.

Amitriptyline-related peripheral neuropathy relieved during pyridoxine hydrochloride administration.

Meadows GG, Huff MR, Fredericks S.

Tricyclic antidepressants rarely cause peripheral neuropathy. In fact, this class of drugs has been used to control the symptoms of pain and paresthesia that accompany peripheral neuropathy. We report peripheral paresthesias that occurred in a 39-year-old female during five years of amitriptyline administration. The patient's symptoms were relieved by oral pyridoxine hydrochloride, associated with elevated plasma pyridoxal phosphate.

Scand J Haematol. 1982 Nov;29(5):421-4.

Pyridoxine-responsive primary acquired sideroblastic anaemia. In vitro and in vivo effects of vitamin B6 on decreased 5-aminolaevulinate synthase activity.

Meier PJ, Fehr J, Meyer UA.

The activity of 5-aminolaevulinate (ALA) synthase, the first and rate-limiting of haem synthesis, was markedly reduced (13% of controls) in erythroblasts of a patient with acquired, primary sideroblastic anaemia (PASA). The reduced activity of ALA synthase could not be restored in vitro with 1 mmol/l pyridoxal-5-phosphate (PLP). Treatment of the patient with pyridoxine for several months increased the ALA synthase activity from 13% to 50% of controls in the absence and to 100% in the presence of PLP in the incubation medium. These studies suggest that both increased degradation of apo-ALA synthase and decreased affinity of ALA synthase for PLP may be involved in pyridoxine-responsive PASA.

Vopr Pitan. 1982 Nov-Dec;(6):54-6.

[Enzyme activity changes in chronic alcoholic intoxication and the simultaneous administration of pyridoxine]

[Article in Russian]

Iliev IS, Stoev TS, Damianova MI, Krushkova AM.

After prolonged application of ethanol the liver and brain of rats show an appreciable increase in lactate dehydrogenase activity, noticeable lowering of cytoplasmic aspartate and alanine aminotransferase activity, elevation of liver arginine succinate lyase activity with unchanged activities of other enzymes of the ornithine cycle (ornithine carbamoyltransferase and arginase), reduction of glutamate and malate dehydrogenase and mitochondrial aspartate aminotransferase activity in brain tissue. Concurrent application of ethanol and pyridoxine normalizes the effect of ethanol on liver arginine succinate lyase and on brain tissue lactate and malate dehydrogenase, mitochondrial and cytoplasmic aspartate aminotransferase and alanine aminotransferase.

Z Geburtshilfe Perinatol. 1982 Nov-Dec;186(6):326-34.

[Magnesium aspartate as a cardioprotective agent and adjuvant in tocolysis with betamimetics. Animal experiments on the kinetics and calcium antagonist action of orally administered magnesium aspartate with special reference to simultaneous vitamin B administration]

[Article in German]

Wischnik A, Schroll A, Kollmer WE, Berg D, Wischnik B, Wieshammer E, Weidenbach A.

With pregnant Wistar-rats, suffering from alimentary magnesium deficiency, absorption and distributing of Mg28 has been studied, the latter having been applied as aspartate and as chloride, with and without simultaneous substitution of vitamin B6. Absorption and tissue pooling were found to be augmented when using the aspartate and even more when adding vitamin B6. These differences were significant in the blood as well as in fetal and myocardial tissue. Correlation between blood-Mg28 und Mg28-activities in various tissues shows, that blood magnesium levels indicate a magnesium deficiency at least in the tissues of interest: fetus, myocardium, uterus and placenta. Nevertheless blood magnesium levels fail to reflect an additional tissue pooling, that exerts a beneficial action in the respect of cardio protection and of saving beta-mimetic tocolytics. When measuring magnesium and calcium excretion during chronic experiments with and without oral magnesium aspartate substitution, it could be demonstrated, that the amount of substituted magnesium has been pooled almost totally. Oral magnesium substitution furthermore reduces intestinal calcium absorption. Investigation on calcium uptake into the maternal myocardium revealed, that oral magnesium aspartate substitution significantly diminishes myocardial calcium uptake, the latter among others being responsible for cardiac hazards during tocolysis with beta-mimetic substances, while the pharmacologic calcium-antagonist Verapamil failed to do so.

Am Rev Respir Dis. 1982 Oct;126(4):714-6.

Maternal plasma concentration of pyridoxal phosphate during pregnancy: adequacy of vitamin B6 supplementation during isoniazid therapy.

Atkins JN.

Vitamin B6 is an important supplement both for pregnant patients and for those receiving isoniazid. Therefore, we decided to monitor pyridoxal phosphate (PLP) concentrations in 12 pregnant patients who were receiving isoniazid to be certain that supplementation was adequate. Patients were given a prenatal vitamin preparation and 50 mg of pyridoxine hydrochloride daily. At 1 month 10 of the 12 patients had adequate PLP concentrations. Seven of these 10 patients had elevated PLP concentrations and 3 had normal concentrations. Supplementation with 52 to 60 mg per day of Vitamin B6 produces adequate PLP concentrations in pregnant patients who are also taking isoniazid.

Int J Clin Pharmacol Ther Toxicol. 1982 Sep;20(9):434-7.

Effect of pyridoxine supplementation on recurrent stone formers.

Murthy MS, Farooqui S, Talwar HS, Thind SK, Nath R, Rajendran L, Bapna BC.

Twelve recurrent stone formers with hyperoxaluria were administered pyridoxine-HCl (10 mg/day) daily for a period of 180 days. The pyridoxine status of the patients, as assessed by their erythrocyte transaminase activation indexes, improved significantly (p less than 0.001) after 180 days of supplementation as compared with the basal levels. Although urinary oxalate decreased significantly (p less than 0.05) by the 90th day of pyridoxine therapy, other parameters, e.g., urinary calcium, phosphorus, and creatinine, remained unaltered. Significant correlation was observed between erythrocyte glutamate pyruvate transaminase (EGPT) or erythrocyte glutamate oxaloacetate transaminase (EGOT) activation index and urinary oxalate excretion (p less than 0.01). Pyridoxine in low doses (10 mg/day) is of therapeutic value for hyperoxaluric stone formers.

Ann Clin Res. 1982 Apr;14(2):61-5.

Haema synthesis during pyridoxine therapy in two families with different types of hereditary sideroblastic anaemia.

Pasanen AV, Salmi M, Tenhunen R, Vuopio P.

The activity of delta-aminolaevulinic acid synthase (ALA-S) as well as the concentrations of coproporphyrin and protoporphyrin in peripheral red blood cells were examined in 2 sisters and in 2 brothers with hereditary sideroblastic anaemias (HSA) of different types. The measurements were done before and during treatment by pyridoxal-5-phosphate (PLP) and/or pyridoxine chloride. Previous family studies indicated an X chromosome linked HSA in the 2 brothers, whereas the precise mode of inheritance in the 2 sisters has not been established. Previous and present studies have revealed no characteristic defect in haema synthesis in the 2 sisters and their treatment by PLP or pyridoxine produced no haematologic response although a slight stimulation of haema synthesis was observed. In contrast, the 2 brothers showed decreased activity of ALA-S and decreased protoporphyrin concentration in peripheral red blood cells. After treatment by PLP and/or pyridoxine the ALA-S activity was restored to normal. Corresponding to the stimulation of haema synthesis a partial haematological response was observed in both brothers. Stopping and restarting of pyridoxine therapy in one brother confirmed the above results. These observations indicate the presence of two genetically and biochemically different types of HSA and help us to understand the varying response to pyridoxine therapy in this rare disorder.

J Infect Dis. 1982 Apr;145(4):547-9.

Trial of pyridoxine therapy for tetanus neonatorum.

Godel JC.

Pyridoxine, a coenzyme in the production of gamma-amino-n-butyric acid, was added (100 mg per day) to conventional therapy for tetanus neonatorum in 20 infants who were graded according to prognosis and severity of spasms. Three infants died, for an overall mortality of 15%. All three were in prognostic group V; mortality in group V was 37.5%. Fifteen days after admission, 14 (70%) of the remaining 17 infants were free of spasms and three (15%) had only mild spasms. In comparison to other studies in which conventional therapy alone was used for tetanus neonatorum, the addition of pyridoxine appeared to decrease mortality and the duration of spasms.

Acta Vitaminol Enzymol. 1982;4(1-2):27-44.

Clinical and biological effects of high doses of vitamin B6 and magnesium on autistic children.

Lelord G, Callaway E, Muh JP.

In 1973 Rimland reported that some autistic children responded favorably to high doses of vitamin B6. Since this finding, different studies were performed to identify apparently B6 responsive subjects and to critically evaluate clinical and biological B6 responsiveness. Magnesium was included because large doses of B6 might increase irritability. 44 patients (mean age 9.3 years) were examined. All selected children had marked autistic symptoms. The children received a complete diagnostic work-up, including psychiatric, psychological, neurological and medical evaluation. Clinical data were scored using an estimate of global clinical state and numerical rating on a 18 item scale (Behavior Summarized Evaluation). In a first open trial 15 out of 44 children exhibited moderate clinical improvement with worsening on termination of the trial. Thirteen responders and 8 non responders were re-tested in a 2-week crossover, double-blind trial and the responses to the open trial were confirmed. Biochemical data analysis revealed that a significant decrease in urinary homovanillic acid (HVA) levels was observed during B6-Mg administration. During B6-Mg treatment, middle latency evoked potentials exhibited a significant increase of amplitude.

Acta Vitaminol Enzymol. 1982;4(1-2):45-54.

Therapy of side effects of oral contraceptive agents with vitamin B6.

Bermond P.

Studies carried out in different countries during the last 15 years have provided evidence that supplementation with (or excess of) estro-progestational hormones may be accompanied by an increased urinary excretion of tryptophan metabolites, as happens in pyridoxine deficiency. Further methods of assessment of vitamin B6 in humans have confirmed an impaired status in women using hormonal contraception. Disturbances in the metabolism of tryptophan have been shown to be responsible for such symptoms as depression, anxiety, decrease of libido and impairment of glucose tolerance occurring in some of the OCA users. Administration of 40 mg of vitamin B6 daily not only restores normal biochemical values but also relieves the clinical symptoms in those vitamin B6 deficient women taking OCA's. Further studies are justified to clarify whether vitamin B6 supplementation may contribute to improving depression also in other situations with hyperoestrogenism (pregnancy, puerperium, estro-progestational treatments, etc.), as well as correcting metabolic impairments, such as a minor alteration of glucose tolerance.

PIP: Studies carried out in different countries over the last 15 years have provided evidence that supplementation with or excess of estrogen-progestogen hormones may be accompanied by an increased urinary excretion of tryptophan metabolites, as occurs in pyroxidine deficiency. Further methods of assessment of vitamin B6 in humans have confirmed that there is impaired status in women using oral contraceptives (OCs). Disturbances in the tryptophan metabolism have been shown to be responsible for such symptoms as depression, anxiety, decrease in libido, and impairment of glucose tolerance occurring in some OC users. Administration of 40 mg vitamin B6 daily not only restores the normal biochemical values but also relieves the clinical symptoms in those vitamin B6 deficient women taking OCs. Further studies are justified to clarify whether vitamin B6 supplementation may contribute to improving depression in other situations where there is hyperestrogenism (pregnancy, puerperium, estrogen-progestogen treatments), as well as correcting metabolic impairments, such as a minor alteration in glucose tolerance. (author's modified)

Graefes Arch Clin Exp Ophthalmol. 1982;218(1):21-4.

Biochemical and therapeutical studies in a case of atrophia gyrata.

Behrens-Baumann W, Konig U, Schroder K, Hansmann I, Langenbeck U.

A thirty-six years old man from an inbred family with the typical clinical picture of Atrophia gyrata chorioideae et retinae was found to have hyperornithinemia and a partial deficiency of ornithin-ketoacid-transaminase activity. The residual activity was stimulated in vitro by high concentrations of pyridoxal phosphate. We have initiated a therapeutic study with vitamin B6 per os accordingly. Comparitively low doses may be sufficient for long term treatment. The necessity to start therapy early in life is emphazised. Possible mechanisms of the pathogenesis of Atrophia gyrata are discussed.

Padiatr Padol. 1982;17(2):149-55.

Influence of pyridoxine on the oxygen transport function of blood in the neonatal period in clinical and experimental conditions.

Boda D, Temesvari P, Eck E.

A significant increase of the P50 value of blood (the pO2 value of O2 half saturated blood at 37 degrees C, pH 7.40 and pCO2 of 5.33 kPa) was observed on symptom free premature newborns, mature newborns requiring intensive care and newborn rabbits treated with high dose of pyridoxine (Vitamin B6). The change seemed to be independent of the 2,3-DPG content of blood. The moderate but consistently favourable influence of vitamin B6 treatment on the O2 transport function of blood can be advantageous in early postnatal adaptation disturbances of newborns.

245: Hall MA, Thom H, Russell G. Erythrocyte aspartate amino transferase activity in asthmatic and non-asthmatic children and its enhancement by vitamin B6. Ann Allergy. 1981 Dec;47(6):464-6. No abstract available. PMID: 7325421

246: Wood ER. Isoniazid toxicity. Pyridoxine controlled seizures in a dialysis patient. J Kans Med Soc. 1981 Dec;82(12):551-2. No abstract available.

JAMA. 1981 Sep 4;246(10):1102-4.

Single high-dose pyridoxine treatment for isoniazid overdose.

Wason S, Lacouture PG, Lovejoy FH Jr.

We treated five isoniazid-overdosed patients each with a single dose of pyridoxine hydrochloride equivalent to the gram amount of isoniazid ingested and compared their outcome with that of 41 patients from the literature who received little or no pyridoxine. Recurrent seizures occurred in 60% of patients who had received no pyridoxine vs 0% in our patients. Metabolic acidosis resolved in our cases but was refractory in the literature cases. In our cases, coma lightened more rapidly and was of shorter duration as compared with that in the literature cases (mean, seven hours vs 24 hours). No adverse effects of pyridoxine were seen in our patients.

Res Commun Chem Pathol Pharmacol. 1981 Aug;33(2):331-44.

Therapy with vitamin B6 with and without surgery for treatment of patients having the idiopathic carpal tunnel syndrome.

Ellis J, Folkers K, Levy M, Takemura K, Shizukuishi S, Ulrich R, Harrison P.

Blood samples from four patients at the time of surgery to relieve the compression of the carpal tunnel syndrome, which was diagnosed by clinical and electromyographic evaluation, were differentially assayed to determine the specific activities and the % deficiencies of the erythrocyte glutamic oxaloacetic transaminase (EGOT). The data from these assays revealed that these four patients had a severe deficiency of vitamin B6. These data, in conjunction with previous biochemical and clinical results over five years, underscore the desirability, and even necessity, of testing by the EGOT analysis for the presence of a severe deficiency of vitamin B6 in all such patients before surgery. Treatment with vitamin B6 (pyridoxine) for a minimum period of 12 weeks, depending upon the duration and severity of the symptoms, has been effective without exception. Surgery may relieve compression, but does not correct a deficiency of vitamin B6. Surgery in addition to therapy with vitamin B6 should be reserved for those patients who have had the deficiency for so many years that much tissue damage is irreversible by pyridoxine, and additional relief from pain can be achieved through the surgery.

249: Bukharovich MN, Gridasova VD, Miroshnichenko AG. [Combined treatment of acne using pyridoxine and hydrogen sulfide baths] Vestn Dermatol Venerol. 1981 Aug;(8):46-9. Russian. No abstract available. PMID: 6456617

Biol Psychiatry. 1981 Jul;16(7):627-41.

Effects of vitamin B6 on averaged evoked potentials in infantile autism.

Martineau J, Garreau B, Barthelemy C, Callaway E, Lelord G.

In autistic children, averaged evoked potentials have been reported to have lower amplitudes and shorter latencies than those of normal children. Also, moderate clinical improvement has been observed in some autistic children after treatment with vitamin B6 and magnesium. We have studied biochemical and electrophysiological effects of vitamin B6 and magnesium in 12 autistic children and in 11 normal children. During treatment of the autistic children with B6, an increase of amplitude of middle-latency evoked potentials and a decrease of urinary homovanillic acid were found. The reverse was noted in the normal subjects.

251: Harrison AR, Kasidas GP, Rose GA. Hyperoxaluria and recurrent stone formation apparently cured by short courses of pyridoxine. Br Med J (Clin Res Ed). 1981 Jun 27;282(6282):2097-8. No abstract available. PMID: 6788219

J Autism Dev Disord. 1981 Jun;11(2):219-30.

Effects of pyridoxine and magnesium on autistic symptoms--initial observations.

Lelord G, Muh JP, Barthelemy C, Martineau J, Garreau B, Callaway E.

In an open trial, a heterogeneous group of 44 children with autistic symptoms were treated with large doses of vitamin B6 and magnesium. Clinical improvement with worsening on termination of the trial was observed in 15 children. Thirteen responders and 8 nonresponders were retested in a 2-week, crossover, double-blind trial, and the responses to the open trial were confirmed.

Kidney Int. 1981 May;19(5):694-704.

Daily requirement for pyridoxine supplements in chronic renal failure.

Kopple JD, Mercurio K, Blumenkrantz MJ, Jones MR, Tallos J, Roberts C, Card B, Saltzman R, Casciato DA, Swendseid ME.

Vitamin B6 deficiency was evaluated in 37 patients with chronic renal failure and in 71 patients undergoing maintenance hemodialysis (HD) or intermittent peritoneal dialysis (PD). Vitamin B6 deficiency was assessed by the in vitro activity of erythrocyte glutamic pyruvic transaminase (EGPT), without (basal) and with (stimulated) the addition of pyridoxal-5-phosphate to the assay, and the EGPT index (stimulated activity ./. basal activity). Basal and stimulated EGPT activities were below normal in the HD patients, and the EGPT index was increased in each group of patients, indicating vitamin B6 deficiency. Supplemental pyridoxine hydrochloride was given to 30 HD patients who received 1.25 to 50 mg/day (37 studies), 6 PD patients who were given 1.25 or 2.5 mg/day (7 studies), and 8 nondialyzed patients with mild to severe renal failure who received 2.5 mg/ day. In all HD patients, 10 or 50 mg/day of pyridoxine hydrochloride rapidly corrected the abnormal EGPT index and maintained normal values; with supplements of 5.0 mg/day or less, the index was often abnormal, particularly in those who were septic or taking pyridoxine antagonists. In PD patients and nondialyzed patients with renal failure, 2.5 mg/day of pyridoxine hydrochloride was inadequate to correct rapidly the abnormal index in all patients. These findings suggest that HD patients should receive 10 mg/day of supplemental pyridoxine hydrochloride (8.2 mg/day pyridoxine). PD patients and patients with chronic renal failure should receive about 5.0 mg/day of supplemental pyridoxine hydrochloride (4.1 mg/day pyridoxine). When sepsis intervenes or vitamin B6 antagonists are taken, 10 mg/day of pyridoxine hydrochloride may be a safer supplement for all patients.

Ophthalmology. 1981 Apr;88(4):316-24.

Clinical trial of vitamin B6 for gyrate atrophy of the choroid and retina.

Weleber RG, Kennaway NG.

Seven patients with gyrate atrophy and deficiency of ornithine-delta-aminotransferase were studied for in vivo pyridoxine responsiveness; three responded to oral vitamin B6 with over 50% reduction of serum ornithine levels and return to normal of serum lysine levels. Electrophysiologic studies were performed on two B6-responsive patients and one B6-nonresponder over various time periods with and without pyridoxine supplementation. Electroretinogram (ERG) amplitudes improved 100% in one patient when initially given high doses of vitamin B6. Electro-oculogram light-to-dark ratio also improved for this patient. Withdrawal followed by resumption of B6 supplementation was associated with mild worsening followed by improvement of ERG responses respectively in both patients. Long-term follow-up will be needed to assess whether pyridoxine treatment will slow or halt the progression of the disease.

255: Harpey JP, Rosenblatt DS, Cooper BA, Le Moel G, Roy C, Lafourcade J. Homocystinuria caused by 5,10-methylenetetrahydrofolate reductase deficiency: a case in an infant responding to methionine, folinic acid, pyridoxine, and vitamin B12 therapy. J Pediatr. 1981 Feb;98(2):275-8. No abstract available. PMID: 7007598

Int Pharmacopsychiatry. 1981;16(4):245-50.

The use of nicotinic acid and pyridoxine in the treatment of schizophrenia.

Petrie WM, Ban TA, Ananth JV.

As part of the Canadian Mental Health Association Collaborative Study, the hypothesis that combined administration of nicotinic acid and pyridoxine has greater therapeutic effects than the component drugs in chronic schizophrenic patients was tested. This could not be substantiated in a 48-week study in which supplementation of neuroleptic treatment with a single vitamin, i.e., nicotinic acid or pyridoxine, produced significant therapeutic changes, while supplementation with both vitamins did not.

Vestn Khir Im I I Grek. 1981 Jan;126(1):36-40.

[Pathogenetic treatment of acute pancreatitis]

[Article in Russian]

Suvernev AV.

In acute experiments in albino rats it was shown that mannitol, polyglucin and hemodesis possess antiproteolytic properties. Pyridoxine, hemodesis and polyglucin were also found to be antagonists to the effects of bradykinin. Pyridoxine, polyglucin and hemodesis proved to be most effective in the treatment of experimental trypsinemia. The results of the conservative treatment of patients with acute pancreatitis were better if pyridoxine and polyglucin were added to the complex of curative measures.

Tubercle. 1980 Dec;61(4):191-6.

Pyridoxine supplementation during isoniazid therapy.

Snider DE Jr.

Vitamin B6 (pyridoxine) supplementation during isoniazid (INH) therapy is necessary in some patients to prevent the development of peripheral neuropathy. In vivo pyridoxine is converted into coenzymes which play an essential role in the metabolism of protein, carbohydrates, fatty acids, and several other substances, including brain amines, INH apparently competitively inhibits the action of pyridoxine in these metabolic functions. The reported frequency of INH-induced neuropathy in various studies is reviewed and population groups at relatively high risk of developing this complication are identified. The routine use of pyridoxine supplementation to prevent peripheral neuropathy in high risk populations is recommended.

Farmakol Toksikol. 1980 Sep-Oct;43(5):601-3.

[Effect of the combined use of flavin coenzyme preparations and pyridoxine on the body vitamin balance in animals]

[Article in Russian]

Stroev EA, Kazakova NT.

The effect of combined administration of flavin coenzymes and pyridoxine on B2-avitaminosis rats' supply with these vitamins has been studied. It has been disclosed that pyridoxine promotes more effective normalization of riboflavin and pyridoxine balance in the body, this balance being measured from the excretion of riboflavin and 4-pyridoxin acid with urine as well as from the content of total flavins in blood and tissues. In vitamin B2 lack, it is recommended that pyridoxin be combined with flavin mononucleotide and in particular with flavin adenine dinucleotide.

Am J Hum Genet. 1980 Jul;32(4):529-41.

Gyrate atrophy of the choroid and retina with hyperornithinemia: biochemical and histologic studies and response to vitamin B6.

Kennaway NG, Weleber RG, Buist NR.

Four patients with hyperomithinemia and gyrate atrophy of the choroid and retina age described. In vivo response to vitamin B6 is documented in three of the four patients by significant reduction of fasting serum ornithine and increase of lysine after oral B6 supplementation. Oral glucose tolerance testing in one patient resulted in marked changes in serum ornithine and lysine concentrations, in addition to mild glucose intolerance. Histochemical staining of punch muscle biopsies showed intracellular inclusions in type 2 muscle fibers. Tubular aggregates, approximately 60 nm in diameter and adjacent to the sarcoplasmic membrane, were seen on electron microscopy. Obligate heterozygotes had a mean serum ornithine slightly higher than normal, but there was considerable overlap with the normal range. Oral ornithine tolerance tests distinguished carriers from controls in only one of five cases. Deficient activity of ornithine ketoacid aminotransferase (OKT) in cultured skin fibroblasts was documented in all four patients. Approximately half-normal levels were found in obligate heterozygotes. In vitro response to B6 was manifest by increased OKT activity at increased concentrations of pyridoxal phosphate in fibroblasts from the patients.

261: Gunby P. Vitamin B6 appears useful in treating choroid disorder. JAMA. 1980 May 9;243(18):1792-3. No abstract available. PMID: 7365947

Acta Vitaminol Enzymol. 1980;2(5-6):171-8.

[Effect of vitamin B6 on some immune responses in chronic uremia (author's transl)]

[Article in Italian]

Sorice F, De Simone C, Meli D, Ferrari M, Morellini M, De Luca D, Taccone Gallucci M, Casciani CU.

Patients with chronic uremia undergoing periodic haemodialysis were found to have low levels of vitamin B6 (12 out of 18 patients). The same subjects also showed a reduction of the immunocompetence. The AA. report that the administration of pyridoxine (100 mg/die for 4 weeks) can induce a normalization of the vitamin levels and of some immunological parameters.

263: Cardi E. [Inborn errors of amino acid metabolism treatable with B group vitamins: synoptic aspects] Acta Vitaminol Enzymol. 1980;2(3-4):124-9. Italian. No abstract available. PMID: 7246391

Am J Clin Nutr. 1979 Oct;32(10):2040-6.

Clinical results of a cross-over treatment with pyridoxine and placebo of the carpal tunnel syndrome.

Ellis J, Folkers K, Watanabe T, Kaji M, Saji S, Caldwell JW, Temple CA, Wood FS.

Clinical evaluation was made of cross-over treatments by pyridoxine and a placebo of patient 22 having the carpal tunnel syndrome. Extraordinary monitoring of the specific activities of the erythrocyte glutamic oxaloacetic transaminase proved a severe vitamin B6 deficiency, which was partially corrected by the Recommended Dietary Allowance of 2 mg, and completely corrected by 100 mg. The severity of the syndrome diminished on the Recommended Dietary Allowances and the patient was asymptomatic at the higher dosage. On placebo, both the vitamin B6 deficiency and syndrome reappeared. Retreatment with 100 mg again corrected both the deficiency and syndrome. Measurements (total n = 19) of flexion of proximal interphalangeal joints of the index fingers by a goniometer, and of pinch by the Preston gauge revealed objective normalization. Scores of 17 symptoms revealed reductions at both the 2- (P less than 0.01) and 100-mg (P less than 0.001) dosages. Conduction through the carpal tunnels had improved by electromyography. These and previous data on a total of 22 patients showed the concomitant presence of a deficiency of vitamin B6 and the carpal tunnel syndrome; a causal relationship is apparent.

Biol Psychiatry. 1979 Oct;14(5):741-51.

A preliminary study of the effect of pyridoxine administration in a subgroup of hyperkinetic children: a double-blind crossover comparison with methylphenidate.

Coleman M, Steinberg G, Tippett J, Bhagavan HN, Coursin DB, Gross M, Lewis C, DeVeau L.

A small sample of six patients with the putative "hyperkinetic syndrome" participated in a research protocol comparing administration of pyridoxine, methylphenidate, and placeboes. The children had had low whole blood serotonin levels and a history of previous responsiveness to methylphenidate. The results of the double-blind clinical evaluation showed trends suggesting that both pyridoxine and methylphenidate were more effective than placebo in suppressing the symptoms of hyperkinesis. Pyridoxine elevated whole-blood serotonin levels, methylphenidate did not. Clinical and laboratory evidence indicated that the pyridoxine effects persisted after the 3-week period when the vitamin had been given in this experimental design.

266: Clarke TA, Saunders BS, Feldman B. Pyridoxine-dependent seizures requiring high doses of pyridoxine for control. Am J Dis Child. 1979 Sep;133(9):963-5. No abstract available. PMID: 474552

Cancer Res. 1979 Aug;39(8):2988-94.

Effects of dietary vitamin B6 on the in vitro inactivation of rat tyrosine aminotransferase in host liver and Morris hepatomas.

Reynolds RD, Morris HP.

Control rats or rats bearing Morris hepatoma 5123C (intact), 5123C (adrenalectomized), 7794A, 7800, 8999, 9121, or 9618A were fed a purified diet either deficient or adequate for vitamin B6. The concentration of pyridoxal phosphate in the plasma, host livers, and hepatomas was determined, as well as the in vitro rate of inactivation of induced tyrosine aminotransferase in homogenates of host livers and hepatomas. The results demonstrated the presence of a cysteine-independent inactivating system for tyrosine aminotransferase in hepatomas 5123C (adrenalectomized), 7800, 8999, and 9121. Only in hepatoma 9121 was there a dramatic influence of the dietary vitamin B6 on the rate of cysteine-independent inactivation. A cysteine-dependent inactivating system for the enzyme was present in all host livers and hepatomas. The rate of this in vitro inactivation for both host livers and hepatomas apparently was a function of the concentration of pyridoxal phosphate, but inactivation of tyrosine aminotransferase occurred at a significantly lower concentration of pyridoxal phosphate in the hepatomas than in the host livers.

268: Vainshtok AB. [Treatment of parkinsonism with large doses of vitamin B6] Sov Med. 1979 Jul;(7):14-9. Russian. No abstract available. PMID: 505122

Vopr Pitan. 1979 Jul-Aug;(4):32-40.

[Role of vitamin B6 in treating children with hereditary metabolic pathology]

[Article in Russian]

Barashnev IuI, Rozova IN, Semiachkina AN.

Possibilities of vitamin B6 treatment of patients with hereditary pathology of metabolism are discussed. Special attention is paid to the vitamin B6-dependent conditions characterized by elevated pyridoxine requirements. High pyridoxine doses were successfully used for the treatment of patients with hereditary vitamin B6-dependent xanthurenuria under the control of renal excretion of tryptophan metabolites (xanthurenic and kynurenic acids, kynurenin, N1-methylnicotinamide) and 4-pyridoxic acid. Interrelation was traced between the severity of the disease and the necessary pyridoxine doses. Patients with the most pronounced clinical and biochemical changes needed especially high doses of the vitamin (200 mg/day). Use of vitamin B6 in a dose of 100 mg/day in pyridoxine-dependent homocystinuria induced a remission of the biochemical parameters on the 4th day of the treatment. It is noted that the efficacy of the treatment is dependent on the timely starting of the therapy and pyridoxine doses necessary for normalization of the clinical and biochemical parameters in each patient.

Metabolism. 1979 May;28(5):542-8.

Primary oxalosis: clinical and biochemical response to high-dose pyridoxine therapy.

Will EJ, Bijvoet OL.

Although pyridoxine hydrochloride (vitamin B6) is known to reduce the endogenous production of oxalate in some individuals with primary oxalosis, the dose for a satisfactory trial of treatment is not established. We report two cases of primary oxalosis on a daily regimen of 1 g pyridoxine hydrochloride, in which 24-hr urinary oxalate excretion decreased by 60% and 70%, respectively, with corresponding clinical benefit. The responses have been sustained up to 2.5 yr in one case, and 20 mo in the other. In the patient with renal failure, serum creatinine decreased from 243 to 146 mumole/liter after 15 mo of treatment. The decrease in glycollic acid excretion in both patients was consistent with an increase of glyoxalate transaminase activity by the vitamin. Supranormal levels of erythrocyte glutamic oxaloacetate transaminase (egot) activity were observed during therapy, and these may be useful as a measure of the effective dose of pyridoxine.

Am J Obstet Gynecol. 1979 Mar 1;133(5):499-502.

Pyridoxine treatment of chemical diabetes in pregnancy.

Gillmer MD, Mazibuko D.

Thirteen women with chemical diabetes diagnosed in late pregnancy were found to excrete excessive amounts of urinary xanthurenic acid after a tryptophan load, indicative of a relative pyridoxine (vitamin B6) deficiency. Treatment with 100 mg pyridoxine daily for 14 to 23 days restored the urinary xanthurenic acid excretion to normal in all patients. Improvement of glucose tolerance was observed in only two of the patients studied, deterioration in six, and no significant change in the remaining five. The insulin response to glucose was unaltered during pyridoxine therapy.

Proc Clin Dial Transplant Forum. 1979;9:194-6.

Water soluble vitamins in patients with chronic renal failure and effect of B6 administration of immunological activity.

Kamata K, Okubo M, Marumo F.

Blood concentrations of water soluble vitamins were studied in 29 undialyzed and 35 dialyzed patients with CRF, and 36 healthy volunteers. Effects of B6 administration on immunological parameters were studied in dialyzed patients. In dialyzed patients, whole blood B1 decreased, while plasma B2, B6 and serum B12 and folic acid increased. In undialyzed patients with uremia, plasma B2, serum B12 and folic acid increased, while plasma C decreased in patients with moderate CRF. Oral administration of B6 for 4 wks was associated with improved tuberculin skin tests and PHA mitogen responses in dialyzed patients. Supplementation of B1 is required for patients with CRF while B6 and C may be considered.

Scand J Urol Nephrol. 1979;13(1):101-3.

The influence of vitamin B6 supplementation on the bone marrow morphology in patients on regular haemodialysis treatment. A double-blind study.

Sjogren U, Thysell H, Lindholm T.

Bone marrow smears from 20 patients with chronic renal failure and on regular haemodialysis treatment (RDT) were morphologically analysed. A double-blind study of treatment with high doses of vitamin B6 showed that the patients receiving pyridoxine got raising frequencies of lymphocytes and monocytes in the bone marrow and there were morphologic signs of a normalization within the granulopoiesis. It is suggested that this is a sign of an enhancement of the immune response. The vitamin supplementation had no significant effects on the pronounced anemia of the patients.

Vopr Pitan. 1979 Jan-Feb;(1):26-32.

[Action of biotin-pyridoxine complex on the development of experimental atherosclerosis]

[Article in Russian]

Borets VM, Kishkovich VP, Lis MA, Butkevich ND, Mironchik VV.

Investigations were conducted in two series of tests on 40 rabbits. In the first series a selection of the optimal dose of the vitamins was made and in the II series the action of the optimal dose of the biotin-pyridoxine complex was studied. Each test series included 2 control groups of the animals. The biotin-pyridoxine complex (in doses of 80 gamma and 3.2 mg per 1 kg of the body mass) was shown to exert an inhibitory action on the development of experimental atherosclerosis.

Rev Neurol (Paris). 1978 Dec;134(12):797-801.

[Modifications in urinary homovanillic acid after ingestion of vitamin B6; functional study in autistic children (author's transl)]

[Article in French]

Lelord G, Callaway E, Muh JP, Arlot JC, Sauvage D, Garreau B, Domenech J.

Basing their study on the investigations which led to the dopaminergic theory of the psychoses, the authors studied homovanillic acid (principal derivative from dopamine) levels in the urines of 37 autistic children, and 11 normal children acting as controls. The favourable action of vitamin B6 on autism, reported by anglosaxon authors, was confirmed in 15 of the children. Furthermore, vitamin B6 reduces homovanillic acid levels in 33 autistic chilren and increases them in all the control group children.

Am J Med. 1978 Oct;65(4):655-60.

Response to pyridoxine hydrochloride in refractory anemia due to myelofibrosis.

Rojer RA, Mulder NH, Nieweg HO.

Eleven of 14 patients with primary myelofibrosis were given a therapeutic trial with 250 mg of pyridoxine hydrochloride daily because of refractory anemia. The effect on the hemoglobin level and the hematocrit value was studied and compared to that in a group of untreated patients with the same degree of anemia. Six of 11 treated patients responded within three months with a rise in the hemoglobin level (at least 3 g/100 ml) and/or an increase in the hematocrit value (at least 10 per cent), and transfusions were no longer required. Deliberate discontinuation of pyridoxine treatment in one responding patient was followed by a relapse of the anemia; resumption of therapy once again induced an erythropoietic response. Spontaneous remissions of anemia were not observed in the untreated group. It is concluded that a trial with pyridoxine is warranted in patients with myelofibrosis and refractory anemia.

Am J Clin Nutr. 1978 Aug;31(8):1383-91.

Vitamin B6 status of the hospitalized aged.

Vir SC, Love AH.

Nutritional status of vitamin B6 was investigated in two groups of 102 hospitalized aged. Vitamin B6 intake was estimated. Erythrocyte glutamic-pyruvic transaminase stimulation in vitro with pyridoxal phosphate and SGOT were studied as the biochemical criteria of vitamin B6 status: 18.6% of the subjects consumed less than 0.66 mg of vitamin B6 per day; 28.4% showed a percentage stimulation in vitro with pyridoxal phosphate of more than 15%. There was no significant correlation between basal erythrocyte glutamic-pyruvic transaminase activity and dietary protein, dietary vitamin B6 dietary vitamin B6/100 g of protein, SGOT, hemoglobin, mean corpuscular volume, and iron. All the biochemical parameters used for evaluating vitamin B6 status appeared higher in females, but no statistical difference between male and female groups was noted. Only SGOT levels of female subjects reflected their vitamin B6 status. A large individual variation of vitamin B6 requirement was indicated in both groups studied. Supplements with 2.5 mg of vitamin B6 to deficient subjects caused an increase in transaminase levels, though females showed a higher response. A higher recommended allowance of vitamin B6 for the aged male and female subjects was considered desirable.

Am J Dis Child. 1978 Aug;132(8):773-6.

A pyridoxine-dependent behavioral disorder unmasked by isoniazid.

Brenner A, Wapnir RA.

A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.

J Clin Psychiatry. 1978 Jun;39(6):573-5.

High-dose pyridoxine in tardive dyskinesia.

DeVeaugh-Geiss J, Manion L.

The clinical similarities of tardive dyskinesia and 1-dopa intoxication lend support to the post-synaptic hypersensitivity hypothesis in tardive dyskinesia. Pyridoxine, a co-factor in the decarboxylation of dopa, reverses the movement disorder of l-dopa intoxication. Although early studies of pyridoxine in tardive dyskinesia have not been encouraging, the results of the present study suggest that high doses of pyridoxine may reduce the frequency and severity of involuntary movements in tardive dyskinesia.

Nouv Rev Fr Hematol. 1978 Apr 14;20(1):99-110.

[Anemia with hypersideroblastosis during anti-tuberculosis therapy. Cure with vitamin therapy]

[Article in French]

Vives JF, Rouy JM, Wagner A, Vallat G.

The unusual occurrence of microcytic anemia with hypochromia, high iron blood levels and excess of sideroblasts in the bone marrow, observed during the treatment of tuberculosis with isoniazid and rifampicine is reported. Three particularities were noted. First, in our experience, the occurrence of this type of anemia has never been noted previously as a result of these two drugs. Secondly, the improvement of the blood abnormalities was obtained by the combined use of vitamin B6 and vitamin C. Thirdly, the anemia was associated with neuropathy, characterized by areflexia and dysesthesia, which improved with vitamin B6 therapy (but not with vitamin C). Some mechanisms are discussed as being possibly the origin of this kind of anemia, particularly a lack of vitamin B6 resulting from a massive urinary loss of pyridoxal induced by isoniazid as well as both a tissue depletion and an overconsumption of this vitamin. The anemia may be the consequence of a deficiency of hemoglobin synthesis involving probably the first step of the biosynthesis of heme.

Am J Psychiatry. 1978 Apr;135(4):472-5.

The effect of high doses of vitamin B6 on autistic children: a double-blind crossover study.

Rimland B, Callaway E, Dreyfus P.

The authors used data from an earlier nonblind study to identify 16 autistic-type child outpatients who had apparently improved when given vitamin B6 (pyridoxine). In a double-blind study each child's B6 supplement was replaced during two separate experimental trial periods with either a B6 supplement or a matched placebo. Behavior was rated as deteriorating significantly during the B6 withdrawal.

Fortschr Med. 1978 Feb 9;96(6):299-300.

[Complaints in the lumbosacral region and their management with Dolo-Neurobion]

[Article in German]

Kunt T.

Many patients complaining of acute pain in the lumbosacral area suffer from affections of intrapelvic organs (urinary bladder, prostate glands, female genital-organs). The routine diagnosis in such cases is described. In 53 own patients the analgesic and anti-inflammatory effect of Dolo-Neurobion has been evaluated. It is a combination drug consisting of the neurotropic vitamins B1, B6 and B12 and the analgesic metamizole. The treatment was started parenterally in the recommended doses and continued orally. If there were definite signs of infection in the pelvic area, additional antibiotics were administered after bacteriological tests. Dolo-Neurobion showed good or excellent results in 77,4% and moderate effects in 15,1% of the patients. There were no major side-effects or intolerance.

Acta Chir Acad Sci Hung. 1978;19(4):363-72.

[Clinical studies of Magurlit granulates]

[Article in German]

Frang D, Verebelyi A, Nagy Z.

The possibilities of dissolving by means of medication uric acid and uric acid-calcium oxalate calculi are discussed. The biochemical causes of uric acid lithogenesis was studied. Due to successful pharmacotherapy the number of operations has greatly diminished in recent years. On the basis of experience gained with various citrate mixtures the authors claim that Magurlit is the most advantageous litholytic drug. Due to its magnesium and vitamin B6 content it is also suitable for the dissolution of uric acid calculi containing calcium oxalate in diffuse distribution, i.e. for the prevention of the development of stones of this type.

J Med. 1978;9(3):193-9.

Vitamin B6 responsive infantile convulsions and branched chain amino aciduria.

Scottolini AG, Woo P, Bhagavan NV.

This study reports of a case with neo-natal convulsions and branched amino-aciduria in addition to tryptophanuria. These abnormalities were promptly corrected by administration of pyridoxine.

Zh Nevropatol Psikhiatr Im S S Korsakova. 1978;78(3):402-8.

[Effect of pyridoxine on the psychopathology and pathochemistry of involutional depressions]

[Article in Russian]

Bukreev VI.

In agreement with the catecholamine hypotheses of affective disorders the main role in the pathogenesis of depressive states is allocated to the central "noradrenergic insufficiency". The author thinks it feasible to use pyridoxine (vit. B6) in the treatment of depressive states, inasmuch as it is involved in the process of catecholamine synthesis as a cofactor of DOPA-decarboxylase. The author examined 48 patients among which 31 were with involutional melancholia and 17 with manic-depressive psychoses, manifesting after 40 years. Along with a positive therapeutical effect there was an increase in the noradrenaline excretion and a drop in the relative adrenaline content.

Urology. 1977 Dec;10(6):556-61.

Comparisons of placebo, pyridoxine, and topical thiotepa in preventing recurrence of stage I bladder cancer.

Byar D, Blackard C.

Animal studies have shown that metabolites of tryptophan can cause bladder cancer, and human observations reveal an appreciable incidence of abnormalities of tryptophan metabolism in patients with bladder cancer. It has been suggested that pyridoxine (vitamin B6) may correct this abnormality and prevent recurrences of superficial bladder cancers. Intravesical instillation of thiotepa has been used for more than fifteen years in the treatment of superficial bladder cancer, but no controlled trials have been done. We report here a prospective clinical trial of 121 patients with Stage I bladder cancer randomized to placebo, pyridoxine, or intravesical thiotepa. The percentages of patients with recurrences over the period of study were 60.4, 46.9, and 47.4 for the three groups, respectively, and did not differ significantly. However, if patients having recurrences during the first ten months or followed up less than ten months were excluded, pyridoxine was significantly better than placebo (P = 0.03). Thiotepa significantly reduced the recurrence rate compared with placebo (P = 0.016) or pyridoxine (P = 0.015). These results suggest that a new trial of pyridoxine should be undertaken in which the tryptophan metabolites are measured and that further study of intravesical instillation of chemotherapeutic agents is warranted.

287: Otrokov AN. [New methods of vitamin B treatment of itching dermatoses in middle aged and aged patients] Vestn Dermatol Venerol. 1977 Dec;(12):62-5. Russian. No abstract available. PMID: 146980

Schweiz Med Wochenschr. 1977 Nov 5;107(44):1585-6.

[Protective effect of pyridoxilate on the hypoxic myocardium. Experimental studies]

[Article in French]

Moret PR, Lutzen U.

The protective action of piridoxilate on hypoxic myocardium has been studied on rats in acute hypoxia (isolated heart, perfused with a non-oxygenated solution) and in prolonged hypoxia (3 days at high [3454 m] altitude). Piridoxilate maintained a higher ATP level with a much lower production of lactate. The mechanisms of action of piridoxilate are probably fairly similar to those of Na dichloracetate

J Nutr. 1977 Nov;107(11):1962-8.

Increased muscle phosphorylase in rats fed high levels of vitamin B6.

Black AL, Guirard BM, Snell EE.

The present study was undertaken to test the hypothesis that muscle phosphorylase may function as a repository for vitamin B6 in the animal. Since a repository would be expected to accumulate surplus material, one would predict that phosphorylase, which contains stoichio-metric amounts or pyridoxal phosphate, would increase in muscle of animals surfeited with the vitamin. Rats were fed a vitamin B6-free diet supplemented with pyridoxine providing levels 10, 1.0 and 0.1 of those recommended by the National Research Council (NRC). At the high intake level, muscle phosphorylase and total muscle vitamin B6 increased steadily and in almost constant ratio for at least 6 weeks, whereas both alanine and aspartate transaminase increased initially, but reached a plateau within 2 weeks. At the intermediate level of pyridoxine intake, muscle phosphorylase also increased, but less rapidly than in rats fed the higher level. When vitamin B6 intake was restricted to 10% of the NRC-recommended level, no increase in phosphorylase concentration occurred during a period of 10 weeks. These results support the hypothesis that muscle phosphorylase acts as a reservoir for vitamin B6 in the animal and provide experimental evidence that muscle enzyme content expands as vitamin is accumulated during high dietary intake.

290: Korzon M, Langer H. [Requirement for pyridoxine in bronchospastic conditions in children] Pediatr Pol. 1977 Nov;52(11):1231-5. Polish. u. PMID: 593769

J Pediatr. 1977 Oct;91(4):574-7.

Free amino acids in liver of patients with homocystinuria due to cystathionine synthase deficiency: effects of vitamin B6.

Rassin DK, Longhi RC, Gaull GE.

Patients with homocystinuria due to cystathionine synthase deficiency do not have free homocystine in the liver when it is present in high concentrations in the plasma and the urine. The liver of these patients is capable of maintaining normal concentrations of cystine at a time when the plasma cystine concentration is severely reduced. There is an increase in the methionine concentration of the liver which is reduced to normal concentrations during pyridoxine therapy.

Br J Obstet Gynaecol. 1977 Jun;84(6):444-7.

Treatment of pregnancy sickness.

Wheatley D.

A double-blind comparison was undertaken between Debendox with 10mg of extra pyridoxine and placebo with 10mg of pyridoxine, in 56 women suffering from nausea and/or vomiting during the first 10 weeks of pregnancy. The results of treatment were assessed on the patient's own dialy records of:the time of nausea, the frequency of nausea, and the severity of nausea, retching and vomiting. There were statistically significant differences in favour of Debendox with extra pyridoxine in respect of the days of nausea all day (P les than 0-02), the severity of nausea (P less than 0-05) and the severity of retching (P less than 0.05).

Z Urol Nephrol. 1977 Jun;70(6):419-27.

[Animal-experiment studies on the effect of magnesium and vitamin B 6 on calcium-oxalate nephrolithiasis]

[Article in German]

Schneider HJ, Hesse A, Berg W, Kirsten J, Nickel H.

By chronic intoxication with ethylene glycol or acute intoxication by Na-glyoxalate in the animal experiment a Ca-oxalatenephrolithiasis could be produced. At this model the influence of magnesium, pyridoxine and phosphate was studied. The combination therapy of magnesium and vitamin B6 can completely prevent the formation of Ca-oxalate-microliths in the kidney. The production of a preparation with 200 mg MgO and 10 mg pyridoxine per tablet for the metaphylaxis of oxalate calculi is recommended.

Am J Obstet Gynecol. 1977 Mar 15;127(6):599-602.

Vitamin B6 treatment of gestational diabetes mellitus: studies of blood glucose and plasma insulin.

Spellacy WN, Buhi WC, Birk SA.

Thirteen women with late pregnancy gestational diabetes mellitus were tested with an intravenous glucose tolerance test and both blood glucose and plasma insulin levels were measured. Each woman was then treated with 100 mg. of vitamin B6 per day for 2 weeks and the intravenous glucose tolerance test was then repeated. There was a statistically significant improvement in the glucose tolerance curve after the vitamin B6 treatment, with a lowering of blood glucose levels at all points on the curve except for the 5 minute value. This glucose effect occurred despite an unchanged or lowered plasma insulin level. These results suggest that a relative deficiency in vitamin B6 is associated with some cases of gestational diabetes mellitus and that the replacement of this vitamin improves the metabolic state. The low vitamin B6 levels appear to alter metabolic pathways which result in a lowering of the biologic activity of endogenous insulin.

Pediatr Res. 1977 Feb;11(2):100-3.

Cystathionine beta-synthase deficiency: a qualitative abnormality of the deficient enzyme modified by vitamin B6 therapy.

Longhi RC, Fleisher LD, Tallan HH, Gaull GE.

The thermostability of cystathionine synthase and the effect of pyridoxal phosphate (PLP) on this thermostability were investigated in extracts of normal human liver and in extracts of liver, both before and during pyridoxine (vitamin B6) therapy, from members of a family with three clinically and biochemically typical, B6-responsive, synthase-deficient sibs. Incubation of crude extracts of normal liver at 55 degrees (preincubation) for 3-4 min before assay consistently resulted in a more than 2-fold increase in specific activity (activation) of cystathionine synthase (Fig. 1). With periods of preincubation longer than 4 min, thermal inactivation occurred. When PLP was added to the preincubation mixture, slightly more activation occurred in the first 3-4 min, and there was no observable loss of activity for an additional 25 min. The activation phenomenon was not observed in extracts of liver which had been obtained from three synthase-deficient sibs before therapy with vitamin B6 (Index of activation, Table 1). When extracts of liver obtained during vitamin B6 therapy were studied, however, significant activation was observed. Synthase activity in extracts of liver from the patients' parents, obligate heterozygotes for synthase deficiency, and from a potentially heterozygous sister demonstrated activation similar to that found in control liver extracts. With periods of preincubation longer than 5 min, the inactivation of synthase in liver extracts from patients receiving pyridoxine-HCl occurred at the same rate as in liver extracts from heterozygotes and from normal subjects (Index of inactivation, Table 1). PLP completely prevented heat inactivation of enzyme from normal liver.

Acta Vitaminol Enzymol. 1977;31(6):175-8.

Effect of ACP (pyridoxine-2-oxoglutarate) on CCl4 intoxication and in streptozotocin-induced ketosis in rat.

Garbin L, Plebani M, Terribile PM.

The protective effect of pyridoxine-2-oxoglutarate (ACP) was studied on CCl4-intoxicated rats. A sensitive improvement of hepatic conditions was shown in ACP-treated rats as compared with untreated ones and rats treated with 2-oxoglutarate and pyridoxine. Serum GOT, GPT, OCT activities, composition of serum proteins, liver mitochondria respiratory control index and liver microsomes oxidizing activity were tested. The antiketotic properties of ACP were also demonstrated in Streptozotocin treated rats.

Am J Clin Nutr. 1976 Dec;29(12):1376-83.

Adequacy of vitamin B6 supplementation during pregnancy: a prospective study.

Lumeng L, Cleary RE, Wagner R, Yu P-L, Li T-K.

This prospective study assesses the effect of 2.5, 4, and 10 mg of pyridoxine supplementation during pregnancy on maternal and fetal plasma levels of pyridoxal 5'-phosphate (PLP) and on the degree of coenzyme saturation (activation factor) of aspartate aminotransferase and alanine aminotransferase (alphaEGOT and alphaEGPT) in maternal erythrocytes. More than 4 mg of pyridoxine supplementation daily was required for most pregnancies to maintain maternal plasma PLP levels within the range observed during the first trimester and in the nonpregnant state. The plasma PLP concentrations in maternal and cord blood were highly correlated and indicated a dependence of fetal vitamin B6 nutrition on maternal circulating PLP. Measurements of alphaEGOT and alphaEGPT were not as reproducible as plasma PLP assays and were less sensitive and quantitative indicators. In the majority of subjects, the changes in alphaEGOT and alphaEGPT with time correlated poorly with the changes in plasma PLP. However, when the data were analyzed without regard for their dependence on time, they demonstrated a negative, linear correlation between alphaEGOT and log plasma PLP and between alphaEGPT and log plasma PLP for the group on 2.5 mg of pyridoxine and for all the subjects combined. Finally, the dietary records showed that most of the subjects consumed less than 2 mg of vitamin B6 daily from their food. The results indicate that the current Recommended Dietary Allowance for vitamin B6 during pregnancy (2.5 mg) is too low and that supplementation of this vitamin in an amount more than 4 mg daily is recommended.

J Nutr. 1976 Oct;106(10):1404-14.

Postnatal patterns of brain lipids in progeny of vitamin B-6 deficient rats before and after pyridoxine supplementation.

Thomas MR, Kirksey A.

The influence of deficient and adequate maternal intakes of pyridoxine on lipid profiles in brains of progeny at 5, 10, 15, 25 and 50 days of age was studied. The effects of supplementing deficient dams at two different times with pyridoxine on the brain development of progeny were also examined. Three groups of weanling, female rats were fed diets deficient in pyridoxine (1.2 mg pyridoxine-HC1/kg diet) and another group received a control diet (30.0 mg pyridoxine-HC1/kg diet). One deficient group and the control group were fed their diets throughout growth, gestation and lactation. Two groups of dams were fed the deficient diet through growth, gestation and until 5 or 10 days postpartum when pyridoxine was supplemented by feeding the control diet. Body and brain weights were significantly lower in 15, 25 and 50 day-old progeny of deficient dams and deficient dams supplemented at 10 days postpartum. Cerebroside content at 15 days and ganglioside content at 15 and 25 days were significantly lower in brains of pups from unsupplemented deficient dams and deficient dams supplemented at 10 days postpartum. The postnatal development of cerebroside and ganglioside levels in brain was delayed or retarded in brain of pups from unsupplemented deficient dams. Supplementation of dams fed a low level of pyridoxine (1.2 mg/kg diet) with the vitamin beginning at 5 days postpartum reversed all observed effects of the low vitamin intake on brain lipids in progeny.

J Nutr. 1976 Oct;106(10):1415-20.

Postnatal patterns of fatty acids in brain of progeny from vitamin B-6 deficient rats before and after pyridoxine supplementation.

Thomas MR, Kirksey A.

The influence of deficient and adequate maternal intakes of pyridoxine on fatty acid profiles in brains of progeny at 5, 10, and 15 days of age was studied. The effects of two different times of initiating rehabilitation of deficient dams on the brain development of progeny at 5, 10, 15, 25, and 50 days of age were also examined. Three groups of weanling, female rats were fed diets deficient in pyridoxine (1.2 mg pyridoxine-HC1/kg diet) and a fourth group received a control diet (30.0 mg pyridoxine-HC1/kg diet) throughout growth, gestation and until 5 and 10 days postpartum. Supplementation with 30.0 mg pyridoxine-HC1/kg was begun in two deficient groups at 5 and 10 days postpartum. Fatty acids C18:2, C20:4, and C22:6 in cerebellum were significantly lower in brains of 15 day-old pups from unsupplemented deficient dams compared to values for pups of control dams. Significant reductions in the omega6 fatty acids (C18:2, C20:4, and C22:4) were evident in cerebellum of 15 day-old progeny of unsupplemented deficient dams. Fatty acids C20:1 and C24:0 were not detectable in cerebellum or cerebrum of the deficient group at 15 days but were evident in other groups. Supplementation of deficient dams with vitamin B-6 at 5 and 10 days postpartum prevented the reduction of omega6 fatty acids found in deficient progeny.

Arch Dis Child. 1976 Jul;51(7):567-8.

Neonatal pyridoxine responsive convulsions due to isoniazid therapy.

McKenzie SA, Macnab AJ, Katz G.

A 17-day-old infant on isoniazid therapy 13 mg/kg daily from birth because of maternal tuberculosis was admitted after 4 days of clonic fits. No underlying infective or biochemical cause could be found. The fits ceased within 4 hours of administering intramuscular pyridoxine, suggesting an aetiology of pyridoxine deficiency secondary to isoniazid medication. Arch Dis Child. 1976 Jul;51(7):567-8.

Neonatal pyridoxine responsive convulsions due to isoniazid therapy.

McKenzie SA, Macnab AJ, Katz G.

A 17-day-old infant on isoniazid therapy 13 mg/kg daily from birth because of maternal tuberculosis was admitted after 4 days of clonic fits. No underlying infective or biochemical cause could be found. The fits ceased within 4 hours of administering intramuscular pyridoxine, suggesting an aetiology of pyridoxine deficiency secondary to isoniazid medication.

J Clin Endocrinol Metab. 1976 Jun;42(6):1192-5.

Treatment of women with the galactorrhea-amenorrhea syndrome with pyridoxine (vitamin B6).

McIntosh EN.

Three women with the galactorrhea-amenorrhea syndrome and elevated prolactin concentrations experienced a return of regular ovulatory menses within 37-94 days after starting pyridoxine treatment (200-600 mg/day). In each the galactorrhea ceased and serum prolactin levels were maintained in the normal range while taking pyridoxine. In two other women with prolonged secondary amenorrhea but without hyperprolactinemia or galactorrhea, pyridoxine at dosages up to 600 mg/day did not restore ovulatory menses. Pyridoxine treatment was also ineffective in decreasing profuse galactorrhea in one woman with normal prolactin levels and regular ovulatory menses. In the three women effectively treated with pyridoxine, the galactorrhea returned, serum prolactin levels increased, and the menses ceased after discontinuing pyridoxine. These results imply that pyridoxine, by decreasing the excessive secretion of prolactin, may be useful in the long-term medical management of women with hyperprolactinemia and the galactorrhea-amenorrhea syndrome.

Nutr. 1976 Apr;106(4):509-14.

Influence of pyridoxine supplementation on vitamin B-6 levels in milk of rats deficient in the vitamin.

Thomas MR, Kirksey A.

Levels of vitamin B-6 in milk from pyridoxine deficient dams were used as an indicator of the ability of pyridoxine to protect offspring against the effects of the deficiency. Sprague Dawley rats were fed a basal diet containing 30.0 (control) or 1.2 (deficient) mg pyridoxine-HC1/kg diet from weaning throughout growth, gestation and until 5 days postpartum. At this time, deficient dams were supplemented by a single intraperitoneal injection of 600 mug pyridoxine-HC1, or by adding 30 or 60 mg pyridoxine-HC1/kg to the diet. The vitamin B-6 content in milk form the group supplemented by injection exceeded the control level of 38.8 mug/100 ml milk 30 minutes after the injection, and reached a peak level of 110.7 mug/100 ml at 4 hours with a subsequent decline to 27mug/100 ml at 20 hours. In rats supplemented orally with 30 or 60 mg pyridoxine-HC1/kg diet, the vitamin B-6 level in the milk reached the control value in 24 and 6 hours, respectively. At 120 hours, orally supplemented dams had significantly higher levels of vitamin B-6 in the milk than control animals. Vitamin supplementation of dams by a single injection of pyridoxine-HC1 was sufficient to overcome the pyridoxine deficiency syndrome in the pups, but was not adequate for optimum growth.

Res Commun Chem Pathol Pharmacol. 1976 Apr;13(4):743-57.

Vitamin B6 deficiency in patients with a clinical syndrome including the carpal tunnel defect. Biochemical and clinical response to therapy with pyridoxine.

Ellis JM, Kishi T, Azuma J, Folkers K.

Ten individuals having a severe clinical status associated with the carpal tunnel syndrome were selected for treatment with pyridoxine. The status of vitamin B6, as pyridoxal phosphate, was determined by the specific activities of the glutamic oxaloacetic transaminase of the erythrocytes (EGOT). Before treatment, the patients showed a deficiency of vitamin B6 as determined by 1) a comparison of the specific activities of EGOT with those of a control group (P less than 0.001); and 2) a differential assay based upon the principle of unsaturation and saturation of a Coenzyme-Apoenzyme System (CAS), as applied to EGOT. These patients were treated with pyridoxine, and the specific activities of EGOT were determined after 2 and 4 weeks. Not only was there a disappearance of the deficiency of pyridoxal phosphate, but the level of EGOT activity increased 55-68% during 2-4 weeks, respectively. More apoenzyme was apparently biosynthesized, because the specific activities were significantly higher than before therapy (P less than 0.001/4 wks). Clinical evaluation showed a great improvement in their status, and anticipated surgery for some of the patients became unnecessary. It is concluded that patients with a severe syndrome including the carpal tunnel defect have a deficiency of vitamin B6, and that both the syndrome and the deficiency are relived by therapy with pyridoxine.

South Med J. 1976 Mar;69(3):294-7.

Isoniazid-induced convulsions.

Coyer JR, Nicholson DP.

Acute isoniazid overdose and toxicity may be complicated by convulsions and death. Six patients are reported, one of whom ingested simultaneously 15 gm of isoniazid and 5 gm of pyridoxine hydrochloride (vitamin B6); no convulsions resulted. In the light of this and other experience, suggestions are made for the use of pyridoxine in the treatment and prevention of acute isoniazid poisoning.

305: Spaeth GL. The usefulness of pyridoxine in the treatment of homocystinuria: a review of postulated mechanisms of action and a new hypothesis. Birth Defects Orig Artic Ser. 1976;12(3):347-57. Review. No abstract available. PMID: 782596

Folia Psychiatr Neurol Jpn. 1976;30(2):121-51.

Effects of L-dopa and vitamin B6 on electroencephalograms of schizophrenic patients: a preliminary report.

Yamauchi M.

1. To assess the therapeutic effect of low-dose L-Dopa therapy and associated EEG changes in chronic schizophrenia, 10 patients with a mean duration of illness of 12.4 years were treated with L-Dopa for a period of eight weeks during which the dosage was increased progressively from an initial level of 300 mg q.d. biweekly up to 600 mg q.d. The treatment was moderately effective in one case and slightly efficacious in one, produced no significant change in the conditions of seven patients while the remaining patient showed exacerbation; hence a noticeably low rate of improvement. There occurred no significant changes in the EEG pattern in the series of 10 patients on the average. The individual patients' responses, nevertheless, could be classified into three groups: one with no observable EEG changes, the second showing a slight degree of increase in alpha activity and the third exhibiting diminution of alpha activity in the EEG. The patients in the latter two groups all had durations of disease less than 10 years. 2. Observations were made primarily of changes in the EEG in 20 chronically schizophrenic patients with a mean duration of disease of 13 years receiving 60 mg of vitamin B6 (as pyridoxal-5'-phosphate) daily over a period of four weeks. Slight increase of alpha activity and decrease of theta activity in the EEG were noted on the average of the 20 cases, in response to the vitamin B6 therapy. The increase of alpha activity was frequently seen among patients with a duration of illness less than 10 years whose pretreatment EEG pattern had been alpha dominant (five out of 10 cases), whereas a slight ameliorative tendency of EEG was observed only in one out of 10 patients whose pretreatment EEG pattern had been slow-wave dominant. Symptomatic improvement was evident only in one of the 20 cases studied. 3. Observations were made of the therapeutic effect and associated EEG changes in eight patients receiving combined medication of 200 mg L-Dopa and 30 mg vitamin B6 (as pyridoxal-5'-phosphate) daily for a period of 12 weeks. Of these eight patients with a mean duration of disease of 18.3 years, two showed excellent response, three good and three fair; hence good to excellent responses attained in five out of the eight cases or 62.5%. A marked increase in alpha activity in the EEG occurred from the 2nd to 4th weeks onward in all eight cases. The EEG changes were likely to precede the symptomatic improvement. 4. To sum up the results of these three clinical trials, administration of L-Dopa alone resulted in practically no symptomatic improvement or EEG changes in patients with chronic schizophrenia whilst vitamin B6 administered singly as pyridoxal-5'-phosphate scarcely produced significant symptomatic improvement but brought about a slight ameliorative tendency in the EEG of such patients. Both symptomatic amelioration and EEG improvement occurred following combined medication of L-Dopa and vitamin B6...

J Nutr Sci Vitaminol (Tokyo). 1976;22(1):1-6.

Convulsive seizure induced by intracerebral injection of semicarbazide (an anti-vitamin B6) in the mouse.

Yamashita J.

The direct injection of semicarbazide (SC), an antivitamin B6 (anti-B6), into the lateral ventricle of the mouse brain induced convulsion and tremors at a smaller dose after a shorter latent period than that in systemic administration. The symptoms were prevented by pyridoxine, aminooxyacetic acid or acetone, while they enhanced by pyridoxal, pyridoxal phosphate, or some other anti-B6. In mice fed a vitamin B6 (B6)-deficient diet, convulsion and tremors occurred at smaller doses of SC than those in mice given control food, and were counteracted by pyridoxine. On the other hand, mice into which SC had been injected in the neighboring site of the lambda first showed running fits, which was followed by convulsion and tremors.

308: [No authors listed] Requirement of vitamin B6 during pregnancy. Nutr Rev. 1976 Jan;34(1):15-6. Review. No abstract available. PMID: 765894

Schweiz Med Wochenschr. 1975 Oct 11;105(41):1319-24.

[Vitamin B 6 deficiency anemia]

[Article in German]

Ofori-Nkansah N, Weissenfels I, Pribilla W.

The course of spontaneous vitamin B6 deficiency anemia in a 57-year-old woman is reported. The anemia was characterized by hypochromasia of the erythrocytes, hyperferricemia, absence of hemolysis, and hyperplastic, ineffective, sideroblastic erythropoiesis of the bone marrow. It was corrected by oral vitamin B6 therapy. On interruption of the vitamin B6 therapy the anemia relapsed. On resumption of vitamin B6 medication it responded again with normalization of the hemoglobin and erythrocytes values. The hematological remission could be maintained under longterm vitamin B6 medication. The nosological significant of this rare anemia and its differentiation from other forms of anemia are discussed.

Ann Allergy. 1975 Aug;35(2):93-7.

Pyridoxine treatment of childhood bronchial asthma.

Collipp PJ, Goldzier S 3rd, Weiss N, Soleymani Y, Snyder R.

Urinary xanthurenic and kynurenic acid levels were measured in five patients while they were receiving 50 mg and 100 mg of pyridoxine. The levels of tryptophane metabolite decreased progressively as the dose was increased but remained above basal levels. There was marked clinical improvement in these patients while receiving the higher dose only. The double-blind study with 76 asthmatic children followed for five months indicated significant improvement in asthma following pyridoxine therapy (200 mg daily) and reduction in dosage of bronchodilators and cortisone. The data suggest that these children with severe bronchial asthma had a metabolic block in tryptophane metabolism, which was benefitted by long-term treatment with large doses of pyridoxine.

Am J Obstet Gynecol. 1975 Jul 15;122(6):793.

Letter: supplementary pyridoxine given to women using oral contraceptives.

Winston F.

PIP: This letter is a response to an article describing the efficacy of administering large doses of tryptophan to depressive patients taking oral contraceptives. This letter-writer argues that the salient action of mood elevation is a result of the supplemental pyridoxine (vitamin B) which ameliorates the deficiency induced by oral contraceptive use that leads to depression resulting from inhibition of synthesis of biogenic amines in the central nervous system. Instead of large doses of tryptophan, which may cause dangerous accumulations of possibly carcinogenic and diabetogenic metabolites when therapy for depression is indicated, pyridoxine should be administered together with the tryptophan; the tryptophan should be discontinued once the deficiency is corrected, although the vitamin therapy should continue throughout oral contraceptive use.

Vopr Med Khim. 1975 May-Jun;21(3):299-306.

[Effect of pyridoxine on patterns of lipid metabolism in patients with alimentary obesity]

[Article in Russian]

Frolova IA, Oleneva VA, Sirota II, Nikiforova GD.

Studies of patients with alimentary-metabolic obesity, which were treated with pyridoxine and were maintained on a reduced diet, revealed a normalizing effect of the vitamin on some patterns of lipid metabolism. In patients, treated with pyridoxine, body weight, content of total lipids, cholesterol, phospholipids, glycerids and beta-lipoproteins in blood serum were decreased more distinctly as compared with patients, which were only maintained on a reduced diet. In hyperlipidaemia the positive effect of pyridoxine was more pronounced than in the cases with normal content of lipids in blood.

Int J Vitam Nutr Res. 1975;45(4):411-8.

[Activity studies of an iron-vitamin B6 preparation for euteral treatment of iron deficiency anemia]

[Article in German]

Reinken L, Kurz R.

In 17 respectively 15 children with iron deficiency anemia the effect of a combined orally applicated iron-vitamin B6 therapy and iron therapy only was studied. Pyridoxal phosphate, activities of pyridoxal kinase and red cell GOT, and excretion of 4-pyridoxic acid in urine were measured as indices of vitamin B6 nutriture before therapy was started, on the 3rd and 6th day with therapy and on the 1st and 4th day after therapy was stopped. Red cells, concentration of hemoglobin, reticulocytes and hematokrit were simultaneously counted, whereas serum iron had been measured once only before therapy. A group of 22 hematologically healthy children was studied as controls. After iron therapy a decrease of vitamin B6 nutriture occured as a consequence of an increased requirement for pyridoxal phosphate for heme synthesis. Additional vitamin B6 was followed by a normal vitamin B6 nutriture and a significantly accelerating effect on heme synthesis.

315: Mottram PE, Johnson PB, Hoffman JE. Isoniazid toxicity. Reversal with pyridoxine. Minn Med. 1974 Feb;57(2):81-3. No abstract available. PMID: 4813614

Am Fam Physician. 2003 Jul 1;68(1):121-8.

Nausea and vomiting of pregnancy.

Quinla JD, Hill DA.

Family Practice Residency Program, Naval Hospital, Jacksonville, Florida 32214, USA. jdquinlan@yahoo.com

Nausea and vomiting of pregnancy, commonly known as "morning sickness," affects approximately 80 percent of pregnant women. Although several theories have been proposed, the exact cause remains unclear. Recent research has implicated Helicobacter pylori as one possible cause. Nausea and vomiting of pregnancy is generally a mild, self-limited condition that may be controlled with conservative measures. A small percentage of pregnant women have a more profound course, with the most severe form being hyperemesis gravidarum. Unlike morning sickness, hyperemesis gravidarum may have negative implications for maternal and fetal health. Physicians should carefully evaluate patients with nonresolving or worsening symptoms to rule out the most common pregnancy-related and nonpregnancy-related causes of severe vomiting. Once pathologic causes have been ruled out, treatment is individualized. Initial treatment should be conservative and should involve dietary changes, emotional support, and perhaps alternative therapy such as ginger or acupressure. Women with more complicated nausea and vomiting of pregnancy also may need pharmacologic therapy. Several medications, including pyridoxine and doxylamine, have been shown to be safe and effective treatments. Pregnant women who have severe vomiting may require hospitalization, orally or intravenously administered corticosteroid therapy, and total parenteral nutrition.

Gerontology. 2003 Jul-Aug;49(4):215-24. Variations in nutritional status of elderly men and women according to place of residence.

Sibai AM, Zard C, Adra N, Baydoun M, Hwalla N.

Department of Epidemiology and Biostatistics, Faculty of Health Sciences, American University of Beirut, Lebanon.

OBJECTIVE: The purpose of this study was to assess comprehensively the nutritional status of elderly individuals in institutions and to compare it with that of community based dwellers in an urban setting in Lebanon. METHODS: Participants included 100 elderly men and women (aged 65 years and older) selected randomly from four institutions who were based on sex and neighborhood with 100 free-living individuals. Subjects were mentally and physically capable of responding to an interview schedule. Their nutritional status was assessed by anthropometric measurements, dietary food intake for a 3-day period, and hematological and biochemical variables. Energy and macro- and micronutrient intakes were compared with the US recommended dietary allowances (RDA) or dietary reference intakes (DRI) as appropriate. RESULTS: Elderly living at home had significantly higher mean body mass index and waist circumference than those living in institutions. Although the total energy intake was comparable between the two groups, the elderly in the institutions consumed more fat and had lower intake of dietary fibers. Deficiencies (below 2/3rd RDA/DRI intakes) in zinc, magnesium, alpha-tocopherol, vitamins A and D, and pyridoxine were noted in both study groups with overall higher proportions observed among the institutionalized elderly. These were also anemic (42.5%) and had low levels of albumin (27.5%). In contrast, those living at home showed a higher prevalence of obesity and a lower calcium intake. Multivariate analysis controlling for a number of potential covariates did not change the results observed. CONCLUSIONS: The results of the present study showed a higher prevalence of obesity in those living at home and varying deficiencies by place of residence with no evidence that duration of institutionalization in itself being associated with poor nutritional status. Awareness of the risks associated with these deficiencies and excesses should address the lay and health professionals working in the community and institutions alike. Copyright 2003 S. Karger AG, Basel

Indian Pediatr. 2003 Jul;40(7):633-8. Pyridoxine-dependent seizures: a review.

Rajesh R, Girija AS.

Department of Neurology, Medical College, Calicut, Kerala 673 008, India. drrajeshram@rediffmail.com

Pyridoxine-dependent seizure is a rare autosomal recessive disorder that usually presents with neonatal intractable seizures. This syndrome results from an inborn abnormality of the enzyme glutamic acid decarboxylase, which results in reduced pyridazine-dependent synthesis of the inhibitory neurotransmitter gamma amino butyric acid. The full range of symptomatology is unknown; but can be associated with autism, breath holding and severe mental retardation, bilious vomiting, transient visual agnosia, severe articulatory apraxia motor dyspraxia, microcephaly and intrauterine seizures. Parenteral pyridine injection test is a highly effective and reproducible test in confirming the diagnosis. Pyridoxine should be administered as a diagnostic test in all cases of convulsive disorders of infancy in which no other diagnosis is evident. Epileptic seizure discharges subside within 2-6 minutes after the intravenous injection of 50-100 mg of pyridaoxine. Once the diagnosis is confirmed, maintenance therapy should be continued indefinitely and doses increased with age or intercurrent illnesses. The maintenance dose of Bg needed is still not clear. There is a relatively wide range for the daily B6 dose necessary to control the seizure i.e., 10-200 mg/day.

Int J Food Sci Nutr. 2003 Jul;54(4):281-9.

Influence of a drink containing different antioxidants and Lactobacillus plantarum 299v on plasma total antioxidant capacity, selenium status and faecal microbial flora.

Onning G, Berggren A, Drevelius M, Jeppsson B, Lindberg AM, Johansson Hagslatt ML.

Biomedical Nutrition, Center of Chemistry and Chemical Engineering Lund University SE-221 00 P.O. Box 124 Lund, Sweden.

The aim of the study was to investigate whether a supplement of antioxidants to subjects with a high working pace can influence the antioxidant capacity. The study was parallel and double blind with 98 subjects randomised into two groups. One of the groups was given a test drink with antioxidants for 4 weeks (450 ml/day) while the other group took a corresponding amount of placebo drink. The test drink contained: 2 mg beta-carotene/100 ml, 40 mg alpha-tocopherol/100 ml, 80 mg ascorbic acid/100 ml, 2 mg pyridoxine/100 ml, 15 mg magnesium/100 ml, 0.2 mg manganese/100 ml, 1 mg zinc/100 ml, 0.1 mg copper/100 ml and 10 microg selenium/100 ml. Consumption of the test drink for 4 weeks increased the total plasma antioxidant capacity by 7% (ferric reducing ability of plasma method, P<0.05 compared with the placebo group), and the content of selenium and selenoprotein P in serum was raised by 16-17% (P<0.001 compared with the placebo group). No significant changes were found in the placebo group. The test drink also contained Lactobacillus plantarum 299v (5 x 10(7) cfu/ml) and 4 weeks' consumption led to a significant increase of Lb. plantarum 299v in the faeces. In conclusion, consumption of a drink rich in different antioxidants can increase the antioxidant capacity in subjects with a high working pace. This can be valuable since it may increase the protection against reactive oxygen radicals.

Kekkaku. 2003 Jul;78(7):483-6.

[Tuberculosis in patients undergoing hemodialysis]

[Article in Japanese]

Yokoyama T, Rikimaru T, Gohara R, Watanabe H, Aizawa H.

First Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume-shi, Fukuoka 830-0011, Japan. yokoyama-t@nyc.odn.ne.jp

We studied patients who were diagnosed as active tuberculosis while undergoing hemodialysis at Kurume University Hospital. The observation included immunologic and clinical features. Cellular immunity was depressed in our patients undergoing hemodialysis, as evident from the decreased numbers of lymphocytes and anergy to tuberculin skin tests with purified protein derivative (PPD). Further, in a few patients, hemodialysis was shown to eliminate IFN-gamma from the blood. Various antituberculous chemotherapy regimens have been studied in hemodialysis patients. Although the incidence and mortality of tuberculosis have been reported to be higher in hemodialysis patients than in the general population, the clinical outcome of our cases was favorable in this study. One important notice is to recognize promptly peripheral neuropathy while treating tuberculosis associated with hemodialysis, and this could be prevented by the adequate use of pyridoxine.

Blood. 2003 Jun 1;101(11):4623-4. Epub 2003 Jan 16. Late-onset X-linked sideroblastic anemia following hemodialysis.

Furuyama K, Harigae H, Kinoshita C, Shimada T, Miyaoka K, Kanda C, Maruyama Y, Shibahara S, Sassa S.

Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Japan. k-furuya@mail.cc.tohoku.ac.jp

X-linked sideroblastic anemia (XLSA) is due to deficient activity of erythroid-specific 5-aminolevulinate synthase (ALAS2). We report here a patient who developed sideroblastic anemia at the age of 81 years while undergoing hemodialysis. The diagnosis of sideroblastic anemia was established by the presence of ringed sideroblasts in the bone marrow, and treatment with oral pyridoxine completely eliminated the ringed sideroblasts. We identified a novel point mutation in the fifth exon of this patient's ALAS2 gene, which resulted in an amino acid change at residue 159 from aspartic acid to asparagine (Asp159Asn). In vitro analyses of recombinant Asp159Asn ALAS2 revealed that this mutation accounted for the pyridoxine-responsiveness of this disease. The very late onset in this case of XLSA emphasizes that nutritional deficiencies caused either by dietary irregularities in the elderly or, as in this case, by maintenance hemodialysis therapy, may uncover occult inherited enzymatic deficiencies in the heme biosynthetic pathway.

Transplantation. 2003 May 15;75(9):1551-5. Vitamin supplementation reduces the progression of atherosclerosis in hyperhomocysteinemic renal-transplant recipients.

Marcucci R, Zanazzi M, Bertoni E, Rosati A, Fedi S, Lenti M, Prisco D, Castellani S, Abbate R, Salvadori M.

Surgical and Medical Critical Care, Clinica Medica Generale e Cliniche Specialistiche, University of Florence, Italy.

BACKGROUND: We previously demonstrated among renal-transplant recipients (RTRs) a high prevalence of hyperhomocysteinemia, which might account for their elevated cardiovascular risk. The purpose of our study was to document, in hyperhomocysteinemic RTRs, the effect of vitamin supplementation on carotid intima-media thickness (cIMT), which is an early sign of atherosclerosis. METHODS: A total of 56 stable hyperhomocysteinemic RTRs were randomly assigned to vitamin supplementation (folic acid 5 mg/day; vitamin B(6) 50 mg/day; vitamin B(12) 400 microg) (group A) or placebo treatment (group B) for 6 months. All subjects underwent cardiovascular risk-factor assessment, including fasting homocysteine (Hcy) levels assay, and high resolution B-mode ultrasound to measure the intima-media thickness of common carotid arteries, at time of enrollment and after 6 months. RESULTS: Fasting Hcy levels markedly decreased in group A after treatment (21.8 [15.5-76.6] micromol/L vs. 9.3 [5.8-13] micromol/L; P<0.0001), whereas no significant changes were observed in group B (20.5 [17-37.6] micromol/L vs. 20.7 [15-34] micromol/L; P=not significant). In group A, cIMT significantly decreased after treatment (0.95+/-0.20 mm vs. 0.64+/-0.17 mm; P<0.0001). All except one patient showed a reduction of cIMT and the mean percentage of cIMT decrease was -32.2+/-12.9%. Patients with methylenetetrahydrofolate reductase (MTHFR) C677T +/+ genotype, with higher Hcy levels, had the major percentage of decrease of Hcy with respect to the other genotypes (mean decrease: MTHFR +/+ 74.8+/-5.7%; MTHFR +/- 58.1+/-10%; MTHFR -/- 56.3+/-8.6%). In hyperhomocysteinemic patients without vitamin supplementation (group B) we documented a significant increase in cIMT after 6 months (0.71+/-0.16 mm vs. 0.87+/-0.19 mm; P<0.05). In 19 of 28 subjects we observed an increase in cIMT, and in 9 of 28 the cIMT was unmodified. The mean percentage of cIMT increase was + 23.3+/-21.1%. CONCLUSIONS: Our results demonstrate a beneficial effect of the treatment of hyperhomocysteinemia by vitamin supplementation on cIMT in a group of RTRs.

Pacing Clin Electrophysiol. 2003 May;26(5):1289-91. Electrocardiographic changes due to pyridoxine deficiency.

Malmierca E, Polo J, Castro JR.

Fundacion Jimenez Diaz, Madrid, Spain. edumalmi@yahoo.es

A young woman presented with marked alterations in the ECG without cardiological symptoms or evidence of structural heart disease after further evaluation. There was evidence of vitamin deficiency and the ECG normalized after 10 days of treatment with vitamins. Similar alterations have been described in several experimental studies with rats, but this is the first case reported in humans.

J Agric Food Chem. 2003 Apr 23;51(9):2733-6. Inhibition of diphenolase activity of tyrosinase by vitamin b(6) compounds.

Yokochi N, Morita T, Yagi T.

Department of Bioresources Science, Faculty of Agriculture, Kochi University, Monobe-Otsu 200, Nankoku, Kochi 783-8502, Japan.

The vitamin B(6) compounds pyridoxine (PN), pyridoxamine (PM), pyridoxal (PL), and pyridoxamine 5'-phosphate (PMP) inhibited the diphenolase activity of mushroom tyrosinase. PM showed the highest inhibition; the control activity was inhibited by 38% at 1.5 mM. Each PL, PN, and PMP showed about 30% inhibition at the same concentration. Lineweaver-Burk plots showed that PM and PN were mixed-type inhibitors with K(I) values of 4.3 and 5.2 mM, respectively. Because PM and PN cannot form a Schiff base with a primary amino group of the enzyme, their inhibition is not attributable to the formation of the Schiff base. Alternatively, their quenching function of reactive oxygen species (ROS) was postulated to be responsible for the inhibition. Thus, the inhibitory effect of ROS was examined. The representative singlet oxygen quenchers l-histidine, sodium azide, Trolox, and anthracene-9,10-dipropionic acid (AAP) inhibited the activity. The specific scavenger of superoxide, proxyl fluorescamine, also inhibited the activity. The scavengers of hydroxyl radical, d-mannitol and dimethyl sulfoxide, showed no inhibition. The fluorescence of AAP was decayed during the diphenolase reaction, and PM inhibited the decay. AAP was also a mixed-type inhibitor. The results showed that the vitamin B(6) compounds inhibited the diphenolase activity by quenching ROS (probably singlet oxygen) generated during some reaction step of the diphenolase reaction.

Biochim Biophys Acta. 2003 Apr 11;1647(1-2):225-9. Neuroprotective actions of pyridoxine.

Dakshinamurti K, Sharma SK, Geiger JD.

Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, 770 Bannatyne Avenue, Winnipeg, Manitoba, Canada MB R3E 0W3. dakshin@cc.umanitoba.ca

Electroencephalographic recordings in cerebral cortex of mice given a single sub-convulsive dose of domoic acid exhibited typical spike and wave discharges. Administration of the anti-epileptic drugs sodium valproate, nimodipine, or 5 alpha-pregnan 3 alpha-ol-20-one as well as pyridoxine simultaneously with or after domoic acid treatment resulted in significantly less spike and wave activity. Administration of these same drugs 45 min prior to the administration of domoic acid also significantly reduced EEG background. Mechanistically, sodium valproate and pyridoxine significantly attenuated domoic acid-induced increase in levels of glutamate, increase in levels of calcium influx, decrease in levels of gamma-aminobutyric acid and increase in levels of the protooncogenes c-fos, jun-B and jun-D. In hippocampal cells, domoic acid-induced increases in glutamate and calcium influx were significantly decreased by pyridoxal phosphate or nimodipine. Similarly in neuroblastoma-glioma hybrid cells (NG 108/15), pyridoxine attenuated domoic acid-induced increases in glutamate, influx of extracellular calcium, and enhanced induction of oncoproteins regardless of whether cells were undifferentiated, differentiated or de-differentiated. Pyridoxine has anti-seizure and neuroprotective actions mediated through mechanisms similar to those targeted by current therapeutic strategies.

Biochim Biophys Acta. 2003 Apr 11;1647(1-2):127-30. Antitumor effect of vitamin B6 and its mechanisms.

Komatsu S, Yanaka N, Matsubara K, Kato N.

Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.

Epidemiological studies have reported an inverse association between vitamin B(6) intake and colon cancer risk. Our recent study has been conducted to examine the effect of dietary vitamin B(6) on colon tumorigenesis in mice. Mice were fed diets containing 1, 7, 14 or 36 mg/kg pyridoxine for 22 weeks, and given a weekly injection of azoxymethane (AOM) for the initial 10 weeks. Compared with the 1 mg/kg pyridoxine diet, 7, 14 and 35 mg/kg pyridoxine diets significantly suppressed the incidence and number of colon tumors, colon cell proliferation and expressions of c-myc and c-fos proteins. Supplemental vitamin B(6) lowered the levels of colonic 8-hydroxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE, oxidative stress markers) and inducible nitric oxide (NO) synthase protein. In an ex vivo serum-free matrix culture model using rat aortic ring, supplemental pyridoxine and pyridoxal 5'-phosphate (PLP) had antiangiogenic effect. The results suggest that dietary vitamin B(6) suppresses colon tumorigenesis by reducing cell proliferation, oxidative stress, NO production and angiogenesis.

Biochim Biophys Acta. 2003 Apr 11;1647(1-2):36-41. Pyridoxine-dependent seizures: a clinical and biochemical conundrum.

Baxter P.

Ryegate Centre Paediatric Neurology, Sheffield Childrens Hospital, Tapton Crescent Road, Sheffield S10 5DD, UK. p.s.baxter@shefffield.ac.uk

Pyridoxine-dependent seizures have been recognised for 40 years, but the clinical and biochemical features are still not understood. It is a rare recessively inherited condition where classically a baby starts convulsing in utero and continues to do so after birth, until given pyridoxine. Many of these early onset cases also have an acute encephalopathy and other clinical features. Late onset cases are now recognised with a less severe form of the condition. Seizures can break through with intercurrent illness but otherwise remain controlled on pharmacologic doses of pyridoxine. The long-term outcome is affected by several factors including whether onset is early or late and how soon pyridoxine is given. Biochemical studies have been sparse, on very small numbers. There does not appear to be any defect in the uptake or metabolism of pyridoxine or pyridoxal phosphate (PLP). For a long time glutamic acid decarboxylase (GAD), a pyridoxal-dependent enzyme, has been suspected to be the abnormal gene product, but glutamate and gamma-aminobutyric acid (GABA) studies on the cerebrospinal fluid (CSF) have been contradictory and recent genetic studies have not found any linkage to the two brain isoforms. A recent report describes raised pipecolic acid levels in patients but how this ties in is unexplained.

Biochim Biophys Acta. 2003 Apr 7;1621(1):1-8. ESR study of a biological assay on whole blood: antioxidant efficiency of various vitamins.

Stocker P, Lesgards JF, Vidal N, Chalier F, Prost M.

Institut Mediterranee de Recherche en Nutrition, Service 332, Centre de St-jerome, 13397 cedex 20, Marseille, France. P.stocker@univ.u-3mrs.fr

This study deals with the activity of various vitamins against the radical-mediated oxidative damage in human whole blood. We have used a biological method that allows both the evaluation of plasma and that of red blood cell resistance against the free radicals induced by 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH). Spin trapping measures using mainly 5-(diethoxyphosphoryl)-5-methyl-1-pyrolline N-oxide nitrone (DEPMPO) were carried out under several conditions to identify the free radicals implicated in this test. Only the oxygenated-centred radical generated from AAPH was found highly reactive to initiate red blood cell lysis. With DEPMPO only alkoxyl radicals were observed and no evidence was found for alkylperoxyl radicals. The antioxidant activity of several lipid- and water-soluble vitamins has been assessed by the biological assay and through two chemical methods. We have noticed high antioxidant activities for tocopherols (in the order delta>gamma>alpha) in the biological test but not through chemical methods. At 1 microM, the delta-tocopherol efficiency in inhibiting radical-induced red blood cell hemolysis was three times as high as the alpha-tocopherol efficiency. For beta-carotene no significant activity even in whole blood was shown. Highly surprising antioxidant activities were observed for acid folic and pyridoxine, compared to ascorbic acid. At 10 microM, the effectiveness of folic acid was almost three times as high as vitamin C. The biological test seems clinically more relevant than most other common assays because it can detect several classes of antioxidants.

Space Med Med Eng (Beijing). 2003 Apr;16(2):79-82.

Effects of dietary supplementation of certain nutrients on maze performance and biochemical indices in mice after exposure to high +Gz.

Yang CL, Jin YB, Yu H, Yi CR, Cheng J, Zhan H.

Institute of Aviation Medicine, The Air Force, Beijing, China.

Objective: To explore the possible effects of nutritional supplements on brain function as reflected by Water Maze test performance in mice after +Gz exposure. Method: Mice were arranged into control group (group A), +Gz group without nutritional supplementation (group B) and +Gz plus nutritional supplementation group (group C). Each group contains 12 mice. Mice in group A were not exposed to +Gz while mice in both group B and group C were exposed to 8 min + 10 Gz. Distilled water was gavaged to group B mice 3 h before +Gz exposure. On the day before +Gz exposure pyridoxol fortified water was given and 3 h before exposure mixed amino acids solution were gavaged to group C mice. Water Maze test was done and scores were recorded in all groups. After the Water Maze test was completed, blood was collected through the eyes for serum amino acid determinations and brain tissue was collected by decollation for monoamine determination and gamma-glutamyl transferase (GGT) activity evaluation. Result: After +Gz exposure, longer completion time and more mistakes were observed in Water Maze test in group B as compared with group A and a trend of improvement in group C was noticed. The ratio of brain 5-HT to dopamine (DA) was significantly reduced in group C as compared with group B. Gamma glutamyl transferase (GGT) activity in brain tissue in group C and group B increased significantly. Conclusion: High sustained +Gz exposure significantly reduces Water Maze test performance in mice (longer completion time and more mistakes). It seems that there is a trend of improvement in Water Maze performance in mice in dietary nutritional supplementation group, which might be due to significant reduction in ratio of brain 5-HT to DA in mice with nutritional supplementation.

Med Sci Monit. 2003 Mar;9(3):CR147-51. Is there any relationship between lipids and vitamin B levels in persons with elevated risk of atherosclerosis?

Wasilewska A, Narkiewicz M, Rutkowski B, Lysiak-Szydlowska W.

Department of Clinical Nutrition, Institute of Internal Medicine, Medical University, Gdansk, Poland. awasil@amg.gda.pl

BACKGROUND: There is increasing evidence that plasma homocysteine level is an independent risk factor for atherosclerosis. Low levels of serum folates, cobalamin and pyridoxine are associated with increased risk of cardiovascular disease. Most dietary products contain cholesterol as well as methionine, so hyperlipidemia could be associated with a higher level of homocysteine and inversely with lower levels of B vitamins. The aim of this study was to investigate the differences in levels of lipids and vitamins affecting homocysteine metabolism in different groups of patients. MATERIAL/METHODS: We examined 38 healthy persons, 55 patients hospitalised for cardiac surgery, and 62 patients without clinical evidence of atherosclerosis but with one of the atherosclerosis risk factors (hypercholesterolemia, NIDDM or chronic renal insufficiency). The levels of total cholesterol, triglycerides, vitamin B12, folic acid and vitamin B6 index in serum were determined using routine laboratory methods. RESULTS: We found no association between lipids and B vitamins in any examined group. There were significant differences between concentrations of analysed parameters in all groups of patients as compared to controls. CONCLUSIONS: The lack of correlation between the levels of lipid parameters and B vitamins in serum indicates that these may be independent, additional risk factors for atherosclerosis. Higher vitamin B6 deficiency in dialysis patients is probably caused by low intake combined with the increased requirements of uremic patients. Permanent monitoring of B vitamins in serum is necessary in patients with elevated risk of atherosclerosis, as well as long-term education, careful diet planning and supplementation.

Brain Res Bull. 2003 Feb 15;59(6):421-7. Loss of dendritic connectivity in CA1, CA2, and CA3 neurons in hippocampus in rat under aluminum toxicity: antidotal effect of pyridoxine.

Sreekumaran E, Ramakrishna T, Madhav TR, Anandh D, Prabhu BM, Sulekha S, Bindu PN, Raju TR.

Department of Life Sciences, University of Calicut, Kerala, India.

Aluminum chloride (AlCl(3); 4 mg/kg) was injected into the cerebrospinal fluid of adult rats as a one time dose. Rapid Golgi stained sections of hippocampus were examined for detailed histology of neurons in CA1, CA2, and CA3 areas. The axonal length and number of dendritic branches were seen reduced 30 days later in aluminum (Al)-injected group when compared to vehicle-injected controls. Of these perturbations, dendritic branches were seen reduced significantly. Al toxicity apparently affects neuronal connectivity in hippocampus. These perturbations are reversed by supplementing the feed with pyridoxine (8 mg/kg) for 30 days. As the loss of synaptic connectivity is a predominant feature of neurodegenerative disorders such as Alzheimer disease, this study may have implications in such disorders. Pyridoxine may be considered as a potent antidote to Al toxicity and neurodegenerative disorders such as Alzheimer disease.

J Child Neurol. 2003 Feb;18(2):142-3.

Do not overlook acute isoniazid poisoning in children with status epilepticus.

Caksen H, Odabas D, Erol M, Anlar O, Tuncer O, Atas B.

Department of Pediatrics, Yuzuncu Yyl University, Faculty of Medicine, Van, Turkey. huseyincaksen@hotmail.com

A previously healthy 2-year-old girl was admitted with generalized convulsive status epilepticus. She was in a stupor and could respond only to painful stimuli. She also had severe metabolic acidosis. Although initial liver function tests were normal, they were found to be moderately high on the fifth day of admission; however, they dropped to their normal ranges on the twelfth day of admission. Initially, the patient was diagnosed as having idiopathic status epilepticus, and classic anticonvulsant agents, including diazepam, phenytoin, and then phenobarbital, were given. However, her seizures did not subside, and diazepam infusion was initiated. After initiation of diazepam infusion, the seizures were completely controlled. On the fourth day of admission, her parents said that she had accidentally received 20 tablets (a total dose of 2000 mg) of isoniazid just before admission to our hospital. Later, we injected 200 mg of pyridoxine intravenously. During follow-up, her general condition improved, and anticonvulsant agents were discontinued because an electroencephalogram was found to be norma. She was discharged from the hospital on the twelfth day of admission. At the fourth month of follow-up, she was seizure free. Because of this case, we would like to re-emphasize that acute isoniazid poisoning should also be considered in a child with unexplained status epilepticus.

Nephrol Dial Transplant. 2003 Feb;18(2):273-9. Primary hyperoxaluria type 1 in The Netherlands: prevalence and outcome.

van Woerden CS, Groothoff JW, Wanders RJ, Davin JC, Wijburg FA.

Laboratory for Genetic Metabolic Diseases, Department of Clinical Chemistry, Emma Children's Hospital AMC, 1100 DD Amsterdam, The Netherlands.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a phenotypically heterogeneous disease. To date the relationship between biochemical parameters and outcome is unclear. We therefore undertook a national cohort study on biochemical and clinical parameters and outcome in PH1. METHODS: Review of medical charts of all Dutch PH1 patients, who were identified by sending questionnaires to all Dutch nephrologists for children and adults. RESULTS: Fifty-seven patients were identified. The prevalence and incidence rates were 2.9/10(6) and 0.15/10(6)/year, respectively. Median age at diagnosis was 7.3 years (range 0-57). Seventeen (30%) patients were older than 18 years at time of diagnosis, of whom 10 (59%) presented with end-stage renal disease (ESRD), in contrast to only nine (23%) of those aged under 18 years. Median age at initial symptoms was 6.0 years (range 0-50). In four of nine patients with infantile PH1, normal renal function was preserved after a median follow-up of 7.7 years (range 0.1-16). Progression to renal insufficiency was associated with the presence of nephrocalcinosis, as assessed by ultrasound (relative risk=1.8; 95% CI, 1.0-3.4) and with pyridoxine-unresponsiveness (relative risk=2.2; 95% CI, 1.1-4.2) but not with age at presentation, the extent of hyperoxaluria, or AGT activity. No apparent nephrocalcinosis was found in five of the 19 patients who presented with ESRD. CONCLUSIONS: Although more than one-half of the PH1 patients have symptoms under the age of 10 years, PH1 can present at any age. In adults, PH1 presents predominantly with ESRD, which may be due to misinterpretation of early symptoms. Although nephrocalcinosis is correlated with development of renal insufficiency, the latter can occur even in the absence of nephrocalcinosis. Pyridoxine sensitivity is associated with better outcome in PH1.

Clin Chem. 2003 Jan;49(1):155-61. Plasma vitamin B6 vitamers before and after oral vitamin B6 treatment: a randomized placebo-controlled study.

Bor MV, Refsum H, Bisp MR, Bleie O, Schneede J, Nordrehaug JE, Ueland PM, Nygard OK, Nexo E.

Department of Clinical Biochemistry AKH, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus C, Denmark. vakbor@hotmail.com

BACKGROUND: Vitamin B(6) has attracted renewed interest because of its role in homocysteine metabolism and its possible relation to cardiovascular risk. We examined the plasma B(6) vitamers, pyridoxal 5'-phosphate (PLP), pyridoxal (PL), pyridoxine (PN), and 4-pyridoxic acid (4-PA) before and after vitamin B(6) supplementation. METHODS: Patients (n = 90; age range, 38-80 years) undergoing coronary angiography (part of the homocysteine-lowering Western Norway B-Vitamin Intervention Trial) were allocated to the following daily oral treatment groups: (A), vitamin B(12) (0.4 mg), folic acid (0.8 mg), and vitamin B(6) (40 mg); (B), vitamin B(12) and folic acid; (C), vitamin B(6); or (D), placebo. EDTA blood was obtained before treatment and 3, 14, 28, and 84 days thereafter. RESULTS: Before treatment, PLP (range, 5-111 nmol/L) and 4-PA (6-93 nmol/L) were the predominant B(6) vitamers identified in plasma. During the 84-day study period, the intraindividual variation (CV) in patients not treated with vitamin B(6) (groups B and D) was 45% for PLP and 67% for 4-PA. Three days after the start of treatment, the increases in concentration were approximately 10-, 50-, and 100-fold for PLP, 4-PA, and PL, respectively. No significant additional increase was observed at the later time points. The PLP concentration correlated to the concentrations of 4-PA and PL before treatment, but not after treatment. The PL concentration correlated with 4-PA before and after treatment. CONCLUSIONS: Vitamin B(6) treatment has an immediate effect on the concentrations and the forms of B(6) vitamers present in plasma, and the changes remain the same during prolonged treatment. Our results suggest that the B(6) vitamers in plasma reflect vitamin B(6) intake.

Am Acad Nurse Pract. 2003 Jan;15(1):18-22.

Carpal tunnel syndrome: current theory, treatment, and the use of B6.

Holm G, Moody LE.

University of South Florida, USA. dr.g.holm@usfaccess.com

PURPOSE: To present the current state of the science of pathophysiology, assessment and treatment of carpal tunnel syndrome, including the use of pyridoxine (B6). DATA SOURCES: Selected research articles, texts, Websites, personal communications with experts, and the authors' own clinical experience. CONCLUSIONS: Much is yet to be learned about carpal tunnel syndrome. While the basic treatment of NSAIDs and nighttime splints seems universally accepted, much controversy remains. The use of vitamin B6 as a treatment is one such controversy requiring further investigation. IMPLICATIONS FOR PRACTICE: Current treatment for carpal tunnel syndrome should include NSAIDs, nighttime splinting, ergonomic workstation review, and vitamin B6 200 mg per day.

J Inherit Metab Dis. 2003;26(2-3):259-65. Classical homocystinuria: vascular risk and its prevention.

Yap S.

National Center for Inherited Metabolic Disorders, The Children's University Hospital, Temple Street, Dublin 1, Ireland. sufin.yap@tsch.ie

Homocystinuria due to cystathionine beta-synthase deficiency is the second most treatable aminoacidopathy. The reported incidence varies from 1 in 344,000 worldwide to 1 in 65,000 in Ireland. Untreated patients with homocystinuria have severe hyperhomocysteinaemia. Amongst its pathological sequelae, which include mental retardation, ectopia lentis and osteoporosis, vascular events remain the major cause of morbidity and mortality in untreated patients. Recognized modalities of treatment include pyridoxine, in combination with folic acid and vitamin B12; methionine-restricted, cystine-supplemented diet; and betaine. The natural history of vascular events is such that half will have an event before age 30 years and there is a predicted one event per 25 years at the time of maximal risk. In 158 patients with 2822 patient-years of treatment, there would be a predicted 112 events if left untreated, but instead only 17 vascular events were recorded during treatment (relative risk 0.09, 95% CI 0.036 to 0.228; p < 0.0001). Appropriate chronic treatment to lower hyperhomocysteinaemia is effective in reducing the potentially life-threatening vascular risk in patients with homocystinuria. These findings may also have relevance to the significance of mild hyperhomocysteinaemia that is commonly found in patients with premature vascular disease.

Free Radic Biol Med. 2002 Dec 15;33(12):1615-21.

Effect of high-glucose levels on protein oxidation in cultured lens cells, and in crystalline and albumin solution and its inhibition by vitamin B6 and N-acetylcysteine: its possible relevance to cataract formation in diabetes.

Jain AK, Lim G, Langford M, Jain SK.

Caddo Magnet High School, Shreveport, LA 71130, USA. sjain@lsuhsc.edu

Diabetic patients have elevated levels of glucose in their blood and other body fluids. This project studied the effect of high-glucose concentrations (HG) on the protein oxidation in cultured lens cells and in crystalline protein solution. In addition, we also examined the effect of HG on the oxidation and turbidity (aggregation) of albumin protein solution. This study also examined whether vitamin B6 [pyridoxine (P), pyridoxamine (PM)] or n-acetylcysteine (NAC) is capable of preventing protein oxidation similar to that seen in cataracts. For cell culture studies, rabbit lens cells were cultured in control or HG medium at 37 degrees C for 2 d. For studies with protein solution, a buffered solution of serum albumin or crystalline protein was incubated with normal glucose (5 mM) or HG (50-100 mM) in a water bath at 37 degrees C for 4 d. All treatments were carried out with and without the addition of P, PM, or NAC. We found significantly higher levels of carbonyl protein (an index of protein oxidation) in HG-treated compared with normal glucose-treated lens cells and in crystalline protein solution. P, PM, and NAC significantly decreased the protein oxidation in lens cells and crystalline protein solution. We also found significantly higher levels of protein oxidation and turbidity (an index of protein aggregation) and its inhibition by P, PM, and NAC in HG-treated compared with normal glucose-treated albumin solution. This suggests that HG can cause the oxidation and modification of proteins in the lens, and that vitamin B6 and NAC supplementation may be helpful in slowing the oxidation of lens proteins. This study explains the cause of early cataract development and the potential benefit of supplementation with vitamin B6 and NAC in the prevention of the development of cataract among the diabetic population.

Altern Med Rev. 2002 Dec;7(6):472-99.

Autism, an extreme challenge to integrative medicine. Part 2: medical management.

Kidd PM.

Autism and allied autistic spectrum disorders (ASD) present myriad behavioral, clinical, and biochemical abnormalities. Parental participation, advanced testing protocols, and eclectic treatment strategies have driven progress toward cure. Behavioral modification and structured education are beneficial but insufficient. Dietary restrictions, including removal of milk and other casein dairy products, wheat and other gluten sources, sugar, chocolate, preservatives, and food coloring are beneficial and prerequisite to benefit from other interventions. Individualized IgG or IgE testing can identify other troublesome foods but not non-immune mediated food sensitivities. Gastrointestinal improvement rests on controlling Candida and other parasites, and using probiotic bacteria and nutrients to correct dysbiosis and decrease gut permeability. Detoxification of mercury and other heavy metals by DMSA/DMPS chelation can have marked benefit. Documented sulfoxidation-sulfation inadequacies call for sulfur-sulfhydryl repletion and other liver p450 support. Many nutrient supplements are beneficial and well tolerated, including dimethylglycine (DMG) and a combination of pyridoxine (vitamin B6) and magnesium, both of which benefit roughly half of ASD cases. Vitamins A, B3, C, and folic acid; the minerals calcium and zinc; cod liver oil; and digestive enzymes, all offer benefit. Secretin, a triggering factor for digestion, is presently under investigation. Immune therapies (pentoxifyllin, intravenous immunoglobulin, transfer factor, and colostrum) benefit selected cases. Long-chain omega-3 fatty acids offer great promise. Current pharmaceuticals fail to benefit the primary symptoms and can have marked adverse effects. Individualized, in-depth clinical and laboratory assessments and integrative parent-physician-scientist cooperation are the keys to successful ASD management.

J Child Neurol. 2002 Dec;17 Suppl 3:3S9-13; discussion 3S14.

Infantile epileptic syndromes and metabolic etiologies.

Vigevano F, Bartuli A.

Division of Neurology, Bambino Gesu Children's Hospital, Rome, Italy. vigevano@opbg.net

Inherited metabolic disorders can cause onset of epilepsy in the first year of life. Epilepsy rarely dominates the clinical presentation, which is more frequently associated with other neurologic symptoms, such as mental retardation, hypotonia and/or dystonia, or vigilance disturbances. The pathogenesis of seizures is multifaceted; inherited metabolic disorder can affect the balance between excitatory and inhibitory chemical mediators, eliminate an energetic substrate at the cerebral level, cause in utero brain malformation, or provoke acute brain lesions. Some clinical disorders that strongly suggest particular metabolic etiologies can be identified. For example, specific clinical signs and findings on electroencephalogram (EEG) are characteristic of pyridoxine-dependent seizures, and inherited metabolic disorders associated with early myoclonic encephalopathy are well defined. In most cases, however, epilepsy secondary to inherited metabolic disorders presents with polymorphic clinical and EEG features that are difficult to classify into precise epileptic syndromes. Common characteristics of these seizures include onset in the first months of life; usually partial, multifocal; simple partial motor semiology; successive appearance of tonic seizures, spasms, and massive myoclonus; and resistance to antiepilepsy drugs. Inherited metabolic disorders must be considered in patients presenting with epilepsy and progressive neurologic worsening.

J Nutr. 2002 Dec;132(12):3603-6. Occupancy of glycoprotein IIb/IIIa by B-6 vitamers inhibits human platelet aggregation.

Chang SJ, Chang CN, Chen CW.

Department of Biology, National Cheng Kung University, Tainan, Taiwan. sjchang@mail.ncku.edu.tw

Vitamin B-6 inhibits platelet aggregation. However, the effect of the occupancy of GPIIb/IIIa, a major receptor responsible for aggregation on platelet membranes, by B-6 vitamers on platelet aggregation is unknown. This study was carried out to quantify GPIIb/IIIa occupancy in platelets treated with B-6 vitamers [pyridoxal-5-phosphate (PLP); pyridoxal (PL); pyridoxine (PN); pyridoxamine (PM)], using a monoclonal antibody-based assay, by flow cytometry. Antibody binding was compared with inhibition of platelet aggregation. PLP, PL, PN and PM occupied GPIIb/IIIa with dissociation constants of 1.83 +/- 1.15, 19.43 +/- 7.86, 3.63 +/- 1.67 and 10.89 +/- 2.93 mmol/L, respectively. Occupancy of GPIIb/IIIa by the four B-6 vitamers was negatively correlated with platelet aggregation (r = -0.90 to -0.94, P < 0.001). The concentrations of the four B-6 vitamers that inhibited maximal platelet aggregation were in the order of PLP < PN <PM < PL, the same order in which they occupied > or =80% of the GPII/IIIa receptor. Platelet aggregation was inhibited by B-6 vitamers via the occupancy of GPIIb/IIIa with the potency of PLP > PN > PM > PL.

Magnes Res. 2002 Dec;15(3-4):179-89.

Effect of magnesium supplementation containing mineral bishofit (MgCl2 x 6H2O) solution and pyridoxine hydrochloride on erythrocyte magnesium depletion and behaviour of rats after three-month alcoholization.

Iezhitsa IN, Onishchenko NV, Churbakova NV, Parshev VV, Petrov VI, Spasov AA.

Medical Academy, Research Institute of Pharmacology, 1 Pavshikh Bortsov sq., Volgograd, 400066 Russia. Farm@interdacom.ru

In therapy it is known that the combination of vitamin B6 and magnesium is beneficial in the treatment of several forms of primary magnesium deficiency. The purpose of the present study was to investigate the effect of complex magnesium supplementation containing mineral bishofit solution (MgCl2 x 6H2O) and pyridoxine hydrochloride on behavioural and biochemical parameters of magnesium-deficient alcoholic rats. A complex magnesium supplementation containing mineral bishofit solution and pyridoxine hydrochloride led both to restoration of magnesium level, and to some correction of behavioural disturbances of animals during chronic alcoholization.

Eur J Clin Nutr. 2002 Nov;56(11):1087-93. Biochemical deficiency of pyridoxine does not affect interleukin-2 production of lymphocytes from patients with Sjogren's syndrome.

Tovar AR, Gomez E, Bourges H, Ortiz V, Kraus A, Torres N.

Department of Physiology of Nutrition, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico, Mexico. artovar@quetzal.innsz.mx

BACKGROUND: There is evidence that pyridoxine deficiency may alter the immune response. It is not known whether a deficiency of this vitamin is evident in subjects with primary Sjogren's syndrome (SS). OBJECTIVE: We studied whether subjects with primary SS showed a biochemical deficiency of pyridoxine, and if it is associated with abnormal production of interleukin-2 from lymphocytes stimulated in vitro with phytohemagglutinin (PHA). DESIGN: Two studies were conducted, (i) biochemical and nutritional assessments were performed in a cross-over study in subjects with primary SS, who were supplemented with 25 mg/day of pyridoxine or placebo for 3 months. After 1 month washout, they were supplemented for 3 months with placebo, (ii) patients with SS and matched controls received pyridoxine or placebo for 45 days, and a blood sample was obtained to study IL-2 production and expression in T-lymphocytes stimulated with PHA. RESULTS: Subjects with primary SS showed limited dietary intake of pyridoxine and biochemical deficiency of this vitamin assessed through the activation coefficient of the erythrocyte aspartate aminotransferase. The biochemical deficiency did not affect production nor mRNA expression of IL-2 from T-lymphocytes stimulated in vitro with PHA compared with the control group. Supplementation of subjects with primary SS with 25 mg/day with pyridoxine for 45 days did not produce any significant change as compared to those patients supplemented with placebo. CONCLUSIONS: Subjects with primary SS showed biochemical deficiency of pyridoxine, possibly due to limited intake of this vitamin which was corrected by supplementation with pyridoxine. However, IL-2 production and mRNA expression from stimulated lymphocytes were unaffected by supplementation, probably because the deficiency was not severe enough to affect the immune system. SPONSORSHIP: This work was supported by the National Council of Science and Technology (CONACYT), Mexico, grant no. 212226-5-0902PM.

Expert Opin Pharmacother. 2002 Nov;3(11):1591-8. Pharmacotherapy of hyperhomocysteinaemia in patients with thrombophilia.

O'Donnell J, Perry DJ.

Katherine Dormandy Haemophilia Centre and Haemostasis Unit, Department of Haematology, Royal Free Hospital School of Medicine, Pond Street, London NW3 2QG, UK.

Hyperhomocysteinaemia is often the result of inherited abnormalities of the enzymes involved in homocysteine metabolism or vitamin deficiencies (vitamins B12, B6 or folate) and is present in approximately 5% of the general population. High homocysteine levels in these individuals are associated with a significant increase in relative risk for both arterial and venous thromboembolic disease. Consequently, effective homocysteine-lowering therapeutic strategies have been extensively investigated. Folic acid represents the cornerstone of treatment. In daily doses of at least 0.4 mg, it effectively reduces homocysteine levels, even in non-folate-deficient patients. The addition of vitamins B12 and/or B6, to folic acid supplementation may provide a small further reduction in homocysteine levels in certain groups of patients. Renal impairment is an important cause of hyperhomocysteinaemia. Individuals with hyperhomocysteinaemia secondary to renal disease commonly require significantly higher doses of folic acid (5-40 mg) to achieve maximal therapeutic effect. The important question of whether effective homocysteine-lowering therapy translates into a reduction in vascular disease remains unknown but is being addressed in a series of ongoing prospective trials.

J Child Neurol. 2002 Nov;17(11):859-60.

Homocystinuria presenting as psychosis in an adolescent.

Ryan MM, Sidhu RK, Alexander J, Megerian JT.

Department of Neurology, Children's Hospital Boston, Massachusetts 02115, USA. monique.ryan@tch.harvard.edu

Homocystinuria usually presents with ectopia lentis, mental retardation, thromboembolic complications, and skeletal abnormalities. Whereas neuropsychiatric abnormalities are often recognized in untreated homocystinuria, initial presentation with acute psychosis has only rarely been reported. We describe a previously well 17-year-old adolescent with an acute psychosis characterized by auditory and visual hallucinations and marked paranoia who was found to have pyridoxine-responsive homocystinuria. His mental state normalized within several weeks of inception of pyridoxine and antipsychotic therapy. Pyridoxine-responsive homocystinuria is commonly missed on neonatal screens and should be recognized as a potentially treatable cause of acute psychosis in childhood and adolescence.

Altern Med Rev. 2002 Oct;7(5):389-403.

Intravenous nutrient therapy: the "Myers' cocktail".

Gaby AR.

Building on the work of the late John Myers, MD, the author has used an intravenous vitamin-and-mineral formula for the treatment of a wide range of clinical conditions. The modified "Myers' cocktail," which consists of magnesium, calcium, B vitamins, and vitamin C, has been found to be effective against acute asthma attacks, migraines, fatigue (including chronic fatigue syndrome), fibromyalgia, acute muscle spasm, upper respiratory tract infections, chronic sinusitis, seasonal allergic rhinitis, cardiovascular disease, and other disorders. This paper presents a rationale for the therapeutic use of intravenous nutrients, reviews the relevant published clinical research, describes the author's clinical experiences, and discusses potential side effects and precautions.

Epilepsy Res. 2002 Oct;51(3):237-47. The effect of B-vitamins on hyperhomocysteinemia in patients on antiepileptic drugs.

Apeland T, Mansoor MA, Pentieva K, McNulty H, Seljeflot I, Strandjord RE.

Department of Internal Medicine, Rogaland Central Hospital, 4011 Stavanger, Norway. apeland@online.no

Patients on antiepileptic drugs (AEDs) may have elevated levels of plasma total homocysteine (p-tHcy). The aim of this study was to assess the effect of B-vitamin supplementation on the levels of p-tHcy and markers of endothelial activation and lipid peroxidation. A total of 33 adult patients on AEDs were identified with either fasting (Group 1, n=23) or post methionine load (PML) (Group 2, n=10) hyperhomocysteinemia. Subjects were supplemented with B-vitamins for 30 days: folic acid 0.4 mg, pyridoxine 120 mg and riboflavin 75 mg per day. After supplementation, serum folate and pyridoxal phosphate had increased, while fasting and PML p-tHcy had decreased (P<0.0001) by 36 and 26%, respectively. Prior to supplementation, the Group 1 patients had elevated levels of P-selectin and von Willebrand factor (vWF) (P=0.05 and 0.03, respectively). After supplementation, the levels of intercellular cell adhesion molecules had decreased (P=0.01) and E-selectin decreased nonsignificantly (P=0.07). However, the levels of vascular cell adhesion molecules had increased (P<0.0001), while lipid peroxidation were unchanged. In conclusion, the combined supplementation with folic acid, pyridoxine and riboflavin reduced fasting and PML hyperhomocysteinemia in patients on AEDs. Patients with fasting hyperhomocysteinemia had elevated levels of P-selectin and vWF, which may indicate an increased risk of cardiovascular disease. Furthermore, B-vitamin supplementation influenced endothelial activation, although the clinical implication is uncertain.

J Trop Pediatr. 2002 Oct;48(5):303-6.

Pyridoxine-dependent seizures: long-term follow-up of two cases with clinical and MRI findings, and pyridoxine treatment.

Ulvi H, Mungen B, Yakinci C, Yoldas T.

Firat University Medical Faculty, Department of Neurology, Elazig, Turkey. hizirulvi@yahoo.com

Pyridoxine-dependency is a rare autosomal recessive disorder causing a severe seizure disorder of neonatal onset. There are a few reports including neuroimaging studies, such as cranial CT and MRI, and one report with longitudinal MRI findings in two cases with pyridoxine-dependent seizures (PDS). We report long-term follow-up of two siblngs with PDS in the light of clinical, EEG, CT and MRI findings, and pyridoxine treatment. The first patient, an 8-year-old female who had neonatal seizures, has sequential cranial CT and MRIs which are normal except for mega cistema magna thus far. She still has mild mental retardation, although the accurate diagnosis was made when she was 6 years old and pyridoxine treatment was initiated. The second patient, a 1-year-old female, who is the younger sibling of the first patient, presented with neonatal seizures and PDS was diagnosed immediately, with resulting pyridoxine treatment (10 mg/kg/day). She is now neurologically normal, seizure-free, and has sequential normal CT and MRIs. These patients show rather benign clinical courses.

Nutrition. 2002 Sep;18(9):738-42. Efficacy of a complex multivitamin supplement.

Earnest C, Cooper KH, Marks A, Mitchell TL.

The Cooper Institute for Aerobics Research, Dallas, Texas 75230, USA. cearnest@cooperinst.org

OBJECTIVES: Multivitamin supplements are often sold to consumers with the claim that supplements modify risk factors associated with disease. Because few products are validated scientifically, we examined the effects of a 24-ingredient multivitamin formula in an open-label pilot investigation. METHODS: We examined 150 subjects for specific endpoints including blood concentrations of selected vitamins, homocysteine, lipids, and low-density lipoprotein (LDL) oxidation indices at baseline and at 12 and 24 wk. RESULTS: One hundred forty-one subjects were successfully assayed for and showed significant time effects for homocysteine and vitamin B6 (as pyridoxal-5'-phosphate), B12, and folic acid concentrations during treatment (P < 0.0001). Vitamin B6, B12, and folic acid concentrations were significantly elevated at weeks 12 and 24 (P < 0.05). Homocysteine concentration decreased significantly during the same periods (7.9 +/- 2.4 versus 6.7 +/- 1.7 versus 6.7 +/- 1.9 mM/mL; P < 0.05). There were correlations relating homocysteine to vitamins B6 (P = 0.001, r(2) = 0.03), B12 (P < 0.001, r(2) = 0.09), and folic acid (P = 0.001, r(2) = 0.10). Significant time effects were noted for 121 subjects successfully assayed for vitamin C, E, beta-carotene, LDL oxidation rate, and LDL lag time (P < 0.0001). Post hoc assessment showed elevations in vitamin C, E, and beta-carotene concentrations at 12 and 24 wk (P < 0.05). LDL oxidation lag time at baseline (57.5 +/- 13.9 min) increased by 12 wk (63.5 +/- 19.0 min; P < 0.05) and 24 wk (63.8 +/- 16.3 min; P < 0.05). LDL oxidation rate at baseline (9.7 +/- 3.0 microM x min(-1). g(-1)) was reduced at 12 wk (7.1 +/- 2.5 microM x min(-1) x g(-1); P < 0.05) and 24 wk (6.0 +/- 2.0 microM x min(-1) x g(-1); P < 0.05). Only vitamin C was significantly correlated with LDL oxidation rate (P = 0.05, r(2) = 0.003). CONCLUSIONS: A multi-ingredient vitamin formula with antioxidant properties has measurable effects on homocysteine and LDL oxidation indices.

Seizure. 2002 Sep;11(6):381-3. Add-on treatment with pyridoxine and sulthiame in 12 infants with West syndrome: an open clinical study.

Debus OM, Kohring J, Fiedler B, Franssen M, Kurlemann G.

University Children's Hospital, Department of Neuropediatrics, Westfalische-Wilhelms-Universitat Munster, Albert-Schweitzer-Str. 33, D - 48149 Munster, Germany. debuso@uni-muenster.de

To investigate the effect of sulthiame (STM) in West syndrome (WS) an open, uncontrolled add-on study was undertaken during initial pyridoxine (PDX) therapy in 12 infants, two with idiopathic and ten with symptomatic WS. All patients were initially treated with PDX (150-300 mg x kg (-1)body weight day(-1) ). In seven patients (58%) seizures and hypsarrhythmia stopped during the week after introduction of STM (10 mg x kg (-1)body weight day (-1)). In one the positive effect was temporary. Five of the responders (42%) remained seizure-free and without hypsarrhythmia under STM monotherapy, while one developed complex partial seizures after 25 months. STM was most effective in idiopathic WS (2 /2). During treatment with STM medication no patient suffered side effects attributable to the substance. Further controlled studies are necessary to evaluate the benefit of this potentially effective treatment.

JAMA. 2002 Aug 28;288(8):973-9.

Comment in: • ACP J Club. 2003 Mar-Apr;138(2):33. • J Fam Pract. 2003 Jan;52(1):16-8. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial.

Schnyder G, Roffi M, Flammer Y, Pin R, Hess OM.

Division of Cardiology, Swiss Cardiovascular Center Bern, University Hospital, Switzerland. g.schnyder@lycos.com

CONTEXT: Plasma homocysteine level has been recognized as an important cardiovascular risk factor that predicts adverse cardiac events in patients with established coronary atherosclerosis and influences restenosis rate after percutaneous coronary intervention. OBJECTIVE: To evaluate the effect of homocysteine-lowering therapy on clinical outcome after percutaneous coronary intervention. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind placebo-controlled trial involving 553 patients referred to the University Hospital in Bern, Switzerland, from May 1998 to April 1999 and enrolled after successful angioplasty of at least 1 significant coronary stenosis (> or = 50%). INTERVENTION: Participants were randomly assigned to receive a combination of folic acid (1 mg/d), vitamin B12 (cyanocobalamin, 400 micro g/d), and vitamin B6 (pyridoxine hydrochloride, 10 mg/d) (n = 272) or placebo (n = 281) for 6 months. MAIN OUTCOME MEASURE: Composite end point of major adverse events defined as death, nonfatal myocardial infarction, and need for repeat revascularization, evaluated at 6 months and 1 year. RESULTS: After a mean (SD) follow-up of 11 (3) months, the composite end point was significantly lower at 1 year in patients treated with homocysteine-lowering therapy (15.4% vs 22.8%; relative risk [RR], 0.68; 95% confidence interval [CI], 0.48-0.96; P =.03), primarily due to a reduced rate of target lesion revascularization (9.9% vs 16.0%; RR, 0.62; 95% CI, 0.40-0.97; P =.03). A nonsignificant trend was seen toward fewer deaths (1.5% vs 2.8%; RR, 0.54; 95% CI, 0.16-1.70; P =.27) and nonfatal myocardial infarctions (2.6% vs 4.3%; RR, 0.60; 95% CI, 0.24-1.51; P =.27) with homocysteine-lowering therapy. These findings remained unchanged after adjustment for potential confounders. CONCLUSION: Homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 significantly decreases the incidence of major adverse events after percutaneous coronary intervention.

Thromb Haemost. 2002 Aug;88(2):230-5.

Effect of homocysteine reduction by B-vitamin supplementation on markers of clotting activation.

Klerk M, Verhoef P, Verbruggen B, Schouten EG, Blom HJ, Bos GM, den Heijer M.

Division of Human Nutrition and Epidemiology, Wageningen University, Wageningen Centre for Food Sciences, Wageningen.

Homocysteine may have an effect on risk of cardiovascular disease by stimulating procoagulant factors and/or impair anti-coagulant mechanisms or fibrinolysis. However, data in humans of such effects are sparse. In this intervention study, we examined the effect of homocysteine lowering by B-vitamin supplementation on prothrombin fragments 1 and 2 (F1 + 2), thrombin-antithrombin complex (TAT), and fibrin degradation products (D-dimer). The study comprised 118 healthy volunteers, 50 with homocysteine > 16 mumol/L and 68 with homocysteine < or = 16 mumol/L, who were randomized to placebo or high-dose B-vitamin supplements (5 mg folic acid, 0.4 mg hydroxycobalamin, and 50 mg pyridoxine) daily for 8 weeks. Although homocysteine concentrations were 27.7% (p < 0.0001) reduced in the B-vitamin group compared to the placebo group, no effect on F1 + 2 and TAT concentrations was observed. A 10.4% reduction was observed for D-dimer (p = 0.08). In conclusion, it appears that in healthy subjects homocysteine reduction by B-vitamin supplementation has a modest beneficial effect on clotting activation.

J Pediatr Hematol Oncol. 2002 Jun-Jul;24(5):374-9. Hyperhomocysteinemia is associated with low plasma pyridoxine levels in children with sickle cell disease.

Balasa VV, Kalinyak KA, Bean JA, Stroop D, Gruppo RA.

Cincinnati Comprehensive Sickle Cell Center of the Division of Hematology/Oncology, Children's Hospital Medical Center, Ohio 45229, USA. balav0@chmcc.org

Elevated plasma homocysteine levels have been shown to be a risk factor for endothelial cell damage and thrombosis, which are implicated in sickle cell disease (SCD)-related vaso-occlusion. The aim of this study was to determine the prevalence of hyperhomocysteinemia in SCD. Fasting and postmethionine load (PML) homocysteine, red cell folate, and the MTHFR C677T mutation were determined in 77 patients with SCD and 110 African-American controls. Plasma methylmalonic acid and pyridoxine levels were determined in 54 patients and all controls. For analysis, the subjects were divided into two age groups (2-10 years and 10.1-21 years). In both age groups, median PML homocysteine levels were significantly elevated in patients with SCD compared with controls. Fasting homocysteine levels were elevated in patients with SCD versus controls only in those older than 10 years. Hyperhomocysteinemia was noted in 38% of patients versus 7% in controls. Folate levels were higher among patients than controls and showed a significant negative correlation with PML homocysteine levels in patients with SCD. Pyridoxine levels in patients with SCD were significantly lower than in controls and showed a negative correlation with PML homocysteine levels. Among patients with SCD, pyridoxine deficiency was more common (62%) among those with hyperhomocysteinemia compared with those with normal homocysteine levels (30%). Homozygosity for the MTHFR C677T mutation was rare. These data suggest that children with SCD have significant hyperhomocysteinemia, associated with pyridoxine and relative folate deficiencies.

Pharmacol Toxicol. 2002 Jun;90(6):338-42. Opposite effects of nicotinic acid and pyridoxine on systemic prostacyclin, thromboxane and leukotriene production in man.

Saareks V, Ylitalo P, Mucha I, Riutta A.

Department of Pharmacological Sciences, University of Tampere, Finland. virpi.saareks@uta.fi

The effects of nicotinic acid (2500 mg orally during 12 hr) and pyridoxine (300 mg orally twice daily for seven days) on the excretion of urinary 2,3-dinor-6-ketoprostaglandin F1alpha, 11-dehydrothromboxane B2 and leukotriene E4, the markers of systemic prostacyclin, thromboxane A2 and cysteinyl leukotriene production, respectively, were investigated in healthy male volunteers (n=6-8). Nicotinic acid increased 11-dehydrothromboxane B2 and leukotriene E4 excretions to 2.6- and 2.0 times the initial values (P<0.05), respectively. In the volunteers treated with pyridoxine, 11-dehydrothromboxane B2 and leukotriene E4 excretions were decreased to 70% (P<0.05) and 65% (P<0.01) of the initial values, respectively, but the excretion of 2,3-dinor-6-ketoprostaglandin F1alpha was increased 1.7 times (P<0.01). The results suggest that nicotinic acid increases thromboxane and leukotriene synthesis which may not be beneficial for patients with cardiovascular diseases or asthma. In contrast, the increase in prostacyclin production and the inhibition in thromboxane and leukotriene synthesis by pyridoxine might be beneficial in disorders where the production of prostacyclin is decreased and the formation of thromboxane and cysteinyl leukotrienes is enhanced.

Nephrol Dial Transplant. 2002 May;17(5):865-70. Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic acid in combination with vitamin B6 and B12.

Ducloux D, Aboubakr A, Motte G, Toubin G, Fournier V, Chalopin JM, Drueke T, Massy ZA.

Division of Nephrology, Biochemistry B Laboratory, CHU St Jacques, Besancon, France.

BACKGROUND: In a recent uncontrolled retrospective report we suggested that the long-term supplementation of high-dose, i.v. folinic acid combined with high-dose i.v. pyridoxine was highly effective in correcting plasma total homocysteine (tHcy) concentrations in haemodialysis patients. To confirm these findings, we conducted a randomized, controlled trial aimed at evaluating whether i.v. or oral folinic acid provided improved tHcy-lowering efficacy in haemodialysis patients compared with oral folic acid. METHODS: In a 6-month prospective, randomized, controlled trial, 60 chronic haemodialysis patients, matched for age, gender, dialysis duration, and average screening pre-treatment-fasting tHcy levels, were given either 50 mg/week of i.v. calcium folinate (group 1), 50 mg/week of oral calcium folinate (group 2), or 45 mg/week oral folic acid (group 3). All 60 patients also received 750 mg/week of i.v. vitamin B6 and 3 mg/week of oral vitamin B12. RESULTS: Fasting tHcy decreased significantly and to a similar extent in the three groups after 2 months of treatment and remained stable at 4 and 6 months (16.6+/-3.5, 18.3+/-4, and 19.1+/-3.1, in groups 1, 2, and 3, respectively, P=NS). Mean percentage reduction at 6 months was also similar in the three treatment groups (46, 43, and 42% in groups 1, 2, and 3, respectively, P=NS). CONCLUSIONS: These findings show that the tHcy-lowering effects of high-dose i.v. folinic acid, oral folinic acid, or oral folic acid were comparable, suggesting that the hyperhomocysteinaemia observed in haemodialysis patients is not due to abnormal folate metabolism. Furthermore, they are compatible with the view that other abnormalities are also involved in the impaired clearance of homocysteine in uraemic patients.

Br J Sports Med. 2002 Apr;36(2):126-31. Physical exercise or micronutrient supplementation for the wellbeing of the frail elderly? A randomised controlled trial.

Chin A Paw MJ, de Jong N, Schouten EG, van Staveren WA, Kok FJ.

Division of Human Nutrition and Epidemiology, Wageningen University, The Netherlands. M.Chinapaw.emgo@med.vu.nl

OBJECTIVE: To examine the effects of 17 weeks of physical exercise and micronutrient supplementation on the psychological wellbeing of 139 independently living, frail, elderly subjects (inactive, body mass index < or =25 or experiencing weight loss). METHODS: Participants (mean (SD) age 78.5 (5.7)) were randomly assigned to: (a) comprehensive, moderate intensity, group exercise; (b) daily micronutrient enriched foods (25-100% recommended daily amount); (c) both; (d) neither. A social programme and identical regular foods were offered as attention control and placebo. RESULTS: At baseline, moderate to low but significant correlations were found between general wellbeing scores and physical fitness (r = 0.28), functional performance (r = 0.37), and blood concentrations of pyridoxine (r = 0.20), folate (r = 0.25), and vitamin D (r = 0.23) (all p values < or =0.02), but not with physical activity levels and other blood vitamin concentrations. General wellbeing score and self rated health were not responsive to 17 weeks of exercise or nutritional intervention. CONCLUSION: Psychological wellbeing in frail elderly people was not responsive to 17 weeks of intervention with exercise and/or micronutrient enriched foods. The moderate but significant correlations between wellbeing and physical fitness and several blood vitamin concentrations at baseline suggest that changes in wellbeing may occur after long term interventions.

J Child Neurol. 2002 Mar;17(3):222-4.

Pyridoxine-dependent seizures associated with hypophosphatasia in a newborn.

Nunes ML, Mugnol F, Bica I, Fiori RM.

Division of Neurology, Hospital Sao Lucas, PUCRS School of Medicine, Porto Alegre-RS, Brazil. nunes@pucrs.br

Pyridoxine dependency and congenital hypophosphatasia are unusual metabolic disorders. We report a female infant born from healthy consanguineous parents with shortening of limbs, detected during pregnancy by ultrasonography. Immediately after delivery, the baby was admitted to the neonatal intensive care unit because of respiratory distress. A bone radiograph showed hypomineralization of all bones, and serum alkaline phosphatase was very low (10 U/L). Within the first day of life, seizures (focal clonic and tonic) started. The seizures were refractory to phenobarbital and other antiepileptic drugs. The first electroencephalogram (EEG) showed a burst-suppression pattern. Pyridoxine was administered (50 mg/kg) and completely controlled the seizures. Antiepileptic drugs were discontinued, and a maintenance dose of pyridoxine (10 mg/day) was established. A postpyridoxine EEG revealed the disappearance of the burst-suppression pattern. The patient died at age 26 days. Pyridoxine-dependent seizures, when recognized early and treated, have a more favorable prognosis. However, hypophosphatasia detected at birth almost always has a lethal outcome.

Clin Chem Lab Med. 2002 Feb;40(2):137-42.

Renal function exerts only a minor influence on high plasma homocysteine concentrations in patients with acute coronary syndromes.

Jonasson T, Ohlin H, Andersson A, Arnadottir M, Hultberg B.

Department of Medicine, University of Lund, University Hospital, Sweden. torfi.jonasson@kard.lu.se

It has been suggested that hyperhomocysteinemia observed in patients with occlusive vascular disease is caused by reduced renal function secondary to renovascular disease. We have therefore used serum cystatin C, a new sensitive marker for glomerular filtration, in 59 patients with acute coronary syndromes and high plasma homocysteine (tHcy) concentration to measure renal function. Samples were also obtained from 34 patients with low-normal plasma tHcy and 50 control subjects. The patients with low-normal plasma tHcy concentration showed decreased concentrations of serum cystatin C and serum creatinine and increased concentrations of blood folate and serum cobalamin compared to the controls and to the patients with high plasma tHcy. There was a large overlap in cystatin C concentrations between patients with high and low-normal plasma tHcy. None of the parameters investigated except plasma tHcy were significantly different in the group of patients with high plasma tHcy concentration compared to the control group. In order to further demonstrate the importance of renal impairment, a subgroup of the patients with high plasma tHcy was supplemented daily with folic acid 5 mg, pyridoxine 40 mg and cyancobalamin 1 mg for 3 months. Vitamin therapy reduced plasma tHcy from 18.3+/-4.6 pmol/l to 9.6+/-2.2 pmol/l (p<0.0001). However, vitamin treatment did not strengthen the correlation between cystatin C and plasma tHcy concentrations. These findings do not support the hypothesis that subtle renal dysfunction is an important cause of high plasma tHcy concentration in patients with acute coronary syndromes.

J Nutr Sci Vitaminol (Tokyo). 2002 Feb;48(1):10-7.

Vitamin B6 status of breast-fed infants in relation to pyridoxine HCl supplementation of mothers.

Chang SJ, Kirksey A.

Department of Biology, National Cheng Kung University, Tainan, Taiwan, ROC.

The vitamin B6 nutritue of breast-fed infants was evaluated by vitamin B6 intake, plasma pyridoxal 5'-phosphate (PLP) concentration, and growth patterns during the infants' first 6 mo of age. Vitamin B6 intakes of 47 healthy, term infants were significantly correlated with four levels of maternal vitamin B6 supplements: 2.5, 4.0, 7.5, or 10.0 mg pyridoxine (PN) HCl/d and met the B6 Adequate Intake (AI, 1998) of 0.1 mg/d for infants 0 to 6 mo. Only infants whose mothers received 10.0 mg PN x HCl/d exceeded or met the Recommended Dietary Allowances (RDA, 1989) of 0.3 mg vitamin B6/d from 4 to 6 mo of age. Plasma PLP concentrations of infants, measured at 1, 4, and 6 mo of age paralleled their mother's vitamin B6 intake. Most infants showed normal growth. The findings indicated that a maternal PN x HCl supplement of 2.5 mg/d provided an adequate amount of vitamin B6 in breast milk (0.15 mg/d) for the vitamin B6 status parameters and the growth of breast-fed infants.

J Nutr Sci Vitaminol (Tokyo). 2002 Feb;48(1):65-8.

Dietary vitamin B6 suppresses colon tumorigenesis, 8-hydroxyguanosine, 4-hydroxynonenal, and inducible nitric oxide synthase protein in azoxymethane-treated mice.

Komatsu S, Watanabe H, Oka T, Tsuge H, Kat N.

Faculty of Applied Biological Science, Hiroshima University, Higashi-Hiroshima, Japan.

Recently we reported that the supplementation of vitamin B6 to low vitamin B6 diet caused suppression in colon tumorigenesis and cell proliferation of azoxymethane-treated mice in a dose-dependent manner among 1, 7, and 14 mg pyridoxine HCl/kg diet (J. Nutr. 131: 2204-2207, 2001). To examine the mechanism of the anticolon tumor effect of vitamin B6, male ICR mice were fed the diet containing 1, 7, 14, and 35 mg pyridoxine HCl/kg diet for 22 wk and simultaneously given a weekly injection of azoxymethane for an initial 10 wk. The supplementation of vitamin B6 to a low vitamin B6 diet (1 mg pyridoxine HCl/kg) suppressed the levels of colonic 8-hydroxyguanosine and 4-hydroxynonenal and inducible nitric oxide synthase protein. The results suggest that the preventive effect of vitamin B6 against colon tumorigenesis is at least in part mediated by reducing oxidative stress and nitric oxide production.

Osteoarthritis Cartilage. 2002 Feb;10(2):119-26. Dietary vitamins and selenium diminish the development of mechanically induced osteoarthritis and increase the expression of antioxidative enzymes in the knee joint of STR/1N mice.

Kurz B, Jost B, Schunke M.

Anatomisches Institut der CAU zu Kiel, Olshausenstr. 40, Kiel, Germany. bkurz@anat.uni-kiel.de

OBJECTIVE: To study the influence of dietary vitamins and selenium on mechanically-induced osteoarthritis (OA) and the expression of antioxidative enzymes in male STR/1N and Balb/c mice. Male STR/1N mice are prone to develop OA caused by a varus deformity-induced mechanical overload of the medial tibial plateau. METHODS: After 12 months of feeding (special diet supplemented with the vitamins E, C, A, B6, B2, and selenium) serial histological sections of the knee joints were evaluated for development of osteoarthritic changes (grade 0-4). Serum glutathione peroxidase activity (GSH-px) was measured photometrically. Expression of antioxidative enzymes was demonstrated by immunohistochemistry. RESULTS: All control STR/1N mice showed OA lesions (grade 3-4) while the special diet decreased OA incidence significantly down to approximately 65% (mostly grade 2). Even in Balb/c mice the incidence was decreased by the special diet from approximately 21% (control animals; grade 1) to approximately 14%. Serum GSH-px activity increased diet-dependently in both mouse strains but was generally higher in Balb/c mice. In both mouse strains the special diet increased the expression of GSH-px and Cu/Zn-SOD in articular cartilage while there was no expression of Mn-SOD. There was also a special diet-dependent increase in expression of GSH-px in the synovium of both mouse strains while an increase in expression of Mn-SOD and Cu/Zn-SOD could only be seen in the synovium of STR/1N mice. CONCLUSIONS: A diet supplemented with vitamins/selenium might be important in prevention or therapy of mechanically induced OA. We hypothesize that free oxygen radical species might be involved in the mechanical induction of OA. Copyright 2002 OsteoArthritis Research Society International.

Pediatr Neurol. 2002 Feb;26(2):146-7. Pyridoxal phosphate-responsive epilepsy with resistance to pyridoxine.

Kuo MF, Wang HS.

Division of Pediatric Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.

We present a female infant with seizures responsive to pyridoxal phosphate but that are resistant to pyridoxine. The mechanism by which pyridoxal phosphate controls seizures in this patient is unknown. Her seizures are perhaps not solely caused by pyridoxal phosphate deficiency. It is suggested that in addition to glutamic acid decarboxylase abnormality, the path from the absorption, transportation, phosphorylation, and oxidation of pyridoxine to pyridoxal phosphate in this patient might be defective. It should be considered whether pyridoxal phosphate can be the drug of choice instead of pyridoxine in treating patients suspected of pyridoxine-dependent epilepsy to reduce failure rate and further delay in seizure control.

Pediatrics. 2002 Feb;109(2):325-7. Ginkgo seed poisoning.

Kajiyama Y, Fujii K, Takeuchi H, Manabe Y.

Department of Pediatrics Kyoto Min-i-ren Central Hospital Kyoto, Japan. yo-f@dab.hi-ho.ne.jp

A 2-year-old girl presented with vomiting and diarrhea 7 hours after eating a large quantity of ginkgo seeds. She exhibited an afebrile convulsion 9 hours after ingestion. The serum concentration of 4-metoxypyridoxine was as high as 360 ng/mL. Although reported cases of ginkgo seed poisoning usually involve children who exhibit repetitive seizures that can be fatal, prompt administration of pyridoxal phosphate (2 mg/kg) may have prevented additional seizures. This is the first English-language case report measuring 4-metoxypyridoxine concentration during ginkgo seed poisoning. Awareness of the potential danger of overconsumption of this traditional food and its prompt treatment with pyridoxal phosphate may hasten recovery.

Percept Mot Skills. 2002 Feb;94(1):135-40.

Effects of pyridoxine on dreaming: a preliminary study.

Ebben M, Lequerica A, Spielman A.

City College of New York, USA.

The effect of pyridoxine (Vitamin B-6) on dreaming was investigated in a placebo, double-blind study to examine various claims that Vitamin B-6 increases dream vividness or the ability to recall dreams. 12 college students participated in all three treatment conditions, each of which involved ingesting either 100 mg B-6, 250 mg B-6, or a placebo prior to bedtime for a period of five consecutive days. The treatment conditions were completely counterbalanced and a two-day wash-out period occurred between the three five-day treatment blocks. Morning self-reports indicated a significant difference in dream-salience scores (this is a composite score containing measures on vividness, bizarreness, emotionality, and color) between the 250-mg condition and placebo over the first three days of each treatment. The data for dream salience suggests that Vitamin B-6 may act by increasing cortical arousal during periods of rapid eve movement (REM) sleep. An hypothesis is presented involving the role of B-6 in the conversion of tryptophan to serotonin. However, this first study needs to be replicated using the same procedures and also demonstrated in a sleep laboratory before the results can be considered certain.

Semin Neonatol. 2002 Feb;7(1):17-26. Management and emergency treatments of neonates with a suspicion of inborn errors of metabolism.

Ogier de Baulny H.

Neurology and Metabolic Diseases Unit, Hopital Robert Debre, Paris, France. helene.ogier@rdb.ap-hop-paris.fr

During the neonatal period, inborn errors of metabolism mostly present with an overwhelming illness that requires prompt diagnosis and both supportive and specific treatments. The most frequent situations are due to branched-chain organic acidurias that present with ketoacidosis and urea cycle defects that are characterized by hyperammonaemia. During both situations, toxin removal procedures and nutritional support with a free-protein and high-energy diet are pivotal treatments. In patients presenting with hypoglycaemia blood glucose levels must be corrected. Progress following glucose provision is useful in recognizing the disorders that are mainly implicated. Hyperinsulinism requires high-glucose infusion. Glycogen storage diseases and gluconeogenesis defects are easily treated with a permanent glucose provision while hypoglycaemias quickly recur. In patients with galactosaemia, hereditary fructose intolerance or tyrosinaemia type I, the presentation is dominated by a liver failure requiring galactose and fructose exclusion associated with a low-protein diet. Many patients with beta-oxidation defects may present with hypoglycaemia that is usually easily corrected. The precise diagnosis can be easily missed in those patients that do well in the following weeks but may develop cardiac failure, arrhythmia and/or liver failure. Patients presenting with intractable convulsions, vitamin responsiveness to biotin, pyridoxine and folate must be considered. Copyright 2002 Elsevier Science Ltd. All rights reserved.

Cochrane Database Syst Rev. 2002;(1):CD000145.

Comment in: • ACP J Club. 2002 Sep-Oct;137(2):67.

Update of: • Cochrane Database Syst Rev. 2000;(2):CD000145.

Interventions for nausea and vomiting in early pregnancy.

Jewell D, Young G.

Division of Primary Health Care, University of Bristol, Canynge Hall, Whiteladies Road, Bristol, UK. david.jewell@bristol.ac.uk

BACKGROUND: Nausea and vomiting are the most common symptoms experienced in early pregnancy, with nausea affecting between 70 and 85% of women. About half of pregnant women experience vomiting. OBJECTIVES: The objective of this review was to assess the effects of different methods of treating nausea and vomiting in early pregnancy. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register and the Cochrane Controlled Trials Register. Date of last search: October 2001. SELECTION CRITERIA: Randomised trials of any treatment for nausea and/or vomiting in early pregnancy. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by two reviewers. MAIN RESULTS: Twenty-three trials were included. These trials were of variable quality. Nausea treatments were different anti-histamine medications, vitamin B6 (pyridoxine), the combination tablet Debendox (Bendectin) and P6 acupressure. For hyperemesis gravidarum five trials were identified testing treatments with oral ginger root extract, oral corticosteroids or injected adrenocorticotropic hormone (ACTH) and intravenous diazepam. Based on 13 trials, there was an overall reduction in nausea from anti-emetic medication (odds ratio 0.17, 95% confidence interval 0.13 to 0.21). REVIEWER'S CONCLUSIONS: Anti-emetic medication appears to reduce the frequency of nausea in early pregnancy. There is some evidence of adverse effects, but there is very little information on effects on fetal outcomes from randomised controlled trials. Of newer treatments, pyridoxine (vitamin B6) appears to be more effective in reducing the severity of nausea. The results from trials of P6 acupressure are equivocal. No trials of treatments for hyperemesis gravidarum show any evidence of benefit. Evidence from observational studies suggests no evidence of teratogenicity from any of these treatments.

J Clin Psychiatry. 2002 Jan;63(1):54-8.

Vitamin B6 as add-on treatment in chronic schizophrenic and schizoaffective patients: a double-blind, placebo-controlled study.

Lerner V, Miodownik C, Kaptsan A, Cohen H, Loewenthal U, Kotler M.

Ministry of Health Mental Health Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er-Sheva, Israel. lernervld@yahoo.com

BACKGROUND: Vitamin B6, or pyridoxine, plays an intrinsic role in the synthesis of certain neurotransmitters that take part in development of psychotic states. Several reports indicate that vitamin B6 may be a factor in a number of psychiatric disorders and related conditions, such as autism, Alzheimer's disease, hyperactivity, learning disability, anxiety disorder, and depression. Moreover, there are anecdotal reports of a reduction in psychotic symptoms after vitamin B6 supplementation of psychopharmacologic treatment of patients suffering from schizophrenia or organic mental disorder. The aim of this study was to examine whether vitamin B6 therapy influences psychotic symptoms in patients suffering from schizophrenia and schizoaffective disorder. METHOD: The effects of the supplementation of vitamin B6 to antipsychotic treatment on positive and negative symptoms in 15 schizophrenic and schizoaffective patients (DSM-IV criteria) were examined in a double-blind, placebo-controlled, crossover study spanning 9 weeks. All patients had stable psychopathology for at least 1 month before entry into the study and were maintained on treatment with their prestudy psychoactive and antiparkinsonian medications throughout the study. All patients were assessed using the Positive and Negative Syndrome Scale (PANSS) for schizophrenia on a weekly basis. Patients randomly received placebo or vitamin B6, starting at 100 mg/day in the first week and increasing to 400 mg/day in the fourth week by 100-mg increments each week. RESULTS: PANSS scores revealed no differences between vitamin B6- and placebo-treated patients in amelioration of their mental state. CONCLUSION: Further studies with larger populations and shorter duration of illness are needed to clarify the question of the possible efficacy of vitamin B6 in treatment of psychotic symptoms in schizophrenia.

J Nutr Health Aging. 2002;6(1):69-71.

Homocysteine levels in elderly Spanish people: influence of pyridoxine, vitamin B12 and folic acid intakes.

Ortega RM, Jimenez A, Andres P, Faci M, Lolo JM, Lozano MC, Bermejo LM, Lopez-Sobaler AM, Requejo AM.

Departamento de Nutricion, Facultad de Farmacia, Universidad Complutense deMadrid, Spain. rortega@farm.ucm.es

BACKGROUND: Serum homocysteine levels are a risk factor in cardiovascular disease. Knowledge on how dietary factors might affect these levels is therefore of interest. OBJECTIVE: To evaluate serum homocysteine levels in a group of elderly people and analyse the effect of pyridoxine, vitamin B12 and folic acid intakes on these levels. DESIGN: The study subjects were 130 independently-living elderly people over the age of 65. A dietetic study was performed using a 7-day food record. Serum homocysteine levels were determined by HPLC. RESULTS: Mean pyridoxine, vitamin B12 and folate intakes were 67.2+/-16.8%, 392.8+/-549.2% and 84.5+/-28.3% of recommended values respectively. With regard to sex, differences were seen only for vitamin B12 intake (9.1+/-12.7 microg/day in men, and 6.5+/-8.8 microg/day in women). Some 93.6% of subjects showed pyridoxine intakes below those recommended, as did 17.6% with respect to vitamin B12 and 72.8% with respect to folic acid. Homocysteine levels were 12.4 micromol/l (12.6+/-3.7 micromol/l in men and 12.2+/-7.9 micromol/l in women) (P<0.05). No significant differences were seen in homocysteine levels between subjects with lower than recommended intakes of pyridoxine or vitamin B12 and those with better intakes. However, subjects with folic acid intakes below 200 microg/day showed higher homocysteine levels (13.0+/-6.7 micromol/l) than did subjects with more adequate intakes (10.9+/-4.1 micromol/l) (P<0.05). CONCLUSION: The diet of the study subjects might be improved, especially with respect to pyridoxine and folic acid. Raising the intake of the latter might be especially useful in controlling homocysteine levels and the risk of cardiovascular disease.

J Nutr Health Aging. 2002;6(1):75-7.

Reduced serum concentrations of riboflavine and ascorbic acid, and blood thiamine pyrophosphate and pyridoxal-5-phosphate in geriatric patients with and without pressure sores.

Selvaag E, Bohmer T, Benkestock K.

Department of medicine, Aker University Hospital, Oslo, Norway.

BACKGROUND: Patients with pressure sores have as part of their treatment been reefed with energy and proteins with varying result. It has been uncertain, however, to what an extent these patients also were depleted of micronutrients which might be critical for ulcer healing. OBJECTIVE: To study the nutritional intake and nutritional status of a number of micronutrients in geriatric pressure sore patients and in matched controls. DESIGN: The nutritional intake and nutritional status as anthropometric measures, serum conc. of albumin, zinc, and of vitamins (ascorbic acid, riboflavin, calcidiol), were measured. Thiamin pyrophosphate and pyridoxal-5-phosphate were determined in whole blood from 11 geriatric in-patients with pressure sores and 11 matched controls. RESULTS: The serum conc. of ascorbic acid was significantly (p< 0.05) more reduced in pressure sore patients (mean+/-S.D.) 4.2+/-3.4 (ug/ml) than in control patients 7.4+/-5.4 (ug/ml) which still was lower than in a reference group (10.9+/-1.9) (ug/ml). In all the geriatric patients compared to the reference group, the conc. of serum-riboflavin was reduced to about 15 %, thiamine-pyrophosphate and pyridoxine-5-phosphate in whole blood and serum calcidiol to about 50 %, without any differences between the pressure sore patients and the matched controls. CONCLUSION: Refeeding of pressure sore patients who often are catabolic and have increased needs for protein and energy, should include micronutrients not only to cover recommended dietary allowances, but sufficient to reach normal nutritional status for the individual micronutrient.

Stomatologiia (Mosk). 2002;81(2):45-9.

[Complex diagnosis of congenital cranial dysostosis in children]

[Article in Russian]

Iakubov RK, Azimov MI.

Ten patients (aged 3-15 years) with congenital cranial dysostosis were examined by a pediatrician, geneticist, gastroenterologist, neuropathologist, ophthalmologist, endocrinologist, and orthopaedist. In addition to the clinical signs characteristic of hereditary multiple developmental defects, the study revealed changes in the jaws and temporomandibular joint and local factors promoting the progress of deformations of the jaws. Manifest and inapparent pathological changes and dysfunctions in gastrointestinal organs were paralleled by dysfunctions of the central and autonomic nervous systems, risk of maxillofacial and general deformations, and signs of congenital disorders in calcium, lactic acid, and pyridoxine metabolism. The results necessitate analyses of the blood and urine and development of new methods for the diagnosis of congenital cranial dysostosis and improvement of methods for the correction of this condition.

Turk J Pediatr. 2002 Jan-Mar;44(1):54-7.

Acute isoniazid neurotoxicity in childhood.

Citak A, Kaya O, Ucsel R, Karabocuoglu M, Uzel N.

Department of Pediatric Emergency, Istanbul University Institute of Child Health, , Turkey.

Acute isoniazid (INH) poisoning is uncommon in children. Although most physicians are aware of INH hepatotoxicity, acute INH poisoning and its treatment are not well recognized. INH is increasingly being used to control the spread of tuberculosis, and physicians should know its potentially fatal effects. INH overdose is known to result in rapid onset of seizures, metabolic acidosis and prolonged obtundation. We report two cases of obtundation secondary to INH overdose that was immediately reversed by pyridoxine. Parenteral pyridoxine administration is an effective method in INH intoxication. The intravenous form of pyridoxine must be available in the emergency care units, and INH toxicity should be suspected in any patient with refractory seizures and metabolic acidosis.

Arterioscler Thromb Vasc Biol. 2001 Dec;21(12):2072-9. Long-term homocysteine-lowering treatment with folic acid plus pyridoxine is associated with decreased blood pressure but not with improved brachial artery endothelium-dependent vasodilation or carotid artery stiffness: a 2-year, randomized, placebo-controlled trial.

van Dijk RA, Rauwerda JA, Steyn M, Twisk JW, Stehouwer CD.

Institute for Cardiovascular Research Vrije Universiteit, Department of Internal Medicine, University Hospital Vrije Universiteit, Netherlands.

Homocysteine is associated with atherothrombotic disease, which may be mediated through associations of homocysteine levels with blood pressure, endothelial function, or arterial stiffness. In a placebo-controlled, randomized clinical trial, we measured blood pressure, brachial artery endothelium-dependent vasodilation, and common carotid artery stiffness in 158 clinically healthy siblings of patients with premature atherothrombotic disease at baseline and after 1 and 2 years of homocysteine-lowering treatment with folic acid (5 mg) plus pyridoxine (250 mg). Intention-to-treat analyses limited to participants (n=130) who underwent at least 1 measurement after the baseline visit showed that compared with placebo, treatment with folic acid plus pyridoxine was associated with a 3.7-mm Hg (95% CI -6.8 to -0.6 mm Hg) lower systolic and a 1.9-mm Hg (95% CI -3.7 to -0.02 mm Hg) lower diastolic blood pressure over the 2-year trial period. Together with the decreased occurrence of abnormal exercise electrocardiography tests reported previously, our results support the hypothesis that homocysteine-lowering treatment with folic acid plus pyridoxine has beneficial vascular effects. Because no effects could be demonstrated on brachial artery endothelium-dependent vasodilation or on common carotid artery stiffness, the present study does not support the hypothesis that the cardiovascular effects of homocysteine are mediated through these factors, at least in clinically healthy individuals.

J Inherit Metab Dis. 2001 Dec;24(8):833-42. Impact of new mutations in the methylenetetrahydrofolate reductase gene assessed on biochemical phenotypes: a familial study.

Tonetti C, Amiel J, Munnich A, Zittoun J.

Service d'Hematologie Biologique, Hopital Henri Mondor, Creteil, France.

Methylenetetrahydrofolate reductase (MTHFR) deficiency was identified in two out of four children born from nonconsanguineous parents. One of the affected children exhibited some clinical findings suggesting cystathionine beta-synthase deficiency; MTHFR activity was extremely reduced. In addition, hyperhomocysteinaemia, hypomethioninaemia, low total folate, especially methylfolate in red blood cells, and a reduced methylfolate/total folate ratio were found. Two mutations not yet reported, one on exon 1 of the gene changing an arginine to stop codon and one other on exon 9 changing an arginine to tryptophan were identified in both children in the compound heterozygous state associated with a common polymorphism, 1298A>C, also in the heterozygous state. The mother, homozygous for the mutation on exon 9 and for the polymorphism 1298A>C on exon 7, was clinically and biochemically normal, with normal folate status, mainly methylfolate levels in red blood cells, although MTHFR activity was moderately decreased. The father, heterozygous for the transition arginine to stop codon and for the common polymorphism 677C>T on exon 4, exhibited major biochemical abnormalities, hyperhomocysteinaemia and low methylfolate levels in red blood cells, but was clinically normal. The unaffected children had a biochemical pattern close to that of their mother and were heterozygous for the mutation on exon 9 and also for the two common polymorphisms, 677C>T and 1298A>C. In the affected children, some biochemical abnormalities, including folate status, especially methylfolate levels, were improved with treatment combining methyltetrahydrofolic acid, hydroxocobalamin, pyridoxine and betaine; however, homocysteine concentrations remained high and methionine concentrations were lowered. The father was treated with folic acid, which partially improved biochemical abnormalities. The impact of these mutations is discussed.

J Nutr. 2001 Dec;131(12):3208-11. Bioavailability and antioxidant activity of some food supplements in men and women using the D-Roms test as a marker of oxidative stress.

Cornelli U, Terranova R, Luca S, Cornelli M, Alberti A.

Loyola University Medical Center, Stritch School of Medicine, Maywood, IL 60153, USA. corcon@katamail.com

Most antioxidants show contradictory behaviors because in the biological environment, for unpredictable reasons, they can become prooxidants. Recently, a new simple method to monitor oxidative stress in serum was developed. This test detects the derivatives of reactive oxygen metabolites (D-Roms). Hydroperoxides are converted into radicals that oxidize N,N-diethyl-para-phenylendiamine and that can be detected through spectrophotometric procedures as U.CARR. (Carratelli units). One U.CARR. corresponds to 0.8 mg/L hydrogen peroxide. In normal subjects U.CARR. values range from 250 to 300. Values outside this range indicate a modification of the prooxidant/antioxidant ratio. On the basis of this method, we tested three different formulas of antioxidants (F1, F2, F3) in 14 apparently healthy volunteers (11 men and 3 women). Formula 1 was composed of 5 mg zinc, 48 microg selenium, 400 microg vitamin A (as retinol acetate), 50 microg beta-carotene, 15 mg vitamin E (as dl-alpha-tocopheryl acetate) and 10 mg L-cysteine. Formula 2 was composed of 30 mg bioflavonoids from citrus, 30 mg vitamin C (as L-ascorbic acid), 10 mg coenzyme Q(10) and 1 mg vitamin B-6 (as pyridoxine hydrochloride). Formula 3 was composed of Formula 1 plus Formula 2. Each formula was prepared in dry capsules (formulation D1, D2, D3) or in a fluid form (formulation P1, P2, P3). Each formulation was administered for 1 wk in a crossover design. A 15% deviation of U.CARR. levels was chosen as the cut-off value for a significant change in oxidative stress. Formulas F1 and F3 reduced mean U.CARR. levels in most of the treated subjects (t test, P < 0.05), whereas F2 was not active. Fluid formulations were more active than dry formulations (chi(2) test, P < 0.05). In some cases, a slight increase in oxidative stress was detected. These minimal increases were not related to any particular antioxidant formula. In one subject only, the administration of the dry formulation (D1), increased oxidative stress to a level that reached the cut-off value. In conclusion, when antioxidants are taken in combination at low dosages they reduce oxidative stress, and little relevant prooxidant activity is detectable

J Paediatr Child Health. 2001 Dec;37(6):592-6. Pyridoxine-dependent seizures: a case report and a critical review of the literature.

Gupta VK, Mishra D, Mathur I, Singh KK.

Neonatal Division, Department of Paediatrics, Dr Ram Manohar Lohia Hospital, New Delhi, India.

Pyridoxine-dependent seizures are a recognized, although rare, cause of intractable seizures in neonates. Patients with this autosomal recessive disorder have recurrent seizures that are resistant to conventional anticonvulsants but respond dramatically to intravenous administration of pyridoxine. Life-long supplementation with pyridoxine is required to prevent seizure recurrence. In the absence of a biological marker for the disease, clinical diagnosis is often delayed and severe neurological sequelae are common. Herein, we report on the clinical course of a neonate with pyridoxine-dependent seizures. Delayed normalization of the electroencephalogram and a normal developmental outcome (at 15 months of age) on a dose of 10 mg/kg pyridoxine are distinctive features of the present case. We also review recent clinical observations and neurochemical studies that have added to our knowledge of this disorder.

N Engl J Med. 2001 Nov 29;345(22):1593-600.

Comment in: • N Engl J Med. 2002 Apr 4;346(14):1093-5. • N Engl J Med. 2002 Apr 4;346(14):1093-5. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels.

Schnyder G, Roffi M, Pin R, Flammer Y, Lange H, Eberli FR, Meier B, Turi ZG, Hess OM.

Division of Cardiology, Swiss Cardiovascular Center Bern, University Hospital. g.schnyder@lycos.com

BACKGROUND: We have previously demonstrated an association between elevated total plasma homocysteine levels and restenosis after percutaneous coronary angioplasty. We designed this study to evaluate the effect of lowering plasma homocysteine levels on restenosis after coronary angioplasty. METHODS: A combination of folic acid (1 mg), vitamin B12 (400 microg), and pyridoxine (10 mg)--referred to as folate treatment--or placebo was administered to 205 patients (mean [+/-SD] age, 61+/-11 years) for six months after successful coronary angioplasty in a prospective, double-blind, randomized trial. The primary end point was restenosis within six months as assessed by quantitative coronary angiography. The secondary end point was a composite of major adverse cardiac events. RESULTS: Base-tine characteristics and initial angiographic results after coronary angioplasty were similar in the two study groups. Folate treatment significantly lowered plasma homocysteine levels from 11.1+/-4.3 to 7.2+/-2.4 micromol per liter (P<0.001). At follow-up, the minimal luminal diameter was significantly larger in the group assigned to folate treatment (1.72+/-0.76 vs. 1.45+/-0.88 mm, P=0.02), and the degree of stenosis was less severe (39.9+/-20.3 vs. 48.2+/-28.3 percent, P=0.01). The rate of restenosis was significantly lower in patients assigned to folate treatment (19.6 vs. 37.6 percent, P=0.01), as was the need for revascularization of the target lesion (10.8 vs. 22.3 percent, P=0.047). CONCLUSIONS: Treatment with a combination of folic acid, vitamin B12, and pyridoxine significantly reduces homocysteine levels and decreases the rate of restenosis and the need for revascularization of the target lesion after coronary angioplasty. This inexpensive treatment, which has minimal side effects, should be considered as adjunctive therapy for patients undergoing coronary angioplasty.

Orv Hetil. 2001 Nov 11;142(45):2459-67.

[The pathogenesis of diabetic and hepatic neuropathies]

[Article in Hungarian]

Winkler G, Kempler P.

Fovarosi Szent Janos Korhaz, II. Belgyogyaszati Osztaly.

The pathomechanism of neuropathies associated with diabetes and chronic liver diseases are poorly understood. Both metabolic and vascular factors are involved in the pathogenesis of diabetic neuropathy. It seems likely, that microangiopathy on the one hand and changes of various metabolic pathways due to hyperglycaemia on the other hand are much more related to each other than it was suggested previously. Nitric oxide may be the link between the metabolic and vascular hypotheses of diabetic neuropathy. Both reduced endoneurinal blood flow and increased oxidative stress leads to reduced nitric oxide synthetase activity. There are widespread inter-relationships between the most relevant metabolic changes included polyol pathway hyperactivity, reduced myoinosit concentration, advanced glycation end products formation, increased oxidative stress and lipid peroxidation. Changes of hemorheological conditions and primary hemostasis leeds to hyperviscosity just as to increased activity of the coagulation system. Among patients with chronic alcoholic liver diseases the direct toxic effect of alcohol is of particular relevance, however, malabsorption, impairment of axoplasmatic transport, changes of intermedier metabolism as well as thiamine and pyridoxine deficiency are of importance as well. The role of decreased insulin sensitivity and various degrees of glucose intolerance related to chronic liver diseases are still underestimated. Impairment of proteoglycan metabolism as well as increased oxydative stress are thought to be important factors in the pathogenesis of both diabetic and hepatic neuropathies. Glucose autooxidation and enhanced lipid peroxidation contribute to increased oxidative stress in patients with diabetes and chronic liver diseases as well. Vitamin E deficiency, autoimmun processes, circulating immune complexes, cryoglobulinemia, just as changes of vascular responsiveness associated with nitric oxide activity plays a role in the development of neural damage of hepatic origin. Most likely, similarly to diabetes mellitus, vascular changes contribute to the development of neuropathy in patients with chronic liver diseases.

Int J Mol Med. 2001 Nov;8(5):505-8.

Pyridoxal 5'-phosphate and pyridoxal inhibit angiogenesis in serum-free rat aortic ring assay.

Matsubara K, Mori M, Matsuura Y, Kato N.

Department of Nutritional Science, Faculty of Health and Welfare Science, Okayama Prefectural University, 111 Kuboki, Soja, Okayama 719-1197, Japan. kmatsuba@fhw.oka-pu.ac.jp

Supraphysiological doses of vitamin B6 has been reported to suppress tumor growth and metastasis in rodents. To examine if its anticancer effect is due to suppression in angiogenesis, this study was conducted to investigate the antiangiogenic effect of pyridoxal 5'-phosphate (PLP), pyridoxine, pyridoxal and pyridoxamine in an ex vivo serum-free matrix culture model using rat aortic ring. Rat aortic rings were incubated with PLP or pyridoxine (25 micromol/l to 5 mmol/l). Higher concentrations of PLP (2.5 and 5 mmol/l) and pyridoxine (5 mmol/l) caused complete inhibition of microvessel outgrowth. However, the addition of pyridoxine at 2.5 mmol/l did not show complete inhibition of angiogenesis. PLP inhibited microvessel outgrowth almost completely at a concentration of 500 micromol/l and showed antiangiogenic effect in a dose-dependent manner within the range of 25-500 micromol/l. At 250 micromol/l, pyridoxal was as effective as PLP, but pyridoxamine was inactive, implying that the aldehyde group relates to the antiangiogenic effect. These results indicated the antiangiogenic effect of PLP and pyridoxal, and suggested that the antitumor effect of high levels of vitamin B6 might be mediated through suppression of angiogenesis.

J Hum Nutr Diet. 2001 Oct;14(5):365-70. Riboflavin deficiency in cystic fibrosis: three case reports.

McCabe H.

Newcastle Nutrition, Royal Victoria Infirmary, Newcastle Upon Tyne Hospitals NHS Trust, Newcastle Upon Tyne NE1 4LP, UK. nutrition@trvi.nuth.northy.nhs.uk

Three cases of clinical riboflavin deficiency are reported in children aged 2-10 years attending a regional Cystic Fibrosis clinic. Riboflavin deficiency presented as angular stomatitis in all three patients. Patients were confirmed to be riboflavin deficient by assaying the activity of erythrocyte glutathione reductase. Patients were not on routine supplements of water-soluble vitamins before presentation and were treated with riboflavin supplements as part of a water-soluble vitamin complex. At presentation, one patient had poor nutritional status, but two patients were adequately nourished, receiving overnight Gastrostomy feeds. Data on these two patients indicate an adequate dietary intake of riboflavin, suggesting a mechanism for increased requirements, inadequate absorption or utilization. Additional deficiencies of thiamin, pyridoxine and iron were also observed. This paper reports the occurrence of a vitamin deficiency not previously reported in the cystic fibrosis population.

Am J Psychiatry. 2001 Sep;158(9):1511-4. Vitamin B(6) in the treatment of tardive dyskinesia: a double-blind, placebo-controlled, crossover study.

Lerner V, Miodownik C, Kaptsan A, Cohen H, Matar M, Loewenthal U, Kotler M.

Division of Psychiatry, Ministry of Health Be'er Sheva Mental Health Center, Faculty of Health Sciences Ben-Gurion University of the Negev, Israel. lernervld@yahoo.com

OBJECTIVE: The authors' goal was to conduct a double-blind trial of vitamin B(6) in the treatment of tardive dyskinesia in patients with schizophrenia. METHOD: Fifteen inpatients with schizophrenia who met research diagnostic criteria for tardive dyskinesia were randomly assigned to treatment with either vitamin B(6) or placebo for 4 weeks in a double-blind crossover paradigm. The Extrapyramidal Symptom Rating Scale was used to assess patients weekly. RESULTS: Mean scores on the parkinsonism and dyskinetic movement subscales of the Extrapyramidal Symptom Rating Scale were significantly better in the third week of treatment with vitamin B(6) than during the placebo period. CONCLUSIONS: Vitamin B(6) appears to be effective in reducing symptoms of tardive dyskinesia.

Atherosclerosis. 2001 Sep;158(1):161-4. Vitamin supplementation can markedly reduce the homocysteine elevation induced by fenofibrate.

Dierkes J, Westphal S, Kunstmann S, Banditt P, Lossner A, Luley C.

Institute of Clinical Chemistry and Biochemistry, Leipziger Str. 44, D-39120 Magdeburg, Germany. jutta.dierkes@medizin.uni-magdeburg.de

Elevated homocysteine concentrations are a risk factor for atherosclerotic disease. Recently it was reported that lipid lowering with fibrates increases homocysteine by up to 40%. Since elevated homocysteine concentrations can readily be lowered by vitamin supplementation, a randomized, double-blind crossover study was performed to investigate the effect of fenofibrate plus folic acid, vitamin B6 and B12 versus fenofibrate plus placebo in hyperlipidemic men. The crossover study comprised a run-in period of 6 weeks, a first treatment phase of 6 weeks, a washout phase of 8 weeks and a second treatment phase of 6 weeks. Vitamins were given at doses of 650 microg folic acid, 50 microg vitamin B12 and 5 mg vitamin B6 per day for a period of 6 weeks. After fenofibrate plus placebo the increase in homocysteine concentration was 44+/-47%. After fenofibrate plus vitamins it was 13+/-25%, being significantly lower than without vitamins. The increase in homocysteine in response to fenofibrate may counteract the cardioprotective effect of lipid lowering. The addition of vitamins involved in homocysteine metabolism can prevent most of the homocysteine increase seen after fenofibrate plus placebo. Addition of these vitamins to fenofibrate may therefore be warranted for routine use.

Expert Opin Pharmacother. 2001 Sep;2(9):1449-60. Homocysteine-lowering treatment: an overview.

van Guldener C, Stehouwer CD.

Department of Internal Medicine, University Hospital and Institute of Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands.

Elevated fasting plasma concentrations of homocysteine have a high prevalence in subjects with cardiovascular disease and have also been associated with an increased risk of atherothrombosis in most, but not all, prospective studies. The most frequent causes of hyperhomocysteinaemia are genetic defects, such as cystathionine-beta-synthase (CBS) deficiency, deficiencies of folic acid and/or vitamin B12, renal failure and interference in homocysteine metabolism by drugs or metabolic alterations. In most cases, no underlying cause can be established. Subjects with CBS deficiency are treated with pyridoxine with additional folic acid and betaine if necessary. Folic acid and vitamin B12 deficiencies should be corrected by supplementation. Increases in folate intake by dietary changes or fortification can also lower plasma homocysteine in vitamin-replete subjects with normal plasma homocysteine levels. In renal failure, folic acid treatment (1-5 mg/day) ameliorates the plasma homocysteine level in most cases but hyperhomocysteinaemia persists in the majority of patients. Primary (fasting) hyperhomocysteinaemia can be treated with folic acid (0.5-5 mg/day). An abnormal methionine-loading test identifies additional patients at risk and postmethionine-loading hyperhomocysteinaemia should be treated with a combination of pyridoxine and folic acid. In the absence of dose-effect studies, a combination of pyridoxine (50 mg) and folic acid (5 mg) is advised. Large clinical trials are currently underway to establish the role of homocysteine-lowering therapy in the secondary prevention of atherothrombotic disease. In view of the effective, cheap and safe character of therapy with folic acid and pyridoxine, a policy can be accepted to screen and treat high-risk patients until these trials have been concluded.

Heart Lung Transplant. 2001 Sep;20(9):964-9. Pyridoxine improves endothelial function in cardiac transplant recipients.

Miner SE, Cole DE, Evrovski J, Forrest Q, Hutchison S, Holmes K, Ross HJ.

Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

BACKGROUND: Endothelial dysfunction is common in cardiac transplant recipients and predicts the development of transplant coronary artery disease. Hyperhomocysteinemia is associated with endothelial dysfun