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]
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.
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.
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]
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.
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.