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Vitamin B6: 457 Research Abstracts

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

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

[Article in Russian]

Pichkhadze GM.

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

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

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

Goutieres F, Aicardi J.

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

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

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

Hagen I, Nesheim BI, Tuntland T.

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

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

Vitamin B-6 status of southern adolescent girls.

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

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

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

Controlled trial of pyridoxine in the premenstrual syndrome.

Williams MJ, Harris RI, Dean BC.

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

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

Lupus vulgaris responding to double antituberculous therapy.

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

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

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

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

Folkers K, Wolaniuk A, Vadhanavikit S.

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

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

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

Schuster K, Bailey LB, Mahan CS.

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

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

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

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

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

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

The vitamin B6 status of 60 institutionalised elderly subjects (group A: 31 men, mean age = 77 yr and 29 women, mean age = 84 yr) and 41 healthy young adults (group B or control group: 18 men, mean age = 30 yr and 23 women, mean age = 27 yr) was evaluated using erythrocyte aspartate aminotransferase activity coefficient (alpha EGOT) and plasma pyridoxal phosphate (PLP) level (vitamin B6-deficient subjects = alpha greater than 2.0 and PLP less than 80 nmol/l). The kilocalorie, protein and pyridoxine intakes were also estimated. Regarding calories and protein, the diets may be generally considered satisfactory in respect to the French 1981 RDA. The mean dietary intake of vitamin B6 was less than 2 mg/day in all groups. Ninety per cent of the aged, 80 per cent of females in group B in contrast to 56 per cent of males in group B consumed less than their individual vitamin B6 requirements as determined by a probability method. As the incidence of vitamin B6 biochemical deficiency was much higher in the group A (71% for males and 86% for females) than in the control group (11% for males and 30% for females), it is concluded that the high incidence of biochemical vitamin B6 deficiency noted in the aged appeared more relevant from an altered metabolism of the vitamin than from a too low energy intake. Supplements with high doses of vitamin B6 to aged subjects caused a significant decrease in alpha EGOT and a significant increase in PLP levels.

Nephron. 1984;38(1):9-16.

Immunologic abnormalities in hemodialysis patients: improvement after pyridoxine therapy.

Casciato DA, McAdam LP, Kopple JD, Bluestone R, Goldberg LS, Clements PJ, Knutson DW.

8 male patients undergoing maintenance hemodialysis were studied to determine the effect of administering supplements of pyridoxine hydrochloride, 50 mg/day for 3-5 weeks, on tests of immune function. In the 3 patients who initially had abnormal nitroblue tetrazolium reduction tests, the values returned to normal with therapy (p less than 0.05). The generation of chemotactic factors from plasma was defective in all evaluated patients and improved after pyridoxine therapy in 4 of 5 patients (p less than 0.01). The lymphocyte subpopulations changed with a rise in the populations of null cells after supplementation with pyridoxine. In addition, lymphocyte transformation in response to mitogens improved in the 3 patients who initially showed low values in these assays. The improvements occurred with pyridoxine therapy even though some patients who responded had no evidence for vitamin B6 deficiency before therapy, as indicated by a normal erythrocyte glumatic-pyruvic transaminase index. We conclude that several parameters of immune function are improved with pyridoxine supplementation. Studies are necessary to establish the minimum daily intake of pyridoxine which will maintain improved values of these tests of immune function in hemodialysis patients.

Pediatr Pharmacol (New York). 1984;4(3):199-202.

Acute isoniazid intoxication: reversal of CNS symptoms with large doses of pyridoxine.

Brown A, Mallett M, Fiser D, Arnold WC.

Acute toxicity from ingestion of isoniazid (INH) is manifested by coma and seizures unresponsive to conventional therapy. Though small doses of pyridoxine can reverse the seizure activity of acute isoniazid toxicity, large doses of pyridoxine (B6) are needed to completely reverse the symptoms. A case report is presented demonstrating the need for large doses of pyridoxine to reverse the symptoms of isoniazid intoxication and the literature of isoniazid toxicity in the pediatric age group is reviewed.

223: Brooks SC, D'Angelo L, Chalmeta A, Ahern G, Judson JH. An unusual schizophrenic illness responsive to pyridoxine HCl (B6) subsequent to phenothiazine and butyrophenone toxicities. Biol Psychiatry. 1983 Nov;18(11):1321-8. No abstract available. PMID: 6652165

Int J Radiat Oncol Biol Phys. 1983 Oct;9(10):1513-9.

Misonidazole neurotoxicity in mice decreased by administration with pyridoxine.

Eifel PJ, Brown DM, Lee WW, Brown JM.

A series of toxicological and pharmacological experiments was performed to test the hypothesis that alterations of pyridoxine (Vitamin B6) metabolism may play an important role in the development of misonidazole (MISO) neurotoxicity. The formation of a Schiff's base between the final reduction product of MISO, 2-amino MISO (NH2-MISO), and pyridoxal-HCl in ethanol was demonstrated. Mice receiving daily intraperitoneal injections of MISO suffered significantly less toxicity (as determined by survival, weight gain and neurological tests) when large doses of pyridoxine-HCl (PYR) were delivered concomitantly, and consequently were able to tolerate administration of more than twice as many MISO injections. PYR did not alter the pharmacokinetics of MISO, either when given simultaneously or when given by multiple repeated daily injections prior to MISO. The administration of PYR also did not alter the radiosensitization by MISO in an in vivo-in vitro cloning assay with the EMT6 tumor in BALB/c mice. If depletion or altered metabolism of pyridoxine by reduced metabolites is also responsible for the neurotoxic effects of nitroimidazoles in humans, then concomitant administration of pyridoxine (in doses greater than the molar quantity of NH2-MISO formed) should inhibit the development of such symptoms and allow administration of larger doses of MISO than are currently clinically employable.

Arch Dis Child. 1983 Jun;58(6):415-8.

Pyridoxine dependent seizures--a wider clinical spectrum.

Bankier A, Turner M, Hopkins IJ.

We report 4 infants with pyridoxine dependent seizures who had clinical features that led to diagnostic uncertainty. Their clinical course was unusual in 1 or more of the following: later onset of initial seizures; a seizure free period after taking of anticonvulsants, but before taking of pyridoxine; a long remission after withdrawal of pyridoxine; and atypical seizure type. This report illustrates a broader range of clinical features and highlights the need to consider the diagnosis of pyridoxine dependent seizures in any infant with intractable epilepsy, regardless of the pattern of seizures and the response to anticonvulsant medications. In such a case, 100 mg intravenous pyridoxine should be given and, if a definite clinical response is established, oral pyridoxine should be continued indefinitely.

Ann Emerg Med. 1983 May;12(5):303-5.

Isoniazid overdose treated with high-dose pyridoxine.

Yarbrough BE, Wood JP.

Large doses of pyridoxine recently have been shown to prevent the seizures and acidosis caused by ingestion of more than two to three grams of isoniazid. We present three cases of massive isoniazid ingestion, producing seizures and acidosis, that were treated successfully by administration of one gram of pyridoxine intravenously for each gram of isoniazid ingested.

Scand J Gastroenterol. 1983 Mar;18(2):299-304.

Reversal of psychopathology in adult coeliac disease with the aid of pyridoxine (vitamin B6).

Hallert C, Astrom J, Walan A.

Signs of mental depression are typical in adults presenting with coeliac disease. The response to treatment was evaluated in 12 consecutive patients by means of the Minnesota Multiphasic Personality Inventory (MMPI), with surgical patients serving as controls. The coeliacs reported no change in depressive symptoms after 1 year's gluten withdrawal despite evidence of improvement in the small intestine. When retested after 3 years, however, after 6 months of 80 mg/day of oral pyridoxine (vitamin B6) therapy, they showed a fall in the score of scale 2 ('depression') from 70 to 56 (p less than 0.01), which became normalized like other pretreatment abnormalities in the MMPI. Cholecystectomy in the control subjects produced no alterations in the MMPI profile. The results indicate a causal relationship between adult coeliac disease and concomitant depressive symptoms which seems to implicate metabolic effects from pyridoxine deficiency influencing central mechanisms regulating mood.

Ann Neurol. 1983 Jan;13(1):103-4.

Pyridoxine-dependency seizure: report of a rare presentation.

Krishnamoorthy KS.

A child developed minor motor seizures at the age of 14 months accompanied by an abnormal electroencephalogram showing single spikes and polyspikes over the vertex and frontocentral regions. Seizures continued until the age of 22 months despite administration of several standard anticonvulsants. At age 22 months, pyridoxine, 75 mg daily, was initiated and anticonvulsants were discontinued. Both the seizures and the electroencephalographic abnormality have disappeared over the ensuing 20 months with pyridoxine therapy.

Proc Eur Dial Transplant Assoc. 1983;19:308-12.

Reduction of elevated plasma oxalic acid by pyridoxine therapy in patients on RDT.

Balcke P, Schmidt P, Zazgornik J, Kopsa H.

In eight chronic haemodialysed patients with secondary hyperoxalaemia due to renal insufficiency vitamin B6, an important co-enzyme in oxalic acid metabolism, was administered. Mean plasma oxalic acid values decreased from 149.5 +/- 67.0 mmol/L to 99.0 +/- 36.4 mmol/L within two weeks and to 93.8 +/- 33.1 mmol/L after four weeks of pyridoxine treatment (p less than 0.01, p less than 0.01). The mean reduction was 46 per cent (32.0 to 56.1). Patients with high pre-values of plasma oxalic acid had the most pronounced decrease. In order to prevent calcium oxalate deposition a reduction of plasma oxalic acid in patients on RDT seems to be an important goal in long term haemodialysis treatment.

Proc Eur Dial Transplant Assoc. 1983;20:417-21.

Pyridoxine therapy in patients with renal calcium oxalate calculi.

Balcke P, Schmidt P, Zazgornik J, Kopsa H, Minar E.

In 12 patients with idiopathic calcium oxalate calculi pyridoxine was administered. Within six weeks mean daily oxalic acid excretion decreased from 480 +/- 122 mumol to 336 +/- 83 mumol. Glycolic acid excretion fell from 208 +/- 51 mumol to 153 +/- 26 mumol (normal range: oxalic acid 228-412 mumol/day, glycolic acid 130-290 mumol/day). The reduction of oxalic acid excretion seems to be beneficial in prevention of idiopathic calcium oxalate calculi.

Acta Ophthalmol (Copenh). 1982 Dec;60(6):894-906.

Homocystinuria treated with pyridoxine.

Blika S, Saunte E, Lunde H, Gjessing LR, Ringvold A.

Four cases of homocystinuria with lens luxation have been examined. As judged from the plasma amino acid pattern, they all responded well on pyridoxine treatment. Two of them discontinued the treatment on their own, and one of these died at the age of 17 years. The lens luxation progressed in one case despite adequate treatment. Scanning electron microscopy of one lens revealed partly broken zonules, abnormal zonular attachment, and a spongy appearance of the capsule proper. Hoping that adequate treatment will reduce more serious complications such as thromboembolism in these patients, it is concluded that an early diagnosis largely depends on the ophthalmologist, who should perform the silver-nitroprusside test, specific for homocystinuria, in all patients with non traumatic lens luxation.

Proc Natl Acad Sci U S A. 1982 Dec;79(23):7494-8.

Response of vitamin B-6 deficiency and the carpal tunnel syndrome to pyridoxine.

Ellis JM, Folkers K, Levy M, Shizukuishi S, Lewandowski J, Nishii S, Schubert HA, Ulrich R.

The specific activities and percentage deficiencies of the glutamic oxaloacetic transaminase of erythrocytes (EGOT) were determined for patients with carpal tunnel syndrome (CTS) diagnosed by clinical examination and electrical conduction data; the EGOT data revealed a severe deficiency of vitamin B-6. After double-blind treatment with pyridoxine and placebo, two physicians identified those receiving pyridoxine (clinically improved) and those receiving placebo (did not improve) without error, P less than 0.0078. Correcting a deficiency of the coenzyme at receptors of existing molecules of the apoenzyme appears to take place within days; correction of the deficiency in the number of molecules of the transaminase takes place over 10-12 weeks. The clinical response, appraised by the diminution of the symptoms of CTS, was correlated only with the restored levels of the transaminase which presumably results from a translational long-term increase in the number of molecules of EGOT by a mechanism activated by correcting a deficiency of pyridoxal 5'-phosphate. Apparent Km values of EGOT were identical for groups of patients with CTS and others without CTS but with identical specific activities, indicating that CTS is a primary deficiency of vitamin B-6 rather than one of a dependency state. Clinical improvement of the syndrome with pyridoxine therapy may frequently obviate hand surgery.

Drug Intell Clin Pharm. 1982 Nov;16(11):876-7.

Amitriptyline-related peripheral neuropathy relieved during pyridoxine hydrochloride administration.

Meadows GG, Huff MR, Fredericks S.

Tricyclic antidepressants rarely cause peripheral neuropathy. In fact, this class of drugs has been used to control the symptoms of pain and paresthesia that accompany peripheral neuropathy. We report peripheral paresthesias that occurred in a 39-year-old female during five years of amitriptyline administration. The patient's symptoms were relieved by oral pyridoxine hydrochloride, associated with elevated plasma pyridoxal phosphate.

Scand J Haematol. 1982 Nov;29(5):421-4.

Pyridoxine-responsive primary acquired sideroblastic anaemia. In vitro and in vivo effects of vitamin B6 on decreased 5-aminolaevulinate synthase activity.

Meier PJ, Fehr J, Meyer UA.

The activity of 5-aminolaevulinate (ALA) synthase, the first and rate-limiting of haem synthesis, was markedly reduced (13% of controls) in erythroblasts of a patient with acquired, primary sideroblastic anaemia (PASA). The reduced activity of ALA synthase could not be restored in vitro with 1 mmol/l pyridoxal-5-phosphate (PLP). Treatment of the patient with pyridoxine for several months increased the ALA synthase activity from 13% to 50% of controls in the absence and to 100% in the presence of PLP in the incubation medium. These studies suggest that both increased degradation of apo-ALA synthase and decreased affinity of ALA synthase for PLP may be involved in pyridoxine-responsive PASA.

Vopr Pitan. 1982 Nov-Dec;(6):54-6.

[Enzyme activity changes in chronic alcoholic intoxication and the simultaneous administration of pyridoxine]

[Article in Russian]

Iliev IS, Stoev TS, Damianova MI, Krushkova AM.

After prolonged application of ethanol the liver and brain of rats show an appreciable increase in lactate dehydrogenase activity, noticeable lowering of cytoplasmic aspartate and alanine aminotransferase activity, elevation of liver arginine succinate lyase activity with unchanged activities of other enzymes of the ornithine cycle (ornithine carbamoyltransferase and arginase), reduction of glutamate and malate dehydrogenase and mitochondrial aspartate aminotransferase activity in brain tissue. Concurrent application of ethanol and pyridoxine normalizes the effect of ethanol on liver arginine succinate lyase and on brain tissue lactate and malate dehydrogenase, mitochondrial and cytoplasmic aspartate aminotransferase and alanine aminotransferase.

Z Geburtshilfe Perinatol. 1982 Nov-Dec;186(6):326-34.

[Magnesium aspartate as a cardioprotective agent and adjuvant in tocolysis with betamimetics. Animal experiments on the kinetics and calcium antagonist action of orally administered magnesium aspartate with special reference to simultaneous vitamin B administration]

[Article in German]

Wischnik A, Schroll A, Kollmer WE, Berg D, Wischnik B, Wieshammer E, Weidenbach A.

With pregnant Wistar-rats, suffering from alimentary magnesium deficiency, absorption and distributing of Mg28 has been studied, the latter having been applied as aspartate and as chloride, with and without simultaneous substitution of vitamin B6. Absorption and tissue pooling were found to be augmented when using the aspartate and even more when adding vitamin B6. These differences were significant in the blood as well as in fetal and myocardial tissue. Correlation between blood-Mg28 und Mg28-activities in various tissues shows, that blood magnesium levels indicate a magnesium deficiency at least in the tissues of interest: fetus, myocardium, uterus and placenta. Nevertheless blood magnesium levels fail to reflect an additional tissue pooling, that exerts a beneficial action in the respect of cardio protection and of saving beta-mimetic tocolytics. When measuring magnesium and calcium excretion during chronic experiments with and without oral magnesium aspartate substitution, it could be demonstrated, that the amount of substituted magnesium has been pooled almost totally. Oral magnesium substitution furthermore reduces intestinal calcium absorption. Investigation on calcium uptake into the maternal myocardium revealed, that oral magnesium aspartate substitution significantly diminishes myocardial calcium uptake, the latter among others being responsible for cardiac hazards during tocolysis with beta-mimetic substances, while the pharmacologic calcium-antagonist Verapamil failed to do so.

Am Rev Respir Dis. 1982 Oct;126(4):714-6.

Maternal plasma concentration of pyridoxal phosphate during pregnancy: adequacy of vitamin B6 supplementation during isoniazid therapy.

Atkins JN.

Vitamin B6 is an important supplement both for pregnant patients and for those receiving isoniazid. Therefore, we decided to monitor pyridoxal phosphate (PLP) concentrations in 12 pregnant patients who were receiving isoniazid to be certain that supplementation was adequate. Patients were given a prenatal vitamin preparation and 50 mg of pyridoxine hydrochloride daily. At 1 month 10 of the 12 patients had adequate PLP concentrations. Seven of these 10 patients had elevated PLP concentrations and 3 had normal concentrations. Supplementation with 52 to 60 mg per day of Vitamin B6 produces adequate PLP concentrations in pregnant patients who are also taking isoniazid.

Int J Clin Pharmacol Ther Toxicol. 1982 Sep;20(9):434-7.

Effect of pyridoxine supplementation on recurrent stone formers.

Murthy MS, Farooqui S, Talwar HS, Thind SK, Nath R, Rajendran L, Bapna BC.

Twelve recurrent stone formers with hyperoxaluria were administered pyridoxine-HCl (10 mg/day) daily for a period of 180 days. The pyridoxine status of the patients, as assessed by their erythrocyte transaminase activation indexes, improved significantly (p less than 0.001) after 180 days of supplementation as compared with the basal levels. Although urinary oxalate decreased significantly (p less than 0.05) by the 90th day of pyridoxine therapy, other parameters, e.g., urinary calcium, phosphorus, and creatinine, remained unaltered. Significant correlation was observed between erythrocyte glutamate pyruvate transaminase (EGPT) or erythrocyte glutamate oxaloacetate transaminase (EGOT) activation index and urinary oxalate excretion (p less than 0.01). Pyridoxine in low doses (10 mg/day) is of therapeutic value for hyperoxaluric stone formers.

Ann Clin Res. 1982 Apr;14(2):61-5.

Haema synthesis during pyridoxine therapy in two families with different types of hereditary sideroblastic anaemia.

Pasanen AV, Salmi M, Tenhunen R, Vuopio P.

The activity of delta-aminolaevulinic acid synthase (ALA-S) as well as the concentrations of coproporphyrin and protoporphyrin in peripheral red blood cells were examined in 2 sisters and in 2 brothers with hereditary sideroblastic anaemias (HSA) of different types. The measurements were done before and during treatment by pyridoxal-5-phosphate (PLP) and/or pyridoxine chloride. Previous family studies indicated an X chromosome linked HSA in the 2 brothers, whereas the precise mode of inheritance in the 2 sisters has not been established. Previous and present studies have revealed no characteristic defect in haema synthesis in the 2 sisters and their treatment by PLP or pyridoxine produced no haematologic response although a slight stimulation of haema synthesis was observed. In contrast, the 2 brothers showed decreased activity of ALA-S and decreased protoporphyrin concentration in peripheral red blood cells. After treatment by PLP and/or pyridoxine the ALA-S activity was restored to normal. Corresponding to the stimulation of haema synthesis a partial haematological response was observed in both brothers. Stopping and restarting of pyridoxine therapy in one brother confirmed the above results. These observations indicate the presence of two genetically and biochemically different types of HSA and help us to understand the varying response to pyridoxine therapy in this rare disorder.

J Infect Dis. 1982 Apr;145(4):547-9.

Trial of pyridoxine therapy for tetanus neonatorum.

Godel JC.

Pyridoxine, a coenzyme in the production of gamma-amino-n-butyric acid, was added (100 mg per day) to conventional therapy for tetanus neonatorum in 20 infants who were graded according to prognosis and severity of spasms. Three infants died, for an overall mortality of 15%. All three were in prognostic group V; mortality in group V was 37.5%. Fifteen days after admission, 14 (70%) of the remaining 17 infants were free of spasms and three (15%) had only mild spasms. In comparison to other studies in which conventional therapy alone was used for tetanus neonatorum, the addition of pyridoxine appeared to decrease mortality and the duration of spasms.

Acta Vitaminol Enzymol. 1982;4(1-2):27-44.

Clinical and biological effects of high doses of vitamin B6 and magnesium on autistic children.

Lelord G, Callaway E, Muh JP.

In 1973 Rimland reported that some autistic children responded favorably to high doses of vitamin B6. Since this finding, different studies were performed to identify apparently B6 responsive subjects and to critically evaluate clinical and biological B6 responsiveness. Magnesium was included because large doses of B6 might increase irritability. 44 patients (mean age 9.3 years) were examined. All selected children had marked autistic symptoms. The children received a complete diagnostic work-up, including psychiatric, psychological, neurological and medical evaluation. Clinical data were scored using an estimate of global clinical state and numerical rating on a 18 item scale (Behavior Summarized Evaluation). In a first open trial 15 out of 44 children exhibited moderate clinical improvement with worsening on termination of the trial. Thirteen responders and 8 non responders were re-tested in a 2-week crossover, double-blind trial and the responses to the open trial were confirmed. Biochemical data analysis revealed that a significant decrease in urinary homovanillic acid (HVA) levels was observed during B6-Mg administration. During B6-Mg treatment, middle latency evoked potentials exhibited a significant increase of amplitude.

Acta Vitaminol Enzymol. 1982;4(1-2):45-54.

Therapy of side effects of oral contraceptive agents with vitamin B6.

Bermond P.

Studies carried out in different countries during the last 15 years have provided evidence that supplementation with (or excess of) estro-progestational hormones may be accompanied by an increased urinary excretion of tryptophan metabolites, as happens in pyridoxine deficiency. Further methods of assessment of vitamin B6 in humans have confirmed an impaired status in women using hormonal contraception. Disturbances in the metabolism of tryptophan have been shown to be responsible for such symptoms as depression, anxiety, decrease of libido and impairment of glucose tolerance occurring in some of the OCA users. Administration of 40 mg of vitamin B6 daily not only restores normal biochemical values but also relieves the clinical symptoms in those vitamin B6 deficient women taking OCA's. Further studies are justified to clarify whether vitamin B6 supplementation may contribute to improving depression also in other situations with hyperoestrogenism (pregnancy, puerperium, estro-progestational treatments, etc.), as well as correcting metabolic impairments, such as a minor alteration of glucose tolerance.

PIP: Studies carried out in different countries over the last 15 years have provided evidence that supplementation with or excess of estrogen-progestogen hormones may be accompanied by an increased urinary excretion of tryptophan metabolites, as occurs in pyroxidine deficiency. Further methods of assessment of vitamin B6 in humans have confirmed that there is impaired status in women using oral contraceptives (OCs). Disturbances in the tryptophan metabolism have been shown to be responsible for such symptoms as depression, anxiety, decrease in libido, and impairment of glucose tolerance occurring in some OC users. Administration of 40 mg vitamin B6 daily not only restores the normal biochemical values but also relieves the clinical symptoms in those vitamin B6 deficient women taking OCs. Further studies are justified to clarify whether vitamin B6 supplementation may contribute to improving depression in other situations where there is hyperestrogenism (pregnancy, puerperium, estrogen-progestogen treatments), as well as correcting metabolic impairments, such as a minor alteration in glucose tolerance. (author's modified)

Graefes Arch Clin Exp Ophthalmol. 1982;218(1):21-4.

Biochemical and therapeutical studies in a case of atrophia gyrata.

Behrens-Baumann W, Konig U, Schroder K, Hansmann I, Langenbeck U.

A thirty-six years old man from an inbred family with the typical clinical picture of Atrophia gyrata chorioideae et retinae was found to have hyperornithinemia and a partial deficiency of ornithin-ketoacid-transaminase activity. The residual activity was stimulated in vitro by high concentrations of pyridoxal phosphate. We have initiated a therapeutic study with vitamin B6 per os accordingly. Comparitively low doses may be sufficient for long term treatment. The necessity to start therapy early in life is emphazised. Possible mechanisms of the pathogenesis of Atrophia gyrata are discussed.

Padiatr Padol. 1982;17(2):149-55.

Influence of pyridoxine on the oxygen transport function of blood in the neonatal period in clinical and experimental conditions.

Boda D, Temesvari P, Eck E.

A significant increase of the P50 value of blood (the pO2 value of O2 half saturated blood at 37 degrees C, pH 7.40 and pCO2 of 5.33 kPa) was observed on symptom free premature newborns, mature newborns requiring intensive care and newborn rabbits treated with high dose of pyridoxine (Vitamin B6). The change seemed to be independent of the 2,3-DPG content of blood. The moderate but consistently favourable influence of vitamin B6 treatment on the O2 transport function of blood can be advantageous in early postnatal adaptation disturbances of newborns.

245: Hall MA, Thom H, Russell G. Erythrocyte aspartate amino transferase activity in asthmatic and non-asthmatic children and its enhancement by vitamin B6. Ann Allergy. 1981 Dec;47(6):464-6. No abstract available. PMID: 7325421

246: Wood ER. Isoniazid toxicity. Pyridoxine controlled seizures in a dialysis patient. J Kans Med Soc. 1981 Dec;82(12):551-2. No abstract available.

JAMA. 1981 Sep 4;246(10):1102-4.

Single high-dose pyridoxine treatment for isoniazid overdose.

Wason S, Lacouture PG, Lovejoy FH Jr.

We treated five isoniazid-overdosed patients each with a single dose of pyridoxine hydrochloride equivalent to the gram amount of isoniazid ingested and compared their outcome with that of 41 patients from the literature who received little or no pyridoxine. Recurrent seizures occurred in 60% of patients who had received no pyridoxine vs 0% in our patients. Metabolic acidosis resolved in our cases but was refractory in the literature cases. In our cases, coma lightened more rapidly and was of shorter duration as compared with that in the literature cases (mean, seven hours vs 24 hours). No adverse effects of pyridoxine were seen in our patients.

Res Commun Chem Pathol Pharmacol. 1981 Aug;33(2):331-44.

Therapy with vitamin B6 with and without surgery for treatment of patients having the idiopathic carpal tunnel syndrome.

Ellis J, Folkers K, Levy M, Takemura K, Shizukuishi S, Ulrich R, Harrison P.

Blood samples from four patients at the time of surgery to relieve the compression of the carpal tunnel syndrome, which was diagnosed by clinical and electromyographic evaluation, were differentially assayed to determine the specific activities and the % deficiencies of the erythrocyte glutamic oxaloacetic transaminase (EGOT). The data from these assays revealed that these four patients had a severe deficiency of vitamin B6. These data, in conjunction with previous biochemical and clinical results over five years, underscore the desirability, and even necessity, of testing by the EGOT analysis for the presence of a severe deficiency of vitamin B6 in all such patients before surgery. Treatment with vitamin B6 (pyridoxine) for a minimum period of 12 weeks, depending upon the duration and severity of the symptoms, has been effective without exception. Surgery may relieve compression, but does not correct a deficiency of vitamin B6. Surgery in addition to therapy with vitamin B6 should be reserved for those patients who have had the deficiency for so many years that much tissue damage is irreversible by pyridoxine, and additional relief from pain can be achieved through the surgery.

249: Bukharovich MN, Gridasova VD, Miroshnichenko AG. [Combined treatment of acne using pyridoxine and hydrogen sulfide baths] Vestn Dermatol Venerol. 1981 Aug;(8):46-9. Russian. No abstract available. PMID: 6456617

Biol Psychiatry. 1981 Jul;16(7):627-41.

Effects of vitamin B6 on averaged evoked potentials in infantile autism.

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

In autistic children, averaged evoked potentials have been reported to have lower amplitudes and shorter latencies than those of normal children. Also, moderate clinical improvement has been observed in some autistic children after treatment with vitamin B6 and magnesium. We have studied biochemical and electrophysiological effects of vitamin B6 and magnesium in 12 autistic children and in 11 normal children. During treatment of the autistic children with B6, an increase of amplitude of middle-latency evoked potentials and a decrease of urinary homovanillic acid were found. The reverse was noted in the normal subjects.

251: Harrison AR, Kasidas GP, Rose GA. Hyperoxaluria and recurrent stone formation apparently cured by short courses of pyridoxine. Br Med J (Clin Res Ed). 1981 Jun 27;282(6282):2097-8. No abstract available. PMID: 6788219

J Autism Dev Disord. 1981 Jun;11(2):219-30.

Effects of pyridoxine and magnesium on autistic symptoms--initial observations.

Lelord G, Muh JP, Barthelemy C, Martineau J, Garreau B, Callaway E.

In an open trial, a heterogeneous group of 44 children with autistic symptoms were treated with large doses of vitamin B6 and magnesium. Clinical improvement with worsening on termination of the trial was observed in 15 children. Thirteen responders and 8 nonresponders were retested in a 2-week, crossover, double-blind trial, and the responses to the open trial were confirmed.

Kidney Int. 1981 May;19(5):694-704.

Daily requirement for pyridoxine supplements in chronic renal failure.

Kopple JD, Mercurio K, Blumenkrantz MJ, Jones MR, Tallos J, Roberts C, Card B, Saltzman R, Casciato DA, Swendseid ME.

Vitamin B6 deficiency was evaluated in 37 patients with chronic renal failure and in 71 patients undergoing maintenance hemodialysis (HD) or intermittent peritoneal dialysis (PD). Vitamin B6 deficiency was assessed by the in vitro activity of erythrocyte glutamic pyruvic transaminase (EGPT), without (basal) and with (stimulated) the addition of pyridoxal-5-phosphate to the assay, and the EGPT index (stimulated activity ./. basal activity). Basal and stimulated EGPT activities were below normal in the HD patients, and the EGPT index was increased in each group of patients, indicating vitamin B6 deficiency. Supplemental pyridoxine hydrochloride was given to 30 HD patients who received 1.25 to 50 mg/day (37 studies), 6 PD patients who were given 1.25 or 2.5 mg/day (7 studies), and 8 nondialyzed patients with mild to severe renal failure who received 2.5 mg/ day. In all HD patients, 10 or 50 mg/day of pyridoxine hydrochloride rapidly corrected the abnormal EGPT index and maintained normal values; with supplements of 5.0 mg/day or less, the index was often abnormal, particularly in those who were septic or taking pyridoxine antagonists. In PD patients and nondialyzed patients with renal failure, 2.5 mg/day of pyridoxine hydrochloride was inadequate to correct rapidly the abnormal index in all patients. These findings suggest that HD patients should receive 10 mg/day of supplemental pyridoxine hydrochloride (8.2 mg/day pyridoxine). PD patients and patients with chronic renal failure should receive about 5.0 mg/day of supplemental pyridoxine hydrochloride (4.1 mg/day pyridoxine). When sepsis intervenes or vitamin B6 antagonists are taken, 10 mg/day of pyridoxine hydrochloride may be a safer supplement for all patients.

Ophthalmology. 1981 Apr;88(4):316-24.

Clinical trial of vitamin B6 for gyrate atrophy of the choroid and retina.

Weleber RG, Kennaway NG.

Seven patients with gyrate atrophy and deficiency of ornithine-delta-aminotransferase were studied for in vivo pyridoxine responsiveness; three responded to oral vitamin B6 with over 50% reduction of serum ornithine levels and return to normal of serum lysine levels. Electrophysiologic studies were performed on two B6-responsive patients and one B6-nonresponder over various time periods with and without pyridoxine supplementation. Electroretinogram (ERG) amplitudes improved 100% in one patient when initially given high doses of vitamin B6. Electro-oculogram light-to-dark ratio also improved for this patient. Withdrawal followed by resumption of B6 supplementation was associated with mild worsening followed by improvement of ERG responses respectively in both patients. Long-term follow-up will be needed to assess whether pyridoxine treatment will slow or halt the progression of the disease.

255: Harpey JP, Rosenblatt DS, Cooper BA, Le Moel G, Roy C, Lafourcade J. Homocystinuria caused by 5,10-methylenetetrahydrofolate reductase deficiency: a case in an infant responding to methionine, folinic acid, pyridoxine, and vitamin B12 therapy. J Pediatr. 1981 Feb;98(2):275-8. No abstract available. PMID: 7007598

Int Pharmacopsychiatry. 1981;16(4):245-50.

The use of nicotinic acid and pyridoxine in the treatment of schizophrenia.

Petrie WM, Ban TA, Ananth JV.

As part of the Canadian Mental Health Association Collaborative Study, the hypothesis that combined administration of nicotinic acid and pyridoxine has greater therapeutic effects than the component drugs in chronic schizophrenic patients was tested. This could not be substantiated in a 48-week study in which supplementation of neuroleptic treatment with a single vitamin, i.e., nicotinic acid or pyridoxine, produced significant therapeutic changes, while supplementation with both vitamins did not.

Vestn Khir Im I I Grek. 1981 Jan;126(1):36-40.

[Pathogenetic treatment of acute pancreatitis]

[Article in Russian]

Suvernev AV.

In acute experiments in albino rats it was shown that mannitol, polyglucin and hemodesis possess antiproteolytic properties. Pyridoxine, hemodesis and polyglucin were also found to be antagonists to the effects of bradykinin. Pyridoxine, polyglucin and hemodesis proved to be most effective in the treatment of experimental trypsinemia. The results of the conservative treatment of patients with acute pancreatitis were better if pyridoxine and polyglucin were added to the complex of curative measures.

Tubercle. 1980 Dec;61(4):191-6.

Pyridoxine supplementation during isoniazid therapy.

Snider DE Jr.

Vitamin B6 (pyridoxine) supplementation during isoniazid (INH) therapy is necessary in some patients to prevent the development of peripheral neuropathy. In vivo pyridoxine is converted into coenzymes which play an essential role in the metabolism of protein, carbohydrates, fatty acids, and several other substances, including brain amines, INH apparently competitively inhibits the action of pyridoxine in these metabolic functions. The reported frequency of INH-induced neuropathy in various studies is reviewed and population groups at relatively high risk of developing this complication are identified. The routine use of pyridoxine supplementation to prevent peripheral neuropathy in high risk populations is recommended.

Farmakol Toksikol. 1980 Sep-Oct;43(5):601-3.

[Effect of the combined use of flavin coenzyme preparations and pyridoxine on the body vitamin balance in animals]

[Article in Russian]

Stroev EA, Kazakova NT.

The effect of combined administration of flavin coenzymes and pyridoxine on B2-avitaminosis rats' supply with these vitamins has been studied. It has been disclosed that pyridoxine promotes more effective normalization of riboflavin and pyridoxine balance in the body, this balance being measured from the excretion of riboflavin and 4-pyridoxin acid with urine as well as from the content of total flavins in blood and tissues. In vitamin B2 lack, it is recommended that pyridoxin be combined with flavin mononucleotide and in particular with flavin adenine dinucleotide.

Am J Hum Genet. 1980 Jul;32(4):529-41.

Gyrate atrophy of the choroid and retina with hyperornithinemia: biochemical and histologic studies and response to vitamin B6.

Kennaway NG, Weleber RG, Buist NR.

Four patients with hyperomithinemia and gyrate atrophy of the choroid and retina age described. In vivo response to vitamin B6 is documented in three of the four patients by significant reduction of fasting serum ornithine and increase of lysine after oral B6 supplementation. Oral glucose tolerance testing in one patient resulted in marked changes in serum ornithine and lysine concentrations, in addition to mild glucose intolerance. Histochemical staining of punch muscle biopsies showed intracellular inclusions in type 2 muscle fibers. Tubular aggregates, approximately 60 nm in diameter and adjacent to the sarcoplasmic membrane, were seen on electron microscopy. Obligate heterozygotes had a mean serum ornithine slightly higher than normal, but there was considerable overlap with the normal range. Oral ornithine tolerance tests distinguished carriers from controls in only one of five cases. Deficient activity of ornithine ketoacid aminotransferase (OKT) in cultured skin fibroblasts was documented in all four patients. Approximately half-normal levels were found in obligate heterozygotes. In vitro response to B6 was manifest by increased OKT activity at increased concentrations of pyridoxal phosphate in fibroblasts from the patients.

261: Gunby P. Vitamin B6 appears useful in treating choroid disorder. JAMA. 1980 May 9;243(18):1792-3. No abstract available. PMID: 7365947

Acta Vitaminol Enzymol. 1980;2(5-6):171-8.

[Effect of vitamin B6 on some immune responses in chronic uremia (author's transl)]

[Article in Italian]

Sorice F, De Simone C, Meli D, Ferrari M, Morellini M, De Luca D, Taccone Gallucci M, Casciani CU.

Patients with chronic uremia undergoing periodic haemodialysis were found to have low levels of vitamin B6 (12 out of 18 patients). The same subjects also showed a reduction of the immunocompetence. The AA. report that the administration of pyridoxine (100 mg/die for 4 weeks) can induce a normalization of the vitamin levels and of some immunological parameters.

263: Cardi E. [Inborn errors of amino acid metabolism treatable with B group vitamins: synoptic aspects] Acta Vitaminol Enzymol. 1980;2(3-4):124-9. Italian. No abstract available. PMID: 7246391

Am J Clin Nutr. 1979 Oct;32(10):2040-6.

Clinical results of a cross-over treatment with pyridoxine and placebo of the carpal tunnel syndrome.

Ellis J, Folkers K, Watanabe T, Kaji M, Saji S, Caldwell JW, Temple CA, Wood FS.

Clinical evaluation was made of cross-over treatments by pyridoxine and a placebo of patient 22 having the carpal tunnel syndrome. Extraordinary monitoring of the specific activities of the erythrocyte glutamic oxaloacetic transaminase proved a severe vitamin B6 deficiency, which was partially corrected by the Recommended Dietary Allowance of 2 mg, and completely corrected by 100 mg. The severity of the syndrome diminished on the Recommended Dietary Allowances and the patient was asymptomatic at the higher dosage. On placebo, both the vitamin B6 deficiency and syndrome reappeared. Retreatment with 100 mg again corrected both the deficiency and syndrome. Measurements (total n = 19) of flexion of proximal interphalangeal joints of the index fingers by a goniometer, and of pinch by the Preston gauge revealed objective normalization. Scores of 17 symptoms revealed reductions at both the 2- (P less than 0.01) and 100-mg (P less than 0.001) dosages. Conduction through the carpal tunnels had improved by electromyography. These and previous data on a total of 22 patients showed the concomitant presence of a deficiency of vitamin B6 and the carpal tunnel syndrome; a causal relationship is apparent.

Biol Psychiatry. 1979 Oct;14(5):741-51.

A preliminary study of the effect of pyridoxine administration in a subgroup of hyperkinetic children: a double-blind crossover comparison with methylphenidate.

Coleman M, Steinberg G, Tippett J, Bhagavan HN, Coursin DB, Gross M, Lewis C, DeVeau L.

A small sample of six patients with the putative "hyperkinetic syndrome" participated in a research protocol comparing administration of pyridoxine, methylphenidate, and placeboes. The children had had low whole blood serotonin levels and a history of previous responsiveness to methylphenidate. The results of the double-blind clinical evaluation showed trends suggesting that both pyridoxine and methylphenidate were more effective than placebo in suppressing the symptoms of hyperkinesis. Pyridoxine elevated whole-blood serotonin levels, methylphenidate did not. Clinical and laboratory evidence indicated that the pyridoxine effects persisted after the 3-week period when the vitamin had been given in this experimental design.

266: Clarke TA, Saunders BS, Feldman B. Pyridoxine-dependent seizures requiring high doses of pyridoxine for control. Am J Dis Child. 1979 Sep;133(9):963-5. No abstract available. PMID: 474552

Cancer Res. 1979 Aug;39(8):2988-94.

Effects of dietary vitamin B6 on the in vitro inactivation of rat tyrosine aminotransferase in host liver and Morris hepatomas.

Reynolds RD, Morris HP.

Control rats or rats bearing Morris hepatoma 5123C (intact), 5123C (adrenalectomized), 7794A, 7800, 8999, 9121, or 9618A were fed a purified diet either deficient or adequate for vitamin B6. The concentration of pyridoxal phosphate in the plasma, host livers, and hepatomas was determined, as well as the in vitro rate of inactivation of induced tyrosine aminotransferase in homogenates of host livers and hepatomas. The results demonstrated the presence of a cysteine-independent inactivating system for tyrosine aminotransferase in hepatomas 5123C (adrenalectomized), 7800, 8999, and 9121. Only in hepatoma 9121 was there a dramatic influence of the dietary vitamin B6 on the rate of cysteine-independent inactivation. A cysteine-dependent inactivating system for the enzyme was present in all host livers and hepatomas. The rate of this in vitro inactivation for both host livers and hepatomas apparently was a function of the concentration of pyridoxal phosphate, but inactivation of tyrosine aminotransferase occurred at a significantly lower concentration of pyridoxal phosphate in the hepatomas than in the host livers.

268: Vainshtok AB. [Treatment of parkinsonism with large doses of vitamin B6] Sov Med. 1979 Jul;(7):14-9. Russian. No abstract available. PMID: 505122

Vopr Pitan. 1979 Jul-Aug;(4):32-40.

[Role of vitamin B6 in treating children with hereditary metabolic pathology]

[Article in Russian]

Barashnev IuI, Rozova IN, Semiachkina AN.

Possibilities of vitamin B6 treatment of patients with hereditary pathology of metabolism are discussed. Special attention is paid to the vitamin B6-dependent conditions characterized by elevated pyridoxine requirements. High pyridoxine doses were successfully used for the treatment of patients with hereditary vitamin B6-dependent xanthurenuria under the control of renal excretion of tryptophan metabolites (xanthurenic and kynurenic acids, kynurenin, N1-methylnicotinamide) and 4-pyridoxic acid. Interrelation was traced between the severity of the disease and the necessary pyridoxine doses. Patients with the most pronounced clinical and biochemical changes needed especially high doses of the vitamin (200 mg/day). Use of vitamin B6 in a dose of 100 mg/day in pyridoxine-dependent homocystinuria induced a remission of the biochemical parameters on the 4th day of the treatment. It is noted that the efficacy of the treatment is dependent on the timely starting of the therapy and pyridoxine doses necessary for normalization of the clinical and biochemical parameters in each patient.

Metabolism. 1979 May;28(5):542-8.

Primary oxalosis: clinical and biochemical response to high-dose pyridoxine therapy.

Will EJ, Bijvoet OL.

Although pyridoxine hydrochloride (vitamin B6) is known to reduce the endogenous production of oxalate in some individuals with primary oxalosis, the dose for a satisfactory trial of treatment is not established. We report two cases of primary oxalosis on a daily regimen of 1 g pyridoxine hydrochloride, in which 24-hr urinary oxalate excretion decreased by 60% and 70%, respectively, with corresponding clinical benefit. The responses have been sustained up to 2.5 yr in one case, and 20 mo in the other. In the patient with renal failure, serum creatinine decreased from 243 to 146 mumole/liter after 15 mo of treatment. The decrease in glycollic acid excretion in both patients was consistent with an increase of glyoxalate transaminase activity by the vitamin. Supranormal levels of erythrocyte glutamic oxaloacetate transaminase (egot) activity were observed during therapy, and these may be useful as a measure of the effective dose of pyridoxine.

Am J Obstet Gynecol. 1979 Mar 1;133(5):499-502.

Pyridoxine treatment of chemical diabetes in pregnancy.

Gillmer MD, Mazibuko D.

Thirteen women with chemical diabetes diagnosed in late pregnancy were found to excrete excessive amounts of urinary xanthurenic acid after a tryptophan load, indicative of a relative pyridoxine (vitamin B6) deficiency. Treatment with 100 mg pyridoxine daily for 14 to 23 days restored the urinary xanthurenic acid excretion to normal in all patients. Improvement of glucose tolerance was observed in only two of the patients studied, deterioration in six, and no significant change in the remaining five. The insulin response to glucose was unaltered during pyridoxine therapy.

Proc Clin Dial Transplant Forum. 1979;9:194-6.

Water soluble vitamins in patients with chronic renal failure and effect of B6 administration of immunological activity.

Kamata K, Okubo M, Marumo F.

Blood concentrations of water soluble vitamins were studied in 29 undialyzed and 35 dialyzed patients with CRF, and 36 healthy volunteers. Effects of B6 administration on immunological parameters were studied in dialyzed patients. In dialyzed patients, whole blood B1 decreased, while plasma B2, B6 and serum B12 and folic acid increased. In undialyzed patients with uremia, plasma B2, serum B12 and folic acid increased, while plasma C decreased in patients with moderate CRF. Oral administration of B6 for 4 wks was associated with improved tuberculin skin tests and PHA mitogen responses in dialyzed patients. Supplementation of B1 is required for patients with CRF while B6 and C may be considered.

Scand J Urol Nephrol. 1979;13(1):101-3.

The influence of vitamin B6 supplementation on the bone marrow morphology in patients on regular haemodialysis treatment. A double-blind study.

Sjogren U, Thysell H, Lindholm T.

Bone marrow smears from 20 patients with chronic renal failure and on regular haemodialysis treatment (RDT) were morphologically analysed. A double-blind study of treatment with high doses of vitamin B6 showed that the patients receiving pyridoxine got raising frequencies of lymphocytes and monocytes in the bone marrow and there were morphologic signs of a normalization within the granulopoiesis. It is suggested that this is a sign of an enhancement of the immune response. The vitamin supplementation had no significant effects on the pronounced anemia of the patients.

Vopr Pitan. 1979 Jan-Feb;(1):26-32.

[Action of biotin-pyridoxine complex on the development of experimental atherosclerosis]

[Article in Russian]

Borets VM, Kishkovich VP, Lis MA, Butkevich ND, Mironchik VV.

Investigations were conducted in two series of tests on 40 rabbits. In the first series a selection of the optimal dose of the vitamins was made and in the II series the action of the optimal dose of the biotin-pyridoxine complex was studied. Each test series included 2 control groups of the animals. The biotin-pyridoxine complex (in doses of 80 gamma and 3.2 mg per 1 kg of the body mass) was shown to exert an inhibitory action on the development of experimental atherosclerosis.

Rev Neurol (Paris). 1978 Dec;134(12):797-801.

[Modifications in urinary homovanillic acid after ingestion of vitamin B6; functional study in autistic children (author's transl)]

[Article in French]

Lelord G, Callaway E, Muh JP, Arlot JC, Sauvage D, Garreau B, Domenech J.

Basing their study on the investigations which led to the dopaminergic theory of the psychoses, the authors studied homovanillic acid (principal derivative from dopamine) levels in the urines of 37 autistic children, and 11 normal children acting as controls. The favourable action of vitamin B6 on autism, reported by anglosaxon authors, was confirmed in 15 of the children. Furthermore, vitamin B6 reduces homovanillic acid levels in 33 autistic chilren and increases them in all the control group children.

Am J Med. 1978 Oct;65(4):655-60.

Response to pyridoxine hydrochloride in refractory anemia due to myelofibrosis.

Rojer RA, Mulder NH, Nieweg HO.

Eleven of 14 patients with primary myelofibrosis were given a therapeutic trial with 250 mg of pyridoxine hydrochloride daily because of refractory anemia. The effect on the hemoglobin level and the hematocrit value was studied and compared to that in a group of untreated patients with the same degree of anemia. Six of 11 treated patients responded within three months with a rise in the hemoglobin level (at least 3 g/100 ml) and/or an increase in the hematocrit value (at least 10 per cent), and transfusions were no longer required. Deliberate discontinuation of pyridoxine treatment in one responding patient was followed by a relapse of the anemia; resumption of therapy once again induced an erythropoietic response. Spontaneous remissions of anemia were not observed in the untreated group. It is concluded that a trial with pyridoxine is warranted in patients with myelofibrosis and refractory anemia.

Am J Clin Nutr. 1978 Aug;31(8):1383-91.

Vitamin B6 status of the hospitalized aged.

Vir SC, Love AH.

Nutritional status of vitamin B6 was investigated in two groups of 102 hospitalized aged. Vitamin B6 intake was estimated. Erythrocyte glutamic-pyruvic transaminase stimulation in vitro with pyridoxal phosphate and SGOT were studied as the biochemical criteria of vitamin B6 status: 18.6% of the subjects consumed less than 0.66 mg of vitamin B6 per day; 28.4% showed a percentage stimulation in vitro with pyridoxal phosphate of more than 15%. There was no significant correlation between basal erythrocyte glutamic-pyruvic transaminase activity and dietary protein, dietary vitamin B6 dietary vitamin B6/100 g of protein, SGOT, hemoglobin, mean corpuscular volume, and iron. All the biochemical parameters used for evaluating vitamin B6 status appeared higher in females, but no statistical difference between male and female groups was noted. Only SGOT levels of female subjects reflected their vitamin B6 status. A large individual variation of vitamin B6 requirement was indicated in both groups studied. Supplements with 2.5 mg of vitamin B6 to deficient subjects caused an increase in transaminase levels, though females showed a higher response. A higher recommended allowance of vitamin B6 for the aged male and female subjects was considered desirable.

Am J Dis Child. 1978 Aug;132(8):773-6.

A pyridoxine-dependent behavioral disorder unmasked by isoniazid.

Brenner A, Wapnir RA.

A 3-year-old girl had behavioral deterioration, with hyperkinesis, irritability, and sleeping difficulties after the therapeutic administration of isoniazid. The administration of pharmacologic doses of pyridoxine hydrochloride led to a disappearance of symptoms. After discontinuing isoniazid therapy a similar pattern of behavior was noted that was controlled by pyridoxine. A placebo had no effect, but niacinamide was as effective as pyridoxine. Periodic withdrawal of pyridoxine was associated with return of the hyperkinesis. The level of pyridoxal in the blood was normal during the periods of relapse. Metabolic studies suggested a block in the kynurenine pathway of tryptophan metabolism. The patient has been followed for six years and has required pharmacologic doses of pyridoxine to control her behavior.

J Clin Psychiatry. 1978 Jun;39(6):573-5.

High-dose pyridoxine in tardive dyskinesia.

DeVeaugh-Geiss J, Manion L.

The clinical similarities of tardive dyskinesia and 1-dopa intoxication lend support to the post-synaptic hypersensitivity hypothesis in tardive dyskinesia. Pyridoxine, a co-factor in the decarboxylation of dopa, reverses the movement disorder of l-dopa intoxication. Although early studies of pyridoxine in tardive dyskinesia have not been encouraging, the results of the present study suggest that high doses of pyridoxine may reduce the frequency and severity of involuntary movements in tardive dyskinesia.

Nouv Rev Fr Hematol. 1978 Apr 14;20(1):99-110.

[Anemia with hypersideroblastosis during anti-tuberculosis therapy. Cure with vitamin therapy]

[Article in French]

Vives JF, Rouy JM, Wagner A, Vallat G.

The unusual occurrence of microcytic anemia with hypochromia, high iron blood levels and excess of sideroblasts in the bone marrow, observed during the treatment of tuberculosis with isoniazid and rifampicine is reported. Three particularities were noted. First, in our experience, the occurrence of this type of anemia has never been noted previously as a result of these two drugs. Secondly, the improvement of the blood abnormalities was obtained by the combined use of vitamin B6 and vitamin C. Thirdly, the anemia was associated with neuropathy, characterized by areflexia and dysesthesia, which improved with vitamin B6 therapy (but not with vitamin C). Some mechanisms are discussed as being possibly the origin of this kind of anemia, particularly a lack of vitamin B6 resulting from a massive urinary loss of pyridoxal induced by isoniazid as well as both a tissue depletion and an overconsumption of this vitamin. The anemia may be the consequence of a deficiency of hemoglobin synthesis involving probably the first step of the biosynthesis of heme.

Am J Psychiatry. 1978 Apr;135(4):472-5.

The effect of high doses of vitamin B6 on autistic children: a double-blind crossover study.

Rimland B, Callaway E, Dreyfus P.

The authors used data from an earlier nonblind study to identify 16 autistic-type child outpatients who had apparently improved when given vitamin B6 (pyridoxine). In a double-blind study each child's B6 supplement was replaced during two separate experimental trial periods with either a B6 supplement or a matched placebo. Behavior was rated as deteriorating significantly during the B6 withdrawal.

Fortschr Med. 1978 Feb 9;96(6):299-300.

[Complaints in the lumbosacral region and their management with Dolo-Neurobion]

[Article in German]

Kunt T.

Many patients complaining of acute pain in the lumbosacral area suffer from affections of intrapelvic organs (urinary bladder, prostate glands, female genital-organs). The routine diagnosis in such cases is described. In 53 own patients the analgesic and anti-inflammatory effect of Dolo-Neurobion has been evaluated. It is a combination drug consisting of the neurotropic vitamins B1, B6 and B12 and the analgesic metamizole. The treatment was started parenterally in the recommended doses and continued orally. If there were definite signs of infection in the pelvic area, additional antibiotics were administered after bacteriological tests. Dolo-Neurobion showed good or excellent results in 77,4% and moderate effects in 15,1% of the patients. There were no major side-effects or intolerance.

Acta Chir Acad Sci Hung. 1978;19(4):363-72.

[Clinical studies of Magurlit granulates]

[Article in German]

Frang D, Verebelyi A, Nagy Z.

The possibilities of dissolving by means of medication uric acid and uric acid-calcium oxalate calculi are discussed. The biochemical causes of uric acid lithogenesis was studied. Due to successful pharmacotherapy the number of operations has greatly diminished in recent years. On the basis of experience gained with various citrate mixtures the authors claim that Magurlit is the most advantageous litholytic drug. Due to its magnesium and vitamin B6 content it is also suitable for the dissolution of uric acid calculi containing calcium oxalate in diffuse distribution, i.e. for the prevention of the development of stones of this type.

J Med. 1978;9(3):193-9.

Vitamin B6 responsive infantile convulsions and branched chain amino aciduria.

Scottolini AG, Woo P, Bhagavan NV.

This study reports of a case with neo-natal convulsions and branched amino-aciduria in addition to tryptophanuria. These abnormalities were promptly corrected by administration of pyridoxine.

Zh Nevropatol Psikhiatr Im S S Korsakova. 1978;78(3):402-8.

[Effect of pyridoxine on the psychopathology and pathochemistry of involutional depressions]

[Article in Russian]

Bukreev VI.

In agreement with the catecholamine hypotheses of affective disorders the main role in the pathogenesis of depressive states is allocated to the central "noradrenergic insufficiency". The author thinks it feasible to use pyridoxine (vit. B6) in the treatment of depressive states, inasmuch as it is involved in the process of catecholamine synthesis as a cofactor of DOPA-decarboxylase. The author examined 48 patients among which 31 were with involutional melancholia and 17 with manic-depressive psychoses, manifesting after 40 years. Along with a positive therapeutical effect there was an increase in the noradrenaline excretion and a drop in the relative adrenaline content.

Urology. 1977 Dec;10(6):556-61.

Comparisons of placebo, pyridoxine, and topical thiotepa in preventing recurrence of stage I bladder cancer.

Byar D, Blackard C.

Animal studies have shown that metabolites of tryptophan can cause bladder cancer, and human observations reveal an appreciable incidence of abnormalities of tryptophan metabolism in patients with bladder cancer. It has been suggested that pyridoxine (vitamin B6) may correct this abnormality and prevent recurrences of superficial bladder cancers. Intravesical instillation of thiotepa has been used for more than fifteen years in the treatment of superficial bladder cancer, but no controlled trials have been done. We report here a prospective clinical trial of 121 patients with Stage I bladder cancer randomized to placebo, pyridoxine, or intravesical thiotepa. The percentages of patients with recurrences over the period of study were 60.4, 46.9, and 47.4 for the three groups, respectively, and did not differ significantly. However, if patients having recurrences during the first ten months or followed up less than ten months were excluded, pyridoxine was significantly better than placebo (P = 0.03). Thiotepa significantly reduced the recurrence rate compared with placebo (P = 0.016) or pyridoxine (P = 0.015). These results suggest that a new trial of pyridoxine should be undertaken in which the tryptophan metabolites are measured and that further study of intravesical instillation of chemotherapeutic agents is warranted.

287: Otrokov AN. [New methods of vitamin B treatment of itching dermatoses in middle aged and aged patients] Vestn Dermatol Venerol. 1977 Dec;(12):62-5. Russian. No abstract available. PMID: 146980

Schweiz Med Wochenschr. 1977 Nov 5;107(44):1585-6.

[Protective effect of pyridoxilate on the hypoxic myocardium. Experimental studies]

[Article in French]

Moret PR, Lutzen U.

The protective action of piridoxilate on hypoxic myocardium has been studied on rats in acute hypoxia (isolated heart, perfused with a non-oxygenated solution) and in prolonged hypoxia (3 days at high [3454 m] altitude). Piridoxilate maintained a higher ATP level with a much lower production of lactate. The mechanisms of action of piridoxilate are probably fairly similar to those of Na dichloracetate

J Nutr. 1977 Nov;107(11):1962-8.

Increased muscle phosphorylase in rats fed high levels of vitamin B6.

Black AL, Guirard BM, Snell EE.

The present study was undertaken to test the hypothesis that muscle phosphorylase may function as a repository for vitamin B6 in the animal. Since a repository would be expected to accumulate surplus material, one would predict that phosphorylase, which contains stoichio-metric amounts or pyridoxal phosphate, would increase in muscle of animals surfeited with the vitamin. Rats were fed a vitamin B6-free diet supplemented with pyridoxine providing levels 10, 1.0 and 0.1 of those recommended by the National Research Council (NRC). At the high intake level, muscle phosphorylase and total muscle vitamin B6 increased steadily and in almost constant ratio for at least 6 weeks, whereas both alanine and aspartate transaminase increased initially, but reached a plateau within 2 weeks. At the intermediate level of pyridoxine intake, muscle phosphorylase also increased, but less rapidly than in rats fed the higher level. When vitamin B6 intake was restricted to 10% of the NRC-recommended level, no increase in phosphorylase concentration occurred during a period of 10 weeks. These results support the hypothesis that muscle phosphorylase acts as a reservoir for vitamin B6 in the animal and provide experimental evidence that muscle enzyme content expands as vitamin is accumulated during high dietary intake.

290: Korzon M, Langer H. [Requirement for pyridoxine in bronchospastic conditions in children] Pediatr Pol. 1977 Nov;52(11):1231-5. Polish. u. PMID: 593769

J Pediatr. 1977 Oct;91(4):574-7.

Free amino acids in liver of patients with homocystinuria due to cystathionine synthase deficiency: effects of vitamin B6.

Rassin DK, Longhi RC, Gaull GE.

Patients with homocystinuria due to cystathionine synthase deficiency do not have free homocystine in the liver when it is present in high concentrations in the plasma and the urine. The liver of these patients is capable of maintaining normal concentrations of cystine at a time when the plasma cystine concentration is severely reduced. There is an increase in the methionine concentration of the liver which is reduced to normal concentrations during pyridoxine therapy.

Br J Obstet Gynaecol. 1977 Jun;84(6):444-7.

Treatment of pregnancy sickness.

Wheatley D.

A double-blind comparison was undertaken between Debendox with 10mg of extra pyridoxine and placebo with 10mg of pyridoxine, in 56 women suffering from nausea and/or vomiting during the first 10 weeks of pregnancy. The results of treatment were assessed on the patient's own dialy records of:the time of nausea, the frequency of nausea, and the severity of nausea, retching and vomiting. There were statistically significant differences in favour of Debendox with extra pyridoxine in respect of the days of nausea all day (P les than 0-02), the severity of nausea (P less than 0-05) and the severity of retching (P less than 0.05).

Z Urol Nephrol. 1977 Jun;70(6):419-27.

[Animal-experiment studies on the effect of magnesium and vitamin B 6 on calcium-oxalate nephrolithiasis]

[Article in German]

Schneider HJ, Hesse A, Berg W, Kirsten J, Nickel H.

By chronic intoxication with ethylene glycol or acute intoxication by Na-glyoxalate in the animal experiment a Ca-oxalatenephrolithiasis could be produced. At this model the influence of magnesium, pyridoxine and phosphate was studied. The combination therapy of magnesium and vitamin B6 can completely prevent the formation of Ca-oxalate-microliths in the kidney. The production of a preparation with 200 mg MgO and 10 mg pyridoxine per tablet for the metaphylaxis of oxalate calculi is recommended.

Am J Obstet Gynecol. 1977 Mar 15;127(6):599-602.

Vitamin B6 treatment of gestational diabetes mellitus: studies of blood glucose and plasma insulin.

Spellacy WN, Buhi WC, Birk SA.

Thirteen women with late pregnancy gestational diabetes mellitus were tested with an intravenous glucose tolerance test and both blood glucose and plasma insulin levels were measured. Each woman was then treated with 100 mg. of vitamin B6 per day for 2 weeks and the intravenous glucose tolerance test was then repeated. There was a statistically significant improvement in the glucose tolerance curve after the vitamin B6 treatment, with a lowering of blood glucose levels at all points on the curve except for the 5 minute value. This glucose effect occurred despite an unchanged or lowered plasma insulin level. These results suggest that a relative deficiency in vitamin B6 is associated with some cases of gestational diabetes mellitus and that the replacement of this vitamin improves the metabolic state. The low vitamin B6 levels appear to alter metabolic pathways which result in a lowering of the biologic activity of endogenous insulin.

Pediatr Res. 1977 Feb;11(2):100-3.

Cystathionine beta-synthase deficiency: a qualitative abnormality of the deficient enzyme modified by vitamin B6 therapy.

Longhi RC, Fleisher LD, Tallan HH, Gaull GE.

The thermostability of cystathionine synthase and the effect of pyridoxal phosphate (PLP) on this thermostability were investigated in extracts of normal human liver and in extracts of liver, both before and during pyridoxine (vitamin B6) therapy, from members of a family with three clinically and biochemically typical, B6-responsive, synthase-deficient sibs. Incubation of crude extracts of normal liver at 55 degrees (preincubation) for 3-4 min before assay consistently resulted in a more than 2-fold increase in specific activity (activation) of cystathionine synthase (Fig. 1). With periods of preincubation longer than 4 min, thermal inactivation occurred. When PLP was added to the preincubation mixture, slightly more activation occurred in the first 3-4 min, and there was no observable loss of activity for an additional 25 min. The activation phenomenon was not observed in extracts of liver which had been obtained from three synthase-deficient sibs before therapy with vitamin B6 (Index of activation, Table 1). When extracts of liver obtained during vitamin B6 therapy were studied, however, significant activation was observed. Synthase activity in extracts of liver from the patients' parents, obligate heterozygotes for synthase deficiency, and from a potentially heterozygous sister demonstrated activation similar to that found in control liver extracts. With periods of preincubation longer than 5 min, the inactivation of synthase in liver extracts from patients receiving pyridoxine-HCl occurred at the same rate as in liver extracts from heterozygotes and from normal subjects (Index of inactivation, Table 1). PLP completely prevented heat inactivation of enzyme from normal liver.

Acta Vitaminol Enzymol. 1977;31(6):175-8.

Effect of ACP (pyridoxine-2-oxoglutarate) on CCl4 intoxication and in streptozotocin-induced ketosis in rat.

Garbin L, Plebani M, Terribile PM.

The protective effect of pyridoxine-2-oxoglutarate (ACP) was studied on CCl4-intoxicated rats. A sensitive improvement of hepatic conditions was shown in ACP-treated rats as compared with untreated ones and rats treated with 2-oxoglutarate and pyridoxine. Serum GOT, GPT, OCT activities, composition of serum proteins, liver mitochondria respiratory control index and liver microsomes oxidizing activity were tested. The antiketotic properties of ACP were also demonstrated in Streptozotocin treated rats.

Am J Clin Nutr. 1976 Dec;29(12):1376-83.

Adequacy of vitamin B6 supplementation during pregnancy: a prospective study.

Lumeng L, Cleary RE, Wagner R, Yu P-L, Li T-K.

This prospective study assesses the effect of 2.5, 4, and 10 mg of pyridoxine supplementation during pregnancy on maternal and fetal plasma levels of pyridoxal 5'-phosphate (PLP) and on the degree of coenzyme saturation (activation factor) of aspartate aminotransferase and alanine aminotransferase (alphaEGOT and alphaEGPT) in maternal erythrocytes. More than 4 mg of pyridoxine supplementation daily was required for most pregnancies to maintain maternal plasma PLP levels within the range observed during the first trimester and in the nonpregnant state. The plasma PLP concentrations in maternal and cord blood were highly correlated and indicated a dependence of fetal vitamin B6 nutrition on maternal circulating PLP. Measurements of alphaEGOT and alphaEGPT were not as reproducible as plasma PLP assays and were less sensitive and quantitative indicators. In the majority of subjects, the changes in alphaEGOT and alphaEGPT with time correlated poorly with the changes in plasma PLP. However, when the data were analyzed without regard for their dependence on time, they demonstrated a negative, linear correlation between alphaEGOT and log plasma PLP and between alphaEGPT and log plasma PLP for the group on 2.5 mg of pyridoxine and for all the subjects combined. Finally, the dietary records showed that most of the subjects consumed less than 2 mg of vitamin B6 daily from their food. The results indicate that the current Recommended Dietary Allowance for vitamin B6 during pregnancy (2.5 mg) is too low and that supplementation of this vitamin in an amount more than 4 mg daily is recommended.

J Nutr. 1976 Oct;106(10):1404-14.

Postnatal patterns of brain lipids in progeny of vitamin B-6 deficient rats before and after pyridoxine supplementation.

Thomas MR, Kirksey A.

The influence of deficient and adequate maternal intakes of pyridoxine on lipid profiles in brains of progeny at 5, 10, 15, 25 and 50 days of age was studied. The effects of supplementing deficient dams at two different times with pyridoxine on the brain development of progeny were also examined. Three groups of weanling, female rats were fed diets deficient in pyridoxine (1.2 mg pyridoxine-HC1/kg diet) and another group received a control diet (30.0 mg pyridoxine-HC1/kg diet). One deficient group and the control group were fed their diets throughout growth, gestation and lactation. Two groups of dams were fed the deficient diet through growth, gestation and until 5 or 10 days postpartum when pyridoxine was supplemented by feeding the control diet. Body and brain weights were significantly lower in 15, 25 and 50 day-old progeny of deficient dams and deficient dams supplemented at 10 days postpartum. Cerebroside content at 15 days and ganglioside content at 15 and 25 days were significantly lower in brains of pups from unsupplemented deficient dams and deficient dams supplemented at 10 days postpartum. The postnatal development of cerebroside and ganglioside levels in brain was delayed or retarded in brain of pups from unsupplemented deficient dams. Supplementation of dams fed a low level of pyridoxine (1.2 mg/kg diet) with the vitamin beginning at 5 days postpartum reversed all observed effects of the low vitamin intake on brain lipids in progeny.

J Nutr. 1976 Oct;106(10):1415-20.

Postnatal patterns of fatty acids in brain of progeny from vitamin B-6 deficient rats before and after pyridoxine supplementation.

Thomas MR, Kirksey A.

The influence of deficient and adequate maternal intakes of pyridoxine on fatty acid profiles in brains of progeny at 5, 10, and 15 days of age was studied. The effects of two different times of initiating rehabilitation of deficient dams on the brain development of progeny at 5, 10, 15, 25, and 50 days of age were also examined. Three groups of weanling, female rats were fed diets deficient in pyridoxine (1.2 mg pyridoxine-HC1/kg diet) and a fourth group received a control diet (30.0 mg pyridoxine-HC1/kg diet) throughout growth, gestation and until 5 and 10 days postpartum. Supplementation with 30.0 mg pyridoxine-HC1/kg was begun in two deficient groups at 5 and 10 days postpartum. Fatty acids C18:2, C20:4, and C22:6 in cerebellum were significantly lower in brains of 15 day-old pups from unsupplemented deficient dams compared to values for pups of control dams. Significant reductions in the omega6 fatty acids (C18:2, C20:4, and C22:4) were evident in cerebellum of 15 day-old progeny of unsupplemented deficient dams. Fatty acids C20:1 and C24:0 were not detectable in cerebellum or cerebrum of the deficient group at 15 days but were evident in other groups. Supplementation of deficient dams with vitamin B-6 at 5 and 10 days postpartum prevented the reduction of omega6 fatty acids found in deficient progeny.

Arch Dis Child. 1976 Jul;51(7):567-8.

Neonatal pyridoxine responsive convulsions due to isoniazid therapy.

McKenzie SA, Macnab AJ, Katz G.

A 17-day-old infant on isoniazid therapy 13 mg/kg daily from birth because of maternal tuberculosis was admitted after 4 days of clonic fits. No underlying infective or biochemical cause could be found. The fits ceased within 4 hours of administering intramuscular pyridoxine, suggesting an aetiology of pyridoxine deficiency secondary to isoniazid medication. Arch Dis Child. 1976 Jul;51(7):567-8.

Neonatal pyridoxine responsive convulsions due to isoniazid therapy.

McKenzie SA, Macnab AJ, Katz G.

A 17-day-old infant on isoniazid therapy 13 mg/kg daily from birth because of maternal tuberculosis was admitted after 4 days of clonic fits. No underlying infective or biochemical cause could be found. The fits ceased within 4 hours of administering intramuscular pyridoxine, suggesting an aetiology of pyridoxine deficiency secondary to isoniazid medication.

J Clin Endocrinol Metab. 1976 Jun;42(6):1192-5.

Treatment of women with the galactorrhea-amenorrhea syndrome with pyridoxine (vitamin B6).

McIntosh EN.

Three women with the galactorrhea-amenorrhea syndrome and elevated prolactin concentrations experienced a return of regular ovulatory menses within 37-94 days after starting pyridoxine treatment (200-600 mg/day). In each the galactorrhea ceased and serum prolactin levels were maintained in the normal range while taking pyridoxine. In two other women with prolonged secondary amenorrhea but without hyperprolactinemia or galactorrhea, pyridoxine at dosages up to 600 mg/day did not restore ovulatory menses. Pyridoxine treatment was also ineffective in decreasing profuse galactorrhea in one woman with normal prolactin levels and regular ovulatory menses. In the three women effectively treated with pyridoxine, the galactorrhea returned, serum prolactin levels increased, and the menses ceased after discontinuing pyridoxine. These results imply that pyridoxine, by decreasing the excessive secretion of prolactin, may be useful in the long-term medical management of women with hyperprolactinemia and the galactorrhea-amenorrhea syndrome.

Nutr. 1976 Apr;106(4):509-14.

Influence of pyridoxine supplementation on vitamin B-6 levels in milk of rats deficient in the vitamin.

Thomas MR, Kirksey A.

Levels of vitamin B-6 in milk from pyridoxine deficient dams were used as an indicator of the ability of pyridoxine to protect offspring against the effects of the deficiency. Sprague Dawley rats were fed a basal diet containing 30.0 (control) or 1.2 (deficient) mg pyridoxine-HC1/kg diet from weaning throughout growth, gestation and until 5 days postpartum. At this time, deficient dams were supplemented by a single intraperitoneal injection of 600 mug pyridoxine-HC1, or by adding 30 or 60 mg pyridoxine-HC1/kg to the diet. The vitamin B-6 content in milk form the group supplemented by injection exceeded the control level of 38.8 mug/100 ml milk 30 minutes after the injection, and reached a peak level of 110.7 mug/100 ml at 4 hours with a subsequent decline to 27mug/100 ml at 20 hours. In rats supplemented orally with 30 or 60 mg pyridoxine-HC1/kg diet, the vitamin B-6 level in the milk reached the control value in 24 and 6 hours, respectively. At 120 hours, orally supplemented dams had significantly higher levels of vitamin B-6 in the milk than control animals. Vitamin supplementation of dams by a single injection of pyridoxine-HC1 was sufficient to overcome the pyridoxine deficiency syndrome in the pups, but was not adequate for optimum growth.

Res Commun Chem Pathol Pharmacol. 1976 Apr;13(4):743-57.

Vitamin B6 deficiency in patients with a clinical syndrome including the carpal tunnel defect. Biochemical and clinical response to therapy with pyridoxine.

Ellis JM, Kishi T, Azuma J, Folkers K.

Ten individuals having a severe clinical status associated with the carpal tunnel syndrome were selected for treatment with pyridoxine. The status of vitamin B6, as pyridoxal phosphate, was determined by the specific activities of the glutamic oxaloacetic transaminase of the erythrocytes (EGOT). Before treatment, the patients showed a deficiency of vitamin B6 as determined by 1) a comparison of the specific activities of EGOT with those of a control group (P less than 0.001); and 2) a differential assay based upon the principle of unsaturation and saturation of a Coenzyme-Apoenzyme System (CAS), as applied to EGOT. These patients were treated with pyridoxine, and the specific activities of EGOT were determined after 2 and 4 weeks. Not only was there a disappearance of the deficiency of pyridoxal phosphate, but the level of EGOT activity increased 55-68% during 2-4 weeks, respectively. More apoenzyme was apparently biosynthesized, because the specific activities were significantly higher than before therapy (P less than 0.001/4 wks). Clinical evaluation showed a great improvement in their status, and anticipated surgery for some of the patients became unnecessary. It is concluded that patients with a severe syndrome including the carpal tunnel defect have a deficiency of vitamin B6, and that both the syndrome and the deficiency are relived by therapy with pyridoxine.

South Med J. 1976 Mar;69(3):294-7.

Isoniazid-induced convulsions.

Coyer JR, Nicholson DP.

Acute isoniazid overdose and toxicity may be complicated by convulsions and death. Six patients are reported, one of whom ingested simultaneously 15 gm of isoniazid and 5 gm of pyridoxine hydrochloride (vitamin B6); no convulsions resulted. In the light of this and other experience, suggestions are made for the use of pyridoxine in the treatment and prevention of acute isoniazid poisoning.

305: Spaeth GL. The usefulness of pyridoxine in the treatment of homocystinuria: a review of postulated mechanisms of action and a new hypothesis. Birth Defects Orig Artic Ser. 1976;12(3):347-57. Review. No abstract available. PMID: 782596

Folia Psychiatr Neurol Jpn. 1976;30(2):121-51.

Effects of L-dopa and vitamin B6 on electroencephalograms of schizophrenic patients: a preliminary report.

Yamauchi M.

1. To assess the therapeutic effect of low-dose L-Dopa therapy and associated EEG changes in chronic schizophrenia, 10 patients with a mean duration of illness of 12.4 years were treated with L-Dopa for a period of eight weeks during which the dosage was increased progressively from an initial level of 300 mg q.d. biweekly up to 600 mg q.d. The treatment was moderately effective in one case and slightly efficacious in one, produced no significant change in the conditions of seven patients while the remaining patient showed exacerbation; hence a noticeably low rate of improvement. There occurred no significant changes in the EEG pattern in the series of 10 patients on the average. The individual patients' responses, nevertheless, could be classified into three groups: one with no observable EEG changes, the second showing a slight degree of increase in alpha activity and the third exhibiting diminution of alpha activity in the EEG. The patients in the latter two groups all had durations of disease less than 10 years. 2. Observations were made primarily of changes in the EEG in 20 chronically schizophrenic patients with a mean duration of disease of 13 years receiving 60 mg of vitamin B6 (as pyridoxal-5'-phosphate) daily over a period of four weeks. Slight increase of alpha activity and decrease of theta activity in the EEG were noted on the average of the 20 cases, in response to the vitamin B6 therapy. The increase of alpha activity was frequently seen among patients with a duration of illness less than 10 years whose pretreatment EEG pattern had been alpha dominant (five out of 10 cases), whereas a slight ameliorative tendency of EEG was observed only in one out of 10 patients whose pretreatment EEG pattern had been slow-wave dominant. Symptomatic improvement was evident only in one of the 20 cases studied. 3. Observations were made of the therapeutic effect and associated EEG changes in eight patients receiving combined medication of 200 mg L-Dopa and 30 mg vitamin B6 (as pyridoxal-5'-phosphate) daily for a period of 12 weeks. Of these eight patients with a mean duration of disease of 18.3 years, two showed excellent response, three good and three fair; hence good to excellent responses attained in five out of the eight cases or 62.5%. A marked increase in alpha activity in the EEG occurred from the 2nd to 4th weeks onward in all eight cases. The EEG changes were likely to precede the symptomatic improvement. 4. To sum up the results of these three clinical trials, administration of L-Dopa alone resulted in practically no symptomatic improvement or EEG changes in patients with chronic schizophrenia whilst vitamin B6 administered singly as pyridoxal-5'-phosphate scarcely produced significant symptomatic improvement but brought about a slight ameliorative tendency in the EEG of such patients. Both symptomatic amelioration and EEG improvement occurred following combined medication of L-Dopa and vitamin B6...

J Nutr Sci Vitaminol (Tokyo). 1976;22(1):1-6.

Convulsive seizure induced by intracerebral injection of semicarbazide (an anti-vitamin B6) in the mouse.

Yamashita J.

The direct injection of semicarbazide (SC), an antivitamin B6 (anti-B6), into the lateral ventricle of the mouse brain induced convulsion and tremors at a smaller dose after a shorter latent period than that in systemic administration. The symptoms were prevented by pyridoxine, aminooxyacetic acid or acetone, while they enhanced by pyridoxal, pyridoxal phosphate, or some other anti-B6. In mice fed a vitamin B6 (B6)-deficient diet, convulsion and tremors occurred at smaller doses of SC than those in mice given control food, and were counteracted by pyridoxine. On the other hand, mice into which SC had been injected in the neighboring site of the lambda first showed running fits, which was followed by convulsion and tremors.

308: [No authors listed] Requirement of vitamin B6 during pregnancy. Nutr Rev. 1976 Jan;34(1):15-6. Review. No abstract available. PMID: 765894

Schweiz Med Wochenschr. 1975 Oct 11;105(41):1319-24.

[Vitamin B 6 deficiency anemia]

[Article in German]

Ofori-Nkansah N, Weissenfels I, Pribilla W.

The course of spontaneous vitamin B6 deficiency anemia in a 57-year-old woman is reported. The anemia was characterized by hypochromasia of the erythrocytes, hyperferricemia, absence of hemolysis, and hyperplastic, ineffective, sideroblastic erythropoiesis of the bone marrow. It was corrected by oral vitamin B6 therapy. On interruption of the vitamin B6 therapy the anemia relapsed. On resumption of vitamin B6 medication it responded again with normalization of the hemoglobin and erythrocytes values. The hematological remission could be maintained under longterm vitamin B6 medication. The nosological significant of this rare anemia and its differentiation from other forms of anemia are discussed.

Ann Allergy. 1975 Aug;35(2):93-7.

Pyridoxine treatment of childhood bronchial asthma.

Collipp PJ, Goldzier S 3rd, Weiss N, Soleymani Y, Snyder R.

Urinary xanthurenic and kynurenic acid levels were measured in five patients while they were receiving 50 mg and 100 mg of pyridoxine. The levels of tryptophane metabolite decreased progressively as the dose was increased but remained above basal levels. There was marked clinical improvement in these patients while receiving the higher dose only. The double-blind study with 76 asthmatic children followed for five months indicated significant improvement in asthma following pyridoxine therapy (200 mg daily) and reduction in dosage of bronchodilators and cortisone. The data suggest that these children with severe bronchial asthma had a metabolic block in tryptophane metabolism, which was benefitted by long-term treatment with large doses of pyridoxine.

Am J Obstet Gynecol. 1975 Jul 15;122(6):793.

Letter: supplementary pyridoxine given to women using oral contraceptives.

Winston F.

PIP: This letter is a response to an article describing the efficacy of administering large doses of tryptophan to depressive patients taking oral contraceptives. This letter-writer argues that the salient action of mood elevation is a result of the supplemental pyridoxine (vitamin B) which ameliorates the deficiency induced by oral contraceptive use that leads to depression resulting from inhibition of synthesis of biogenic amines in the central nervous system. Instead of large doses of tryptophan, which may cause dangerous accumulations of possibly carcinogenic and diabetogenic metabolites when therapy for depression is indicated, pyridoxine should be administered together with the tryptophan; the tryptophan should be discontinued once the deficiency is corrected, although the vitamin therapy should continue throughout oral contraceptive use.

Vopr Med Khim. 1975 May-Jun;21(3):299-306.

[Effect of pyridoxine on patterns of lipid metabolism in patients with alimentary obesity]

[Article in Russian]

Frolova IA, Oleneva VA, Sirota II, Nikiforova GD.

Studies of patients with alimentary-metabolic obesity, which were treated with pyridoxine and were maintained on a reduced diet, revealed a normalizing effect of the vitamin on some patterns of lipid metabolism. In patients, treated with pyridoxine, body weight, content of total lipids, cholesterol, phospholipids, glycerids and beta-lipoproteins in blood serum were decreased more distinctly as compared with patients, which were only maintained on a reduced diet. In hyperlipidaemia the positive effect of pyridoxine was more pronounced than in the cases with normal content of lipids in blood.

Int J Vitam Nutr Res. 1975;45(4):411-8.

[Activity studies of an iron-vitamin B6 preparation for euteral treatment of iron deficiency anemia]

[Article in German]

Reinken L, Kurz R.

In 17 respectively 15 children with iron deficiency anemia the effect of a combined orally applicated iron-vitamin B6 therapy and iron therapy only was studied. Pyridoxal phosphate, activities of pyridoxal kinase and red cell GOT, and excretion of 4-pyridoxic acid in urine were measured as indices of vitamin B6 nutriture before therapy was started, on the 3rd and 6th day with therapy and on the 1st and 4th day after therapy was stopped. Red cells, concentration of hemoglobin, reticulocytes and hematokrit were simultaneously counted, whereas serum iron had been measured once only before therapy. A group of 22 hematologically healthy children was studied as controls. After iron therapy a decrease of vitamin B6 nutriture occured as a consequence of an increased requirement for pyridoxal phosphate for heme synthesis. Additional vitamin B6 was followed by a normal vitamin B6 nutriture and a significantly accelerating effect on heme synthesis.

315: Mottram PE, Johnson PB, Hoffman JE. Isoniazid toxicity. Reversal with pyridoxine. Minn Med. 1974 Feb;57(2):81-3. No abstract available. PMID: 4813614

Am Fam Physician. 2003 Jul 1;68(1):121-8.

Nausea and vomiting of pregnancy.

Quinla JD, Hill DA.

Family Practice Residency Program, Naval Hospital, Jacksonville, Florida 32214, USA.

Nausea and vomiting of pregnancy, commonly known as "morning sickness," affects approximately 80 percent of pregnant women. Although several theories have been proposed, the exact cause remains unclear. Recent research has implicated Helicobacter pylori as one possible cause. Nausea and vomiting of pregnancy is generally a mild, self-limited condition that may be controlled with conservative measures. A small percentage of pregnant women have a more profound course, with the most severe form being hyperemesis gravidarum. Unlike morning sickness, hyperemesis gravidarum may have negative implications for maternal and fetal health. Physicians should carefully evaluate patients with nonresolving or worsening symptoms to rule out the most common pregnancy-related and nonpregnancy-related causes of severe vomiting. Once pathologic causes have been ruled out, treatment is individualized. Initial treatment should be conservative and should involve dietary changes, emotional support, and perhaps alternative therapy such as ginger or acupressure. Women with more complicated nausea and vomiting of pregnancy also may need pharmacologic therapy. Several medications, including pyridoxine and doxylamine, have been shown to be safe and effective treatments. Pregnant women who have severe vomiting may require hospitalization, orally or intravenously administered corticosteroid therapy, and total parenteral nutrition.

Gerontology. 2003 Jul-Aug;49(4):215-24. Variations in nutritional status of elderly men and women according to place of residence.

Sibai AM, Zard C, Adra N, Baydoun M, Hwalla N.

Department of Epidemiology and Biostatistics, Faculty of Health Sciences, American University of Beirut, Lebanon.

OBJECTIVE: The purpose of this study was to assess comprehensively the nutritional status of elderly individuals in institutions and to compare it with that of community based dwellers in an urban setting in Lebanon. METHODS: Participants included 100 elderly men and women (aged 65 years and older) selected randomly from four institutions who were based on sex and neighborhood with 100 free-living individuals. Subjects were mentally and physically capable of responding to an interview schedule. Their nutritional status was assessed by anthropometric measurements, dietary food intake for a 3-day period, and hematological and biochemical variables. Energy and macro- and micronutrient intakes were compared with the US recommended dietary allowances (RDA) or dietary reference intakes (DRI) as appropriate. RESULTS: Elderly living at home had significantly higher mean body mass index and waist circumference than those living in institutions. Although the total energy intake was comparable between the two groups, the elderly in the institutions consumed more fat and had lower intake of dietary fibers. Deficiencies (below 2/3rd RDA/DRI intakes) in zinc, magnesium, alpha-tocopherol, vitamins A and D, and pyridoxine were noted in both study groups with overall higher proportions observed among the institutionalized elderly. These were also anemic (42.5%) and had low levels of albumin (27.5%). In contrast, those living at home showed a higher prevalence of obesity and a lower calcium intake. Multivariate analysis controlling for a number of potential covariates did not change the results observed. CONCLUSIONS: The results of the present study showed a higher prevalence of obesity in those living at home and varying deficiencies by place of residence with no evidence that duration of institutionalization in itself being associated with poor nutritional status. Awareness of the risks associated with these deficiencies and excesses should address the lay and health professionals working in the community and institutions alike. Copyright 2003 S. Karger AG, Basel

Indian Pediatr. 2003 Jul;40(7):633-8. Pyridoxine-dependent seizures: a review.

Rajesh R, Girija AS.

Department of Neurology, Medical College, Calicut, Kerala 673 008, India.

Pyridoxine-dependent seizure is a rare autosomal recessive disorder that usually presents with neonatal intractable seizures. This syndrome results from an inborn abnormality of the enzyme glutamic acid decarboxylase, which results in reduced pyridazine-dependent synthesis of the inhibitory neurotransmitter gamma amino butyric acid. The full range of symptomatology is unknown; but can be associated with autism, breath holding and severe mental retardation, bilious vomiting, transient visual agnosia, severe articulatory apraxia motor dyspraxia, microcephaly and intrauterine seizures. Parenteral pyridine injection test is a highly effective and reproducible test in confirming the diagnosis. Pyridoxine should be administered as a diagnostic test in all cases of convulsive disorders of infancy in which no other diagnosis is evident. Epileptic seizure discharges subside within 2-6 minutes after the intravenous injection of 50-100 mg of pyridaoxine. Once the diagnosis is confirmed, maintenance therapy should be continued indefinitely and doses increased with age or intercurrent illnesses. The maintenance dose of Bg needed is still not clear. There is a relatively wide range for the daily B6 dose necessary to control the seizure i.e., 10-200 mg/day.

Int J Food Sci Nutr. 2003 Jul;54(4):281-9.

Influence of a drink containing different antioxidants and Lactobacillus plantarum 299v on plasma total antioxidant capacity, selenium status and faecal microbial flora.

Onning G, Berggren A, Drevelius M, Jeppsson B, Lindberg AM, Johansson Hagslatt ML.

Biomedical Nutrition, Center of Chemistry and Chemical Engineering Lund University SE-221 00 P.O. Box 124 Lund, Sweden.

The aim of the study was to investigate whether a supplement of antioxidants to subjects with a high working pace can influence the antioxidant capacity. The study was parallel and double blind with 98 subjects randomised into two groups. One of the groups was given a test drink with antioxidants for 4 weeks (450 ml/day) while the other group took a corresponding amount of placebo drink. The test drink contained: 2 mg beta-carotene/100 ml, 40 mg alpha-tocopherol/100 ml, 80 mg ascorbic acid/100 ml, 2 mg pyridoxine/100 ml, 15 mg magnesium/100 ml, 0.2 mg manganese/100 ml, 1 mg zinc/100 ml, 0.1 mg copper/100 ml and 10 microg selenium/100 ml. Consumption of the test drink for 4 weeks increased the total plasma antioxidant capacity by 7% (ferric reducing ability of plasma method, P<0.05 compared with the placebo group), and the content of selenium and selenoprotein P in serum was raised by 16-17% (P<0.001 compared with the placebo group). No significant changes were found in the placebo group. The test drink also contained Lactobacillus plantarum 299v (5 x 10(7) cfu/ml) and 4 weeks' consumption led to a significant increase of Lb. plantarum 299v in the faeces. In conclusion, consumption of a drink rich in different antioxidants can increase the antioxidant capacity in subjects with a high working pace. This can be valuable since it may increase the protection against reactive oxygen radicals.

Kekkaku. 2003 Jul;78(7):483-6.

[Tuberculosis in patients undergoing hemodialysis]

[Article in Japanese]

Yokoyama T, Rikimaru T, Gohara R, Watanabe H, Aizawa H.

First Department of Internal Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume-shi, Fukuoka 830-0011, Japan.

We studied patients who were diagnosed as active tuberculosis while undergoing hemodialysis at Kurume University Hospital. The observation included immunologic and clinical features. Cellular immunity was depressed in our patients undergoing hemodialysis, as evident from the decreased numbers of lymphocytes and anergy to tuberculin skin tests with purified protein derivative (PPD). Further, in a few patients, hemodialysis was shown to eliminate IFN-gamma from the blood. Various antituberculous chemotherapy regimens have been studied in hemodialysis patients. Although the incidence and mortality of tuberculosis have been reported to be higher in hemodialysis patients than in the general population, the clinical outcome of our cases was favorable in this study. One important notice is to recognize promptly peripheral neuropathy while treating tuberculosis associated with hemodialysis, and this could be prevented by the adequate use of pyridoxine.

Blood. 2003 Jun 1;101(11):4623-4. Epub 2003 Jan 16. Late-onset X-linked sideroblastic anemia following hemodialysis.

Furuyama K, Harigae H, Kinoshita C, Shimada T, Miyaoka K, Kanda C, Maruyama Y, Shibahara S, Sassa S.

Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, Sendai, Japan.

X-linked sideroblastic anemia (XLSA) is due to deficient activity of erythroid-specific 5-aminolevulinate synthase (ALAS2). We report here a patient who developed sideroblastic anemia at the age of 81 years while undergoing hemodialysis. The diagnosis of sideroblastic anemia was established by the presence of ringed sideroblasts in the bone marrow, and treatment with oral pyridoxine completely eliminated the ringed sideroblasts. We identified a novel point mutation in the fifth exon of this patient's ALAS2 gene, which resulted in an amino acid change at residue 159 from aspartic acid to asparagine (Asp159Asn). In vitro analyses of recombinant Asp159Asn ALAS2 revealed that this mutation accounted for the pyridoxine-responsiveness of this disease. The very late onset in this case of XLSA emphasizes that nutritional deficiencies caused either by dietary irregularities in the elderly or, as in this case, by maintenance hemodialysis therapy, may uncover occult inherited enzymatic deficiencies in the heme biosynthetic pathway.

Transplantation. 2003 May 15;75(9):1551-5. Vitamin supplementation reduces the progression of atherosclerosis in hyperhomocysteinemic renal-transplant recipients.

Marcucci R, Zanazzi M, Bertoni E, Rosati A, Fedi S, Lenti M, Prisco D, Castellani S, Abbate R, Salvadori M.

Surgical and Medical Critical Care, Clinica Medica Generale e Cliniche Specialistiche, University of Florence, Italy.

BACKGROUND: We previously demonstrated among renal-transplant recipients (RTRs) a high prevalence of hyperhomocysteinemia, which might account for their elevated cardiovascular risk. The purpose of our study was to document, in hyperhomocysteinemic RTRs, the effect of vitamin supplementation on carotid intima-media thickness (cIMT), which is an early sign of atherosclerosis. METHODS: A total of 56 stable hyperhomocysteinemic RTRs were randomly assigned to vitamin supplementation (folic acid 5 mg/day; vitamin B(6) 50 mg/day; vitamin B(12) 400 microg) (group A) or placebo treatment (group B) for 6 months. All subjects underwent cardiovascular risk-factor assessment, including fasting homocysteine (Hcy) levels assay, and high resolution B-mode ultrasound to measure the intima-media thickness of common carotid arteries, at time of enrollment and after 6 months. RESULTS: Fasting Hcy levels markedly decreased in group A after treatment (21.8 [15.5-76.6] micromol/L vs. 9.3 [5.8-13] micromol/L; P<0.0001), whereas no significant changes were observed in group B (20.5 [17-37.6] micromol/L vs. 20.7 [15-34] micromol/L; P=not significant). In group A, cIMT significantly decreased after treatment (0.95+/-0.20 mm vs. 0.64+/-0.17 mm; P<0.0001). All except one patient showed a reduction of cIMT and the mean percentage of cIMT decrease was -32.2+/-12.9%. Patients with methylenetetrahydrofolate reductase (MTHFR) C677T +/+ genotype, with higher Hcy levels, had the major percentage of decrease of Hcy with respect to the other genotypes (mean decrease: MTHFR +/+ 74.8+/-5.7%; MTHFR +/- 58.1+/-10%; MTHFR -/- 56.3+/-8.6%). In hyperhomocysteinemic patients without vitamin supplementation (group B) we documented a significant increase in cIMT after 6 months (0.71+/-0.16 mm vs. 0.87+/-0.19 mm; P<0.05). In 19 of 28 subjects we observed an increase in cIMT, and in 9 of 28 the cIMT was unmodified. The mean percentage of cIMT increase was + 23.3+/-21.1%. CONCLUSIONS: Our results demonstrate a beneficial effect of the treatment of hyperhomocysteinemia by vitamin supplementation on cIMT in a group of RTRs.

Pacing Clin Electrophysiol. 2003 May;26(5):1289-91. Electrocardiographic changes due to pyridoxine deficiency.

Malmierca E, Polo J, Castro JR.

Fundacion Jimenez Diaz, Madrid, Spain.

A young woman presented with marked alterations in the ECG without cardiological symptoms or evidence of structural heart disease after further evaluation. There was evidence of vitamin deficiency and the ECG normalized after 10 days of treatment with vitamins. Similar alterations have been described in several experimental studies with rats, but this is the first case reported in humans.

J Agric Food Chem. 2003 Apr 23;51(9):2733-6. Inhibition of diphenolase activity of tyrosinase by vitamin b(6) compounds.

Yokochi N, Morita T, Yagi T.

Department of Bioresources Science, Faculty of Agriculture, Kochi University, Monobe-Otsu 200, Nankoku, Kochi 783-8502, Japan.

The vitamin B(6) compounds pyridoxine (PN), pyridoxamine (PM), pyridoxal (PL), and pyridoxamine 5'-phosphate (PMP) inhibited the diphenolase activity of mushroom tyrosinase. PM showed the highest inhibition; the control activity was inhibited by 38% at 1.5 mM. Each PL, PN, and PMP showed about 30% inhibition at the same concentration. Lineweaver-Burk plots showed that PM and PN were mixed-type inhibitors with K(I) values of 4.3 and 5.2 mM, respectively. Because PM and PN cannot form a Schiff base with a primary amino group of the enzyme, their inhibition is not attributable to the formation of the Schiff base. Alternatively, their quenching function of reactive oxygen species (ROS) was postulated to be responsible for the inhibition. Thus, the inhibitory effect of ROS was examined. The representative singlet oxygen quenchers l-histidine, sodium azide, Trolox, and anthracene-9,10-dipropionic acid (AAP) inhibited the activity. The specific scavenger of superoxide, proxyl fluorescamine, also inhibited the activity. The scavengers of hydroxyl radical, d-mannitol and dimethyl sulfoxide, showed no inhibition. The fluorescence of AAP was decayed during the diphenolase reaction, and PM inhibited the decay. AAP was also a mixed-type inhibitor. The results showed that the vitamin B(6) compounds inhibited the diphenolase activity by quenching ROS (probably singlet oxygen) generated during some reaction step of the diphenolase reaction.

Biochim Biophys Acta. 2003 Apr 11;1647(1-2):225-9. Neuroprotective actions of pyridoxine.

Dakshinamurti K, Sharma SK, Geiger JD.

Department of Biochemistry and Medical Genetics, Faculty of Medicine, University of Manitoba, 770 Bannatyne Avenue, Winnipeg, Manitoba, Canada MB R3E 0W3.

Electroencephalographic recordings in cerebral cortex of mice given a single sub-convulsive dose of domoic acid exhibited typical spike and wave discharges. Administration of the anti-epileptic drugs sodium valproate, nimodipine, or 5 alpha-pregnan 3 alpha-ol-20-one as well as pyridoxine simultaneously with or after domoic acid treatment resulted in significantly less spike and wave activity. Administration of these same drugs 45 min prior to the administration of domoic acid also significantly reduced EEG background. Mechanistically, sodium valproate and pyridoxine significantly attenuated domoic acid-induced increase in levels of glutamate, increase in levels of calcium influx, decrease in levels of gamma-aminobutyric acid and increase in levels of the protooncogenes c-fos, jun-B and jun-D. In hippocampal cells, domoic acid-induced increases in glutamate and calcium influx were significantly decreased by pyridoxal phosphate or nimodipine. Similarly in neuroblastoma-glioma hybrid cells (NG 108/15), pyridoxine attenuated domoic acid-induced increases in glutamate, influx of extracellular calcium, and enhanced induction of oncoproteins regardless of whether cells were undifferentiated, differentiated or de-differentiated. Pyridoxine has anti-seizure and neuroprotective actions mediated through mechanisms similar to those targeted by current therapeutic strategies.

Biochim Biophys Acta. 2003 Apr 11;1647(1-2):127-30. Antitumor effect of vitamin B6 and its mechanisms.

Komatsu S, Yanaka N, Matsubara K, Kato N.

Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima 739-8528, Japan.

Epidemiological studies have reported an inverse association between vitamin B(6) intake and colon cancer risk. Our recent study has been conducted to examine the effect of dietary vitamin B(6) on colon tumorigenesis in mice. Mice were fed diets containing 1, 7, 14 or 36 mg/kg pyridoxine for 22 weeks, and given a weekly injection of azoxymethane (AOM) for the initial 10 weeks. Compared with the 1 mg/kg pyridoxine diet, 7, 14 and 35 mg/kg pyridoxine diets significantly suppressed the incidence and number of colon tumors, colon cell proliferation and expressions of c-myc and c-fos proteins. Supplemental vitamin B(6) lowered the levels of colonic 8-hydroxyguanosine (8-OHdG), 4-hydroxy-2-nonenal (4-HNE, oxidative stress markers) and inducible nitric oxide (NO) synthase protein. In an ex vivo serum-free matrix culture model using rat aortic ring, supplemental pyridoxine and pyridoxal 5'-phosphate (PLP) had antiangiogenic effect. The results suggest that dietary vitamin B(6) suppresses colon tumorigenesis by reducing cell proliferation, oxidative stress, NO production and angiogenesis.

Biochim Biophys Acta. 2003 Apr 11;1647(1-2):36-41. Pyridoxine-dependent seizures: a clinical and biochemical conundrum.

Baxter P.

Ryegate Centre Paediatric Neurology, Sheffield Childrens Hospital, Tapton Crescent Road, Sheffield S10 5DD, UK.

Pyridoxine-dependent seizures have been recognised for 40 years, but the clinical and biochemical features are still not understood. It is a rare recessively inherited condition where classically a baby starts convulsing in utero and continues to do so after birth, until given pyridoxine. Many of these early onset cases also have an acute encephalopathy and other clinical features. Late onset cases are now recognised with a less severe form of the condition. Seizures can break through with intercurrent illness but otherwise remain controlled on pharmacologic doses of pyridoxine. The long-term outcome is affected by several factors including whether onset is early or late and how soon pyridoxine is given. Biochemical studies have been sparse, on very small numbers. There does not appear to be any defect in the uptake or metabolism of pyridoxine or pyridoxal phosphate (PLP). For a long time glutamic acid decarboxylase (GAD), a pyridoxal-dependent enzyme, has been suspected to be the abnormal gene product, but glutamate and gamma-aminobutyric acid (GABA) studies on the cerebrospinal fluid (CSF) have been contradictory and recent genetic studies have not found any linkage to the two brain isoforms. A recent report describes raised pipecolic acid levels in patients but how this ties in is unexplained.

Biochim Biophys Acta. 2003 Apr 7;1621(1):1-8. ESR study of a biological assay on whole blood: antioxidant efficiency of various vitamins.

Stocker P, Lesgards JF, Vidal N, Chalier F, Prost M.

Institut Mediterranee de Recherche en Nutrition, Service 332, Centre de St-jerome, 13397 cedex 20, Marseille, France.

This study deals with the activity of various vitamins against the radical-mediated oxidative damage in human whole blood. We have used a biological method that allows both the evaluation of plasma and that of red blood cell resistance against the free radicals induced by 2,2'-azobis (2-amidinopropane) hydrochloride (AAPH). Spin trapping measures using mainly 5-(diethoxyphosphoryl)-5-methyl-1-pyrolline N-oxide nitrone (DEPMPO) were carried out under several conditions to identify the free radicals implicated in this test. Only the oxygenated-centred radical generated from AAPH was found highly reactive to initiate red blood cell lysis. With DEPMPO only alkoxyl radicals were observed and no evidence was found for alkylperoxyl radicals. The antioxidant activity of several lipid- and water-soluble vitamins has been assessed by the biological assay and through two chemical methods. We have noticed high antioxidant activities for tocopherols (in the order delta>gamma>alpha) in the biological test but not through chemical methods. At 1 microM, the delta-tocopherol efficiency in inhibiting radical-induced red blood cell hemolysis was three times as high as the alpha-tocopherol efficiency. For beta-carotene no significant activity even in whole blood was shown. Highly surprising antioxidant activities were observed for acid folic and pyridoxine, compared to ascorbic acid. At 10 microM, the effectiveness of folic acid was almost three times as high as vitamin C. The biological test seems clinically more relevant than most other common assays because it can detect several classes of antioxidants.

Space Med Med Eng (Beijing). 2003 Apr;16(2):79-82.

Effects of dietary supplementation of certain nutrients on maze performance and biochemical indices in mice after exposure to high +Gz.

Yang CL, Jin YB, Yu H, Yi CR, Cheng J, Zhan H.

Institute of Aviation Medicine, The Air Force, Beijing, China.

Objective: To explore the possible effects of nutritional supplements on brain function as reflected by Water Maze test performance in mice after +Gz exposure. Method: Mice were arranged into control group (group A), +Gz group without nutritional supplementation (group B) and +Gz plus nutritional supplementation group (group C). Each group contains 12 mice. Mice in group A were not exposed to +Gz while mice in both group B and group C were exposed to 8 min + 10 Gz. Distilled water was gavaged to group B mice 3 h before +Gz exposure. On the day before +Gz exposure pyridoxol fortified water was given and 3 h before exposure mixed amino acids solution were gavaged to group C mice. Water Maze test was done and scores were recorded in all groups. After the Water Maze test was completed, blood was collected through the eyes for serum amino acid determinations and brain tissue was collected by decollation for monoamine determination and gamma-glutamyl transferase (GGT) activity evaluation. Result: After +Gz exposure, longer completion time and more mistakes were observed in Water Maze test in group B as compared with group A and a trend of improvement in group C was noticed. The ratio of brain 5-HT to dopamine (DA) was significantly reduced in group C as compared with group B. Gamma glutamyl transferase (GGT) activity in brain tissue in group C and group B increased significantly. Conclusion: High sustained +Gz exposure significantly reduces Water Maze test performance in mice (longer completion time and more mistakes). It seems that there is a trend of improvement in Water Maze performance in mice in dietary nutritional supplementation group, which might be due to significant reduction in ratio of brain 5-HT to DA in mice with nutritional supplementation.

Med Sci Monit. 2003 Mar;9(3):CR147-51. Is there any relationship between lipids and vitamin B levels in persons with elevated risk of atherosclerosis?

Wasilewska A, Narkiewicz M, Rutkowski B, Lysiak-Szydlowska W.

Department of Clinical Nutrition, Institute of Internal Medicine, Medical University, Gdansk, Poland.

BACKGROUND: There is increasing evidence that plasma homocysteine level is an independent risk factor for atherosclerosis. Low levels of serum folates, cobalamin and pyridoxine are associated with increased risk of cardiovascular disease. Most dietary products contain cholesterol as well as methionine, so hyperlipidemia could be associated with a higher level of homocysteine and inversely with lower levels of B vitamins. The aim of this study was to investigate the differences in levels of lipids and vitamins affecting homocysteine metabolism in different groups of patients. MATERIAL/METHODS: We examined 38 healthy persons, 55 patients hospitalised for cardiac surgery, and 62 patients without clinical evidence of atherosclerosis but with one of the atherosclerosis risk factors (hypercholesterolemia, NIDDM or chronic renal insufficiency). The levels of total cholesterol, triglycerides, vitamin B12, folic acid and vitamin B6 index in serum were determined using routine laboratory methods. RESULTS: We found no association between lipids and B vitamins in any examined group. There were significant differences between concentrations of analysed parameters in all groups of patients as compared to controls. CONCLUSIONS: The lack of correlation between the levels of lipid parameters and B vitamins in serum indicates that these may be independent, additional risk factors for atherosclerosis. Higher vitamin B6 deficiency in dialysis patients is probably caused by low intake combined with the increased requirements of uremic patients. Permanent monitoring of B vitamins in serum is necessary in patients with elevated risk of atherosclerosis, as well as long-term education, careful diet planning and supplementation.

Brain Res Bull. 2003 Feb 15;59(6):421-7. Loss of dendritic connectivity in CA1, CA2, and CA3 neurons in hippocampus in rat under aluminum toxicity: antidotal effect of pyridoxine.

Sreekumaran E, Ramakrishna T, Madhav TR, Anandh D, Prabhu BM, Sulekha S, Bindu PN, Raju TR.

Department of Life Sciences, University of Calicut, Kerala, India.

Aluminum chloride (AlCl(3); 4 mg/kg) was injected into the cerebrospinal fluid of adult rats as a one time dose. Rapid Golgi stained sections of hippocampus were examined for detailed histology of neurons in CA1, CA2, and CA3 areas. The axonal length and number of dendritic branches were seen reduced 30 days later in aluminum (Al)-injected group when compared to vehicle-injected controls. Of these perturbations, dendritic branches were seen reduced significantly. Al toxicity apparently affects neuronal connectivity in hippocampus. These perturbations are reversed by supplementing the feed with pyridoxine (8 mg/kg) for 30 days. As the loss of synaptic connectivity is a predominant feature of neurodegenerative disorders such as Alzheimer disease, this study may have implications in such disorders. Pyridoxine may be considered as a potent antidote to Al toxicity and neurodegenerative disorders such as Alzheimer disease.

J Child Neurol. 2003 Feb;18(2):142-3.

Do not overlook acute isoniazid poisoning in children with status epilepticus.

Caksen H, Odabas D, Erol M, Anlar O, Tuncer O, Atas B.

Department of Pediatrics, Yuzuncu Yyl University, Faculty of Medicine, Van, Turkey.

A previously healthy 2-year-old girl was admitted with generalized convulsive status epilepticus. She was in a stupor and could respond only to painful stimuli. She also had severe metabolic acidosis. Although initial liver function tests were normal, they were found to be moderately high on the fifth day of admission; however, they dropped to their normal ranges on the twelfth day of admission. Initially, the patient was diagnosed as having idiopathic status epilepticus, and classic anticonvulsant agents, including diazepam, phenytoin, and then phenobarbital, were given. However, her seizures did not subside, and diazepam infusion was initiated. After initiation of diazepam infusion, the seizures were completely controlled. On the fourth day of admission, her parents said that she had accidentally received 20 tablets (a total dose of 2000 mg) of isoniazid just before admission to our hospital. Later, we injected 200 mg of pyridoxine intravenously. During follow-up, her general condition improved, and anticonvulsant agents were discontinued because an electroencephalogram was found to be norma. She was discharged from the hospital on the twelfth day of admission. At the fourth month of follow-up, she was seizure free. Because of this case, we would like to re-emphasize that acute isoniazid poisoning should also be considered in a child with unexplained status epilepticus.

Nephrol Dial Transplant. 2003 Feb;18(2):273-9. Primary hyperoxaluria type 1 in The Netherlands: prevalence and outcome.

van Woerden CS, Groothoff JW, Wanders RJ, Davin JC, Wijburg FA.

Laboratory for Genetic Metabolic Diseases, Department of Clinical Chemistry, Emma Children's Hospital AMC, 1100 DD Amsterdam, The Netherlands.

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a phenotypically heterogeneous disease. To date the relationship between biochemical parameters and outcome is unclear. We therefore undertook a national cohort study on biochemical and clinical parameters and outcome in PH1. METHODS: Review of medical charts of all Dutch PH1 patients, who were identified by sending questionnaires to all Dutch nephrologists for children and adults. RESULTS: Fifty-seven patients were identified. The prevalence and incidence rates were 2.9/10(6) and 0.15/10(6)/year, respectively. Median age at diagnosis was 7.3 years (range 0-57). Seventeen (30%) patients were older than 18 years at time of diagnosis, of whom 10 (59%) presented with end-stage renal disease (ESRD), in contrast to only nine (23%) of those aged under 18 years. Median age at initial symptoms was 6.0 years (range 0-50). In four of nine patients with infantile PH1, normal renal function was preserved after a median follow-up of 7.7 years (range 0.1-16). Progression to renal insufficiency was associated with the presence of nephrocalcinosis, as assessed by ultrasound (relative risk=1.8; 95% CI, 1.0-3.4) and with pyridoxine-unresponsiveness (relative risk=2.2; 95% CI, 1.1-4.2) but not with age at presentation, the extent of hyperoxaluria, or AGT activity. No apparent nephrocalcinosis was found in five of the 19 patients who presented with ESRD. CONCLUSIONS: Although more than one-half of the PH1 patients have symptoms under the age of 10 years, PH1 can present at any age. In adults, PH1 presents predominantly with ESRD, which may be due to misinterpretation of early symptoms. Although nephrocalcinosis is correlated with development of renal insufficiency, the latter can occur even in the absence of nephrocalcinosis. Pyridoxine sensitivity is associated with better outcome in PH1.

Clin Chem. 2003 Jan;49(1):155-61. Plasma vitamin B6 vitamers before and after oral vitamin B6 treatment: a randomized placebo-controlled study.

Bor MV, Refsum H, Bisp MR, Bleie O, Schneede J, Nordrehaug JE, Ueland PM, Nygard OK, Nexo E.

Department of Clinical Biochemistry AKH, Aarhus University Hospital, Norrebrogade 44, DK-8000 Aarhus C, Denmark.

BACKGROUND: Vitamin B(6) has attracted renewed interest because of its role in homocysteine metabolism and its possible relation to cardiovascular risk. We examined the plasma B(6) vitamers, pyridoxal 5'-phosphate (PLP), pyridoxal (PL), pyridoxine (PN), and 4-pyridoxic acid (4-PA) before and after vitamin B(6) supplementation. METHODS: Patients (n = 90; age range, 38-80 years) undergoing coronary angiography (part of the homocysteine-lowering Western Norway B-Vitamin Intervention Trial) were allocated to the following daily oral treatment groups: (A), vitamin B(12) (0.4 mg), folic acid (0.8 mg), and vitamin B(6) (40 mg); (B), vitamin B(12) and folic acid; (C), vitamin B(6); or (D), placebo. EDTA blood was obtained before treatment and 3, 14, 28, and 84 days thereafter. RESULTS: Before treatment, PLP (range, 5-111 nmol/L) and 4-PA (6-93 nmol/L) were the predominant B(6) vitamers identified in plasma. During the 84-day study period, the intraindividual variation (CV) in patients not treated with vitamin B(6) (groups B and D) was 45% for PLP and 67% for 4-PA. Three days after the start of treatment, the increases in concentration were approximately 10-, 50-, and 100-fold for PLP, 4-PA, and PL, respectively. No significant additional increase was observed at the later time points. The PLP concentration correlated to the concentrations of 4-PA and PL before treatment, but not after treatment. The PL concentration correlated with 4-PA before and after treatment. CONCLUSIONS: Vitamin B(6) treatment has an immediate effect on the concentrations and the forms of B(6) vitamers present in plasma, and the changes remain the same during prolonged treatment. Our results suggest that the B(6) vitamers in plasma reflect vitamin B(6) intake.

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

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

Holm G, Moody LE.

University of South Florida, USA.

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

J Inherit Metab Dis. 2003;26(2-3):259-65. Classical homocystinuria: vascular risk and its prevention.

Yap S.

National Center for Inherited Metabolic Disorders, The Children's University Hospital, Temple Street, Dublin 1, Ireland.

Homocystinuria due to cystathionine beta-synthase deficiency is the second most treatable aminoacidopathy. The reported incidence varies from 1 in 344,000 worldwide to 1 in 65,000 in Ireland. Untreated patients with homocystinuria have severe hyperhomocysteinaemia. Amongst its pathological sequelae, which include mental retardation, ectopia lentis and osteoporosis, vascular events remain the major cause of morbidity and mortality in untreated patients. Recognized modalities of treatment include pyridoxine, in combination with folic acid and vitamin B12; methionine-restricted, cystine-supplemented diet; and betaine. The natural history of vascular events is such that half will have an event before age 30 years and there is a predicted one event per 25 years at the time of maximal risk. In 158 patients with 2822 patient-years of treatment, there would be a predicted 112 events if left untreated, but instead only 17 vascular events were recorded during treatment (relative risk 0.09, 95% CI 0.036 to 0.228; p < 0.0001). Appropriate chronic treatment to lower hyperhomocysteinaemia is effective in reducing the potentially life-threatening vascular risk in patients with homocystinuria. These findings may also have relevance to the significance of mild hyperhomocysteinaemia that is commonly found in patients with premature vascular disease.

Free Radic Biol Med. 2002 Dec 15;33(12):1615-21.

Effect of high-glucose levels on protein oxidation in cultured lens cells, and in crystalline and albumin solution and its inhibition by vitamin B6 and N-acetylcysteine: its possible relevance to cataract formation in diabetes.

Jain AK, Lim G, Langford M, Jain SK.

Caddo Magnet High School, Shreveport, LA 71130, USA.

Diabetic patients have elevated levels of glucose in their blood and other body fluids. This project studied the effect of high-glucose concentrations (HG) on the protein oxidation in cultured lens cells and in crystalline protein solution. In addition, we also examined the effect of HG on the oxidation and turbidity (aggregation) of albumin protein solution. This study also examined whether vitamin B6 [pyridoxine (P), pyridoxamine (PM)] or n-acetylcysteine (NAC) is capable of preventing protein oxidation similar to that seen in cataracts. For cell culture studies, rabbit lens cells were cultured in control or HG medium at 37 degrees C for 2 d. For studies with protein solution, a buffered solution of serum albumin or crystalline protein was incubated with normal glucose (5 mM) or HG (50-100 mM) in a water bath at 37 degrees C for 4 d. All treatments were carried out with and without the addition of P, PM, or NAC. We found significantly higher levels of carbonyl protein (an index of protein oxidation) in HG-treated compared with normal glucose-treated lens cells and in crystalline protein solution. P, PM, and NAC significantly decreased the protein oxidation in lens cells and crystalline protein solution. We also found significantly higher levels of protein oxidation and turbidity (an index of protein aggregation) and its inhibition by P, PM, and NAC in HG-treated compared with normal glucose-treated albumin solution. This suggests that HG can cause the oxidation and modification of proteins in the lens, and that vitamin B6 and NAC supplementation may be helpful in slowing the oxidation of lens proteins. This study explains the cause of early cataract development and the potential benefit of supplementation with vitamin B6 and NAC in the prevention of the development of cataract among the diabetic population.

Altern Med Rev. 2002 Dec;7(6):472-99.

Autism, an extreme challenge to integrative medicine. Part 2: medical management.

Kidd PM.

Autism and allied autistic spectrum disorders (ASD) present myriad behavioral, clinical, and biochemical abnormalities. Parental participation, advanced testing protocols, and eclectic treatment strategies have driven progress toward cure. Behavioral modification and structured education are beneficial but insufficient. Dietary restrictions, including removal of milk and other casein dairy products, wheat and other gluten sources, sugar, chocolate, preservatives, and food coloring are beneficial and prerequisite to benefit from other interventions. Individualized IgG or IgE testing can identify other troublesome foods but not non-immune mediated food sensitivities. Gastrointestinal improvement rests on controlling Candida and other parasites, and using probiotic bacteria and nutrients to correct dysbiosis and decrease gut permeability. Detoxification of mercury and other heavy metals by DMSA/DMPS chelation can have marked benefit. Documented sulfoxidation-sulfation inadequacies call for sulfur-sulfhydryl repletion and other liver p450 support. Many nutrient supplements are beneficial and well tolerated, including dimethylglycine (DMG) and a combination of pyridoxine (vitamin B6) and magnesium, both of which benefit roughly half of ASD cases. Vitamins A, B3, C, and folic acid; the minerals calcium and zinc; cod liver oil; and digestive enzymes, all offer benefit. Secretin, a triggering factor for digestion, is presently under investigation. Immune therapies (pentoxifyllin, intravenous immunoglobulin, transfer factor, and colostrum) benefit selected cases. Long-chain omega-3 fatty acids offer great promise. Current pharmaceuticals fail to benefit the primary symptoms and can have marked adverse effects. Individualized, in-depth clinical and laboratory assessments and integrative parent-physician-scientist cooperation are the keys to successful ASD management.

J Child Neurol. 2002 Dec;17 Suppl 3:3S9-13; discussion 3S14.

Infantile epileptic syndromes and metabolic etiologies.

Vigevano F, Bartuli A.

Division of Neurology, Bambino Gesu Children's Hospital, Rome, Italy.

Inherited metabolic disorders can cause onset of epilepsy in the first year of life. Epilepsy rarely dominates the clinical presentation, which is more frequently associated with other neurologic symptoms, such as mental retardation, hypotonia and/or dystonia, or vigilance disturbances. The pathogenesis of seizures is multifaceted; inherited metabolic disorder can affect the balance between excitatory and inhibitory chemical mediators, eliminate an energetic substrate at the cerebral level, cause in utero brain malformation, or provoke acute brain lesions. Some clinical disorders that strongly suggest particular metabolic etiologies can be identified. For example, specific clinical signs and findings on electroencephalogram (EEG) are characteristic of pyridoxine-dependent seizures, and inherited metabolic disorders associated with early myoclonic encephalopathy are well defined. In most cases, however, epilepsy secondary to inherited metabolic disorders presents with polymorphic clinical and EEG features that are difficult to classify into precise epileptic syndromes. Common characteristics of these seizures include onset in the first months of life; usually partial, multifocal; simple partial motor semiology; successive appearance of tonic seizures, spasms, and massive myoclonus; and resistance to antiepilepsy drugs. Inherited metabolic disorders must be considered in patients presenting with epilepsy and progressive neurologic worsening.

J Nutr. 2002 Dec;132(12):3603-6. Occupancy of glycoprotein IIb/IIIa by B-6 vitamers inhibits human platelet aggregation.

Chang SJ, Chang CN, Chen CW.

Department of Biology, National Cheng Kung University, Tainan, Taiwan.

Vitamin B-6 inhibits platelet aggregation. However, the effect of the occupancy of GPIIb/IIIa, a major receptor responsible for aggregation on platelet membranes, by B-6 vitamers on platelet aggregation is unknown. This study was carried out to quantify GPIIb/IIIa occupancy in platelets treated with B-6 vitamers [pyridoxal-5-phosphate (PLP); pyridoxal (PL); pyridoxine (PN); pyridoxamine (PM)], using a monoclonal antibody-based assay, by flow cytometry. Antibody binding was compared with inhibition of platelet aggregation. PLP, PL, PN and PM occupied GPIIb/IIIa with dissociation constants of 1.83 +/- 1.15, 19.43 +/- 7.86, 3.63 +/- 1.67 and 10.89 +/- 2.93 mmol/L, respectively. Occupancy of GPIIb/IIIa by the four B-6 vitamers was negatively correlated with platelet aggregation (r = -0.90 to -0.94, P < 0.001). The concentrations of the four B-6 vitamers that inhibited maximal platelet aggregation were in the order of PLP < PN <PM < PL, the same order in which they occupied > or =80% of the GPII/IIIa receptor. Platelet aggregation was inhibited by B-6 vitamers via the occupancy of GPIIb/IIIa with the potency of PLP > PN > PM > PL.

Magnes Res. 2002 Dec;15(3-4):179-89.

Effect of magnesium supplementation containing mineral bishofit (MgCl2 x 6H2O) solution and pyridoxine hydrochloride on erythrocyte magnesium depletion and behaviour of rats after three-month alcoholization.

Iezhitsa IN, Onishchenko NV, Churbakova NV, Parshev VV, Petrov VI, Spasov AA.

Medical Academy, Research Institute of Pharmacology, 1 Pavshikh Bortsov sq., Volgograd, 400066 Russia.

In therapy it is known that the combination of vitamin B6 and magnesium is beneficial in the treatment of several forms of primary magnesium deficiency. The purpose of the present study was to investigate the effect of complex magnesium supplementation containing mineral bishofit solution (MgCl2 x 6H2O) and pyridoxine hydrochloride on behavioural and biochemical parameters of magnesium-deficient alcoholic rats. A complex magnesium supplementation containing mineral bishofit solution and pyridoxine hydrochloride led both to restoration of magnesium level, and to some correction of behavioural disturbances of animals during chronic alcoholization.

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

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

Department of Physiology of Nutrition, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico, Mexico.

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

Expert Opin Pharmacother. 2002 Nov;3(11):1591-8. Pharmacotherapy of hyperhomocysteinaemia in patients with thrombophilia.

O'Donnell J, Perry DJ.

Katherine Dormandy Haemophilia Centre and Haemostasis Unit, Department of Haematology, Royal Free Hospital School of Medicine, Pond Street, London NW3 2QG, UK.

Hyperhomocysteinaemia is often the result of inherited abnormalities of the enzymes involved in homocysteine metabolism or vitamin deficiencies (vitamins B12, B6 or folate) and is present in approximately 5% of the general population. High homocysteine levels in these individuals are associated with a significant increase in relative risk for both arterial and venous thromboembolic disease. Consequently, effective homocysteine-lowering therapeutic strategies have been extensively investigated. Folic acid represents the cornerstone of treatment. In daily doses of at least 0.4 mg, it effectively reduces homocysteine levels, even in non-folate-deficient patients. The addition of vitamins B12 and/or B6, to folic acid supplementation may provide a small further reduction in homocysteine levels in certain groups of patients. Renal impairment is an important cause of hyperhomocysteinaemia. Individuals with hyperhomocysteinaemia secondary to renal disease commonly require significantly higher doses of folic acid (5-40 mg) to achieve maximal therapeutic effect. The important question of whether effective homocysteine-lowering therapy translates into a reduction in vascular disease remains unknown but is being addressed in a series of ongoing prospective trials.

J Child Neurol. 2002 Nov;17(11):859-60.

Homocystinuria presenting as psychosis in an adolescent.

Ryan MM, Sidhu RK, Alexander J, Megerian JT.

Department of Neurology, Children's Hospital Boston, Massachusetts 02115, USA.

Homocystinuria usually presents with ectopia lentis, mental retardation, thromboembolic complications, and skeletal abnormalities. Whereas neuropsychiatric abnormalities are often recognized in untreated homocystinuria, initial presentation with acute psychosis has only rarely been reported. We describe a previously well 17-year-old adolescent with an acute psychosis characterized by auditory and visual hallucinations and marked paranoia who was found to have pyridoxine-responsive homocystinuria. His mental state normalized within several weeks of inception of pyridoxine and antipsychotic therapy. Pyridoxine-responsive homocystinuria is commonly missed on neonatal screens and should be recognized as a potentially treatable cause of acute psychosis in childhood and adolescence.

Altern Med Rev. 2002 Oct;7(5):389-403.

Intravenous nutrient therapy: the "Myers' cocktail".

Gaby AR.

Building on the work of the late John Myers, MD, the author has used an intravenous vitamin-and-mineral formula for the treatment of a wide range of clinical conditions. The modified "Myers' cocktail," which consists of magnesium, calcium, B vitamins, and vitamin C, has been found to be effective against acute asthma attacks, migraines, fatigue (including chronic fatigue syndrome), fibromyalgia, acute muscle spasm, upper respiratory tract infections, chronic sinusitis, seasonal allergic rhinitis, cardiovascular disease, and other disorders. This paper presents a rationale for the therapeutic use of intravenous nutrients, reviews the relevant published clinical research, describes the author's clinical experiences, and discusses potential side effects and precautions.

Epilepsy Res. 2002 Oct;51(3):237-47. The effect of B-vitamins on hyperhomocysteinemia in patients on antiepileptic drugs.

Apeland T, Mansoor MA, Pentieva K, McNulty H, Seljeflot I, Strandjord RE.

Department of Internal Medicine, Rogaland Central Hospital, 4011 Stavanger, Norway.

Patients on antiepileptic drugs (AEDs) may have elevated levels of plasma total homocysteine (p-tHcy). The aim of this study was to assess the effect of B-vitamin supplementation on the levels of p-tHcy and markers of endothelial activation and lipid peroxidation. A total of 33 adult patients on AEDs were identified with either fasting (Group 1, n=23) or post methionine load (PML) (Group 2, n=10) hyperhomocysteinemia. Subjects were supplemented with B-vitamins for 30 days: folic acid 0.4 mg, pyridoxine 120 mg and riboflavin 75 mg per day. After supplementation, serum folate and pyridoxal phosphate had increased, while fasting and PML p-tHcy had decreased (P<0.0001) by 36 and 26%, respectively. Prior to supplementation, the Group 1 patients had elevated levels of P-selectin and von Willebrand factor (vWF) (P=0.05 and 0.03, respectively). After supplementation, the levels of intercellular cell adhesion molecules had decreased (P=0.01) and E-selectin decreased nonsignificantly (P=0.07). However, the levels of vascular cell adhesion molecules had increased (P<0.0001), while lipid peroxidation were unchanged. In conclusion, the combined supplementation with folic acid, pyridoxine and riboflavin reduced fasting and PML hyperhomocysteinemia in patients on AEDs. Patients with fasting hyperhomocysteinemia had elevated levels of P-selectin and vWF, which may indicate an increased risk of cardiovascular disease. Furthermore, B-vitamin supplementation influenced endothelial activation, although the clinical implication is uncertain.

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

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

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

Firat University Medical Faculty, Department of Neurology, Elazig, Turkey.

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

Nutrition. 2002 Sep;18(9):738-42. Efficacy of a complex multivitamin supplement.

Earnest C, Cooper KH, Marks A, Mitchell TL.

The Cooper Institute for Aerobics Research, Dallas, Texas 75230, USA.

OBJECTIVES: Multivitamin supplements are often sold to consumers with the claim that supplements modify risk factors associated with disease. Because few products are validated scientifically, we examined the effects of a 24-ingredient multivitamin formula in an open-label pilot investigation. METHODS: We examined 150 subjects for specific endpoints including blood concentrations of selected vitamins, homocysteine, lipids, and low-density lipoprotein (LDL) oxidation indices at baseline and at 12 and 24 wk. RESULTS: One hundred forty-one subjects were successfully assayed for and showed significant time effects for homocysteine and vitamin B6 (as pyridoxal-5'-phosphate), B12, and folic acid concentrations during treatment (P < 0.0001). Vitamin B6, B12, and folic acid concentrations were significantly elevated at weeks 12 and 24 (P < 0.05). Homocysteine concentration decreased significantly during the same periods (7.9 +/- 2.4 versus 6.7 +/- 1.7 versus 6.7 +/- 1.9 mM/mL; P < 0.05). There were correlations relating homocysteine to vitamins B6 (P = 0.001, r(2) = 0.03), B12 (P < 0.001, r(2) = 0.09), and folic acid (P = 0.001, r(2) = 0.10). Significant time effects were noted for 121 subjects successfully assayed for vitamin C, E, beta-carotene, LDL oxidation rate, and LDL lag time (P < 0.0001). Post hoc assessment showed elevations in vitamin C, E, and beta-carotene concentrations at 12 and 24 wk (P < 0.05). LDL oxidation lag time at baseline (57.5 +/- 13.9 min) increased by 12 wk (63.5 +/- 19.0 min; P < 0.05) and 24 wk (63.8 +/- 16.3 min; P < 0.05). LDL oxidation rate at baseline (9.7 +/- 3.0 microM x min(-1). g(-1)) was reduced at 12 wk (7.1 +/- 2.5 microM x min(-1) x g(-1); P < 0.05) and 24 wk (6.0 +/- 2.0 microM x min(-1) x g(-1); P < 0.05). Only vitamin C was significantly correlated with LDL oxidation rate (P = 0.05, r(2) = 0.003). CONCLUSIONS: A multi-ingredient vitamin formula with antioxidant properties has measurable effects on homocysteine and LDL oxidation indices.

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

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

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

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

JAMA. 2002 Aug 28;288(8):973-9.

Comment in: • ACP J Club. 2003 Mar-Apr;138(2):33. • J Fam Pract. 2003 Jan;52(1):16-8. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial.

Schnyder G, Roffi M, Flammer Y, Pin R, Hess OM.

Division of Cardiology, Swiss Cardiovascular Center Bern, University Hospital, Switzerland.

CONTEXT: Plasma homocysteine level has been recognized as an important cardiovascular risk factor that predicts adverse cardiac events in patients with established coronary atherosclerosis and influences restenosis rate after percutaneous coronary intervention. OBJECTIVE: To evaluate the effect of homocysteine-lowering therapy on clinical outcome after percutaneous coronary intervention. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind placebo-controlled trial involving 553 patients referred to the University Hospital in Bern, Switzerland, from May 1998 to April 1999 and enrolled after successful angioplasty of at least 1 significant coronary stenosis (> or = 50%). INTERVENTION: Participants were randomly assigned to receive a combination of folic acid (1 mg/d), vitamin B12 (cyanocobalamin, 400 micro g/d), and vitamin B6 (pyridoxine hydrochloride, 10 mg/d) (n = 272) or placebo (n = 281) for 6 months. MAIN OUTCOME MEASURE: Composite end point of major adverse events defined as death, nonfatal myocardial infarction, and need for repeat revascularization, evaluated at 6 months and 1 year. RESULTS: After a mean (SD) follow-up of 11 (3) months, the composite end point was significantly lower at 1 year in patients treated with homocysteine-lowering therapy (15.4% vs 22.8%; relative risk [RR], 0.68; 95% confidence interval [CI], 0.48-0.96; P =.03), primarily due to a reduced rate of target lesion revascularization (9.9% vs 16.0%; RR, 0.62; 95% CI, 0.40-0.97; P =.03). A nonsignificant trend was seen toward fewer deaths (1.5% vs 2.8%; RR, 0.54; 95% CI, 0.16-1.70; P =.27) and nonfatal myocardial infarctions (2.6% vs 4.3%; RR, 0.60; 95% CI, 0.24-1.51; P =.27) with homocysteine-lowering therapy. These findings remained unchanged after adjustment for potential confounders. CONCLUSION: Homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 significantly decreases the incidence of major adverse events after percutaneous coronary intervention.

Thromb Haemost. 2002 Aug;88(2):230-5.

Effect of homocysteine reduction by B-vitamin supplementation on markers of clotting activation.

Klerk M, Verhoef P, Verbruggen B, Schouten EG, Blom HJ, Bos GM, den Heijer M.

Division of Human Nutrition and Epidemiology, Wageningen University, Wageningen Centre for Food Sciences, Wageningen.

Homocysteine may have an effect on risk of cardiovascular disease by stimulating procoagulant factors and/or impair anti-coagulant mechanisms or fibrinolysis. However, data in humans of such effects are sparse. In this intervention study, we examined the effect of homocysteine lowering by B-vitamin supplementation on prothrombin fragments 1 and 2 (F1 + 2), thrombin-antithrombin complex (TAT), and fibrin degradation products (D-dimer). The study comprised 118 healthy volunteers, 50 with homocysteine > 16 mumol/L and 68 with homocysteine < or = 16 mumol/L, who were randomized to placebo or high-dose B-vitamin supplements (5 mg folic acid, 0.4 mg hydroxycobalamin, and 50 mg pyridoxine) daily for 8 weeks. Although homocysteine concentrations were 27.7% (p < 0.0001) reduced in the B-vitamin group compared to the placebo group, no effect on F1 + 2 and TAT concentrations was observed. A 10.4% reduction was observed for D-dimer (p = 0.08). In conclusion, it appears that in healthy subjects homocysteine reduction by B-vitamin supplementation has a modest beneficial effect on clotting activation.

J Pediatr Hematol Oncol. 2002 Jun-Jul;24(5):374-9. Hyperhomocysteinemia is associated with low plasma pyridoxine levels in children with sickle cell disease.

Balasa VV, Kalinyak KA, Bean JA, Stroop D, Gruppo RA.

Cincinnati Comprehensive Sickle Cell Center of the Division of Hematology/Oncology, Children's Hospital Medical Center, Ohio 45229, USA.

Elevated plasma homocysteine levels have been shown to be a risk factor for endothelial cell damage and thrombosis, which are implicated in sickle cell disease (SCD)-related vaso-occlusion. The aim of this study was to determine the prevalence of hyperhomocysteinemia in SCD. Fasting and postmethionine load (PML) homocysteine, red cell folate, and the MTHFR C677T mutation were determined in 77 patients with SCD and 110 African-American controls. Plasma methylmalonic acid and pyridoxine levels were determined in 54 patients and all controls. For analysis, the subjects were divided into two age groups (2-10 years and 10.1-21 years). In both age groups, median PML homocysteine levels were significantly elevated in patients with SCD compared with controls. Fasting homocysteine levels were elevated in patients with SCD versus controls only in those older than 10 years. Hyperhomocysteinemia was noted in 38% of patients versus 7% in controls. Folate levels were higher among patients than controls and showed a significant negative correlation with PML homocysteine levels in patients with SCD. Pyridoxine levels in patients with SCD were significantly lower than in controls and showed a negative correlation with PML homocysteine levels. Among patients with SCD, pyridoxine deficiency was more common (62%) among those with hyperhomocysteinemia compared with those with normal homocysteine levels (30%). Homozygosity for the MTHFR C677T mutation was rare. These data suggest that children with SCD have significant hyperhomocysteinemia, associated with pyridoxine and relative folate deficiencies.

Pharmacol Toxicol. 2002 Jun;90(6):338-42. Opposite effects of nicotinic acid and pyridoxine on systemic prostacyclin, thromboxane and leukotriene production in man.

Saareks V, Ylitalo P, Mucha I, Riutta A.

Department of Pharmacological Sciences, University of Tampere, Finland.

The effects of nicotinic acid (2500 mg orally during 12 hr) and pyridoxine (300 mg orally twice daily for seven days) on the excretion of urinary 2,3-dinor-6-ketoprostaglandin F1alpha, 11-dehydrothromboxane B2 and leukotriene E4, the markers of systemic prostacyclin, thromboxane A2 and cysteinyl leukotriene production, respectively, were investigated in healthy male volunteers (n=6-8). Nicotinic acid increased 11-dehydrothromboxane B2 and leukotriene E4 excretions to 2.6- and 2.0 times the initial values (P<0.05), respectively. In the volunteers treated with pyridoxine, 11-dehydrothromboxane B2 and leukotriene E4 excretions were decreased to 70% (P<0.05) and 65% (P<0.01) of the initial values, respectively, but the excretion of 2,3-dinor-6-ketoprostaglandin F1alpha was increased 1.7 times (P<0.01). The results suggest that nicotinic acid increases thromboxane and leukotriene synthesis which may not be beneficial for patients with cardiovascular diseases or asthma. In contrast, the increase in prostacyclin production and the inhibition in thromboxane and leukotriene synthesis by pyridoxine might be beneficial in disorders where the production of prostacyclin is decreased and the formation of thromboxane and cysteinyl leukotrienes is enhanced.

Nephrol Dial Transplant. 2002 May;17(5):865-70. Hyperhomocysteinaemia therapy in haemodialysis patients: folinic versus folic acid in combination with vitamin B6 and B12.

Ducloux D, Aboubakr A, Motte G, Toubin G, Fournier V, Chalopin JM, Drueke T, Massy ZA.

Division of Nephrology, Biochemistry B Laboratory, CHU St Jacques, Besancon, France.

BACKGROUND: In a recent uncontrolled retrospective report we suggested that the long-term supplementation of high-dose, i.v. folinic acid combined with high-dose i.v. pyridoxine was highly effective in correcting plasma total homocysteine (tHcy) concentrations in haemodialysis patients. To confirm these findings, we conducted a randomized, controlled trial aimed at evaluating whether i.v. or oral folinic acid provided improved tHcy-lowering efficacy in haemodialysis patients compared with oral folic acid. METHODS: In a 6-month prospective, randomized, controlled trial, 60 chronic haemodialysis patients, matched for age, gender, dialysis duration, and average screening pre-treatment-fasting tHcy levels, were given either 50 mg/week of i.v. calcium folinate (group 1), 50 mg/week of oral calcium folinate (group 2), or 45 mg/week oral folic acid (group 3). All 60 patients also received 750 mg/week of i.v. vitamin B6 and 3 mg/week of oral vitamin B12. RESULTS: Fasting tHcy decreased significantly and to a similar extent in the three groups after 2 months of treatment and remained stable at 4 and 6 months (16.6+/-3.5, 18.3+/-4, and 19.1+/-3.1, in groups 1, 2, and 3, respectively, P=NS). Mean percentage reduction at 6 months was also similar in the three treatment groups (46, 43, and 42% in groups 1, 2, and 3, respectively, P=NS). CONCLUSIONS: These findings show that the tHcy-lowering effects of high-dose i.v. folinic acid, oral folinic acid, or oral folic acid were comparable, suggesting that the hyperhomocysteinaemia observed in haemodialysis patients is not due to abnormal folate metabolism. Furthermore, they are compatible with the view that other abnormalities are also involved in the impaired clearance of homocysteine in uraemic patients.

Br J Sports Med. 2002 Apr;36(2):126-31. Physical exercise or micronutrient supplementation for the wellbeing of the frail elderly? A randomised controlled trial.

Chin A Paw MJ, de Jong N, Schouten EG, van Staveren WA, Kok FJ.

Division of Human Nutrition and Epidemiology, Wageningen University, The Netherlands.

OBJECTIVE: To examine the effects of 17 weeks of physical exercise and micronutrient supplementation on the psychological wellbeing of 139 independently living, frail, elderly subjects (inactive, body mass index < or =25 or experiencing weight loss). METHODS: Participants (mean (SD) age 78.5 (5.7)) were randomly assigned to: (a) comprehensive, moderate intensity, group exercise; (b) daily micronutrient enriched foods (25-100% recommended daily amount); (c) both; (d) neither. A social programme and identical regular foods were offered as attention control and placebo. RESULTS: At baseline, moderate to low but significant correlations were found between general wellbeing scores and physical fitness (r = 0.28), functional performance (r = 0.37), and blood concentrations of pyridoxine (r = 0.20), folate (r = 0.25), and vitamin D (r = 0.23) (all p values < or =0.02), but not with physical activity levels and other blood vitamin concentrations. General wellbeing score and self rated health were not responsive to 17 weeks of exercise or nutritional intervention. CONCLUSION: Psychological wellbeing in frail elderly people was not responsive to 17 weeks of intervention with exercise and/or micronutrient enriched foods. The moderate but significant correlations between wellbeing and physical fitness and several blood vitamin concentrations at baseline suggest that changes in wellbeing may occur after long term interventions.

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

Pyridoxine-dependent seizures associated with hypophosphatasia in a newborn.

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

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

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