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Vitamin B6 |
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Vitamin B6 (Pyridoxine)
Vitamin B-6, otherwise known as pyridoxine, performs as a coenzyme to carry out metabolic processes that affect the body’s use of protein, carbohydrates, and fat. It helps to convert tryptophan to niacin, and may be found in meat, fish, eggs, milk, and whole grain foods.
How This Vitamin Works in Your Body:
Treatment of cycloserine and isoniazid poisoning
The following people may benefit from taking this
Vitamin:
Where This Vitamin is Found:
How to Use: Tablets: available
Recommended Daily Intakes
Cautions:
Over 55:
Pregnancy:
Breastfeeding:
Storage:
Symptoms of Deficiency:
Overdose:
Side Effects:
Interactions: Phenytoin : Large doses affect medicine absorption.
Vitamin B6 TRADE NAMES Releaf PMS (Lake Consumer Products), Bedoxine 100 (Ampharco Inc.), VitaBee 6 (Consolidated Midland Corp.), Pyri-500 (Miller Pharmacal), Rodex (Legere Pharmaceuticals), Aminoxin (Tyson Neutraceuticals), Vitelle Nestrex (Fielding Pharmaceutical), Ginkai (Lichtwer Pharm). DESCRIPTION Vitamin B6 is the collective term for a group of three related compounds, pyridoxine (PN), pyridoxal (PL) and pyridoxamine (PM), and their phosphorylated derivatives, pyridoxine 5'-phosphate (PNP), pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP). Although all six of these vitamers should technically be referred to as vitamin B6, the term vitamin B6 is commonly used interchangeably with just one of the vitamers, pyridoxine. Vitamin B6, principally in the form of the coenzyme pyridoxal 5'-phosphate, is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA). Food sources of vitamin B6, include meat, poultry, fish, eggs, white potatoes and other starchy vegetables, noncitrus fruits, fortified ready-to-eat cereals and fortified soy-based meat substitutes. The principal forms of vitamin B6 in animal products are pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate. In plant-derived foods, the major forms of vitamin B6 are pyridoxine, pyridoxine 5'-phosphate and pyridoxine glucosides. Glycosylated forms of pyridoxine range from approximately 5% to 75% of the total vitamin B6 content in fruits, vegetables and grains, with little to none in animal products. Pyridoxine appears to be the only glycosylated form of vitamin B6. The major glycosylated form of pyridoxine in most plant-derived foods is pyridoxine 5'-beta-D-glucoside. Pyridoxine hydrochloride is the form of vitamin B6 most commonly used for fortification of foods and in nutritional supplements. The classical symptoms and signs of vitamin B6 deficiency are a microcytic, hypochromic anemia, seizure activity, seborrheic dermatitis, confusion and depression. Vitamin B6-deficiency states in infants and children primarily result in electroencephalogram abnormalities and seizure activity, while in adults, vitamin B6 deficiency primarily results in cheilosis (chapping and fissuring of the lips), glossitis (inflammation of the tongue), stomatitis (inflammation of the oral mucosa), anemia, irritability, confusion and depression. Many of these signs are not specific for vitamin B6 deficiency and may be due to deficiencies of other vitamins or result from other causes. Vitamin B6 deficiency may result from the use of certain drugs, including isoniazid (isonicotinic acid hydrazide or INH), penicillamine, cycloserine, ethionamide, hydralazine and theophylline. Subclinical vitamin B6 deficiency frequently occurs in those with malabsorption syndromes, uremia, cancer, heart failure and cirrhosis, and in alcoholics, the elderly and adolescent females and during pregnancy. In the elderly and in those with malabsorption syndromes, clinical deficiency of the vitamin may occur.
In addition to vitamin B6 deficiency conditions, vitamin B6-dependency conditions exist. Certain inborn errors of metabolism exist in which a vitamin B6-dependent enzyme is defective in the coenzyme (pyridoxal 5'-phosphate) binding site, and the enzyme only has significant activity when the tissue concentration of pyridoxine 5'-phosphate, the biologically active form of vitamin B6, is much higher than normal. These vitamin B6-dependent conditions, which may be responsive to treatment with large doses of the vitamin, include convulsions of the newborn secondary to glutamate decarboxylase (GAD) deficiency, cystathionuria secondary to cystathionase deficiency, gyrate atrophy with ornithinuria secondary to ornithinine-delta-aminotransferase deficiency, homocystinuria secondary to cystathionine beta-synthase deficiency, primary hyperoxaluria type 1 secondary to peroxisomal alanine-glyoxylate transaminase deficiency, sideroblastic anemia secondary to delta-aminolevulinate synthase deficiency and xanthurenic aciduria secondary to kynureninase deficiency. These genetic disorders are all rare. Vitamin B6 in the form of pyridoxal 5'-phosphate is a coenzyme for over 100 enzymes. Most of these enzymes are involved in amino acid metabolism and include aminotransferases (transaminases), decarboxylases. Pyridoxal 5'-phosphate is sometimes referred to as codecarboxylase, dehydratases and racemases. The basic chemistry accounting for the broad range of reactions of B6 is Schiff's base formation. Schiff's bases are reaction products of aldehyde and amino groups. In the resting state of the above enzymes, the aldehyde group of pyridoxal 5'-phosphate is covalently linked to the epsilon-amino group of a lysine residue at the active site of the enzyme. Upon binding of the amino acid substrate, the lysine is exchanged for the alpha-amino group of the substrate, forming a Schiff's base with the aldehyde group of pyridoxal 5'-phosphate. A quinonoid intermediate follows the formation of the Schiff's base, which in turn is followed by the formation of the reaction products. Schiff's base chemistry is the mechanism of almost all of the reactions in which pyridoxal 5'-phosphate participates. One exception is the glycogen phosphorylase reaction. Glycogen phosphorylase catalyzes the breakdown of the storage polysaccharide glycogen to yield glucose 1-phosphate. Much of the total pyridoxal 5'-phosphate in the body is found in muscle bound to glycogen phosphorylase. In glycogen phosphorylase, the phosphate group of pyridoxal 5'-phosphate, rather than its aldehye group, participates in the catalytic role of the enzyme. Vitamin B6 is involved in several key biological processes. Pyridoxal 5'-phosphate is the coenzyme for delta-aminolevulinate synthase, the first step in the synthesis of porphyrins. Heme is derived from protoporphyrin IX. Heme is the iron-containing prosthetic group that is an essential component of such proteins as hemoglobin, myoglobin and the cytochromes. Homocysteine is an intermediate in methionine metabolism and may undergo one of two metabolic fates, remethylation to L-methionine or further metabolism, leading to the synthesis of L-cysteine. The pathway leading to the synthesis of cysteine is known as the transsulfuration pathway. This pathway has two pyridoxal 5'-phosphate-dependent enzymes: cystathionine beta-synthase and cystathionase. The conversion of tryptophan to niacin also requires pyridoxal-5'-phosphate, this time as a cofactor for the pyridoxal 5'-phosphate-dependent enzyme kynureninase. And, via its role in transamination, pyridoxal 5'-phosphate is involved in the production of energy. Decarboxylation of amino acids yields amines, including gamma-aminobutyrate, dopamine, norepinephrine, epinephrine and serotonin, which play important roles as neurotransmitters or hormones. The amino acid decarboxylases are also pyridoxal 5'-phosphate-dependent enzymes. Pyridoxal 5'-phosphate plays a role in the regulation of steroid hormone activity: Physiological levels of pyridoxal 5'-phosphate interact with glucocorticoid receptors to downregulate their activity. Pyridoxal 5'-phosphate has also been shown to negatively modulate steroid-dependent gene expression induced by progesterone, androgen and estrogen hormones. Finally, serine hydroxymethyltransferase is a pyridoxal 5'-phosphate-dependent enzyme which catalyzes the interconversion of serine and glycine, both of which are major sources of one-carbon units necessary for the de novo synthesis of purine nucleotides and thymidylate. Purine nucleotides are precursors of DNA and RNA, and thymidylate is a precursor of DNA. The vitamers comprising the vitamin B6 family are pyridine derivatives. Specifically, they are derivatives of 3-hydroxy-5-hydroxymethyl-2-methyl pyridine. The vitamers differ by the nature of the chemical group occupying the 4 position of the parent compound. In the case of pyridoxine, the 4 position is occupied by an hydroxymethyl group. Pyridoxine is also known as 5-hydroxy-6-methyl-3, 4-pyridinedimethanol, 2-methyl-3-hydroxy-4,5-bis(hydroxymethyl)pyridine and pyridoxol. Its molecular formula is C8H11NO3 and its molecular weight is 169.17 daltons. Pyridoxine hydrochloride is the principal form of vitamin B6 used in nutritional supplements and for food fortification. Pyridoxal is also known as 3-hydroxy-5-(hydroxymethyl)-2-methyl-4-pyridinecarboxaldehyde and 2-methyl-3-hydroxy-4-formyl-5-hydroxymethylpyridine. In the case of pyridoxal, the 4 position of the parent compound is occupied by a formyl group. The molecular formula of pyridoxal is C8H9NO3 and its molecular weight is 167.16 daltons. Pyridoxamine has an aminomethyl group occupying the 4 position of the parent structure. Pyridoxamine is also known as 4-(aminomethyl)-5-hydroxy-6-methyl-3-pyridinemethanol and 2-methyl-3-hydroxy-4-aminomethyl-5-hydroxymethylpyridine. Its molecular formula is C8H12N2O2 and its molecular weight is 168.18. ACTIONS AND PHARMACOLOGY ACTIONS Vitamin B6 has antineurotoxic activity and may have activity in a number of inborn errors of metabolism, including pyridoxine-dependent seizures in infants, sideroblastic anemia, primary hyperoxaluria, homocystinuria and cystathioninuria. Vitamin B6 has putative antiatherogenic, immunomodulatory, anticarcinogenic and mood-modulatory activities.
MECHANISM OF ACTIONS Vitamin B6 is used in the prophylaxis and treatment of vitamin B6 deficiency and peripheral neuropathy in those receiving isoniazid (isonicotinic acid hydrazide, INH). The antituberculosis drug isoniazid reacts non-enzymatically with pyridoxal 5'-phosphate to form a metabolically inactive hydrazone. This can result in vitamin B6 deficiency and peripheral neuropathy. It may also result in pellagra. The formation of niacin from tryptophan is catalyzed by, among other enzymes, kynureninase. Kynureninase is a vitamin B6-dependent enzyme. Therefore, vitamin B6 deficiency resulting from isoniazid, particularly in the context of marginal or clinical niacin deficiency, may lead to the niacin deficiency disorder pellagra. The peripheral neuropathy resulting from isoniazid does not appear to be due to vitamin B6 deficiency, but to isoniazid itself. The antineurotoxic effect of vitamin B6 in the case of isoniazid appears to be accounted for by the reaction of the vitamin with the drug, thus lowering its tissue level and its neurotoxicity. High theophylline levels may cause seizures. It is thought that this is due to reaction of theophylline with pyridoxal 5'-phosphate, leading to lowered plasma levels of the vitamin. Pyridoxal 5'-phosphate is involved in the metabolism of gamma-aminobutyric acid (GABA). GABA is a major inhibitory neurotransmitter in the central nervous system. When the concentration of GABA in the brain decreases to below a threshold level, seizures and other neurological disorders, may occur. The concentration of GABA in the brain is controlled by two pyridoxal 5'-phosphate-dependent enzymes, glutamate decarboxylase (GAD) and GABA transaminase (GABA-T). A decrease in the levels of GABA in the brain secondary to decreased levels of pyridoxal 5'-phosphate can lead to seizures. It has been found that the administration of vitamin B6 to mice treated with theophylline reduced the number of seizures, and the vitamin administered to rabbits reversed electroencephalogram changes caused by high doses of theophylline. Seven inborn errors of metabolism are known in which a vitamin B6-dependent enzyme has a defect in the coenzyme (pyridoxal 5'-phosphate) binding site, and the enzyme only has significant activity when the tissue concentration of pyridoxine 5'-phosphate is much higher than normal. The disorders and their enzyme defects are pyridoxine-dependent seizures in infants (glutamate decarboxylase deficiency resulting in decreased CNS levels of GABA), pyridoxine-responsive sideroblastic anemia (delta-aminolevulinate synthase deficiency resulting in decreased synthesis of hemogloblin), primary hyperoxaluria type 1 (peroxisomal alanine-glyoxylate transaminase deficiency), homocystinuria (cystathionine beta-synthase deficiency), cystathioninuria (gamma-cystathionase deficiency), xanthurenic aciduria (kynureninase deficiency) and gyrate atrophy of the choroid and retina (ornithine-delta-aminotransferase deficiency). These disorders may be responsive to high doses of vitamin B6, which increase tissue levels of pyridoxal 5'-phosphate. The putative antiatherogenic activity of vitamin B6 may be accounted for by a few different mechanisms. Hyperhomocysteinemia is an independent risk factor for atherosclerosis and coronary heart disease. Homocysteine is an intermediate in the metabolism of L-methionine and is either remethylated to L-methionine or, via the transsulfuration pathway, is converted to L-cysteine.
Two pyridoxal 5'-phosphate-dependent enzymes are involved in the conversion of homocysteine to cysteine: cystathionine beta-synthase and gamma-cystathionase. Studies to date, indicate that folic acid (see Folate) is more important than vitamin B6 in lowering homocysteine levels in those with moderate hyperhomocysteinemia (folic acid is involved in the remethylation of homocysteine), but it has not been ruled out that supplementary vitamin B6 may also aid in lowering homocysteine levels in some with hyperhomocysteinemia. Those who are deficient in vitamin B6 would be expected to have their homocysteine levels lowered with administration of the vitamin. Vitamin B6, in the form of pyridoxine hydrochloride, has been found to lower systolic and diastolic blood pressure in a small group of subjects with essential hypertension. Hypertension is another risk factor for atherosclerosis and coronary heart disease. The mechanism of action of the antihypertensive effect of vitamin B6 is unknown. Another study showed pyridoxine hydrochloride to inhibit ADP- or epinephrine-induced platelet aggregation and to lower total cholesterol levels and increase HDL-cholesterol levels, again in a small group of subjects. The mechanisms of action of the possible platelet and lipid effects of vitamin B6 are unknown. Vitamin B6, in the form of pyridoxal 5'-phosphate, was found to protect vascular endothelial cells in culture from injury by activated platelets. Endothelial injury and dysfunction are critical initiating events in the pathogenesis of atherosclerosis. The mechanism of the possible endothelial-protective effect of vitamin B6 is unclear. It is thought that vitamin B6 plays a role in the maintenance of endothelial integrity. Finally, vitamin B6 has been shown to have singlet oxygen quenching activity in vitro. Single oxygen is a reactive oxygen species and oxidative stress is thought to play a major role in the pathogenesis of atherosclerosis. Both animal and human studies have demonstrated that vitamin B6 deficiency affects cellular and humoral responses of the immune system. Vitamin B6 deficiency results in altered lymphocyte differentiation and maturation, reduced delayed-type hypersensitivity (DTH) responses, impaired antibody production, decreased lymphocyte proliferation and decreased interleukin (IL)-2 production, among other immunologic activities. Those at risk for vitamin B6 deficiency and associated immunological dysfunction are the elderly, those with uremia and those with HIV (human immunodeficiency virus) disease. Repletion of vitamin B6 in those with vitamin B6 deficiency can correct immunological dysfunctions. Supplementation of the vitamin in those who are vitamin B6 sufficient, has not to date shown immune-enhancing or immunomodulatory effects. The mechanism through which vitamin B6 deficiency alters immune responses is not well understood. Vitamin B6 deficiency appears to impair nucleic acid synthesis. The impaired nucleic acid synthesis is associated with altered one-carbon metabolism, particularly the activity of serine hydroxymethyltransferase. Serine hydroxymethyltransferase is a pyridoxal 5'-phosphate-dependent enzyme which catalyzes the interconversion of serine and glycine, both of which are major sources of one-carbon units necessary for the synthesis of purine nucleotides and thymidylate. Impairment of purine nucleotide and thymidylate synthesis would impair the synthesis of nucleic acids. Serine hydroxymethyltransferase activity appears to be low in resting lymphocytes. Antigenic or mitogenic stimulation of immune cells triggers their proliferation. Serine hydroxymethyltransferase activity increases in immune cells under the influence of antigenic or mitogenic stimulation, thus supplying the increased demand for nucleic acid synthesis during an immune response. Since vitamin B6 is involved in the synthesis of nucleic acids, via serine hydromethyltransferase, deficiency of the vitamin would result in decreased DNA replication, with consequent decreases in RNA and protein synthesis and immune cell proliferation. Pyridoxal has been found to inhibit the growth of human malignant melanoma cells in vitro. It has also been found to inhibit the growth of melanoma cells injected into mice. There is one report of topical vitamin B6 inducing lesion regression in two patients with melanoma. The mechanism of the putative anticarcinogenic activity of vitamin B6 is unknown. Vitamin B6 may be useful in managing the depressive symptoms in some women with premenstrual dysphoric disorder (PMDD), also known as premenstrual syndrome (PMS). However, the evidence for this comes mainly from poor-quality trials. The mechanism of this putative effect may be accounted for, in part, by the participation of pyridoxal 5'-phosphate as a coenzyme in the synthesis of the neurotransmitters serotonin and dopamine. Modulation of steroid-dependent gene expression, by the vitamin, may also play some role in this putative effect. PHARMACOKINETICS The major forms of vitamin B6 from animal products are pryridoxal 5'-phosphate and pyridoxamine 5'-phosphate. The major forms of vitamin B6 from plant-derived foods are pyridoxine, pyridoxine 5'-phosphate and pyridoxine glucosides. Pyridoxine hydrochloride is the principal form of vitamin B6 used for food fortification and in nutritional supplements. Pyridoxal 5'-phosphate is also available as a nutritional supplement. The phosphylated forms of vitamin B6 undergo hydrolysis in the small intestine via alkaline phosphatase, and the nonphosphorylated forms of the vitamin are absorbed by a nonsaturable passive diffusion process, mainly in the jejunum. The efficacy of absorption of vitamin B6 is high and even extremely high doses of vitamin B6 are well absorbed. The pyridoxine glucosides are less efficiently absorbed than the other vitamin B6 forms. The pyridoxine glucosides are deconjugated by a mucosal glucosidase. A fraction of the pyridoxine glucosides is absorbed intact and hydrolyzed in various tissues. Some vitamin B6 is converted to pyridoxal 5'-phosphate in the enterocytes where it is used in various metabolic reactions. Most of the absorbed vitamin B6 is transported via the portal circulation to the liver. In the liver, pyridoxine, pyridoxal and pyridoxamine are metabolized to pyridoxine 5'-phosphate, pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate, by pyridoxal 5'-phosphate kinase. Pyridoxal 5'-phosphate is secreted by the liver and transported by the systemic circulation to the various tissues of the body. Pyridoxal 5'-phosphate is the primary form of vitamin B6 in the circulation and is bound to serum albumin. The major body pool of vitamin B6 is in muscle, where most of the vitamin is present as pyridoxal 5'-phosphate bound to glycogen phosphorylase. The principal catabolite of vitamin B6 is 4-pyridoxic acid which is the primary form of the vitamin excreted in the urine. 4-Pyridoxic acid, which is principally formed in the liver, accounts for approximately 50% of the vitamin B6 compounds in the urine. At very high doses of vitamin B6, which is mainly in the form of pyridoxine, much of the dose is excreted unchanged in the urine. INDICATIONS AND USAGE INDICATIONS Vitamin B6 is used for the treatment of vitamin B6 deficiency and for the prophylaxis of isoniazid-induced peripheral neuropathy. It may also be helpful in treatment of convulsions of the newborn secondary to glutamate decarboxylase deficiency, sideroblastic anemia secondary to delta-aminolevulinate synthase deficiency, primary hyperoxaluria type 1 secondary to peroxisomal alanine-glyoxylate transaminase deficiency, homocystinuria secondary to cystathionine beta-synthase deficiency, cystathioninuria secondary to gamma-cystathionase deficiency, xanthurenic aciduria secondary to kynureninase deficiency and gyrate atrophy of choroid and retina secondary to ornithinine-delta-aminotransferase deficiency. Vitamin B6 may be helpful in some women with premenstrual dysphoric disorder (PMDD), also known as premenstrual syndrome (PMS), and may be useful in some cases of gestational diabetes and for protection against metabolic imbalances associated with the use of some oral contraceptives. Results are mixed and largely negative with the respect to claims that vitamin B6 is an effective treatment of carpal tunnel syndrome. There is very preliminary evidence that vitamin B6 may help protect against atherosclerosis, that it might show some activity against melanoma and that it might be helpful in some neurologic conditions. It has some immune stimulating properties. It is an anti-emetic in some circumstances. There is little evidence to support claims that vitamin B6 is an effective treatment for depression (other than, possibly, the depression associated with premenstrual syndrome), autism, schizophrenia, atopic dermatitis, alcoholism, diabetic peripheral neuropathy, Down's syndrome, dental caries, Huntington's chorea or steroid-dependent asthma. RESEARCH SUMMARY A recent review of randomized, double-blind, placebo-controlled trials of vitamin B6 in the treatment of premenstrual syndrome (PMS) concluded that the treatment significantly relieves overall premenstrual and premenstrual-associated depressive symptoms. Doses ranged between 50 milligrams and 600 milligrams of vitamin B6 daily. Only one of 940 subjects included in these studies reported symptoms suggestive of sensory neuropathy, the principal adverse reaction of high dose vitamin B6. Premenstrual symptoms were significantly relieved by 100 milligrams of vitamin B6 daily (typically in divided 50 milligrams doses). There was less evidence of efficacy at a 50 milligram daily dose. Though the review authors found methodological flaws in many of the studies, they have stated that the available evidence warrants a large scale multicenter clinical trial. Vitamin B6's apparent efficacy in PMS has been speculatively attributed, in part, to its role as a cofactor in the synthesis of serotonin and dopamine, deficits in the availability and function of which may play a part in the pathogenesis of PMS. There are reports that vitamin B6 supplementation can help normalize disturbances in the metabolism of tryptophan associated with the use of some oral contraceptives. Studies suggest that 5 to 50 milligrams daily are adequate for this purpose. Improved glucose tolerance has been reported in some of these studies. Some other studies, however, have shown no vitamin B6 effect on the nausea, vomiting, dizziness and irritability sometimes associated with the use of oral contraceptives. Evidence is conflicting and inconclusive with respect to vitamin B6's impact on depression linked to the use of oral contraceptives. Claims that vitamin B6 is useful in improving glucose tolerance in diabetics in general is poorly supported except in gestational diabetes where the evidence is somewhat better, though still far from conclusive. More research is needed. Studies on the use of vitamin B6 in the treatment of carpal tunnel syndrome have produced mixed results which, on balance, suggest little benefit. Some open trials have found that vitamin B6 is helpful, but most double-blind, placebo-controlled trials have reported no benefit. Until larger, better-designed studies are conducted, no useful conclusion can be reached with respect to vitamin B6's role, if any, in treating carpal tunnel syndrome. It has been suggested that vitamin B6 might have cardioprotective effects. Reduced levels of vitamin B6 have been associated with elevated levels of homocysteine, a risk factor for atherosclerosis. Results have been mixed on the ability of supplemental vitamin B6 to lower homocysteine levels. There is one uncontrolled report associating supplemental vitamin B6 use with reduced incidence of acute cardiac chest pain and myocardial infarction. And there is a recent study showing a significant protective effect of vitamin B6 on function and integrity of vascular endothelium subjected to experimental injury by activated platelets. There are also preliminary reports that supplemental vitamin B6 can reduce hypertension in some. This work needs confirmation. There was a report in 1985 that a topical application of pyridoxal produced significant regression in the metastatic melanoma of two patients. Greater than 50% regression of lesions was noted after two weeks of treatment. Untreated lesions did not regress. This preliminary report needs followup. Vitamin B6 is an effective treatment for seizures in infants caused by a specific inborn metabolic disorder. Deficiencies in vitamin B6 have been associated with a number of neurologic and behavioral disorders, but interventive data are largely lacking. There is a study of Egyptian mothers and their infants significantly relating the vitamin B6 nutritional status of the mother to infant behavior. Some studies have indicated that, even in the United States, a significant percentage of women of child-bearing age, as well as pregnant and lactating women, may have vitamin B6 intakes below the recommended dietary allowance. Studies are needed to determine the effects of low maternal vitamin B6 intake on neurologic and behavioral development in offspring: Experiments with vitamin B6-deficient maternal rats have demonstrated effects that might impair developmental processes related to learning and memory in offspring. Vitamin B6 plays an active role in the immune system. Even marginal deficiency, such as is found in many of the elderly, may result in some immune deficits. Chronically ill patients, notably those with HIV-disease, also often exhibit marginal or frank vitamin B6 deficiency. Both humoral and cell-mediated immune responses have been shown to be impaired in those with vitamin B6 deficiencies. Supplementation to normal levels generally restores immune function due to deficiency. Higher doses have not been reported to further stimulate or modulate the immune system. In one study, approximately one-third of a healthy elderly population had marginal vitamin B6 deficiency. Supplementation with the vitamin in elderly subjects has produced significant improvement in immune function as determined by a number of laboratory measures, including lymphocyte proliferative responses to both T- and B-cell mitogens. Percentages of CD3+ and CD4+ (but not CD8+) cells increased significantly in elderly subjects receiving 50 milligrams of vitamin B6 daily. Vitamin B6 has been used with some success as an anti-emetic in a dose range of 50-200 milligrams daily. It has been effective in treating nausea subsequent to radiotherapy and nausea associated with pregnancy ("morning sickness"). In one double-blind trial, vitamin B6 alleviated the severe nausea and significantly reduced the vomiting of those who received the vitamin in 25 milligram doses every eight hours for three days. CONTRAINDICATIONS, PRECAUTIONS, ADVERSE REACTIONS CONTRAINDICATIONS Vitamin B6 is contraindicated in those hypersensitive to any component of a vitamin B6-containing product. PRECAUTIONS Pre- and postnatal vitamin/mineral supplements typically deliver vitamin B6 (as pyridoxine) at a dose of between 2 to 20 milligrams daily. Pregnant women and nursing mothers should avoid doses of vitamin B6 greater than these doses, unless higher doses are prescribed by their physicians. Those who are being treated with levodopa without concurrently taking carbidopa should avoid doses of vitamin B6 of 5 milligrams or greater daily. The use of vitamin B6 for the treatment of vitamin B6 deficiency, for the prophylaxis of isoniazid-induced peripheral neuropathy, for the treatment of vitamin B6-dependency disorders (see Indications) or for the treatment of any other medical condition requires medical supervision. ADVERSE REACTIONS Doses of vitamin B6, typically in the form of pyridoxine, of up to 200 milligrams daily are generally well tolerated. One report showed severe sensory neuropathy in seven adults after pyridoxine intakes that started at 50 to 100 milligrams/day and were steadily increased to 2 to 6 grams/day over 2 to 40 months. None of the subjects in the report showed sensory neuropathy at doses of pyridoxine of less than 2 grams/day. There is one report of a woman who had been taking 200 milligrams/day of pyridoxine for 2 years without showing sensory neuropathy who developed sensory neuropathy after she increased her pyridoxine dose to 500 milligrams/day. There are rare reports of sensory neuropathy occurring at pyridoxine doses in the range of 100 to 200 milligrams/day. The Food and Nutrition Board of the Institute of Medicine of the U.S. National Academy of Sciences has concluded that reports and studies showing sensory neuropathy at doses of pyridoxine less than 200 milligrams/day are weak and inconsistent, with the weight of evidence indicating that sensory neuropathy is unlikely to occur in adults taking pyridoxine at doses less than 500 milligrams/day. Other adverse reactions reported with high doses of pyridoxine, include nausea, vomiting, abdominal pain, loss of appetite and breast soreness. Rare cases of pyridoxine-induced photosensitivity have been reported. INTERACTIONS DRUGS Amiodarone: Concomitant use of vitamin B6 and amiodarone may enhance amiodarone-induced photosensitivity reactions. Doses of vitamin B6 greater than 5-10 milligrams/day should be avoided by those taking amiodarone. Carbamazepine: Chronic use of carbamazepine may result in a significant decrease in plasma pyridoxal 5'-phosphate levels. Cycloserine: Cycloserine may react with pyridoxal 5'-phosphate to form a metabolically inactive oxime, which may result in a functional vitamin B6 deficiency. Ethionamide: The use of ethionamide may increase vitamin B6 requirements. Fosphenytoin: High doses of vitamin B6 may lower plasma levels of phenytoin. Fosphenytoin is a prodrug of phenytoin. Hydralazine: The use of hydralazine may increase vitamin B6 requirements. Isoniazid: (isonicotinic acid, INH). Isoniazid reacts with pyridoxal 5'-phosphate to form a metabolically inactive hydrazone, which may result in functional vitamin B6 deficiency. Levodopa: Concomitant use of levodopa and vitamin B6 in doses of 5 milligrams or more daily may reverse the therapeutic effects of levodopa. Vitamin B6 does not reverse the therapeutic effects of levodopa if levodopa is taken concurrently with the levodopa decarboxylase inhibitor carbidopa. Levodopa is typically administered as a combination product with carbidopa. Oral contraceptives: The use of oral contraceptives may increase vitamin B6 requirements. This was more the case with the older oral contraceptive agents with high-dose estrogen/progestin. It appears to be less the case with the newer low-dose estrogen/progestin products. Penicillamine: Penicillamine may react with pyridoxal 5'-phosphate to form a metabolically inactive thiazolidine, which may result in a functional vitamin B6 deficiency. Phenelzine: Phenelzine may react with pyridoxal 5'-phosphate to yield a metabolically inactive hydrazone compound. Phenobarbital: High doses of vitamin B6 may lower plasma levels of phenobarbital. Phenytoin: High doses of vitamin B6 may lower plasma levels of phenytoin. Theophylline: Theophylline may react with pyridoxal 5'-phosphate leading to low plasma levels of the coenzyme. This may increase the risk of theophylline-induced seizures. Valproic acid: Chronic use of valproic acid may result in a significant decrease in plasma pyridoxal 5'-phosphate levels. FOODS Alcoholic beverages: Alcohol may increase the catabolism of pyridoxal 5'-phosphate. Chronic and excessive use of alcoholic beverages can result in vitamin B6 deficiency. OVERDOSAGE No reports. DOSAGE AND ADMINISTRATION Vitamin B6 is available in nutritional supplements principally in the form of pyridoxine hydrochloride. Pyridoxal 5'-phosphate is also available as a nutritional supplement. Pyridoxine hydrochloride is available in multivitamin and multivitamin/multimineral products as well as products that, in addition to vitamins and minerals, contain other nutritional substances. Single ingredient pyridoxine products are also available. Some products are available which contain mixtures of pyridoxine hydrochloride and pyridoxal 5'-phosphate. Typical doses of pyridoxine used for nutritional supplementation range from 2 to 20 milligrams/day. Those who use pyridoxine for the management of premenstrual syndrome, typically use doses ranging from 50 to 100 milligrams/day. Those who use pyridoxine for the management of carpal tunnel syndrome, typically use doses ranging from 100 to 200 milligrams/day. The Food and Nutrition Board of the Institute of Medicine of the National Academy of Sciences has recommended the following Dietary Reference Intakes (DRI) for vitamin B6:
The U.S. RDA for vitamin B6, which is used for determining percentage of nutrient daily values on nutritional supplement and food labels, is 2.0 mg/day. The Food and Nutrition Board has identified a Lowest-Observed-Adverse-Effect Level (LOAEL) for vitamin B6 of 500 milligrams/day (See Adverse Reactions) and a No-Observed-Adverse-Effect Level (NOAEL) of 200 milligrams/day. Based on the NOAEL and an uncertainty factor of 2, the Food and Nutrition Board has recommended the following Tolerable Upper Intake Levels (UL) for vitamin B6:
HOW SUPPLIED Vitamin B6 is available in the following forms and strengths for OTC use: Capsules — 150 mg, 500 mg Enteric Coated Tablets — 20 mg Tablets — 10 mg, 25 mg, 32.5 mg, 50 mg, 100 mg, 250 mg, 500 mg Tablets Extended Release — 200 mg Vitamin B6 is available in the following forms and strengths for Rx use: Injection — 100 mg/mL LITERATURE Anon. Vitamin B6 for melanoma. Medical World News. February 11, 1985. Aybak M, Sermet A, Ayylidiz MO, Karakilcik AZ. Effect of oral pyridoxine hydrochloride supplementation on arterial blood pressure in patients with essential hypertension. Arzneimittelforschung. 1995; 45:1271-1273. |
