Pyridoxine (B6)
Sources and Physiologic Functions Sources: Poultry, fish, liver, and eggs are good sources of this vitamin; meat and milk contain lesser amounts. Pyridoxine in animal sources is 96% bioavailable. Vitamin B6 can be made by intestinal bacteria in healthy persons. Plant foods such as legumes, peanuts, potatoes, yeast, bananas, corn, cabbage, yams, prunes, watermelon, and avocados also contain this vitamin.
Populations at risk: As this vitamin is widely distributed, deficiency is rare except in chronic alcoholics and among women taking oral contraceptives. Elderly persons and infants of preeclamptic mothers or mothers deficient in B6 are at risk. Patients on Cycloserine, hydantoin, hydralazine, isoniazid, and penicillamine should be given B6 supplementation. High protein diet increases the needs of this vitamin.
Severe deficiencies of vitamin B6 are rare, but mild deficiencies are extremely common. Dietary data from Second National Health and Nutrition Examination Survey (NHANES II) in 11,658 adults aged 19-74 y showed that 71% of males and 90% of females consumed less than the 1980 recommended dietary allowance (RDA) of vitamin B6. Vitamin B6 is the most common deficient water soluble vitamin in elderly. Single drug and drug combinations taken by elderly individuals may impose nutritional risk. Unwanted outcomes of drug-food and drug-nutrient interactions can be minimized by instructing elderly men and women and their caregivers to avoid timing errors in drug-taking behavior and toxic reactions due to food incompatibility. In addition, drug-induced nutritional deficiencies can be avoided by advising drug-taking elderly on the appropriate levels of nutrient intake. In a study which compared the nutrient intakes of American children aged 2 to 10 years, vitamin B6 was found to be below the RDA in more than 50% of the population.
Birth control pill usage and occupational exposure to carbon disulfide induce vitamin B6 deficiency and/or enhance vitamin B6 requirement. Both compounds cause adverse psychological/neurological disorders such as extreme irritability, manic depressive tendencies, headaches, and other variables, but related disorders presumably by disrupting normal vitamin B6 metabolism and vitamin B6 administration has been found to alleviate their adverse psychological symptoms. Further studies are needed to experimentally evaluate this interrelation. Conjoined exposure to OCs and CS2 may result in an enhanced disruption of tryptophan metabolism which may in turn cause exaggerated psychological sequelae associated with CS2 exposure.
Signs and Symptoms of Deficiency: In infants, convulsive seizures and hyperactivity are the usual presenting symptoms. Diarrhea is also common. Anemia and peripheral neuritis are seen in tuberculosis patients on isoniazid who develop pyridoxine deficiency. 20-30% of homocystinuric patients with dislocation of the lens of the eye, osteoporosis (brittle spine), mental retardation, and a tendency for spontaneous blood clots that can lead to heart attacks and death, respond to vitamin B6 therapy.
Biochemistry: Vitamin B6 isa collective term for pyridoxine, pyridoxal, and pyridoxamine, all of which serve as precursors of the biologically active coenzyme, pyridoxal phosphate. Pyridoxal phosphate functions as a coenzyme that catalyze reactions in protein metabolism, conversion of tryptophan to niacin, fat metabolism, carbohydrate metabolism, folic acid synthesis, glandular and endocrine functions, and for the nerve and brain energy. Vitamin B6 has a clear benefit in lessening the severity of homocystinuria, a rare disease that usually results from a defect in an enzyme used for degrading homocysteine.
Safety: Deficient and excess intakes of pyridoxine can produce neurologic disturbances. Most cases of sensory neuropathy have resulted from intakes of over 600 mg/day, but some evidence suggests that it may result from doses as low as 300-500 mg/d and that the total exposure over time is the determinant of toxicity. There is one report that a daily intake of 117 mg/day (on average) for 2.9 years may be related to some toxicity. In the same study however, the control group that did not get any neuropathy had an average intake of 116 mg/day for an average of 1.6 years, and some women in both groups had been taking as little as 50 mg/day, questioning the accuracy of the telephone survey method used to determine neuropathy.
Vitamin B6 is toxic at doses that are 1000 times the RDA. Daily doses of 2 to 5 g of pyridoxine can produce difficulty in walking and tingling sensations in the legs and soles of the feet. Continued consumption of the toxic dose results in further unsteadiness of walking, difficulty in handling small objects, and numbness and clumsiness of the hands. Where vitamin B6 supplementation is stopped, recovery begins after 2 months. Complete recovery may occur after 2 to 3 years of discontinuing consumption of the vitamin B6 supplements. One study showed development of pure central-peripheral distal axonopathy with pyridoxine abuse. Pyridoxine dose was 0.2 to 5 g/d, and duration of consumption before symptoms was inversely proportional to the daily intake. In all patients with adequate follow-up, improvement followed discontinuation of pyridoxine.
Is pyridoxine safe for long-term use in large segments of the population, including children? It would appear from retrospective analysis of several studies that pyridoxine is safe at doses of 100mg/day or less in adults. In children, there is not enough data to make any sort of suggestion. Because the major neurologic complication is a peripheral neuropathy, and the causes of this condition are myriad, pyridoxine may cause neuropathy only in patients with a pre-existing susceptibility to this condition. Family histories, drugs, alcohol, nutritional status, and toxic exposure at home or in the work place may all be predisposing factors which, in combination with pyridoxine, produce the peripheral neuropathy that is not seen in other patients taking the same dosages. The duration of exposure that causes neuropathy is still a major question. Extremely high doses cause neurologic injury within a few days, and chronic low doses seem relatively safe.
Deterioration of acne vulgaris or eruption of an acneiform exanthema was demonstrated during treatment with vitamin B6 and/or vitamin B12 in 14 patients. Females were, by far, the more frequently affected. The appearance of skin symptoms, even outside the age groups typically affected by acne vulgaris, is characteristic. The clinical appearance of acneiform exanthema occurring during treatment with vitamin B6 or B12 consists of loosely disseminated small papules or papulopustules on the face (especially on the forehead and chin), on the upper parts of the back and chest, and spreading to the upper arm. The pathogensis of the change is not yet certain. The acneiform rash generally fades within a short time after vitamin B6 or vitamin B12 treatment has been stopped.
Recommendations: RDA in mg.
Infants birth to 6 mos - 0.3mg
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Infants 6 mos to 1 yr - 0.6mg
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Children 1 yr to 3 yr - 1.0mg
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Children 4 yr to 6 yr - 1.1mg
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Children 7 yr to 10 yr - 1.4mg
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Adolescent males 11yr to 14 yr - 1.7mg
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Adolescent females 11 yr to 14 yr - 1.4 mg
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Adolescent males 15 yr to 18 yr - 2.0mg
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Adolescent females 15 yr to 18 yr - 1.5mg
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Adult males 19 yr to 50 yr - 2.0mg
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Adult females 19 yr to 50 yr - 1.6mg
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Adult males 51 yr plus - 2.0mg
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Adult females 51 yr plus - 1.6mg
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Pregnant Women - 2.2mg
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Lactating Mothers (1st 6 months) - 2.1mg
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Lactating Mothers (2nd 6 months) - 2.1mg
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Pyridoxine B6
Food Source Serving Size/Amount # of mg/serving
Chicken (dark meat) 3.5 oz 0.37 mg
Chicken (light meat) 3.5 oz 0.63 mg
Atlantic Salmon (wild, raw) 3.0 oz 0.70 mg
Tuna (canned in water) 3.0 oz 0.30 mg
Liver (beef braised) 3.5 oz 0.91 mg
Live (veal braised 3.5 oz 0.91 mg
Navy beans (boiled) 1 cup 0.30 mg
Peanuts (dry roasted) 1 oz 0.07 mg
Potato (boiled) 1 medium 0.40 mg
Banana 1 medium 0.66 mg
Prunes (dried) 10 0.22 mg
Watermelon 1 cup 0.23 mg
Avocado 1 medium 0.48 mg
The Literature: Heart disease Prevention:
Homocysteine
Hyperhomocysteinemia, a risk factor for atherosclerosis, is associated with deficiencies of vitamin B6, folate, and cobalamin. Patients who were given vitamin B6 for carpal tunnel syndrome and other degenerative diseases were found to have 27% of the risk of developing acute cardiac chest pain or myocardial infarction, compared with patients who had not taken vitamin B6. Dr. Ellis found that among his elderly patients expiring at home, the average age at death from myocardial infarction was 8 years later in those who had taken vitamin B6, compared with those who had not taken vitamin B6. The preventive effect of vitamin B6 on progression of coronary heart disease may be related to increased formation of pyridoxal phosphate, the coenzyme that is required for catabolism of the atherogenic amino acid, homocysteine.
The total homocysteine (tHcy) level in the serum is related to pregnancy complications, neural tube defects, mental disorder, and cognitive impairment in the elderly. In addition, over 80 clinical and epidemiological studies provide ample evidence that an elevated tHcy level is a common cardiovascular risk factor. Oral treatment with pyridoxine up to 300mg/d does not lower the fasting tHcy level in healthy subjects or vascular patients. However, pyridoxine (10 - 250 mg/d) lowers an abnormal postmethionine load tHcy level in most patients and, when combined with folic acid, nearly all obtain a normal postmethionine tHcy level.
Platelet aggregation:
In a randomized trial, Pyridoxine inhibited ADP- or epinephrine-induced aggregation by 48% and 41% (p < 0.001), respectively. It also prolonged both bleeding and coagulation time. Pyridoxine significantly reduced total plasma lipid and cholesterol levels, whereas it enhanced HDL-cholesterol level. Thus, it is suggested that oral vitamin B6 inhibits platelet aggregation in normal subjects.
Essential Hypertension:
In a study, treatment of hypertensive patients with pyridoxine significantly reduced systolic (p < 0.01) and diastolic blood pressure (p < 0.005), plasma NE (p < 0.005), and E (p < 0.05) within 4 weeks. The dose of pyridoxine used in these patients was 5 mg/kg body weight/d. Thus, pyridoxine may be beneficial in the treatment of hypertension.
Neurotransmitter Production
Pyridoxine has been known as an essential cofactor in the production of neurotransmitters. For this reason, it has been considered a therapeutic adjunct in a variety of conditions with known or suspected neurotransmitter abnormalities. Among these conditions are seizures, Parkinson's disease, depression, chronic pain, headache, behavior abnormalities of adults and children, and peripheral neuropathy. Other clinical uses for pyridoxine include treatment of premenstrual syndrome and carpal tunnel syndrome. The potential neurotoxicity of pyridoxine makes it essential that vitamin intake be included as part of medical history.
Diabetic neuropathy:
Vitamin B6 has been recommended in the treatment of diabetic neuropathy. Vitamin B6 deficiency was thought to be the causative factor for neuropathy in diabetes. However, several studies show that vitamin B6 supplements may not be beneficial in these patients. In one of these studies, 18 patients with symptomatic diabetic neuropathy were treated with placebo or pyridoxine. After 4 months of follow-up, there was no difference between the two groups with regard to fasting plasma glucose, motor nerve conduction velocity, or ophthalmologic examination at the beginning or at the conclusion of the study. These results suggest that vitamin B6 deficiency is not a factor in the etiology of diabetic peripheral neuropathy.
Gestational diabetes:
In a study of 14 pregnant women with gestational diabetes, a relative pyridoxine deficiency was thought to exist. After treatment with vitamin B6 (pyridoxine) 100 mg/day for 14 days, the oral glucose tolerance improved considerably. It was hypothesized that increased xanthurenic-acid synthesis during pregnancy may cause gestational diabetes. Treatment with vitamin B6 makes the production of xanthurenic-acid normal by restoring tryptophan metabolism and improves the oral glucose tolerance in patients with gestational diabetes.
Kidney Stones:
Weak evidence suggests that pyridoxine may be useful in the therapy of kidney stones. Twelve recurrent stone formers with hyperoxaluria were administered pyridoxine-HCl (10 mg/day) daily for a period of 180 days. Urinary oxalate decreased significantly (p less than 0.05) by the 90th day of pyridoxine therapy, and thus, pyridoxine in low doses (10 mg/day) is of therapeutic value for hyperoxaluric stone formers.
Autism:
A review of four therapeutic crossed-sequential double-blind trials with 60 autistic children examined the effects of vitamin B6 alone, magnesium alone, and in combination on behavioral improvement. Modest behavioral improvement was observed among children taking both magnesium and B6, but not when either one of those taken alone.
Cognitive Development
Vitamin B6 is an essential cofactor in the developing central nervous system and may influence brain development and cognitive function. Recent work in animal models suggests that vitamin B6 deficiency during gestation and lactation alters the function of receptors thought to play an important role in learning and memory. A deficiency of vitamin B6 during brain development has been shown to result in neurochemical and morphological changes that are expressed behaviorally as tremors, irritability, abnormalities in motor function, and spontaneous seizures, although the specific mechanism is still not understood. Numerous studies have suggested that pregnant and lactating women may have dietary intakes of vitamin B6 that are well below the recommended dietary allowance, which may affect the vitamin B6 status of their offspring. Reports indicate that unsupplemented lactating mothers have a milk vitamin B6 level that, in some cases, is lower than 100 μg/L, a concentration that places infants at risk of development of seizures. Although this level of vitamin B6 in milk does not always result in clinical signs of frank vitamin B6 deficiency, it may influence the normal development of the child. Evidence for such an effect was noted in an Egyptian study where abnormalities in behavior were observed in infants whose mothers had vitamin B6 levels in milk below 85 mg/L.
Thus, many conditions in clinical neurology may be responsive to pyridoxine as a therapeutic agent. The observations that serotonin deficiency is a common thread in patients with headache, chronic pain, and depression, and that pyridoxine can raise serotonin levels open a wide range of therapeutic options. Comparison with amitriptyline in the treatment of headache appears to show about equal efficacy, although side effects would be expected to be more of a problem with the amitriptyline. Some medical authorities have taken this so far as to suggest that many of the behavioral disorder problems are caused by "toxic" exposures to chemicals that are pyridoxine antagonists and that supplementation at early stages may reduce the incidence of hyperactivity and aggressive behavior.
Interaction with Medications
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 routine use of pyridoxine supplementation to prevent peripheral neuropathy in high risk populations is recommended.
Carpal Tunnel Syndrome
Vitamin B6 is effective in the treatment of carpal tunnel syndrome and related disorders in patients with vitamin B6 deficiency. A study found that higher plasma pyridoxal 5'-phosphate (PLP) concentrations, particularly in unsupplemented males, appeared to be associated with less frequent pain/discomfort, tingling and nocturnal awakening. In contrast, higher vitamin C concentrations or a relative deficit of plasma PLP in comparison to the plasma vitamin C (higher ASC/PLP ratio) were, in some analyses, associated with greater sensory latencies or with more prevalent and frequent symptoms. This raises the possibility that vitamin C supplementation in the presence of vitamin B6 deficit might be injurious to the median nerve and thus promote the development of the hand/wrist symptoms of CTS. Thus, there are significant relationships between plasma vitamin levels and both components of CTS (specific symptoms and median nerve slowing). The interaction between plasma PLP and ASC appears to be particularly important with respect to symptoms. Hence, vitamin B6 is commonly recommended for carpal tunnel syndrome.
Premenstrual Syndrome
A review of 12 controlled trials on vitamin B6 in the treatment of the premenstrual syndrome showed a weak evidence of positive effects of vitamin B6. A major drawback of the trials is the limited number of patients included. In a more recent well designed study, 120 women were randomized to receive active drug or placebo. Pyridoxine at 300 mg/d showed no greater benefit compared to placebo in symptom reduction.
Vitamin B6 and Exercise
Vitamin B6 may play an important role in exercise response. Vitamin B6 is essential to the production of energy during exercise. If vitamin B6 status is poor, exercise performance may be impaired. Vitamin B6 supplementation may increase the levels of plasma growth hormone during exercise and immediately following exercise. The physiologic significance of these changes has not been explored but are thought to increase muscle mass and reduce body fat. Female athletes and those who participate in sports which emphasize low body weights (e.g., dancers, wrestlers, gymnasts and runners) may be prone to low dietary vitamin B6 intakes.
Asthma:
Weak evidence suggests that vitamin B6 may be useful in asthma. A 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 tryptophan metabolism, which was benefitted by long-term treatment with large doses of pyridoxine. In another double-blind placebo-controlled trial, 31 patients requiring steroids (oral or inhaled) for the treatment of their asthma received pyridoxine 300 mg per day or placebo. After a 9 week follow-up, treatment with oral pyridoxine failed to improve the outcome variables in patients requiring steroids for the treatment of their asthma.
Depression:
Weak evidence suggests that vitamin B6 may be beneficial in the treatment of depression. The augmentation effect of 10 mg each of vitamins B1, B2, and B6 in 14 geriatric inpatients with depression who were treated with tricyclic antidepressant treatment was assessed in a well-designed study. The vitamin treated group showed trends toward greater improvement in scores on ratings of depression and cognitive function, as well as in serum nortriptyline levels compared with placebo-treated subjects. Thus, B complex vitamin augmentation in the treatment of geriatric depression should be considered.
Summary: Pyridoxine is essential for protein, fat and carbohydrate metabolism, folic acid synthesis, glandular and endocrine function. It is also essential for the formation of serotonin, and dopamine, and aids in the formation of several neurotransmitters and is therefore, an essential nutrient in the regulation of mental processes and the mood.
A number of claims have been made about the beneficial effects of vitamin B6 on numerous conditions: atherosclerosis, attention deficit disorder, autism, alcohol withdrawal syndrome, diabetes, fibrocystic breast disease, carpal tunnel syndrome, chemotherapy, HIV patients, nephrolithiasis, osteoporosis, photosensitivity, retinopathy, and canker sores.
Evidence strongly suggests that vitamin B6 has a preventive effect in the progression of coronary artery disease. Although it did not show any effect in lowering the fasting plasma homocysteine level, vitamin B6 supplementation is shown to lower postmethionine load tHcy, which might be the reason for its cardioprotective effect.
In well done studies it has shown efficacy on par with amitriptyline in the treatment of chronic headaches. Many clinical conditions like chronic pain and depression, which are caused by serotonin deficiency, might benefit from vitamin B6 therapy. As it functions as an essential cofactor in the production of several neurotransmitters, it may be considered a therapeutic adjunct in the treatment of several conditions like seizures, Parkinson's disease, behavioral abnormalities of adults and children, and peripheral neuropathy. Vitamin B6 is also found to be effective in the treatment of carpal tunnel syndrome in patients with vitamin B6 deficiency. Exercise performance is improved with vitamin B6 supplementation.
Populations who are prone to be deficient in this vitamin such as chronic alcoholics, women on oral contraceptives, patients on Isoniazid, and athletes should receive supplementation. Pregnant and lactating women should consume adequate amounts of vitamin B6 in their diets for the normal development of central nervous system and cognitive function and for the prevention of abnormal behavioral development.
Our recommendations for adults is 40 mg/d, as there is weak evidence of some toxicity at 50 mg/d. Vitamin B6 is usually safe and can be consumed in amounts of 10-300 mg/d. Although side effects are rare, doses over 300 mg/d may result in adverse neurological outcomes. Pregnant and lactating women should not consume more than 100 mg/d. Vitamin B6 supplementation should be stopped immediately when sensory neuropathy with numbness in the hands and feet and/or difficulty in walking develops while on therapy.
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