Nutritional Supplement

Vitamin B6

  • Heart and Circulatory Health

    High Homocysteine

    Vitamin B6, folic acid, and vitamin B12 all play a role in converting homocysteine to other substances within the body and have consistently lowered homocysteine levels in trials.
    High Homocysteine
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    Vitamin B6, folic acid, and vitamin B12 all play a role in converting homocysteine to other substances within the body. By so doing, they consistently lower homocysteine levels in research trials,1,2,3 a finding that is now well accepted. Several studies have used (and some doctors recommend) 400–1,000 mcg of folic acid per day, 10–50 mg of vitamin B6 per day, and 50–300 mcg of vitamin B12 per day.

    Of these three vitamins, folic acid supplementation lowers homocysteine levels the most for the average person.4,5 It also effectively lowers homocysteine in people on kidney dialysis.6 In 1996, the FDA required that all enriched flour, rice, pasta, cornmeal, and other grain products contain 140 mcg of folic acid per 3½ ounces.7 This level of fortification has led to a measurable decrease in homocysteine levels.8 However, even higher levels of food fortification with folic acid have been reported to be more effective in lowering homocysteine,9 suggesting that the FDA-mandated supplementation is inadequate to optimally protect people against high homocysteine levels. Therefore, people wishing to lower their homocysteine levels should continue to take folic acid supplements despite the FDA-mandated fortification program.

    Anemia

    Vitamin B6 deficiency can contribute to anemia, supplementing with this vitamin may restore levels and improve symptoms.
    Anemia
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    Deficiencies of iron, vitamin B12, and folic acid are the most common nutritional causes of anemia.10 Although rare, severe deficiencies of several other vitamins and minerals, including vitamin A,11,12vitamin B2,13vitamin B6,14,15vitamin C,16 and copper,17,18 can also cause anemia by various mechanisms. Rare genetic disorders can cause anemias that may improve with large amounts of supplements such as vitamin B1.19,20

    Intermittent Claudication

    In one study, men with intermittent claudication who drank a milk product fortified with fish oil, vitamin B6, folic acid, vitamin E, oleic acid, and alpha-linolenic acid could walk further without pain than those who drank regular milk.
    Intermittent Claudication
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    Men with intermittent claudication consumed a fortified milk product or regular milk daily for one year. The fortified product provided daily 130 mg of eicosapentaenoic acid and 200 mg of docosahexaenoic acid (EPA and DHA, two fatty acids in fish oil), small amounts of supplemental vitamin E, folic acid, and vitamin B6, and additional amounts of oleic acid and alpha-linolenic acid. Compared with regular milk, the fortified milk product significantly increased the distance the participants could walk before the onset of pain.21

    Atherosclerosis

    Blood levels of the amino acid homocysteine have been linked to atherosclerosis and heart disease in most research. Taking vitamin B6 may help lower homocysteine levels.
    Atherosclerosis
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    Blood levels of an amino acid called homocysteine have been linked to atherosclerosis and heart disease in most research,22,23 though uncertainty remains about whether elevated homocysteine actually causes heart disease.24,25 Although some reports have found associations between homocysteine levels and dietary factors, such as coffee and protein intakes,26 evidence linking specific foods to homocysteine remains preliminary. Higher blood levels of vitamin B6, vitamin B12, and folic acid are associated with low levels of homocysteine27 and supplementing with these vitamins lowers homocysteine levels.28,29

    While several trials have consistently shown that B6, B12, and folic acid lower homocysteine, the amounts used vary from study to study. Many doctors recommend 50 mg of vitamin B6, 100–300 mcg of vitamin B12, and 500–800 mcg of folic acid. Even researchers finding only inconsistent links between homocysteine and heart disease have acknowledged that a B vitamin might offer protection against heart disease independent of the homocysteine-lowering effect.24 In one trial, people with normal homocysteine levels had demonstrable reversal of atherosclerosis when supplementing B vitamins (2.5 mg folic acid, 25 mg vitamin B6, and 250 mcg of vitamin B12 per day).31 Similar results were seen in another study.32

    For the few cases in which vitamin B6, vitamin B12, and folic acid fail to normalize homocysteine, adding 6 grams per day of betaine (trimethylglycine) may be effective.33 Of these four supplements, folic acid appears to be the most important.28 Attempts to lower homocysteine by simply changing the diet rather than by using vitamin supplements have not been successful.35

    Heart Attack

    Taking vitamin B6 may reduce blood levels of homocysteine. High homocysteine levels have been linked to an increased heart attack risk.
    Heart Attack
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    High blood levels of the amino acid homocysteine have been linked to an increased risk of heart attack in most,34,35,36,37 though not all,38,39 studies. A blood test screening for levels of homocysteine, followed by supplementation with 400 mcg of folic acid and 500 mcg of vitamin B12 per day could prevent a significant number of heart attacks, according to one analysis.40Folic acid41,42 and vitamins B6 and B12 are known to lower homocysteine.43

    There is a clear association between low blood levels of folate and increased risk of heart attacks in men.44 Based on the available research, some doctors recommend 50 mg of vitamin B6, 100–300 mcg of vitamin B12, and 500–800 mcg of folic acid per day for people at high risk of heart attack.

    Stroke and High Homocysteine

    Elevated blood levels of homocysteine have been linked to stroke risk in most studies. Supplementing with vitamin B6 may lower homocysteine levels and reduce stroke risk.
    Stroke and High Homocysteine
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    Elevated blood levels of homocysteine, a toxic amino acid byproduct, have been linked to risk of stroke in most studies.45,46,47 Supplementation with folic acid, vitamin B6, and vitamin B12 generally lowers homocysteine levels in humans.48,49,50 In a pooled analysis (meta-analysis) of eight randomized trials, folic acid supplementation in varying amounts (usually 0.5 mg to 5 mg per day) reduced stroke risk by 18%.51

  • Digestive Support

    Morning Sickness

    In two double-blind trials, supplementation with vitamin B6 significantly reduced the severity of morning sickness.
    Morning Sickness
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    In two double-blind trials, supplementation with vitamin B6 (10 or 25 mg three times per day) significantly reduced the severity of morning sickness.52,53

    Celiac Disease

    Daily supplementation with a combination of vitamin B6 (3 mg), folic acid (0.8 mg), and vitamin B12 (0.5 mg) have been shown to help relieve depression in people with celiac disease.
    Celiac Disease
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    In one trial, 11 people with celiac disease suffered from persistent depression despite being on a gluten-free diet for more than two years. However, after supplementation with vitamin B6 (80 mg per day) for six months, the depression disappeared.54 Daily supplementation with a combination of vitamin B6 (3 mg), folic acid (0.8 mg), and vitamin B12 (0.5 mg) for 6 months also improved psychological well-being in people with long-standing celiac disease who had poor psychological well-being despite being on a strict gluten-free diet.55

    Celiac Disease

    For people with celiac disease who experience depression even after following a gluten-free diet, supplementing with vitamin B6 may be beneficial.
    Celiac Disease
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    In one trial, 11 people with celiac disease suffered from persistent depression despite being on a gluten-free diet for more than two years. However, after supplementation with vitamin B6 (80 mg per day) for six months, the depression disappeared.56
  • Women's Health

    Premenstrual Syndrome

    Many clinical trials show that taking vitamin B6 helps relieve PMS symptoms.
    Premenstrual Syndrome
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    Many,57,58,59,60,61 though not all,62 clinical trials show that taking 50–400 mg of vitamin B6 per day for several months help relieve symptoms of PMS. A composite analysis of the best designed controlled trials shows that vitamin B6 is more than twice as likely to reduce symptoms of PMS as is placebo.63 Many doctors suggest 100–400 mg per day for at least three months. However, intakes greater than 200 mg per day can cause side effects and should never be taken without the supervision of a healthcare professional.Vitamin B6 has also been reported to relieve cyclic breast pain.64

    Pregnancy and Postpartum Support and High Homocysteine

    Women who habitually miscarry have been found to have high homocysteine levels. Vitamin B6 may reduce these levels and increase the chances of a successful pregnancy.
    Pregnancy and Postpartum Support and High Homocysteine
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    The relationship between folate status and the risk of miscarriage is also somewhat unclear. In some studies, women who have had habitual miscarriages were found to have elevated levels of homocysteine (a marker of folate deficiency).65,66,67,68 In a preliminary study, 22 women with recurrent miscarriages who had elevated levels of homocysteine were treated with 15 mg per day of folic acid and 750 mg per day of vitamin B6, prior to and throughout their next pregnancy. This treatment reduced homocysteine levels to normal and was associated with 20 successful pregnancies.69 It is not known whether supplementing with these vitamins would help prevent miscarriages in women with normal homocysteine levels. As the amounts of folic acid and vitamin B6 used in this study were extremely large and potentially toxic, this treatment should be used only with the supervision of a doctor.

    Amenorrhea

    Preliminary evidence found that vitamin B6 restored menstruation and normalized hormone levels in three women with amenorrhea who had high prolactin levels.
    Amenorrhea
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    Prolactin is a hormone that may be elevated in some cases of amenorrhea. A preliminary trial of 200 to 600 mg daily of vitamin B6 restored menstruation and normalized prolactin levels in three amenorrheic women with high initial prolactin levels; however, 600 mg daily of vitamin B6 had no effect on amenorrheic women who did not have high prolactin levels.70 A number of other small, preliminary trials have not demonstrated an effect of either oral or injected vitamin B6 on prolactin levels,71,72,73,74,75 and they also have reported inconsistent effects on restoring menstruation.74,73,71 Larger, controlled trials are needed to better determine the usefulness of vitamin B6 in amenorrhea.

    Bulimia

    Vitamin B6, when taken with L-tryptophan, has been shown to improve eating behavior, feelings about eating, and mood among women with bulimia.
    Bulimia
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    People with eating disorders who restrict their food intake are at risk for multiple nutrient deficiencies, including protein, calcium, iron, riboflavin, niacin,76folic acid,77vitamin A, vitamin C,78 and vitamin B6,79 and essential fatty acids.80 A general multivitamin-mineral formula can reduce the detrimental health effects of these deficiencies.

    Serotonin, a hormone that helps regulate food intake and appetite, is synthesized in the brain from the amino acid L-tryptophan. Preliminary data suggest that some people with bulimia have low serotonin levels.81 Researchers have reported that bulimic women with experimentally induced tryptophan deficiency tend to eat more and become more irritable compared to healthy women fed the same diet,82,83 though not all studies have demonstrated these effects.84

    Weight-loss diets result in lower L-tryptophan and serotonin levels in women,85 which could theoretically trigger bingeing and purging in susceptible people. However, the benefits of L-tryptophan supplementation are unclear. One small, double-blind trial reported significant improvement in eating behavior, feelings about eating, and mood among women with bulimia who were given 1 gram of L-tryptophan and 45 mg of vitamin B6 three times per day.86 Other double-blind studies using only L-tryptophan have failed to confirm these findings.87,88 L-tryptophan is available by prescription only; most drug stores do not carry it, but “compounding” pharmacies do. Most cities have at least one compounding pharmacy, which prepares customized prescription medications to meet individual patient’s needs.

  • Menstrual and PMS Support

    Premenstrual Syndrome

    Many clinical trials show that taking vitamin B6 helps relieve PMS symptoms.
    Premenstrual Syndrome
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    Many,89,90,91,92,93 though not all,94 clinical trials show that taking 50–400 mg of vitamin B6 per day for several months help relieve symptoms of PMS. A composite analysis of the best designed controlled trials shows that vitamin B6 is more than twice as likely to reduce symptoms of PMS as is placebo.95 Many doctors suggest 100–400 mg per day for at least three months. However, intakes greater than 200 mg per day can cause side effects and should never be taken without the supervision of a healthcare professional.Vitamin B6 has also been reported to relieve cyclic breast pain.96

    Amenorrhea

    Preliminary evidence found that vitamin B6 restored menstruation and normalized hormone levels in three women with amenorrhea who had high prolactin levels.
    Amenorrhea
    ×
     

    Prolactin is a hormone that may be elevated in some cases of amenorrhea. A preliminary trial of 200 to 600 mg daily of vitamin B6 restored menstruation and normalized prolactin levels in three amenorrheic women with high initial prolactin levels; however, 600 mg daily of vitamin B6 had no effect on amenorrheic women who did not have high prolactin levels.97 A number of other small, preliminary trials have not demonstrated an effect of either oral or injected vitamin B6 on prolactin levels,98,99,100,101,102 and they also have reported inconsistent effects on restoring menstruation.101,100,98 Larger, controlled trials are needed to better determine the usefulness of vitamin B6 in amenorrhea.

  • Stress and Mood Management

    Depression

    Oral contraceptives can deplete the body of vitamin B6, a nutrient needed for normal mental functioning. In such cases, vitamin B6 supplementation may improve mood.
    Depression
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    Oral contraceptives can deplete the body of vitamin B6, a nutrient needed for maintenance of normal mental functioning. Double-blind research shows that women who are depressed and who have become depleted of vitamin B6 while taking oral contraceptives typically respond to vitamin B6 supplementation.103 In one trial, 20 mg of vitamin B6 were taken twice per day. Some evidence suggests that people who are depressed—even when not taking the oral contraceptive—are still more likely to be B6 deficient than people who are not depressed.104

    Several clinical trials also indicate that vitamin B6 supplementation helps alleviate depression associated with premenstrual syndrome (PMS),105 although the research remains inconsistent.106 Many doctors suggest that women who have depression associated with PMS take 100–300 mg of vitamin B6 per day—a level of intake that requires supervision by a doctor.

    Depression and Premenstrual Syndrome

    Several studies indicate that supplementing with vitamin B6 helps alleviate depression, including depression associated with PMS.
    Depression and Premenstrual Syndrome
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    Oral contraceptives can deplete the body of vitamin B6, a nutrient needed for maintenance of normal mental functioning. Double-blind research shows that women who are depressed and who have become depleted of vitamin B6 while taking oral contraceptives typically respond to vitamin B6 supplementation.107 In one trial, 20 mg of vitamin B6 were taken twice per day. Some evidence suggests that people who are depressed—even when not taking the oral contraceptive—are still more likely to be B6 deficient than people who are not depressed.108

    Several clinical trials also indicate that vitamin B6 supplementation helps alleviate depression associated with premenstrual syndrome (PMS),109 although the research remains inconsistent.110 Many doctors suggest that women who have depression associated with PMS take 100–300 mg of vitamin B6 per day—a level of intake that requires supervision by a doctor.

    Schizophrenia and High Homocysteine

    People with schizophrenia who have high homocysteine levels may improve symptoms by supplementing with folic acid, vitamin B6, and vitamin B12.
    Schizophrenia and High Homocysteine
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    In another double-blind study, daily supplementation with folic acid (2 mg), vitamin B6 (25 mg), and vitamin B12 (400 mcg) for three months improved symptoms of schizophrenia compared with a placebo.111 All of the participants in this study had elevated blood levels of homocysteine, which can be decreased by taking these three B vitamins. Based on this study, it would seem reasonable to measure homocysteine levels in people with schizophrenia and, if they are elevated, to supplement with folic acid, vitamin B6, and vitamin B12.
  • Healthy Aging/Senior Health

    Macular Degeneration

    In a double-blind study of female health professionals who had cardiovascular disease or risk factors, daily supplementation with folic acid, vitamin B6, and vitamin B12 significantly decreased age-related macular degeneration.
    Macular Degeneration
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    In a double-blind study of female health professionals who had cardiovascular disease or cardiovascular disease risk factors, daily supplementation with folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg) for 7.3 years significantly decreased the incidence of age-related macular degeneration.112 

    Age-Related Cognitive Decline

    There is evidence that supplementing with vitamin B6 (pyridoxine) may improve memory performance, especially in people who are deficient.
    Age-Related Cognitive Decline
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    Vitamin B6 (pyridoxine) deficiency is common among people over age 65.113 A Finnish study demonstrated that approximately 25% of Finnish and Dutch elderly people are deficient in vitamin B6 as compared to younger adults. In a double-blind trial, correcting this deficiency with 2 mg of pyridoxine per day resulted in small psychological improvements in the elderly group. However, the study found no direct correlation between amounts of vitamin B6 in the cells or blood and psychological parameters.114 A more recent double-blind trial of 38 healthy men, aged 70 to 79 years, showed that 20 mg pyridoxine per day improved memory performance, especially long-term memory.115

    Age-Related Cognitive Decline

    In women with cardiovascular disease or related risk factors and low dietary intake of folic acid, vitamin B6, and vitamin B12, supplementing with a combination of these nutrients may protect against age-related cognitive decline.
    Age-Related Cognitive Decline
    ×

    In a study of female health professionals who had cardiovascular disease or cardiovascular disease risk factors, daily supplementation with folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg) for 5.4 years had no effect on cognitive function. However, supplementation appeared to prevent age-related cognitive decline in the 30% of women who had low dietary intake of B vitamins.116

    Supplementation with homocysteine-lowering B vitamins (folic acid, vitamin B12, and vitamin B6) also slowed the rate of brain atrophy in elderly people who had mild cognitive impairment and high homocysteine levels.117

    Alzheimer’s Disease

    A combination of coenzyme Q10, iron (sodium ferrous citrate), and vitamin B6 may improve mental status in people with Alzheimer’s disease.
    Alzheimer’s Disease
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    In a preliminary report, two people with a hereditary form of Alzheimer’s disease received daily: coenzyme Q10 (60 mg), iron (150 mg of sodium ferrous citrate), and vitamin B6 (180 mg). Mental status improved in both patients, and one became almost normal after six months.118

  • Joint Health

    Low Back Pain

    A combination of vitamin B1, vitamin B6, and vitamin B12 may prevent a common type of back pain linked to vertebral syndromes and may reduce the need for anti-inflammatory medications.
    Low Back Pain
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    A combination of vitamin B1, vitamin B6, and vitamin B12 has proved useful for preventing a relapse of a common type of back pain linked to vertebral syndromes,119 as well as reducing the amount of anti-inflammatory medications needed to control back pain, according to double-blind trials.120 Typical amounts used have been 50–100 mg each of vitamins B1 and B6, and 250–500 mcg of vitamin B12, all taken three times per day.121,122 Such high amounts of vitamin B6 require supervision by a doctor.

    Carpal Tunnel Syndrome

    Vitamin B6 deficiency is common in people with carpal tunnel syndrome, supplementing with the vitamin has reportedly relieved symptoms.
    Carpal Tunnel Syndrome
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    Some, but not all, studies have found vitamin B6 deficiency to be common in people with CTS.123 Supplementation with vitamin B6 has reportedly relieved the symptoms of CTS,124 but some researchers have not found this treatment to be beneficial.125,126

    Several studies report that people with CTS are helped when given 100 mg of vitamin B6 three times per day.127,128 Although some researchers have found benefits with lesser amounts,129,130,131,132 using less than 100 mg taken three times per day for several months has often failed.126,134,135 Most doctors assume that people with CTS who respond to vitamin B6 supplementation do so because of an underlying deficiency. However, at least one group of researchers has found vitamin B6 to “dramatically” reduce pain in people with CTS who did not appear to be B6-deficient.136 Some doctors believe that B6 is therapeutic because it reduces swelling around the carpal tunnel in the wrist; this theory remains completely undocumented.

    Very high levels of vitamin B6 can damage sensory nerves, leading to numbness in the hands and feet as well as difficulty in walking; supplementation should be stopped if these symptoms develop after beginning vitamin B6 supplementation. Vitamin B6 is usually safe in amounts of 200 to 500 mg per day,137 although occasional problems have been reported in this range.138 Higher amounts are clearly toxic.139 Any adult taking more than 200 mg of vitamin B6 per day for more than a few months should consult a doctor.

    In order to be effective, vitamin B6 must be transformed in the body to pyridoxal-5’-phosphate (PLP). Some doctors have suggested that people who do not respond well to vitamin B6 supplements should try 50 mg of PLP three times per day. There is no clear evidence that using PLP provides any advantage in reducing symptoms of CTS.

  • Brain Health

    Age-Related Cognitive Decline

    There is evidence that supplementing with vitamin B6 (pyridoxine) may improve memory performance, especially in people who are deficient.
    Age-Related Cognitive Decline
    ×
     

    Vitamin B6 (pyridoxine) deficiency is common among people over age 65.139 A Finnish study demonstrated that approximately 25% of Finnish and Dutch elderly people are deficient in vitamin B6 as compared to younger adults. In a double-blind trial, correcting this deficiency with 2 mg of pyridoxine per day resulted in small psychological improvements in the elderly group. However, the study found no direct correlation between amounts of vitamin B6 in the cells or blood and psychological parameters.140 A more recent double-blind trial of 38 healthy men, aged 70 to 79 years, showed that 20 mg pyridoxine per day improved memory performance, especially long-term memory.141

    Age-Related Cognitive Decline

    In women with cardiovascular disease or related risk factors and low dietary intake of folic acid, vitamin B6, and vitamin B12, supplementing with a combination of these nutrients may protect against age-related cognitive decline.
    Age-Related Cognitive Decline
    ×

    In a study of female health professionals who had cardiovascular disease or cardiovascular disease risk factors, daily supplementation with folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg) for 5.4 years had no effect on cognitive function. However, supplementation appeared to prevent age-related cognitive decline in the 30% of women who had low dietary intake of B vitamins.142

    Supplementation with homocysteine-lowering B vitamins (folic acid, vitamin B12, and vitamin B6) also slowed the rate of brain atrophy in elderly people who had mild cognitive impairment and high homocysteine levels.143

    Schizophrenia

    Vitamin B6 has been used in combination with niacin in the treatment of schizophrenia with some reported benefits.
    Schizophrenia
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    The term “orthomolecular psychiatry” was coined by Linus Pauling in 1968 to refer to the treatment of psychiatric illnesses with substances (such as vitamins) that are normally present in the body. In orthomolecular psychiatry, high amounts of vitamins are sometimes used, not to correct a deficiency per se, but to create a more optimal biochemical environment. The mainstay of the orthomolecular approach to schizophrenia is niacin or niacinamide (vitamin B3) in high amounts. In early double-blind trials, 3 grams of niacin daily resulted in a doubling of the recovery rate, a 50% reduction in hospitalization rates, and a dramatic reduction in suicide rates.144 In a preliminary trial, some schizophrenic patients continued a course of vitamins (4 to 10 grams of niacin or niacinamide, 4 grams of vitamin C, and 50 mg or more of vitamin B6) after being discharged from the hospital, while another group of patients discontinued the vitamins upon discharge. Both groups continued to take their psychiatric medications. Those who continued to take the vitamins had a 50% lower re-admission rate compared with those who did not.144 Several later double-blind trials, including trials undertaken by the Canadian Mental Health Association, have been unable to reproduce these positive results.146,147 Early supporters of niacin therapy contend that many of these trials were poorly designed.148 One clinical trial reported no greater improvement in a group of schizophrenic patients given 6 grams of niacin than in others given 3 mg of niacin; all patients were also being treated with psychiatric medications.149

    There are potential side-effects of niacin therapy, including an uncomfortable flushing sensation, dermatitis (skin inflammation), heartburn, aggravation of peptic ulcers, increased blood sugar, increased panic and anxiety, and elevation of liver enzymes, which may indicate damage to liver cells. A positive side effect of niacin therapy is reduction of cholesterol levels. Some of these effects, such as flushing, gastric upset, and reduction of serum cholesterol, do not occur with the use of niacinamide.150 Because of the seriousness of some of these side effects, high amounts of niacin should not be used without the supervision of a healthcare practitioner.

    Vitamin B6 has been used in combination with niacin in the orthomolecular approach to schizophrenia. Pioneers of orthomolecular medicine reported benefits from this combination. However, although two placebo-controlled trials found significant improvement when schizophrenic patients were given either 3 grams of niacin or 75 mg of pyridoxine along with their psychiatric medications, this improvement was lost when the two vitamins were combined.151,152 In a double-blind trial, schizophrenic patients were given either a vitamin program based on their individual laboratory tests or a placebo (25 mg of vitamin C) in addition to their psychiatric medications. The vitamin program included large amounts of various B vitamins, as well as vitamin C and vitamin E. After five months, the number of patients who improved was not different in the vitamin group compared with the placebo group.153

    Clinical trials of the effects of vitamin B6 have yielded differing results. The results of supplementation with 100 mg daily in one schizophrenic patient included dramatic reduction in side effects from medication, as well as reduction in schizophrenic symptoms.154 In a preliminary trial, 60 mg per day of vitamin B6 resulted in symptomatic improvement in only 5% of schizophrenic patients after four weeks.155 Another preliminary trial, however, found that a higher amount of vitamin B6—50 mg three times daily given for eight to twelve weeks—in addition to psychiatric medications, did bring about significant improvements in schizophrenic patients. These patients experienced a better sense of well-being, increased motivation, and greater interest in their “personal habits and their environment.”156

    L-tryptophan is the amino acid precursor of serotonin, a neurotransmitter (chemical messenger in the brain). There is evidence that L-tryptophan levels in schizophrenic people are lower than in non-schizophrenics157 and the way the body uses L-tryptophan is altered in people with schizophrenia.158,159 In a preliminary trial, patients with schizophrenia were given 2–8 grams of L-tryptophan and 100 mg of vitamin B6 daily. This resulted in decreased agitation and less fear and anxiety, but these improvements were not as great as those achieved with psychiatric medications.160 It is not clear whether the benefits seen in this trial were due to vitamin B6, L-tryptophan, or a combination of the two. No other clinical trials using L-tryptophan have been published. L-tryptophan is currently available by prescription only.

  • Blood Sugar and Diabetes Support

    Type 1 Diabetes

    People with diabetes may have an increased need for vitamin B6. Supplementing with the vitamin may help maintain normal levels and prevent type 1 diabetes complications.
    Type 1 Diabetes
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    People with type 1 diabetes may have impaired vitamin B6 metabolism, resulting in increased susceptibility to deficiency.160 Vitamin B6, along with other B vitamins, is critical for homocysteine metabolism and may thereby reduce their risk of vascular complications of diabetes, particularly diabetes-related kidney disease. Research in people with type 1 diabetes showed supplementation with B1, B6, and B12 lowered elevated homocysteine levels and improved kidney function.161 Vitamin B6 alone, at doses of 100 to 500 mg per day, also improved kidney function in a group of people with type 1 diabetes-related kidney impairment.162 In children with type 1 diabetes, taking 100 mg of B6 per day for eight weeks led to improvements in blood vessel function.163 The benefits of B6 in people with diabetes may also be related to its apparent ability to prevent the formation of damaging advanced glycation end-products (AGEs).164

    Type 2 Diabetes

    People with type 2 diabetes, and especially those with diabetes complication, tend to have low levels of active vitamin B6, a nutrient needed for healthy metabolism.
    Type 2 Diabetes
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    Pyridoxal 5-phosphate (PLP), the active form of vitamin B6, is needed in the body for a wide array of metabolic processes. It also serves as an antioxidant and reduces formation of advanced glycation end-products (AGEs), which cause widespread damage to proteins and DNA.165 Laboratory and animal research suggests PLP inhibits enzymes involved in carbohydrate digestion and absorption, resulting in lower spikes in blood glucose levels after eating.166 Many people with diabetes have low blood levels of PLP, and levels are even lower in people with diabetes complications such as nerve damage (neuropathy) and kidney damage (nephropathy).167,168,169 In a preliminary trial, subjects with neuropathy due to type 2 diabetes were treated with 35 mg of PLP, along with 3 mg of methylfolate and 2 mg of methylcobalamin (B12), twice per day for four weeks, followed by the same regimen once per day for the rest of a full year. Nerve function was significantly improved after six months and further improved after one year of treatment.170 This same combination of B vitamins was found helpful in people with mild-to-moderate type 2 diabetes-related retinopathy after six months.171

    Type 2 Diabetes and Diabetic Neuropathy

    Taking vitamin B1 combined with vitamin B6 may improve symptoms of diabetic neuropathy.
    Type 2 Diabetes and Diabetic Neuropathy
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    A controlled trial in Africa found that supplementing with both vitamin B1 (25 mg per day) and vitamin B6 (50 mg per day) led to significant improvement of symptoms of diabetic neuropathy after four weeks.172 However, since this was a trial conducted among people in a vitamin B1–deficient developing country, these improvements might not occur in other people with diabetes. Another trial found that combining vitamin B1 (in a special fat-soluble form) and vitamin B6 plus vitamin B12 in high but variable amounts led to improvement in some aspects of diabetic neuropathy in 12 weeks.173 As a result, some doctors recommend that people with diabetic neuropathy supplement with vitamin B1, though the optimal level of intake remains unknown.

    Hypoglycemia

    Vitamin B6 helps control blood sugar levels in people with diabetes, and since there are similarities in the way the body regulates high and low blood sugar levels, it might be helpful for hypoglycemia as well.
    Hypoglycemia
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    Research has shown that supplementing with chromium (200 mcg per day)174 or magnesium (340 mg per day)175 can prevent blood sugar levels from falling excessively in people with hypoglycemia. Niacinamide (vitamin B3) has also been found to be helpful for hypoglycemic people.176 Other nutrients, including vitamin C, vitamin E, zinc, copper, manganese, and vitamin B6, may help control blood sugar levels in diabetics.177 Since there are similarities in the way the body regulates high and low blood sugar levels, these nutrients might be helpful for hypoglycemia as well, although the amounts needed for that purpose are not known.

  • Pain Management

    Low Back Pain

    A combination of vitamin B1, vitamin B6, and vitamin B12 may prevent a common type of back pain linked to vertebral syndromes and may reduce the need for anti-inflammatory medications.
    Low Back Pain
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    A combination of vitamin B1, vitamin B6, and vitamin B12 has proved useful for preventing a relapse of a common type of back pain linked to vertebral syndromes,178 as well as reducing the amount of anti-inflammatory medications needed to control back pain, according to double-blind trials.179 Typical amounts used have been 50–100 mg each of vitamins B1 and B6, and 250–500 mcg of vitamin B12, all taken three times per day.180,181 Such high amounts of vitamin B6 require supervision by a doctor.

  • Allergy and Lung Support

    Asthma

    Vitamin B6 deficiency is common in asthmatics. Supplementing with the vitamin may decrease the frequency and severity of asthma attacks.
    Asthma
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    Vitamin B6 deficiency is common in asthmatics.182 This deficiency may relate to the asthma itself or to certain asthma drugs (such as theophylline and aminophylline) that deplete vitamin B6.183 In a double-blind trial, 200 mg per day of vitamin B6 for two months reduced the severity of asthma in children and reduced the amount of asthma medication they needed.184 In another trial, asthmatic adults experienced a dramatic decrease in the frequency and severity of asthma attacks while taking 50 mg of vitamin B6 twice a day.185 Nonetheless, the research remains somewhat inconsistent, and one double-blind trial found that high amounts of B6 supplements did not help asthmatics who required the use of steroid drugs.186

  • Oral Health

    Tooth Decay

    Vitamin B6 appears to increase growth of beneficial mouth bacteria and decrease growth of cavity-causing bacteria.
    Tooth Decay
    ×
     

    Test tube studies show that vitamin B6 increases growth of beneficial mouth bacteria and decreases growth of cavity-causing bacteria.187 A double-blind study found that pregnant women who supplemented with 20 mg per day of vitamin B6 had significantly fewer new caries and fillings during pregnancy.188 Lozenges containing vitamin B6 were more effective than capsules in this study, suggesting an important topical effect. Another double-blind study gave children oral lozenges containing 3 mg of vitamin B6 three times per day for eight months, but reported only insignificant reductions in new cavities.189

  • Eye Health Support

    Macular Degeneration

    In a double-blind study of female health professionals who had cardiovascular disease or risk factors, daily supplementation with folic acid, vitamin B6, and vitamin B12 significantly decreased age-related macular degeneration.
    Macular Degeneration
    ×

    In a double-blind study of female health professionals who had cardiovascular disease or cardiovascular disease risk factors, daily supplementation with folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg) for 7.3 years significantly decreased the incidence of age-related macular degeneration.190 

  • Ear Health Support

    Vertigo

    Studies have shown vitamin B6 to be effective at reducing symptoms.
    Vertigo
    ×
     

    Two preliminary human studies reported that vitamin B6 supplementation reduced symptoms of vertigo produced with drugs in a laboratory setting.191 Vitamin B6 supplementation has not been studied in BPPV or other forms of vertigo and may not share the same causative mechanism as experimentally induced vertigo.

  • Children's Health

    Autism

    Research shows that vitamin B6 can be helpful for autistic children.
    Autism
    ×
     

    Uncontrolled and double-blind research shows that vitamin B6 can be helpful for autistic children.192,193,194 In these trials, children typically took between 3.5 mg and almost 100 mg of B6 for every 2.2 pounds of body weight, with some researchers recommending 30 mg per 2.2 pounds of body weight. Although toxicity was not reported, such amounts are widely considered to have potential toxicity that can damage the nervous system; these amounts should only be administered by a doctor. One prominent researcher has suggested that vitamin B6 is better supported by research than is drug treatment in dealing with autism.195

    Attention Deficit–Hyperactivity Disorder

    In one study, high amounts of vitamin B6 was more effective than methylphenidate (Ritalin). A healthcare practitioner knowledgeable in nutrition must be consulted when using high amounts of this vitamin.
    Attention Deficit–Hyperactivity Disorder
    ×
     

    B vitamins, particularly vitamin B6, have also been used for ADHD. Deficient levels of vitamin B6 have been detected in some ADHD patients.196 In a study of six children with low blood levels of the neurotransmitter (chemical messenger) serotonin, vitamin B6 supplementation (15–30 mg per 2.2 pounds of body weight per day) was found to be more effective than methylphenidate (Ritalin®). However, lower amounts of vitamin B6 were not beneficial.197 The effective amount of vitamin B6 in this study was extremely large and could potentially cause nerve damage, although none occurred in this study. A practitioner knowledgeable in nutrition must be consulted when using high amounts of vitamin B6. High amounts of other B vitamins have shown mixed results in relieving ADHD symptoms.198,199

    Osgood-Schlatter Disease

    Some doctors have reported good results using a combination of zinc, manganese, and vitamin B6 for people with Osgood-Schlatter disease.
    Osgood-Schlatter Disease
    ×
     

    Another group of doctors has reported good results using a combination of zinc, manganese, and vitamin B6 for people with Osgood-Schlatter disease; however, the amounts of these supplements were not mentioned in the report.200 Most physicians would consider reasonable daily amounts of these nutrients for adolescents to be 15 mg of zinc, 5 to 10 mg of manganese, and 25 mg of vitamin B6. Larger amounts might be used with medical supervision.

  • Kidney and Urinary Tract Health

    Kidney Stones

    Taking vitamin B6 with magnesium can inhibit oxalate stone formation.
    Kidney Stones
    ×
     

    Both magnesium and vitamin B6 are used by the body to convert oxalate into other substances. Vitamin B6 deficiency leads to an increase in kidney stones as a result of elevated urinary oxalate.201 Vitamin B6 is also known to reduce elevated urinary oxalate in some stone formers who are not necessarily B6 deficient.202,203

    Years ago, the Merck Manual recommended 100–200 mg of vitamin B6 and 200 mg of magnesium per day for some kidney stone formers with elevated urinary oxalate.204 Most trials have shown that supplementing with magnesium205,206,207 and/or vitamin B6205,209 significantly lowers the risk of forming kidney stones. Results have varied from only a slight reduction in recurrences210 to a greater than 90% decrease in recurrences.206

    Optimal supplemental levels of vitamin B6 and magnesium for people with kidney stones remain unknown. Some doctors advise 200–400 mg per day of magnesium. While the effective intake of vitamin B6 appears to be as low as 10–50 mg per day, certain people with elevated urinary oxalate may require much higher amounts, and therefore require medical supervision. In some cases, as much as 1,000 mg of vitamin B6 per day (a potentially toxic level) has been used successfully.212

    Doctors who do advocate use of magnesium for people with a history of stone formation generally suggest the use of magnesium citrate because citrate itself reduces kidney stone recurrences. As with calcium supplementation, it appears important to take magnesium with meals in order for it to reduce kidney stone risks by lowering urinary oxalate.213

  • Skin Protection

    Acne Vulgaris

    While not proven in research, some reports suggest that it may alleviate adolescent and premenstrual acne, however, another report has suggested that it might make acne worse.
    Acne Vulgaris
    ×
     

    A preliminary report suggested that vitamin B6 at 50 mg per day may alleviate premenstrual flare-ups of acne experienced by some women.212 While no controlled research has evaluated this possibility, an older controlled trial of resistant adolescent acne found that 50–250 mg per day decreased skin oiliness and improved acne in 75% of the participants.213 However, another preliminary report suggested that vitamin B6 supplements might exacerbate acne vulgaris.214

    Photosensitivity

    Vitamin B6 has been used to successfully reduce reactions to sunlight.
    Photosensitivity
    ×
     

    Cases have been reported of people with photosensitivity who responded to vitamin B6 supplementation.215,216 Amounts of vitamin B6 used to successfully reduce reactions to sunlight have varied considerably. Some doctors suggest a trial of 100 to 200 mg per day for three months. People wishing to take more than 200 mg of vitamin B6 per day should do so only under medical supervision.

  • Bone Support

    Osteoporosis and High Homocysteine

    Homocystinuria, a condition associated with high homocysteine levels, frequently causes osteoporosis. By lowering homocysteine levels, vitamin B6 may help prevent osteoporosis.
    Osteoporosis and High Homocysteine
    ×
    Folic acid, vitamin B6, and vitamin B12 are known to reduce blood levels of the amino acid homocysteine, and homocystinuria, a condition associated with high homocysteine levels, frequently causes osteoporosis. Therefore, some researchers have suggested that these vitamins might help prevent osteoporosis by lowering homocysteine levels.217 In a double-blind study of people who had suffered a stroke and had high homocysteine levels, daily supplementation with 5 mg of folic acid and 1,500 mcg of vitamin B12 for two years reduced the incidence of fractures by 78%, compared with a placebo.218 The reduction in fracture risk appeared to be due to an improvement in bone quality, rather than to a change in bone mineral density. However, supplementation with these vitamins did not reduce fracture risk in people who had only mildly elevated homocysteine levels and relatively high pretreatment folic acid levels.219 For the purpose of lowering homocysteine, amounts of folic acid and vitamins B6 and B12 found in high-potency B-complex supplements and multivitamins should be adequate.
  • Healthy Pregnancy and New Baby

    Pregnancy and Postpartum Support and High Homocysteine

    Women who habitually miscarry have been found to have high homocysteine levels. Vitamin B6 may reduce these levels and increase the chances of a successful pregnancy.
    Pregnancy and Postpartum Support and High Homocysteine
    ×
    The relationship between folate status and the risk of miscarriage is also somewhat unclear. In some studies, women who have had habitual miscarriages were found to have elevated levels of homocysteine (a marker of folate deficiency).220,221,222,223 In a preliminary study, 22 women with recurrent miscarriages who had elevated levels of homocysteine were treated with 15 mg per day of folic acid and 750 mg per day of vitamin B6, prior to and throughout their next pregnancy. This treatment reduced homocysteine levels to normal and was associated with 20 successful pregnancies.224 It is not known whether supplementing with these vitamins would help prevent miscarriages in women with normal homocysteine levels. As the amounts of folic acid and vitamin B6 used in this study were extremely large and potentially toxic, this treatment should be used only with the supervision of a doctor.

    Preeclampsia

    Supplementing with vitamin B6 and folic acid may lower homocysteine levels. Elevated homocysteine damages the lining of blood vessels and can lead to the preeclamptic symptoms.
    Preeclampsia
    ×
      

    Women with preeclampsia have been shown to have elevated blood levels of homocysteine.225,226,227,228 Research indicates elevated homocysteine occurs prior to the onset of preeclampsia.229 Elevated homocysteine damages the lining of blood vessels,226,231,229,233,234,235,236 which can lead to the preeclamptic signs of elevated blood pressure, swelling, and protein in the urine.237

    In one preliminary trial, women with a previous pregnancy complicated by preeclampsia and high homocysteine supplemented with 5 mg of folic acid and 250 mg of vitamin B6 per day, successfully lowering homocysteine levels.225 In another trial studying the effect of vitamin B6 on preeclampsia incidence, supplementation with 5 mg of vitamin B6 twice per day significantly reduced the incidence of preeclampsia. Women in that study were not, however, evaluated for homocysteine levels.239 In fact, no studies have yet determined whether lowering elevated homocysteine reduces the incidence or severity of preeclampsia. Nevertheless, despite a lack of proof that elevated homocysteine levels cause preeclampsia, many doctors believe that pregnant women with elevated homocysteine should attempt to reduce those levels to normal.

  • Immune System Support

    Pre- and Post-Surgery Health

    In one trial, a combination of vitamins B1, B6, and B12 before and after surgery prevented post-surgical reductions in immune activity.
    Pre- and Post-Surgery Health
    ×
      

    Vitamin B1, given as intramuscular injections of 120 mg daily for several days before surgery, resulted in less reduction of immune system activity after surgery in a preliminary trial.237 In a controlled trial, an oral B vitamin combination providing 100 mg of B1, 200 mg of vitamin B6, and 200 mcg of vitamin B12 daily given for five weeks before surgery and for two weeks following surgery also prevented post-surgical reductions in immune activity.238 However, no research has explored any other benefits of B vitamin supplementation in surgery patients.

    HIV and AIDS Support

    Vitamin B6 deficiency was found in more than one-third of HIV-positive men, deficiency was associated with decreased immune function in this group. Supplementing with the vitamin may improve survival rate.
    HIV and AIDS Support
    ×
     

    In HIV-positive people with B-vitamin deficiency, the use of B-complex vitamin supplements appears to delay progression to and death from AIDS.239 Thiamine (vitamin B1) deficiency has been identified in nearly one-quarter of people with AIDS.240 It has been suggested that a thiamine deficiency may contribute to some of the neurological abnormalities that are associated with AIDS. Vitamin B6 deficiency was found in more than one-third of HIV-positive men; vitamin B6 deficiency was associated with decreased immune function in this group.241 In a population study of HIV-positive people, intake of vitamin B6 at more than twice the recommended dietary allowance (RDA is 2 mg per day for men and 1.6 mg per day for women) was associated with improved survival.242 Low blood levels of folic acid and vitamin B12 are also common in HIV-positive people.243

What Are Star Ratings?
×
Reliable and relatively consistent scientific data showing a substantial health benefit.
Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.
For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

Our proprietary “Star-Rating” system was developed to help you easily understand the amount of scientific support behind each supplement in relation to a specific health condition. While there is no way to predict whether a vitamin, mineral, or herb will successfully treat or prevent associated health conditions, our unique ratings tell you how well these supplements are understood by the medical community, and whether studies have found them to be effective for other people.

For over a decade, our team has combed through thousands of research articles published in reputable journals. To help you make educated decisions, and to better understand controversial or confusing supplements, our medical experts have digested the science into these three easy-to-follow ratings. We hope this provides you with a helpful resource to make informed decisions towards your health and well-being.

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References

1. Glueck CJ, Shaw P, Land JE, et al. Evidence that homocysteine is an independent risk factor for atherosclerosis in hyperlipidemic patients. Am J Cardiol 1995;75:132-6.

2. Ubbink JB, Vermaak WJH, van der Merwe A, Becker PJ. Vitamin B12, vitamin B6, and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr 1993;57:47-53.

3. Ubbink JB, Vermaak WJH, ven der Merwe A, et al. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 1994;124:1927-33.

4. Dierkes J, Kroesen M, Pietrzik K. Folic acid and vitamin B6 supplementation and plasma homocysteine concentrations in healthy young women. Int J Vitam Nutr Res 1998;68:98-103.

5. Stein JH, McBride PE. Hyperhomocysteinemia and atherosclerotic vascular disease: pathophysiology, screening, and treatment. Arch Intern Med 1998;158:1301-6.

6. McGregor D, Shand B, Lynn K. A controlled trial of the effect of folate supplements on homocysteine, lipids and hemorheology in end-stage renal disease. Nephron 2000;85:215-20.

7. Food standards: amendment of standards of identity for enriched grain products to require addition of folic acid. Fed Regist 1996;61:8781-97.

8. Jacques PF, Selhub J, Bostom AG, et al. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 1999;340:1449-54.

9. Malinow MR, Duell PB, Hess DL, et al. Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. N Engl J Med 1998;338:1009-15.

10. Little DR. Ambulatory management of common forms of anemia. Am Fam Physician 1999;59:1598-604 [review].

11. Hodges RE, Sauberlich HE, Canham JE, et al. Hematopoietic studies in vitamin A deficiency. Am J Clin Nutr 1978;31:876-85 [review].

12. Bloem MW. Interdependence of vitamin A and iron: an important association for programmes of anaemia control. Proc Nutr Soc 1995;54:501-8 [review].

13. Lane M, Alfrey CP. The anemia of human riboflavin deficiency. Blood 1965;25:432-42.

14. Orehek AJ, Kollas CD. Refractory postpartum anemia due to vitamin B6 deficiency. Ann Intern Med 1997;126(10):834-5 [letter].

15. Iwama H, Iwase O, Hayashi S, et al. Macrocytic anemia with anisocytosis due to alcohol abuse and vitamin B6 deficiency. Rinsho Ketsueki 1998;39:1127-30 [in Japanese].

16. Hirschmann JV, Raugi GJ. Adult scurvy. J Am Acad Dermatol 1999;41:895-906 [review].

17. Summerfield AL, Steinberg FU, Gonzalez JG. Morphologic findings in bone marrow precursor cells in zinc-induced copper deficiency anemia. Am J Clin Pathol 1992;97:665-8.

18. Freycon F, Pouyau G. Rare nutritional deficiency anemia: deficiency of copper and vitamin E. Sem Hop 1983;59:488-93 [review] [in French].

19. Borgna-Pignatti C, Marradi P, Pinelli L, et al. Thiamine-responsive anemia in DIDMOAD syndrome. J Pediatr 1989;114:405-10.

20. Neufeld EJ, Mandel H, Raz T, et al. Localization of the gene for thiamine-responsive megaloblastic anemia syndrome, on the long arm of chromosome 1, by homozygosity mapping. Am J Hum Genet 1997;61:1335-41.

21. Carrero JJ, Lopez-Huertas E, Salmeron LM, et al. Daily supplementation with (n-3) PUFAs, oleic acid, folic acid, and vitamins B-6 and E increases pain-free walking distance and improves risk factors in men with peripheral vascular disease. J Nutr2005;135:1393-9.

22. Stampfer MJ, Malinow R, Willett WC, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 1992;268:877-81.

23. Bostom AG, Silbershatz H, Rosenberg IH, et al. Nonfasting plasma total homocysteine levels and all-cause and cardiobascular disease mortality in elderly Framingham men and women. Arch Intern Med 1999;159:1077-80.

24. Folsom AR, Nieto FJ, McGovern PG, et al. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins. Circulation 1998;98:204-10.

25. Kuller LH, Evans RW. Homocysteine, vitamins, and cardiovascular disease. Circulation 1998;98:196-9 [editorial/review].

26. Stolzen berg-Solomon RZ, Miller ER III, Maguire MG, et al. Association of dietary protein intake and coffee consumption with serum homocysteine concentrations in an older population. Am J Clin Nutr 1999;69:467-75.

27. Selhub J, Jacques PF, Wilson PW, et al. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 1993;270:2693-8.

28. Ubbink JB, Vermaak WJH, ven der Merwe A, et al. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 1994;124:1927-33.

29. Manson JB, Miller JW. The effects of vitamin B12, B6, and folate on blood homocysteine levels. Ann NY Acad Sci 1992;669:197-204 [review].

30. Hackam DG, Peterson JC, Spence JD. What level of plasma homocyst(e)ine should be treated? Am J Hypertens 2000;13:105-10.

31. Till U, Rohl P, Jentsch A, et al. Decrease of carotid intima-media thickness in patients at risk to cerebral ischemia after supplementation with folic acid, vitamins B6 and B12. Atherosclerosis2005;181:131-5.

32. Franken DG, Boers GHJ, Blom HJ, et al. Treatment of mild hyperhomocysteinemia in vascular disease patients. Arterioscler Thromb 1994;14:465-70.

33. Ubbink JB, van der Merwe A, Vermaak WJH, Delport R. Hyperhomocysteinemia and the response to vitamin supplementation. Clin Investig 1993;71:993-8.

34. Israelsson B, Brattstrom LE, Hultberg BL. Homocysteine and myocardial infarction. Atherosclerosis 1988;71:227-33.

35. Ridker PM, Manson JE, Buring JE, et al. Homocysteine and risk of cardiovascular disease among postmenopausal women. JAMA 1999;281:1817-21.

36. Bots ML, Launer LJ, Lindemans J, et al. Homocysteine and short-term risk of myocardial infarction and stroke in the elderly: the Rotterdam Study. Arch Intern Med 1999;159:38-44.

37. Stampfer MJ, Malinow R, Willett WC, et al. A prospective study of plasma homocyst(e)ine and risk of myocardial infarction in US physicians. JAMA 1992;268:877-81.

38. Folsom AR, Nieto FJ, McGovern PG, et al. Prospective study of coronary heart disease incidence in relation to fasting total homocysteine, related genetic polymorphisms, and B vitamins. Circulation 1998;98:204-10.

39. Kuller LH, Evans RW. Homocysteine, vitamins, and cardiovascular disease. Circulation 1998;98:196-9 [editorial/review].

40. Nallamothu BK, Fendrick AM, Rubenfire M, et al. Potential clinical and economic effects of homocyst(e)ine lowering. Arch Intern Med 2000;160:3406-12.

41. Landgren F, Israelsson B, Lindgren A, et al. Plasma homocysteine in acute myocardial infarction: homocysteine-lowering effect of folic acid. J Intern Med 1995;237:381-8.

42. Ward M, McNulty H, McPartlin J, et al. Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid. QJM 1997;90:519-24.

43. Lobo A, Naso A, Arheart K, et al. Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B6 and B12. Am J Cardiol 1999;83:821-5.

44. Voutilainen S, Lakka TA, Porkkala-Sarataho E, et al. Low serum folate concentrations are associated with an excess incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study. Eur J Clin Nutr 2000;54:424-8.

45. Lalouschek W, Aull S, Serles W, et al. Genetic and nongenetic factors influencing plasma homocysteine levels in patients with ischemic cerebrovascular disease and in healthy control subjects. J Lab Clin Med 1999;133:575-82.

46. Ridker PM, Manson JE, Buring JE, et al. Homocysteine and risk of cardiovascular disease among postmenopausal women. JAMA 1999;281:1817-21.

47. Perry IJ. Homocysteine, hypertension and stroke. J Hum Hypertens 1999;13:289-93 [review].

48. Genest J Jr. Hyperhomocyst(e)inemia—determining factors and treatment. Can J Cardiol 1999;15:35B-38B [review].

49. Ubbink JB, Vermaak WJH, ven der Merwe A, et al. Vitamin requirements for the treatment of hyperhomocysteinemia in humans. J Nutr 1994;124:1927-33.

50. Manson JB, Miller JW. The effects of vitamin B12, B6, and folate on blood homocysteine levels. Ann NY Acad Sci 1992;669:197-204 [review].

51. Wang X, Qin X, Demirtas H, et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet 2007;369:1876-82.

52. Sahakian V, Rouse D, Sipes S, et al. Vitamin B6 is effective therapy for nausea and vomiting of pregnancy: a randomized, double-blind placebo-controlled study. Obstet Gynecol 1991;78:33-6.

53. Vutyavanich T, Wongtra-ngan S, Ruangsri R. Pyridoxine for nausea and vomiting of pregnancy: a randomized, double blind, placebo-controlled trial. Am J Obstet Gynecol 1995;173:881-4.

54. Hallert C, Astrom J, Walan A. Reversal of psychopathology in adult celiac disease with the aid of pyridoxine (vitamin B6). Scand J Gastroenterol 1983;18:299-304.

55. Hallert C, Svensson M, Tholstrup J, Hultberg B. Clinical trial: B vitamins improve health in patients with coeliac disease living on a gluten-free diet. Aliment Pharmacol Ther 2009;29:811-6.

56. Hallert C, Astrom J, Walan A. Reversal of psychopathology in adult celiac disease with the aid of pyridoxine (vitamin B6). Scand J Gastroenterol 1983;18:299-304.

57. Barr W. Pyridoxine supplements in the premenstrual syndrome. Practitioner 1984;228:425-7.

58. Gunn ADG. Vitamin B6 and the premenstrual syndrome (PMS). Int J Vitam Nutr Res 1985;(Suppl 27):213-24 [review].

59. Kleijnen J, Riet GT, Knipschild P. Vitamin B6 in the treatment of the premenstrual syndrome—a review. Br J Obstet Gynaecol 1990;97:847-52.

60. Williams MJ, Harris RI, Deand BC. Controlled trial of pyridoxine in the treatment of premenstrual syndrome. J Int Med Res 1985;13:174-9.

61. Brush MG, Perry M. Pyridoxine and the premenstrual syndrome. Lancet 1985;i:1399 [letter].

62. Hagen I, Nesheim B-I, Tuntland T. No effect of vitamin B6 against premenstrual tension. Acta Obstet Gynecol Scand 1985;64:667-70.

63. Wyatt KM, Dimmock PW, Jones PW, Shaughn O'Brien PM. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review. BMJ 1999;318:1375-81.

64. Smallwood J, Ah-Kye D, Taylor I. Vitamin B6 in the treatment of pre-menstrual mastalgia. Br J Clin Pract 1986;40:532-3.

65. Sutterlin M, Bussen S, Ruppert D, Steck T. Serum levels of folate and cobalamin in women with recurrent spontaneous abortion. Hum Reprod 1997;12:2292-6.

66. Wouters MG, Boers GH, Blom HJ, et al. Hyperhomocysteinemia: a risk factor in women with unexplained recurrent early pregnancy loss. Fertil Steril 1993;60:820-5.

67. Steegers-Theunissen RP, Boers GH, Blom HJ, et al. Hyperhomocysteinaemia and recurrent spontaneous abortion or abruptio placentae. Lancet 1992;339:1122-3 [letter].

68. Quere I, Bellet H, Hoffet M, et al. A woman with five consecutive fetal deaths: case report and retrospective analysis of hyperhomocysteinemia prevalence in 100 consecutive women with recurrent miscarriages. Fertil Steril 1998;69:152-4.

69. Quere I, Mercier E, Bellet H, et al. Vitamin supplementation and pregnancy outcome in women with recurrent early pregnancy loss and hyperhomocysteinemia. Fertil Steril 2001;75:823-5.

70. McIntosh EN. Treatment of women with the galactorrhea-amenorrhea syndrome with pyridoxine (vitamin B6). J Clin Endocrinol Metab 1976;42:1192-5.

71. Kidd GS, Dimond R, Kark JA, et al. The effects of pyridoxine on pituitary hormone secretion in amenorrhea-galactorrhea syndromes. J Clin Endocrinol Metab 1982;54:872-5.

72. Spiegel AM, Rosen SW, Weintraub BD, Marynick SP. Effect of intravenous pyridoxine on plasma prolactin in hyperprolactinemic subjects. J Clin Endocrinol Metab 1978;46:686-8.

73. Lehtovirta P, Ranta T, Seppala M. Pyridoxine treatment of galactorrhoea-amenorrhoea syndromes. Acta Endocrinol (Copenh) 1978;87:682-6.

74. Tolis G, Laliberte R, Guyda H, Naftolin F. Ineffectiveness of pyridoxine (B6) to alter secretion of growth hormone and prolactin and absence of therapeutic effects on galactorrhea-amenorrhea syndromes. J Clin Endocrinol Metab 1977;44:1197-9.

75. Goodenow TJ, Malarkey WB. Ineffectiveness of pyridoxine in evaluation and treatment of the hyperprolactinemic amenorrhea-galactorrhea syndrome. Am J Obstet Gynecol 1979;133:161-4.

76. Thibault L, Roberge AG. The nutritional status of subjects with anorexia nervosa. Int J Vitam Nutr Res 1987;57:447-52.

77. Abou-Saleh MT, Coppen A. The biology of folate in depression: implications for nutritional hypotheses of the psychoses. J Psychiatr Res 1986;20:91-101 [review].

78. Beaumont PJ, Chambers TL, Rouse L, Abraham SF. The diet composition and nutritional knowledge of patients with anorexia nervosa. J Hum Nutr 1981;35:265-73.

79. Rock CL, Vasantharajan S. Vitamin status of eating disorder patients: relationship to clinical indices and effect of treatment. Int J Eat Disord 1995;18:257-62.

80. Langan SM, Farrell PM. Vitamin E, vitamin A and essential fatty acid status of patients hospitalized for anorexia nervosa. Am J Clin Nutr 1985;41:1054-60.

81. Kaye WH, Weltzin TE. Serotonin activity in anorexia and bulimia nervosa: relationship to the modulation of feeding and mood. J Clin Psychiatry 1991;52 Suppl:41-8 [review].

82. Smith KA, Fairburn CG, Cowen PJ. Symptomatic relapse in bulimia nervosa following acute tryptophan depletion. Arch Gen Psychiatry 1999;56:171-6.

83. Weltzin TE, Fernstrom MH, Fernstrom JD, et al. Acute tryptophan depletion and increased food intake and irritability in bulimia nervosa. Am J Psychiatry 1995;152:1668-71.

84. Oldman AD, Walsh AES, Salkovskis P, et al. Biochemical and behavioural effects of acute tryptophan depletion in abstinent bulimic subjects: a pilot study. Psychol Med 1995;25:995-1001.

85. Anderson IM, Parry-Billings M, Newsholme EA, et al. Dieting reduces plasma tryptophan and alters brain 5-HT function in women. Psychol Med 1990;20:785-91.

86. Mira M, Abraham S. L-tryptophan as an adjunct to treatment of bulimia nervosa. Lancet 1989;ii:1162-3 [letter].

87. Krahn D, Mitchell J. Use of L-tryptophan in treating bulimia. Am J Psychiatry 1985;142:1130 [letter].

88. Brewerton TD, Murphy DL, Jimerson DC. Testmeal responses following m-chlorophenylpiperazine and L-tryptophan in bulimics and controls. Neuropsychopharmacology 1994;11:63-71.

89. Barr W. Pyridoxine supplements in the premenstrual syndrome. Practitioner 1984;228:425-7.

90. Gunn ADG. Vitamin B6 and the premenstrual syndrome (PMS). Int J Vitam Nutr Res 1985;(Suppl 27):213-24 [review].

91. Kleijnen J, Riet GT, Knipschild P. Vitamin B6 in the treatment of the premenstrual syndrome—a review. Br J Obstet Gynaecol 1990;97:847-52.

92. Williams MJ, Harris RI, Deand BC. Controlled trial of pyridoxine in the treatment of premenstrual syndrome. J Int Med Res 1985;13:174-9.

93. Brush MG, Perry M. Pyridoxine and the premenstrual syndrome. Lancet 1985;i:1399 [letter].

94. Hagen I, Nesheim B-I, Tuntland T. No effect of vitamin B6 against premenstrual tension. Acta Obstet Gynecol Scand 1985;64:667-70.

95. Wyatt KM, Dimmock PW, Jones PW, Shaughn O'Brien PM. Efficacy of vitamin B-6 in the treatment of premenstrual syndrome: systematic review. BMJ 1999;318:1375-81.

96. Smallwood J, Ah-Kye D, Taylor I. Vitamin B6 in the treatment of pre-menstrual mastalgia. Br J Clin Pract 1986;40:532-3.

97. McIntosh EN. Treatment of women with the galactorrhea-amenorrhea syndrome with pyridoxine (vitamin B6). J Clin Endocrinol Metab 1976;42:1192-5.

98. Kidd GS, Dimond R, Kark JA, et al. The effects of pyridoxine on pituitary hormone secretion in amenorrhea-galactorrhea syndromes. J Clin Endocrinol Metab 1982;54:872-5.

99. Spiegel AM, Rosen SW, Weintraub BD, Marynick SP. Effect of intravenous pyridoxine on plasma prolactin in hyperprolactinemic subjects. J Clin Endocrinol Metab 1978;46:686-8.

100. Lehtovirta P, Ranta T, Seppala M. Pyridoxine treatment of galactorrhoea-amenorrhoea syndromes. Acta Endocrinol (Copenh) 1978;87:682-6.

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