Sideroblastic anemia refers to a category of anemia featuring a buildup of iron-containing immature red blood cells (sideroblasts). One type of sideroblastic anemia is due to a genetic defect in an enzyme that uses vitamin B6 as a cofactor.^{1 , 2} Vitamin B6 supplements of 50 to 200 mg per day partially correct the anemia, but must be taken for life.³

Deficiencies of iron, vitamin B12, and folic acid are the most common nutritional causes of anemia.⁴ Although rare, severe deficiencies of several other vitamins and minerals, including vitamin A,^{5 , 6} vitamin B2,⁷ vitamin B6,^{8 , 9} vitamin C,¹⁰ and copper,^{11 , 12} 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.^{13 , 14}

Uncontrolled and double-blind research shows that vitamin B6 can be helpful for autistic children.^{15 , 16 , 17} 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.¹⁸

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.¹⁹ 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.²⁰

Several clinical trials also indicate that vitamin B6 supplementation helps alleviate depression associated with premenstrual syndrome (PMS),²¹ although the research remains inconsistent.²² 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.

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,^{23, 24, 25} 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.^{26 , 27} It also effectively lowers homocysteine in people on kidney dialysis.²⁸ 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.²⁹ This level of fortification has led to a measurable decrease in homocysteine levels.³⁰ However, even higher levels of food fortification with folic acid have been reported to be more effective in lowering homocysteine,³¹ 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.

In two double-blind trials, supplementation with vitamin B6 (10 or 25 mg three times per day) significantly reduced the severity of morning sickness.^{32 , 33}

Many,^{34 , 35 , 36 , 37 , 38} though not all,³⁹ 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.⁴⁰ 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 (pyridoxine) deficiency is common among people over age 65.⁴¹ 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.⁴² 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.⁴³

Vitamin B6 deficiency is common in asthmatics.⁴⁴ This deficiency may relate to the asthma itself or to certain asthma drugs (such as theophylline and aminophylline) that deplete vitamin B6.⁴⁵ 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.⁴⁶ 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.⁴⁷ 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.⁴⁸

Some, but not all, studies have found vitamin B6 deficiency to be common in people with CTS.⁴⁹ Supplementation with vitamin B6 has reportedly relieved the symptoms of CTS,⁵⁰ but some researchers have not found this treatment to be beneficial.^{51 , 52}

Several studies report that people with CTS are helped when given 100 mg of vitamin B6 three times per day.^{53 , 54} Although some researchers have found benefits with lesser amounts,^{55 , 56 , 57 , 58} using less than 100 mg taken three times per day for several months has often failed.^{59 , 60 , 61} 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.⁶² 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,⁶³ although occasional problems have been reported in this range.⁶⁴ Higher amounts are clearly toxic.⁶⁵ 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.

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.⁶⁸ 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.⁶⁹

Several clinical trials also indicate that vitamin B6 supplementation helps alleviate depression associated with premenstrual syndrome (PMS),⁷⁰ although the research remains inconsistent.⁷¹ 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.

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.⁷²

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,⁷³ as well as reducing the amount of anti-inflammatory medications needed to control back pain, according to double-blind trials.⁷⁴ 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.^{75 , 76} Such high amounts of vitamin B6 require supervision by a doctor.

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.⁷⁷ 

Years ago, researchers discovered that animals who were deficient in vitamin B6 could not properly process MSG.⁷⁸ Typical reactions to MSG have also been linked to vitamin B6 deficiency in people.⁷⁹ In one study, eight out of nine such people stopped reacting to MSG when given 50 mg of vitamin B6 per day for at least 12 weeks.

The actual percentage of people with MSG sensitivity who are deficient in vitamin B6 and who respond to B6 supplementation is unknown. Nonetheless, many doctors suggest that people having MSG-sensitivity symptoms try supplementing with vitamin B6 for three months as a trial.

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.⁸⁵ 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.⁸⁶ Several later double-blind trials, including trials undertaken by the Canadian Mental Health Association, have been unable to reproduce these positive results.^{87 , 88} Early supporters of niacin therapy contend that many of these trials were poorly designed.⁸⁹ 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.⁹⁰

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.⁹¹ 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.^{92, 93} 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.⁹⁴

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.⁹⁵ In a preliminary trial, 60 mg per day of vitamin B6 resulted in symptomatic improvement in only 5% of schizophrenic patients after four weeks.⁹⁶ 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.”⁹⁷

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-schizophrenics⁹⁸ and the way the body uses L-tryptophan is altered in people with schizophrenia.^{99 , 100} 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.¹⁰¹ 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.

People with schizophrenia may have a greater tendency to be deficient in folic acid, than the general population¹⁰² and they may show improvement when given supplements. A preliminary trial found that, among schizophrenic patients with folic acid deficiency, those given folic acid supplements had more improvement, and shorter hospital stays than those not given supplements.¹⁰³ In a double-blind trial, a very high amount of folic acid (15 mg daily) was given to schizophrenic patients being treated with psychiatric medications who had low or borderline folic acid levels. The patients receiving the folic acid supplements had significant improvement, which became more significant over the six-month course of the trial.¹⁰⁴ The symptoms of folic acid deficiency can be similar to those of schizophrenia, and two cases of wrong “schizophrenia” diagnoses have been reported.^{105 , 106} In one of these cases, an initial supplement of 20 mg daily of folic acid and a maintenance supplemental intake of 10 mg daily, led to resolution of symptoms.¹⁰⁷

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.¹⁰⁸ 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.

Test tube studies show that vitamin B6 increases growth of beneficial mouth bacteria and decreases growth of cavity-causing bacteria.¹⁰⁹ 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.¹¹⁰ 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.¹¹¹

Blood levels of vitamin B1 (thiamine) have been found to be low in people with type 1 diabetes.¹¹² 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 nerve damage (neuropathy) after four weeks.¹¹³ 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.¹¹⁴ As a result, some doctors recommend that people with diabetic neuropathy supplement with vitamin B1, though the optimal level of intake remains unknown.

¹¹⁵

Many people with diabetes have low blood levels of vitamin B6.^{121 , 122} Levels are even lower in people with diabetes who also have nerve damage (neuropathy).¹²³ Vitamin B6 supplementation has improved glucose tolerance in women with diabetes caused by pregnancy.^{124 , 125} Vitamin B6 supplementation is also effective for glucose intolerance induced by birth control pills.¹²⁶ In a trial that included people with type 2 diabetes, 1,800 mg per day of a special form of vitamin B6—pyridoxine alpha-ketoglutarate—improved glucose tolerance dramatically.¹²⁷ Standard vitamin B6 has helped in some,¹²⁸ but not all, trials.¹²⁹

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.¹³⁰ 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.¹³¹ As a result, some doctors recommend that people with diabetic neuropathy supplement with vitamin B1, though the optimal level of intake remains unknown.

Two preliminary human studies reported that vitamin B6 supplementation reduced symptoms of vertigo produced with drugs in a laboratory setting.¹³² 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.

A preliminary report suggested that vitamin B6 at 50 mg per day may alleviate premenstrual flare-ups of acne experienced by some women.¹³³ 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.¹³⁴ However, another preliminary report suggested that vitamin B6 supplements might exacerbate acne vulgaris.¹³⁵

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.¹³⁶

The daily combination of 3 grams of vitamin C, 3 grams of niacin, 600 mg of vitamin B6, and 600 IU of vitamin E has been used by researchers from the University of Mississippi Medical Center in an attempt to reduce anxiety and depression in alcoholics.¹³⁷ Although the effect of vitamin supplementation was no better than placebo in treating alcohol-associated depression, the vitamins did result in a significant drop in anxiety within three weeks of use. Because of possible side effects, anyone taking such high amounts of niacin and vitamin B6 must do so only under the care of a doctor.

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.¹³⁸

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.¹³⁹ A number of other small, preliminary trials have not demonstrated an effect of either oral or injected vitamin B6 on prolactin levels,^{140 , 141 , 142 , 143 , 144} and they also have reported inconsistent effects on restoring menstruation.^{145 , 146 , 147} Larger, controlled trials are needed to better determine the usefulness of vitamin B6 in amenorrhea.

Blood levels of an amino acid called homocysteine have been linked to atherosclerosis and heart disease in most research,^{148 , 149} though uncertainty remains about whether elevated homocysteine actually causes heart disease.^{150 , 151} Although some reports have found associations between homocysteine levels and dietary factors, such as coffee and protein intakes,¹⁵² 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 homocysteine¹⁵³ and supplementing with these vitamins lowers homocysteine levels.^{154 , 155}

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.¹⁵⁶ 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).¹⁵⁷ Similar results were seen in another study.¹⁵⁸

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.¹⁵⁹ Of these four supplements, folic acid appears to be the most important.¹⁶⁰ Attempts to lower homocysteine by simply changing the diet rather than by using vitamin supplements have not been successful.¹⁶¹

B vitamins, particularly vitamin B6, have also been used for ADHD. Deficient levels of vitamin B6 have been detected in some ADHD patients.¹⁶² 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.¹⁶³ 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.^{164, 165}

People with eating disorders who restrict their food intake are at risk for multiple nutrient deficiencies, including protein, calcium, iron, riboflavin, niacin,¹⁶⁶ folic acid,¹⁶⁷ vitamin A, vitamin C,¹⁶⁸ and vitamin B6,¹⁶⁹ and essential fatty acids.¹⁷⁰ 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.¹⁷¹ 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,^{172 , 173} though not all studies have demonstrated these effects.¹⁷⁴

Weight-loss diets result in lower L-tryptophan and serotonin levels in women,¹⁷⁵ 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.¹⁷⁶ Other double-blind studies using only L-tryptophan have failed to confirm these findings.^{177 , 178} 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.

Vitamin B6 has been used to treat infants and small children who have seizures related to a genetic enzyme defect.^{179, 180, 181, 182} However, this condition is not considered true epilepsy, and whether people with epilepsy would benefit from taking vitamin B6 supplements is unknown.

The effectiveness of vitamin B6 remains uncertain. Some,¹⁸³ but not all,¹⁸⁴ studies find that B6 supplementation reduces symptoms. Since vitamin B6 supplementation is effective for relieving the symptoms of premenstrual syndrome (PMS), in addition to breast tenderness, women should discuss the use of vitamin B6 with their healthcare provider.

High blood levels of the amino acid homocysteine have been linked to an increased risk of heart attack in most,^{185 , 186 , 187 , 188} though not all,^{189 , 190} 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.¹⁹¹ Folic acid^{192 , 193} and vitamins B6 and B12 are known to lower homocysteine.¹⁹⁴

There is a clear association between low blood levels of folate and increased risk of heart attacks in men.¹⁹⁵ 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.

In HIV-positive people with B-vitamin deficiency, the use of B-complex vitamin supplements appears to delay progression to and death from AIDS.¹⁹⁶ Thiamine (vitamin B1) deficiency has been identified in nearly one-quarter of people with AIDS.¹⁹⁷ 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.¹⁹⁸ 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.¹⁹⁹ Low blood levels of folic acid and vitamin B12 are also common in HIV-positive people.²⁰⁰

Research has shown that supplementing with chromium (200 mcg per day)²⁰¹ or magnesium (340 mg per day)²⁰² 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.²⁰³ Other nutrients, including vitamin C, vitamin E, zinc, copper, manganese, and vitamin B6, may help control blood sugar levels in diabetics.²⁰⁴ 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.

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.²⁰⁵ Vitamin B6 is also known to reduce elevated urinary oxalate in some stone formers who are not necessarily B6 deficient.^{206 , 207}

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.²⁰⁸ Most trials have shown that supplementing with magnesium^{209 , 210 , 211} and/or vitamin B6^{212 , 213} significantly lowers the risk of forming kidney stones. Results have varied from only a slight reduction in recurrences²¹⁴ to a greater than 90% decrease in recurrences.²¹⁵

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.²¹⁶

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.²¹⁷

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.²¹⁸ 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.

Cases have been reported of people with photosensitivity who responded to vitamin B6 supplementation.^{222 , 223} 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.

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.²²⁴ 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.²²⁵ However, no research has explored any other benefits of B vitamin supplementation in surgery patients.

Women with preeclampsia have been shown to have elevated blood levels of homocysteine.^{226 , 227 , 228 , 229} Research indicates elevated homocysteine occurs prior to the onset of preeclampsia.²³⁰ Elevated homocysteine damages the lining of blood vessels,^{231 , 232 , 233 , 234 , 235 , 236 , 237} which can lead to the preeclamptic signs of elevated blood pressure, swelling, and protein in the urine.²³⁸

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.²³⁹ 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.²⁴⁰ 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.

Preliminary research has found that patients with sickle cell anemia are more likely to have elevated blood levels of homocysteine compared to healthy people.^{241 , 242} Elevated homocysteine is recognized as a risk factor for cardiovascular disease.²⁴³ In particular, high levels of homocysteine in sickle cell anemia patients have been associated with a higher incidence of stroke.²⁴⁴ Deficiencies of vitamin B6, vitamin B12, and folic acid occur more frequently in people with sickle cell anemia than in others^{245 , 246 , 247} and are a cause of high homocysteine levels.²⁴⁸ A controlled trial found homocysteine levels were reduced 53% in children with sickle cell anemia receiving a 2–4 mg supplement of folic acid per day, depending on age, but vitamin B6 or B12 had no effect on homocysteine levels.²⁴⁹ A double-blind trial of children with sickle cell anemia found that children given 5 mg of folic acid per day had less painful swelling of the hands and feet compared with those receiving placebo, but blood abnormalities and impaired growth rate associated with sickle cell anemia were not improved.²⁵⁰ In the treatment of sickle cell anemia, folic acid is typically supplemented in amounts of 1,000 mcg daily.²⁵¹ Anyone taking this amount of folic acid should have vitamin B12 status assessed by a healthcare professional.

In test tube studies, vitamin B6 has been shown to have anti-sickling effects on the red blood cells of people with sickle cell anemia.^{252 , 253} Vitamin B6 deficiency has been reported in some research to be more common in people with sickle cell anemia than in healthy people.^{254 , 255} In a controlled trial, five sickle cell anemia patients with evidence of vitamin B6 deficiency were given 50 mg of vitamin B6 twice daily. The deficiency was reversed with this supplement, but improvement in anemia was slight and considered insignificant.²⁵⁶ Therefore, evidence in support of vitamin B6 supplementation for people with sickle cell anemia remains weak.

Elevated blood levels of homocysteine, a toxic amino acid byproduct, have been linked to risk of stroke in most studies.^{257 , 258 , 259} Supplementation with folic acid, vitamin B6, and vitamin B12 generally lowers homocysteine levels in humans.^{260 , 261 , 262} 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%.²⁶³

During a ten-year period, doctors at the North Nassau Mental Health Center in New York treated approximately 11,000 people with schizophrenia with a megavitamin regimen that included vitamin C (up to 4 grams per day), vitamin B3—either as niacin or niacinamide—(up to 4 grams per day), vitamin B6 (up to 800 mg per day), and vitamin E (up to 1,200 IU per day). During that time, not a single new case of TD was seen, even though many of the people were taking neuroleptic drugs.²⁶⁴ Another psychiatrist who routinely used niacinamide, vitamin C, and vitamin B-complex over a 28-year period rarely saw TD develop in her patients.²⁶⁵ Further research is needed to determine which nutrients or combinations of nutrients were most important for preventing TD. The amounts of niacinamide and vitamin B6 used in this research may cause significant side effects and may require monitoring by a doctor.