In a preliminary trial, administration of 1 mg of vitamin B12 per day (by the intranasal route) for 3 months reduced the frequency of migraine attacks by at least 50% in 10 of 19 people with recurrent migraines.¹ A placebo-controlled study is needed to determine how much of this improvement was due to a placebo effect.

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,² as well as reducing the amount of anti-inflammatory medications needed to control back pain, according to double-blind trials.³ 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.^4,5 Such high amounts of vitamin B6 require supervision by a doctor.

Vitamin B12 has exhibited pain-killing properties in animal studies.⁶ In humans with vertebral pain syndromes, injections of massive amounts of vitamin B12 (5,000 to 10,000 mcg per day) have reportedly provided pain relief.⁷ Further studies are needed to confirm the efficacy of this treatment.

Some doctors have observed that injections of vitamin B12 appear to relieve the symptoms of postherpetic neuralgia.^8,9 However, since these studies did not include a control group, the possibility of a placebo effect cannot be ruled out. Oral vitamin B12 supplements have not been tested, but they are not likely to be effective against postherpetic neuralgia.

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,^10,11,12 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.^13,14 It also effectively lowers homocysteine in people on kidney dialysis.¹⁵ 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.¹⁶ This level of fortification has led to a measurable decrease in homocysteine levels.¹⁷ However, even higher levels of food fortification with folic acid have been reported to be more effective in lowering homocysteine,¹⁸ 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.

Blood levels of an amino acid called homocysteine have been linked to atherosclerosis and heart disease in most research,^19,20 though uncertainty remains about whether elevated homocysteine actually causes heart disease.^21,22 Although some reports have found associations between homocysteine levels and dietary factors, such as coffee and protein intakes,²³ 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 homocysteine²⁴ and supplementing with these vitamins lowers homocysteine levels.^25,26

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.²¹ 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).²⁸ Similar results were seen in another study.²⁹

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.³⁰ Of these four supplements, folic acid appears to be the most important.²⁵ Attempts to lower homocysteine by simply changing the diet rather than by using vitamin supplements have not been successful.³²

High blood levels of the amino acid homocysteine have been linked to an increased risk of heart attack in most,^31,32,33,34 though not all,^35,36 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.³⁷Folic acid^38,39 and vitamins B6 and B12 are known to lower homocysteine.⁴⁰

There is a clear association between low blood levels of folate and increased risk of heart attacks in men.⁴¹ 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.

Elevated blood levels of homocysteine, a toxic amino acid byproduct, have been linked to risk of stroke in most studies.^42,43,44 Supplementation with folic acid, vitamin B6, and vitamin B12 generally lowers homocysteine levels in humans.^45,46,47 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%.⁴⁸

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.⁴⁹ 

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.⁵⁰

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.⁵¹

Supplementation with vitamin B12 may improve cognitive function in elderly people who have been diagnosed with a B12 deficiency. Such a deficiency in older people is not uncommon. In a preliminary trial, intramuscular injections of 1,000 mcg of vitamin B12 were given once per day for a week, then weekly for a month, then monthly thereafter for 6 to 12 months. Researchers noted “striking” improvements in cognitive function among 22 elderly people with vitamin B12 deficiency and cognitive decline.⁵² Cognitive disorders due to vitamin B12 deficiency may also occur in people who do not exhibit the anemia that often accompanies vitamin B12 deficiency. For example, in a study of 141 elderly people with cognitive abnormalities due to B12 deficiency, 28% had no anemia. All participants were given intramuscular injections of vitamin B12, and all showed subsequent improvement in cognitive function.⁵³

Vitamin B12 injections put more B12 into the body than is achievable with absorption from oral supplementation. Therefore, it is unclear whether the improvements in cognitive function described above were due simply to correcting the B12 deficiency or to a therapeutic effect of the higher levels of vitamin B12 obtained through injection. Elderly people with ARCD should be evaluated by a healthcare professional to see if they have a B12 deficiency. If a deficiency is present, the best way to proceed would be initially to receive vitamin B12 injections. If the injections result in cognitive improvement, some doctors would then recommend an experimental trial with high amounts of oral B12, despite a current lack of scientific evidence. If oral vitamin B12 is found to be less effective than B12 shots, the appropriate treatment would be to revert to injectable B12. At present, no research trials support the use of any vitamin B12 supplementation in people who suffer from ARCD but are not specifically deficient in vitamin B12.

Some researchers have found an association between Alzheimer’s disease and deficiencies of vitamin B12 and folic acid;^54,55 however, other researchers consider such deficiencies to be of only minor importance.⁵⁶ In a study of elderly Canadians, those with low blood levels of folate were more likely to have dementia of all types, including Alzheimer’s disease, than those with higher levels of folate.⁵⁷ Little is known about whether supplementation with either vitamin would significantly help people with this disease. Nonetheless, it makes sense for people with Alzheimer’s disease to be medically tested for vitamin B12 and folate deficiencies and to be treated if they are deficient.

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.⁵⁸

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.⁵⁹

Supplementation with vitamin B12 may improve cognitive function in elderly people who have been diagnosed with a B12 deficiency. Such a deficiency in older people is not uncommon. In a preliminary trial, intramuscular injections of 1,000 mcg of vitamin B12 were given once per day for a week, then weekly for a month, then monthly thereafter for 6 to 12 months. Researchers noted “striking” improvements in cognitive function among 22 elderly people with vitamin B12 deficiency and cognitive decline.⁶⁰ Cognitive disorders due to vitamin B12 deficiency may also occur in people who do not exhibit the anemia that often accompanies vitamin B12 deficiency. For example, in a study of 141 elderly people with cognitive abnormalities due to B12 deficiency, 28% had no anemia. All participants were given intramuscular injections of vitamin B12, and all showed subsequent improvement in cognitive function.⁶¹

Vitamin B12 injections put more B12 into the body than is achievable with absorption from oral supplementation. Therefore, it is unclear whether the improvements in cognitive function described above were due simply to correcting the B12 deficiency or to a therapeutic effect of the higher levels of vitamin B12 obtained through injection. Elderly people with ARCD should be evaluated by a healthcare professional to see if they have a B12 deficiency. If a deficiency is present, the best way to proceed would be initially to receive vitamin B12 injections. If the injections result in cognitive improvement, some doctors would then recommend an experimental trial with high amounts of oral B12, despite a current lack of scientific evidence. If oral vitamin B12 is found to be less effective than B12 shots, the appropriate treatment would be to revert to injectable B12. At present, no research trials support the use of any vitamin B12 supplementation in people who suffer from ARCD but are not specifically deficient in vitamin B12.

Both folic acid and vitamin B12 are used in the body to manufacture serotonin and other neurotransmitters. It is well known that deficiency of either nutrient is associated with depression.^62,63 There is some evidence that patients diagnosed with mania are also more likely to have folate deficiencies than healthy controls.⁶⁴ Other studies, however, have found that folic acid deficiency was not more common in bipolar patients taking lithium than in healthy people.^65,66,67 Some studies have found that people who take lithium long term, and who also have high blood levels of folic acid, respond better to lithium.^68,66 Not all studies have confirmed these findings, however.⁶⁷ A double-blind study of patients receiving lithium therapy showed that the addition of 200 mcg of folic acid per day resulted in clinical improvement, whereas placebo did not.⁷¹

There have been case reports of both mania and depression associated with vitamin B12 deficiency, and these symptoms cleared after treatment with injections of B12.^72,73 However, B12 deficiency has not been reported in bipolar disorder patients, and no studies have been published investigating the effects of vitamin B12 supplementation in people with bipolar disorder.

Vitamin B12 deficiency can cause symptoms that are similar to those of schizophrenia and one case has been reported in which such symptoms cleared after supplementation with vitamin B12.⁷² Some studies have reported finding lower levels of vitamin B12 in people with schizophrenia than in the general population,⁷² but others have found no difference.⁷⁴ No trials of vitamin B12 supplementation in schizophrenic patients have been published.

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,⁷⁴ as well as reducing the amount of anti-inflammatory medications needed to control back pain, according to double-blind trials.⁷⁵ 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.^76,77 Such high amounts of vitamin B6 require supervision by a doctor.

In a preliminary study, intramuscular injections of vitamin B12^78,79 relieved the symptoms of acute subdeltoid (shoulder) bursitis and also decreased the amount of calcification in some cases. This mechanism is not understood. Oral B vitamins are unlikely to have the same effect, since the body’s absorption of vitamin B12 is quite limited. A doctor should be consulted regarding B12 or B12 injections.

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.⁸⁰ 

One study investigated the effect of adding 100 mcg per day of vitamin B12 to the insulin injections of 15 children with diabetic retinopathy.⁸¹ After one year, signs of retinopathy disappeared in 7 of 15 cases; after two years, 8 of 15 were free of retinopathy. Adults with diabetic retinopathy did not benefit from vitamin B12 injections. Consultation with a physician is necessary before adding injectable vitamin B12 to insulin.

Vitamin B12 supplementation may be beneficial for a subset of people suffering from indigestion: those with delayed emptying of the stomach contents in association with Helicobacter pylori infection and low blood levels of vitamin B12. In a double-blind study of people who satisfied those criteria, treatment with vitamin B12 significantly reduced symptoms of dyspepsia and improved stomach-emptying times.⁸⁴

Crohn’s disease often leads to malabsorption. As a result, deficiencies of many nutrients are common. For this reason, it makes sense for people with Crohn’s disease to take a high potency multivitamin-mineral supplement. In particular, deficiencies in zinc, folic acid, vitamin B12, vitamin D, and iron have been reported.^85,86,87 Zinc, folic acid, and vitamin B12 are all needed to repair intestinal cells damaged by Crohn’s disease. Some doctors recommend 25 to 50 mg of zinc (balanced with 2 to 4 mg of copper), 800 mcg of folic acid, and 800 mcg of vitamin B12. Iron status should be evaluated by a doctor before considering supplementation.

Vitamin B12 deficiency may cause fatigue. However, some reports,⁹⁵ even double-blind ones,⁹⁶ have shown that people who are not deficient in B12 have increased energy following a series of vitamin B12 injections. Some sources in conventional medicine have discouraged such people from taking B12 shots despite this evidence.⁹⁷ Nonetheless, some doctors have continued to take the limited scientific support for B12 seriously.⁹⁸ In one preliminary trial, 2,500 to 5,000 mcg of vitamin B12 given by injection every two to three days led to improvement in 50 to 80% of a group of people with CFS; most improvement appeared after several weeks of B12 shots.⁹⁹ While the research in this area remains preliminary, people with CFS considering a trial of vitamin B12 injections should consult a doctor. Oral or sublingual B12 supplements are unlikely to obtain the same results as injectable B12, because the body’s ability to absorb large amounts is relatively poor.

Vitamin B12 is needed to maintain fertility. Vitamin B12 injections have increased sperm counts for men with low numbers of sperm.¹⁰⁰ These results have been duplicated in double-blind research.¹⁰¹ In one study, a group of infertile men were given oral vitamin B12 supplements (1,500 mcg per day of methylcobalamin) for 2 to 13 months. Approximately 60% of those taking the supplement experienced improved sperm counts.¹⁰² However, controlled trials are needed to confirm these preliminary results. Men seeking vitamin B12 injections should consult a physician.

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.¹⁰⁴ 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.¹⁰⁵ However, no research has explored any other benefits of B vitamin supplementation in surgery patients.

In HIV-positive people with B-vitamin deficiency, the use of B-complex vitamin supplements appears to delay progression to and death from AIDS.¹⁰⁶ Thiamine (vitamin B1) deficiency has been identified in nearly one-quarter of people with AIDS.¹⁰⁷ 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.¹⁰⁸ 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.¹⁰⁹ Low blood levels of folic acid and vitamin B12 are also common in HIV-positive people.¹¹⁰

In some people with asthma, symptoms can be triggered by ingestion of food additives known as sulfites. Pretreatment with a large amount of vitamin B12 (1,500 mcg orally) reduced the asthmatic reaction to sulfites in children with sulfite sensitivity in one preliminary trial.¹¹¹ The trace mineral molybdenum also helps the body detoxify sulfites.¹¹² While some doctors use molybdenum to treat selected patients with asthma, there is little published research on this treatment, and it is not known what an appropriate level of molybdenum supplementation would be. A typical American diet contains about 200 to 500 mcg per day,¹¹³ and preliminary short-term trials have used supplemental amounts of 500 mcg per day.¹¹⁴ People who suspect sulfite-sensitive asthma should consult with a physician before taking molybdenum.

Vitamin B12 has been reported to reduce the severity of acute hives as well as to reduce the frequency and severity of outbreaks in chronic cases.^115,116 The amount used in these reported case studies was 1,000 mcg by injection per week. Whether taking B12 supplements orally would have these effects remains unknown. On rare occasions, vitamin B12 injections cause hives in susceptible people.¹¹⁷ Whether such reactions are actually triggered by exposure to large amounts of vitamin B12 or to preservatives and other substances found in most vitamin B12 injections remains unclear.

In two small preliminary trials, people with insomnia resulting from disorders of the sleep-wake rhythm improved after supplementing with vitamin B12 (1,500 to 3,000 mcg per day).^118,119

One study investigated the effect of adding 100 mcg per day of vitamin B12 to the insulin injections of 15 children with diabetic retinopathy.¹³³ After one year, signs of retinopathy disappeared in 7 of 15 cases; after two years, 8 of 15 were free of retinopathy. Adults with diabetic retinopathy did not benefit from vitamin B12 injections. Consultation with a physician is necessary before adding injectable vitamin B12 to insulin.

Several preliminary studies,^{134,135,136,137} though not all,¹³⁸ have found a surprisingly high incidence of iron and B vitamin deficiency among people with recurrent canker sores. Treating these deficiencies has been reported in preliminary and controlled studies to reduce or eliminate recurrences in most cases.^139,140,141 In addition, a double-blind study found that supplementing with vitamin B12 prevented recurrences even in people who were not deficient in the vitamin.¹⁴² The amount used in that study was 1,000 mcg twice a day for six months. Supplementing daily with B vitamins—300 mg vitamin B1, 20 mg vitamin B2, and 150 mg vitamin B6—has been reported to provide some people with relief.¹⁴³ Thiamine (B1) deficiency specifically has been linked to an increased risk of canker sores.¹⁴⁴ The right supplemental level of iron requires diagnosis of an iron deficiency by a healthcare professional using lab tests.

People exposed to loud noise on the job who develop tinnitus are commonly deficient in Vitamin B12.¹⁴⁵ Intramuscular injections of vitamin B12 reduced the severity of tinnitus in some of these people. Injectable vitamin B12 is available only by prescription. The effect of oral vitamin B12 on tinnitus has not been studied.

Deficiency of vitamin B12 can create disturbances in mood that respond to B12 supplementation.¹⁴⁶ Significant vitamin B12 deficiency is associated with a doubled risk of severe depression, according to a study of physically disabled older women.¹⁴⁷ Depression caused by vitamin B12 deficiency can occur even if there is no B12 deficiency-related anemia.¹⁴⁸

Mood has been reported to sometimes improve with high amounts of vitamin B12 (given by injection), even in the absence of a B12 deficiency.¹⁴⁹ Supplying the body with high amounts of vitamin B12 can only be done by injection. However, in the case of overcoming a diagnosed B12 deficiency, one can follow an initial injection with oral maintenance supplementation (1 mg per day), even when the cause of the deficiency is a malabsorption problem such as pernicious anemia.

A clinical report describes the use of vitamin supplements in the treatment of vitiligo.¹⁵¹Folic acid and/or vitamin B12 and vitamin C levels were abnormally low in most of the 15 people studied. Supplementation with large amounts of folic acid (1–10 mg per day), along with vitamin C (1 gram per day) and intramuscular vitamin B12 injections (1,000 mcg every two weeks), produced marked repigmentation in eight people. These improvements became apparent after three months, but complete repigmentation required one to two years of continuous supplementation. In another study of people with vitiligo, oral supplementation with folic acid (10 mg per day) and vitamin B12 (2,000 mcg per day), combined with sun exposure, resulted in some repigmentation after three to six months in about half of the participants.¹⁵² This combined regimen was more effective than either vitamin supplementation or sun exposure alone.