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Nutritional Supplement

Vitamin B12

  • Pain Management

    Migraine Headache

    In a preliminary trial, vitamin B12 reduced the frequency of migraine attacks by at least 50% in 10 of 19 people with recurrent migraines.
    Migraine Headache
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    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.

    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
    ×
     

    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.

    Pain

    Vitamin B12 appears to have pain-killing properties. In people with vertebral pain syndromes, injections of massive amounts of vitamin B12 have reportedly relieved pain.
    Pain
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    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.

    Shingles and Postherpetic Neuralgia

    Vitamin B12 injections may relieve the symptoms of postherpetic neuralgia.
    Shingles and Postherpetic Neuralgia
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    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.

  • 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,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.

    Atherosclerosis

    Blood levels of the amino acid homocysteine have been linked to atherosclerosis and heart disease in most research. Taking vitamin B12 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,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

    Heart Attack

    Taking vitamin B12 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,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 acid38,39 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.

    Stroke and High Homocysteine

    Elevated blood levels of homocysteine have been linked to stroke risk in most studies. Supplementing with vitamin B12 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.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

  • 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
    ×

    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 

    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.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

    Age-Related Cognitive Decline

    In a double-blind trial, supplementing with vitamin B12 and folic acid for 2 years slowed the rate of cognitive decline, compared with placebo, in elderly volunteers.
    Age-Related Cognitive Decline
    ×
    In a double-blind trial, supplementation with 100 mcg per day of vitamin B12 and 400 mcg per day of folic acid for 2 years slowed the rate of cognitive decline, compared with placebo, in elderly volunteers.52

    Age-Related Cognitive Decline and Vitamin B12 Deficiency

    Improved brain function among seniors has been observed after correcting vitamin B12 deficiency with injections, but oral vitamin B12 has not been studied for ARCD. People with ARCD should be tested for vitamin B12 deficiency.
    Age-Related Cognitive Decline and Vitamin B12 Deficiency
    ×
     

    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.53 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.54

    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.

    Alzheimer’s Disease

    Some researchers feel Alzheimer’s disease may be related to vitamin B12 deficiency.
    Alzheimer’s Disease
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    Some researchers have found an association between Alzheimer’s disease and deficiencies of vitamin B12 and folic acid;55,56 however, other researchers consider such deficiencies to be of only minor importance.57 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.58 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.

  • Brain Health

    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.59

    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.60

    Age-Related Cognitive Decline

    In a double-blind trial, supplementing with vitamin B12 and folic acid for 2 years slowed the rate of cognitive decline, compared with placebo, in elderly volunteers.
    Age-Related Cognitive Decline
    ×
    In a double-blind trial, supplementation with 100 mcg per day of vitamin B12 and 400 mcg per day of folic acid for 2 years slowed the rate of cognitive decline, compared with placebo, in elderly volunteers.61

    Age-Related Cognitive Decline and Vitamin B12 Deficiency

    Improved brain function among seniors has been observed after correcting vitamin B12 deficiency with injections, but oral vitamin B12 has not been studied for ARCD. People with ARCD should be tested for vitamin B12 deficiency.
    Age-Related Cognitive Decline and Vitamin B12 Deficiency
    ×
     

    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.62 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.63

    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.

    Bipolar Disorder

    Vitamin B12 deficiency has been associated with both mania and depression. In one study, these symptoms cleared after treatment with B12 injections.
    Bipolar Disorder
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    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.64,65 There is some evidence that patients diagnosed with mania are also more likely to have folate deficiencies than healthy controls.66 Other studies, however, have found that folic acid deficiency was not more common in bipolar patients taking lithium than in healthy people.67,68,69 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.70,68 Not all studies have confirmed these findings, however.69 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.73

    There have been case reports of both mania and depression associated with vitamin B12 deficiency, and these symptoms cleared after treatment with injections of B12.74,75 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.

    Schizophrenia

    People with schizophrenia may have low vitamin B12 levels. Supplementing with the vitamin may correct an imbalance and improve symptoms.
    Schizophrenia
    ×
     

    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 B12.74 Some studies have reported finding lower levels of vitamin B12 in people with schizophrenia than in the general population,74 but others have found no difference.76 No trials of vitamin B12 supplementation in schizophrenic patients have been published.

  • 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
    ×
     

    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,76 as well as reducing the amount of anti-inflammatory medications needed to control back pain, according to double-blind trials.77 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.78,79 Such high amounts of vitamin B6 require supervision by a doctor.

    Bursitis

    Vitamin B12 injections have been shown to relieve symptoms of acute shoulder bursitis and decrease the amount of calcification in some cases.
    Bursitis
    ×

    In a preliminary study, intramuscular injections of vitamin B1280,81 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.

  • 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.82 

    Retinopathy

    In one study, adding vitamin B12 to the insulin injections of children with diabetic retinopathy helped relieve symptoms.
    Retinopathy
    ×
     

    One study investigated the effect of adding 100 mcg per day of vitamin B12 to the insulin injections of 15 children with diabetic retinopathy.83 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.

  • Digestive Support

    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
    ×
    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.84 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.85

    Indigestion and Vitamin B12 Deficiency, Delayed Gastric Emptying, and Helicobacter Pylori Infection

    Vitamin B12 may be beneficial for people with delayed emptying of the stomach in association with Helicobacter pylori infection and low blood levels of vitamin B12.
    Indigestion and Vitamin B12 Deficiency, Delayed Gastric Emptying, and Helicobacter Pylori Infection
    ×
     

    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.86

    Crohn’s Disease

    Vitamin B12 is needed to repair intestinal cells damaged by Crohn’s disease. Supplementation may offset some of the deficiency caused by Crohn’s-related malabsorption.
    Crohn’s Disease
    ×
     

    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.87,88,89 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.

  • Kidney and Urinary Tract Health

    Urinary Incontinence

    Vitamin B12 deficency can cause urinary incontinence that may be corrected with supplementation.
    Urinary Incontinence
    ×
    Vitamin B12 deficency can cause urinary incontinence that can be cured with B12 supplementation.90 One preliminary study,91 but not others,92,93 have found that low blood levels of B12 were associated with urinary incontinence in older people. Controlled trials are needed to determine whether B12 supplementation might be useful as a treatment for the common types of urinary incontinence.
  • Bone Support

    Osteoporosis and High Homocysteine

    Homocystinuria, a condition associated with high homocysteine levels, frequently causes osteoporosis. By lowering homocysteine levels, vitamin B12 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.94 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.95 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.96 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.
  • Energy Support

    Chronic Fatigue Syndrome

    Vitamin B12 deficiency may cause fatigue, but B12 injections have been reported benefits even without deficiency. A doctor should evaluate deficiency and whether B12 injections may help.
    Chronic Fatigue Syndrome
    ×
     

    Vitamin B12 deficiency may cause fatigue. However, some reports,97 even double-blind ones,98 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.99 Nonetheless, some doctors have continued to take the limited scientific support for B12 seriously.100 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.101 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.

  • Men's Health

    Male Infertility

    Vitamin B12 is needed to maintain fertility. Vitamin B12 injections have been shown to increase sperm counts. Men
    Male Infertility
    ×
     

    Vitamin B12 is needed to maintain fertility. Vitamin B12 injections have increased sperm counts for men with low numbers of sperm.102 These results have been duplicated in double-blind research.103 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.104 However, controlled trials are needed to confirm these preliminary results. Men seeking vitamin B12 injections should consult a physician.

  • Immune System Support

    Immune Function

    A deficiency of vitamin B12 has been associated with decreased immune function. Restoring vitamin B12 levels may improve levels of immune cells.
    Immune Function
    ×
    A deficiency of vitamin B12 has been associated with decreased immune function. In a controlled trial, people with vitamin B12 deficiency anemia were also found to have markedly decreased levels of white blood cells associated with immune function.105 Restoration of vitamin B12 stores by means of injections improved levels of these immune cells, suggesting an important role for vitamin B12 in immune function.

    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.106 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.107 However, no research has explored any other benefits of B vitamin supplementation in surgery patients.

    HIV and AIDS Support

    In HIV-positive people with B-vitamin deficiency, B vitamins appear to delay progression to and death from AIDS.
    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.108 Thiamine (vitamin B1) deficiency has been identified in nearly one-quarter of people with AIDS.109 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.110 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.111 Low blood levels of folic acid and vitamin B12 are also common in HIV-positive people.112

  • Allergy and Lung Support

    Asthma

    In some people, asthma symptoms can be triggered by ingesting sulfites, a food additive. Pretreatment with a large amount of vitamin B12 reduced some children’s asthmatic reaction to sulfites in one trial.
    Asthma
    ×
     

    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.113 The trace mineral molybdenum also helps the body detoxify sulfites.114 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,115 and preliminary short-term trials have used supplemental amounts of 500 mcg per day.116 People who suspect sulfite-sensitive asthma should consult with a physician before taking molybdenum.

    Hives

    Vitamin B12 injections have been reported to reduce the severity of acute hives and the frequency and severity of outbreaks in chronic cases.
    Hives
    ×
     

    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.117,118 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.119 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.

  • Sleep Support

    Insomnia

    In two small preliminary trials, people with insomnia resulting from disorders of the sleep-wake rhythm improved after supplementing with vitamin B12.
    Insomnia
    ×
     

    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).120,121

  • Blood Sugar and Diabetes Support

    Type 1 Diabetes

    Supplementing with vitamin B12 may improve symptoms of diabetic neuropathy.
    Type 1 Diabetes
    ×
    Vitamin B12, or cobalamin, is needed for normal functioning of nerve cells and is also involved in homocysteine metabolism. People with type 1 diabetes have an increased risk of other disorders that can affect their B12 status, such as autoimmune gastritis, celiac disease, and pernicious anemia.122 Vitamin B12, taken at a dose of 1,500 micrograms per day for 24 weeks, has been found to reduce symptoms and disability due to diabetic nerve damage (neuropathy).123 In a preliminary trial that included 544 participants with diabetic neuropathy, supplementing with vitamin B12 (in the form of methylcobalamin) along with folic acid (in the form of methylfolate) and vitamin B6 (in the form of pyridoxal-5-phosphate) for 12 weeks was associated with a 35% drop in symptom scores and a 32% drop in pain scores.124 A comparison trial in 100 subjects with diabetic neuropathy found injections of B12 were more effective than the commonly used pain medication, nortriptyline, for treating symptoms of diabetic neuropathy.125 A number of other studies have shown B12, alone and in combination with other treatments such as alpha-lipoic acid and prostaglandin E1, can be beneficial in those with diabetic neuropathy.126,127 Oral vitamin B12 up to 1,500 micrograms per day is recommended by some practitioners.

    Type 2 Diabetes and Diabetic Neuropathy

    Vitamin B12 deficiency is common in people being treated medically for type 2 diabetes. Supplementation can restore healthy levels and prevent dangerous long-term consequences of B12 deficiency.
    Type 2 Diabetes and Diabetic Neuropathy
    ×
    Multiple studies have reported finding an association between long-term metformin use in people with type 2 diabetes and vitamin B12 deficiency.128,129,130,131 Although this metformin-associated B12 deficiency does not appear to be linked to diabetic neuropathy (nerve dysfunction), it is nonetheless important to restore normal B12 status to avoid complications of B12 deficiency such as anemia, immune dysfunction, and neurological disorders.128,133

    Type 2 Diabetes and Diabetic Neuropathy

    Taking vitamin B1 combined with vitamin B12 may improve symptoms of diabetic neuropathy.
    Type 2 Diabetes and Diabetic Neuropathy
    ×
    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.133 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.134 As a result, some doctors recommend that people with diabetic neuropathy supplement with vitamin B1, though the optimal level of intake remains unknown.

    Retinopathy

    In one study, adding vitamin B12 to the insulin injections of children with diabetic retinopathy helped relieve symptoms.
    Retinopathy
    ×
     

    One study investigated the effect of adding 100 mcg per day of vitamin B12 to the insulin injections of 15 children with diabetic retinopathy.135 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.

  • Oral Health

    Canker Sores

    Recurrent canker sores might be related to vitamin B12 deficiency, but research has shown that even without deficiency supplementing this vitamin may be beneficial.
    Canker Sores
    ×

    Several preliminary studies,136,137,138,139 though not all,140 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.141,142,143 In addition, a double-blind study found that supplementing with vitamin B12 prevented recurrences even in people who were not deficient in the vitamin.144 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.145 Thiamine (B1) deficiency specifically has been linked to an increased risk of canker sores.146 The right supplemental level of iron requires diagnosis of an iron deficiency by a healthcare professional using lab tests.

  • Ear Health Support

    Tinnitus

    Vitamin B12 injections may help reduce the severity of tinnitus in people who are deficient in the vitamin.
    Tinnitus
    ×
     

    People exposed to loud noise on the job who develop tinnitus are commonly deficient in Vitamin B12.147 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.

  • Stress and Mood Management

    Depression and Vitamin B12 Deficiency

    Taking vitamin B12 can help counteract deficiencies related to depression.
    Depression and Vitamin B12 Deficiency
    ×
     

    Deficiency of vitamin B12 can create disturbances in mood that respond to B12 supplementation.148 Significant vitamin B12 deficiency is associated with a doubled risk of severe depression, according to a study of physically disabled older women.149 Depression caused by vitamin B12 deficiency can occur even if there is no B12 deficiency-related anemia.150

    Mood has been reported to sometimes improve with high amounts of vitamin B12 (given by injection), even in the absence of a B12 deficiency.151 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.

    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
    ×
    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.152 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.
  • Skin Protection

    Vitiligo

    Studies have shown vitamin B12 to be effective at skin repigmentation in people with vitiligo.
    Vitiligo
    ×
     

    A clinical report describes the use of vitamin supplements in the treatment of vitiligo.153Folic 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.154 This combined regimen was more effective than either vitamin supplementation or sun exposure alone.

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. van der Kuy PHM, Merkus FWHM, Lohman JJHM, ter Berg JWM, Hooymans PM. Hydroxocobalamin, a nitric oxide scavenger, in the prophylaxis of migraine: an open, pilot study. Cephalalgia 2002;22:513-9.

2. Schwieger G, Karl H, Schonhaber E. Relapse prevention of painful vertebral syndromes in follow-up treatment with a combination of vitamins B1, B6, and B12. Ann NY Acad Sci 1990;585:54-62.

3. Kuhlwein A, Meyer HJ, Koehler CO. Reduced diclofenac administration by B vitamins: results of a randomized double-blind study with reduced daily doses of diclofenac (75 mg diclofenac versus 75 mg diclofenac plus B vitamins) in acute lumbar vertebral syndromes. Klin Wochenschr 1990;68:107-15 [in German].

4. Bruggemann G, Koehler CO, Koch EM. Results of a double-blind study of diclofenac + vitamin B1, B6, B12 versus diclofenac in patients with acute pain of the lumbar vertebrae. A multicenter study. Klin Wochenschr 1990;68:116-20 [in German].

5. Vetter G, Bruggemann G, Lettko M, et al. Shortening diclofenac therapy by B vitamins. Results of a randomized double-blind study, diclofenac 50 mg versus diclofenac 50 mg plus B vitamins, in painful spinal diseases with degenerative changes. Z Rheumatol 1988;47:351-62 [in German].

6. Hanck A, Weiser H. Analgesic and anti-inflammatory properties of vitamins. Int J Vitam Nutr Res Suppl 1985;27:189-206.

7. Hieber H. Treatment of vertebragenous pain and sensitivity disorders using high doses of hydroxocobalamin. Med Monatsschr 1974;28:545-8 [in German].

8. Schiller F. Herpes zoster: review, with preliminary report on new method for treatment of postherpetic neuralgia. J Am Geriatr Soc 1954;2:726-35.

9. Heyblon R. Vitamin B12 in herpes zoster. JAMA 1951;146:1338 (abstract).

10. 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.

11. 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.

12. 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.

13. 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.

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

15. 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.

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

17. 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.

18. 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.

19. 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.

20. 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.

21. 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.

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

23. 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.

24. 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.

25. 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.

26. 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].

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

28. 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.

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

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

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

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

33. 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.

34. 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.

35. 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.

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

37. 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.

38. 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.

39. 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.

40. 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.

41. 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.

42. 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.

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

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

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

46. 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.

47. 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].

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

49. Christen WG, Glynn RJ, Chew EY, et al. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women's Antioxidant and Folic Acid Cardiovascular Study. Arch Intern Med 2009;169:335-41.

50. Kang JH, Cook N, Manson J, Buring JE, Albert CM, Grodstein F. A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease. Am J Clin Nutr 2008;88:1602-10.)

51. Smith AD, Smith SM, de Jager CA, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One 2010;5(9):e12244.

52. Walker JG, Batterham PJ, Mackinnon AJ, et al. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms - the Beyond Ageing Project: a randomized controlled trial. Am J Clin Nutr 2012;95:194-203.

53. Martin DC, Francis J, Protetch J, Huff FJ. Time dependency of cognitive recovery with cobalamin replacement: report of a pilot study. J Am Geriatr Soc 1992;40(2):168-72.

54. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988;318:1720-8.

55. Clarke R, Smith D, Jobst KA, et al. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol 1998;55:1449-55.

56. Snowdon DA, Tully CL, Smith CD, et al. Serum folate and the severity of atrophy of the neocortex in Alzheimer disease: findings from the Nun study. Am J Clin Nutr 2000;71:993-8.

57. Joosten E, Lesaffre E, Riezler R, et al. Is metabolic evidence for vitamin B-12 and folate deficiency more frequent in elderly patients with Alzheimer's disease? J Gastroenterol 1997;52A:M76-M79.

58. Ebly EM, Schaefer JP, Campbell NR, Hogan DB. Folate status, vascular disease and cognition in elderly Canadians. Age Ageing 1998;27:485-91.

59. Kang JH, Cook N, Manson J, Buring JE, Albert CM, Grodstein F. A trial of B vitamins and cognitive function among women at high risk of cardiovascular disease. Am J Clin Nutr 2008;88:1602-10.)

60. Smith AD, Smith SM, de Jager CA, et al. Homocysteine-lowering by B vitamins slows the rate of accelerated brain atrophy in mild cognitive impairment: a randomized controlled trial. PLoS One 2010;5(9):e12244.

61. Walker JG, Batterham PJ, Mackinnon AJ, et al. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms - the Beyond Ageing Project: a randomized controlled trial. Am J Clin Nutr 2012;95:194-203.

62. Martin DC, Francis J, Protetch J, Huff FJ. Time dependency of cognitive recovery with cobalamin replacement: report of a pilot study. J Am Geriatr Soc 1992;40(2):168-72.

63. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988;318:1720-8.

64. Botiglieri T. Folate, vitamin B12, and neuropsychiatric disorders. Nutr Rev 1996;54:382-90 [review].

65. Fine EJ, Soria ED. Myths about vitamin B12 deficiency. Southern Med J 1991;84:1475-81.

66. Hasanah CI, Khan UA, Musalmah M, Razali SM. Reduced red-cell folate in mania. J Affect Disord 1997;46:95-9.

67. McKeon P, Shelley R, O'Regan S, O'Broin J. Serum and red cell folate and affective morbidity in lithium prophylaxis. Acta Psychiatr Scand 1991;83:199-201.

68. Lee S, Chow CC, Shek CC, et al. Folate concentration in Chinese psychiatric outpatients on long-term lithium treatment. J Affect Disord 1992;24:265-70.

69. Stern SL, Brandt JT, Hurley RS, et al. Serum and red cell folate concentrations in outpatients receiving lithium carbonate. Int Clin Psychopharmacol 1988;3:49-52.

70. Coppen A, Abou-Saleh MT. Plasma folate and affective morbidity during long-term lithium therapy. Br J Psychiatry 1982;141:87-9.

71. Coppen A, Chaudrhy S, Swade C. Folic acid enhances lithium prophylaxis. J Affect Disord 1986;10:9-13.

72. Goggans FC. A case of mania secondary to vitamin B12 deficiency. Am J Psychiatry 1984;141:300-1.

73. Verbanck PM, LeBon O. Changing psychiatric symptoms in a patient with vitamin B12 deficiency. J Clin Psychiatry 1991;52:182-3 [letter].

74. Ko SM, Liu TC. Psychiatric syndromes in pernicious anaemia—a case report. Singapore Med J 1992;33:92-4.

75. Majumdar SK, Kakad PP. Serum vitamin B12 status in chronic schizophrenic patients. J Hum Nutr 1981;35:3 [letter].

76. Schwieger G, Karl H, Schonhaber E. Relapse prevention of painful vertebral syndromes in follow-up treatment with a combination of vitamins B1, B6, and B12. Ann NY Acad Sci 1990;585:54-62.

77. Kuhlwein A, Meyer HJ, Koehler CO. Reduced diclofenac administration by B vitamins: results of a randomized double-blind study with reduced daily doses of diclofenac (75 mg diclofenac versus 75 mg diclofenac plus B vitamins) in acute lumbar vertebral syndromes. Klin Wochenschr 1990;68:107-15 [in German].

78. Bruggemann G, Koehler CO, Koch EM. Results of a double-blind study of diclofenac + vitamin B1, B6, B12 versus diclofenac in patients with acute pain of the lumbar vertebrae. A multicenter study. Klin Wochenschr 1990;68:116-20 [in German].

79. Vetter G, Bruggemann G, Lettko M, et al. Shortening diclofenac therapy by B vitamins. Results of a randomized double-blind study, diclofenac 50 mg versus diclofenac 50 mg plus B vitamins, in painful spinal diseases with degenerative changes. Z Rheumatol 1988;47:351-62 [in German].

80. Klemes IS. Vitamin B12 in acute subdeltoid bursitis. Indust Med Surg 1957;26:290-2.

81. Kellman M. Bursitis: a new chemotherapeutic approach. J Am Osteopathic Assoc 1962;61:896-903.

82. Christen WG, Glynn RJ, Chew EY, et al. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women's Antioxidant and Folic Acid Cardiovascular Study. Arch Intern Med 2009;169:335-41.

83. Kornerup T, Strom L. Vitamin B12 and retinopathy in juvenile diabetics. Acta Paediatr 1958:47:646-51.

84. 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.

85. 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.

86. Gumurdulu Y, Serin E, Ozer B, et al. The impact of B12 treatment on gastric emptying time in patients with Helicobacter pylori infection. J Clin Gastroenterol 2003;37:230-3.

87. Imes S, Plinchbeck BR, Dinwoodie A, et al. Iron, folate, vitamin B-12, zinc, and copper status in out-patients with Crohn's disease: effect of diet counseling. J Am Dietet Assoc 1987;87:928-30.

88. Sandstead HH. Zinc deficiency in Crohn's disease. Nutr Rev 1982;40:109-12.

89. Driscoll RH Jr, Meredith SC, Sitrin M, et al. Vitamin D deficiency and bone disease in patients with Crohn's disease. Gastroenterology 1982;83:1252-8.

90. Healton EB, Savage DG, Brust JC, et al. Neurologic aspects of cobalamin deficiency. Medicine (Baltimore) 1991;70:229-45.

91. Rana S, D'Amico F, Merenstein JH. Relationship of vitamin B12 deficiency with incontinence in older people. J Am Geriatr Soc 1998;46:931-2.

92. Garcia A, Smith M, Freedman M. Vitamin B12 deficiency and incontinence in older people. Can J Urol 2000;7:1077-80.

93. Endo JO, Chen S, Potter JF, et al. Vitamin B(12) deficiency and incontinence: is there an association? J Gerontol A Biol Sci Med Sci 2002;57:M583-7.

94. Gaby AR. Preventing and Reversing Osteoporosis. Rocklin, CA: Prima Publishing, 1994, 88-9 [review].

95. Sato Y, Honda Y, Iwamoto J, et al. Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. JAMA 2005;293:1082-8.

96. Sawka AM, Ray JG, Yi Q, et al. Randomized clinical trial of homocysteine level lowering therapy and fractures. Arch Intern Med 2007;167:2136-9.

97. Kaufman W. The use of vitamin therapy to reverse certain concomitants of aging. J Am Geriatr Soc 1955;3:927-36.

98. Ellis FR, Nasser S. A pilot study of vitamin B12 in the treatment of tiredness. Br J Nutr 1973;30:277-83.

99. Lawhorne L, Rindgahl D. Cyanocobalamin injections for patients without documented deficiency. JAMA 1989;261:1920-3.

100. Gaby AR. Literature Review & Commentary. Townsend Letter for Doctors & Patients 1997;Feb/Mar:27 [review].

101. Lapp CW, Cheney PR. The rationale for using high-dose cobalamin (vitamin B12). CFIDS Chronicle Physicians' Forum 1993;Fall:19-20.

102. Sandler B, Faragher B. Treatment of oligospermia with vitamin B12. Infertility 1984;7:133-8.

103. Kumamoto Y, Maruta H, Ishigami J, et al. Clinical efficacy of mecobalamin in treatment of oligozoospermia. Acta Urol Jpn 1988;34:1109-32.

104. Isoyama R, Baba Y, Harada H, et al. Clinical experience of methyl-cobalamin (CH3-B12)/clomiphene citrate combined treatment in male infertility. Hinyokika Kiyo 1986;32:1177-83 [in Japanese].

105. Tamura J, Kubota K, Murakami H, et al. Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment. Clin Exp Immunol 1999;116:28-32.

106. Vinogradov VV, Tarasov IuA, Tishin VS, et al. Thiamin prevention of the corticosteroid reaction after surgery. Probl Endokrinol (Mosk) 1981;27:11-6 [in Russian].

107. Lettko M, Meuer S. Vitamin B-induced prevention of stress-related immunosuppression. Ann NY Acad Sci 1990;585:513-5.

108. Kanter AS, Spencer DC, Steinberg MH, et al. Supplemental vitamin B and progression to AIDS and death in black South African patients infected with HIV. J Acquir Immune Defic Syndr 1999;21:252-3 [letter].

109. Butterworth RF, Gaudreau C, Vincelette J, et al. Thiamine deficiency in AIDS. Lancet 1991;338:1086.

110. Baum MK, Mantero-Atienza E, Shor-Posner G, et al. Association of vitamin B6 status with parameters of immune function in early HIV-1 infection. J Acquir Immune Defic Syndr 1991;4:1122-32.

111. Tang AM, Graham NMH, Saah AJ. Effects of micronutrient intake on survival in human immunodeficiency type 1 infection. Am J Epidemiol 1996;143:1244-56.

112. Boudes P, Zittoun J, Sobel A. Folate, vitamin B12, and HIV infection. Lancet 1990;335:1401-2.

113. Anibarro B, Caballero T, Garcia-Ara C, et al. Asthma with sulfite intolerance in children: A blocking study with cyanocobalamin. J Allergy Clin Immunol 1992;90:103-9.

114. Johnson JL, Wuebbens MM, Mandell R, Shih VE. Molybdenum cofactor deficiency in a patient previously characterized as deficient in sulfite oxidase. Biochem Med Metabol Biol 1988;40:86-93.

115. Sardesai VM. Molybdenum: an essential trace element. Nutr Clin Pract 1993;8:277-81.

116. Moss M. Effects of molybdenum on pain and general health: a pilot study. J Nutr Environ Med 1995;5:55-61.

117. Simon SW. Vitamin B12 therapy in allergy and chronic dermatoses. J Allergy 1951;22:183-5.

118. Simon SW, Edmonds P. Cyanocobalamin (B12): comparison of aqueous and repository preparations in urticaria; possible mode of action. J Am Geriatr Soc 1964;12:79-85.

119. Meyer de Schmid JJ, Zeller J. Urticaria due to vitamin B 12 allergy verified by the lymphoblastic transformation test. Bull Soc Fr Dermatol Syphiligr 1969;76:670-1 [in French].

120. Okawa M, Mishima K, Nanami T, et al. Vitamin B12 treatment for sleep-wake rhythm disorders. Sleep 1990;13:15-23.

121. Ohta T, Ando K, Hayakawa T, et al. Treatment of persistent sleep-wake schedule disorders in adolescents and vitamin B12. Jpn J Psychiatr Neurol 1991;45:167-8.

122. Angelousi A, Larger E. Anaemia, a common but often unrecognized risk in diabetic patients: a review. Diabetes Metab 2015;41:18–27.

123. Li S, Chen X, Li Q, et al. Effects of acetyl-L-carnitine and methylcobalamin for diabetic peripheral neuropathy: A multicenter, randomized, double-blind, controlled trial. J Diabetes Investig 2016;7:777–85.

124. Trippe B, Barrentine L, Curole M, Tipa E. Nutritional management of patients with diabetic peripheral neuropathy with L-methylfolate-methylcobalamin-pyridoxal-5-phosphate: results of a real-world patient experience trial. Curr Med Res Opin 2016;32:219–27.

125. Talaei A, Siavash M, Majidi H, Chehrei A. Vitamin B12 may be more effective than nortriptyline in improving painful diabetic neuropathy. Int J Food Sci Nutr 2009;60:71–6.

126. Xu Q, Pan J, Yu J, et al. Meta-analysis of methylcobalamin alone and in combination with lipoic acid in patients with diabetic peripheral neuropathy. Diabetes Res Clin Pract 2013;101:99–105.

127. Jiang D, Zhao S, Li M, et al. Prostaglandin E1 plus methylcobalamin combination therapy versus prostaglandin E1 monotherapy for patients with diabetic peripheral neuropathy: A meta-analysis of randomized controlled trials. Medicine (Baltimore) 2018;97:e13020.

128. Hasan N, Makki M, Abid I, Abid Butt M. Association Of Vitamin B12 Deficiency With Intake Of Oral Metformin In Diabetic Patients. J Ayub Med Coll Abbottabad 2019;31:72–5.

129. Tavares Bello C, Capitao R, Sequeira Duarte J, et al. Vitamin B12 Deficiency in Type 2 Diabetes Mellitus. Acta Med Port 2017;30:719–26.

130. Owhin S, Adaja T, Fasipe O, et al. Prevalence of vitamin B12 deficiency among metformin-treated type 2 diabetic patients in a tertiary institution, South-South Nigeria. SAGE Open Med 2019;7:2050312119853433.

131. Out M, Kooy A, Lehert P, et al. Long-term treatment with metformin in type 2 diabetes and methylmalonic acid: Post hoc analysis of a randomized controlled 4.3-year trial. J Diabetes Complications 2018;32:171–8.

132. Olt S, Oznas O. Investigation of the vitamin B12 deficiency with peripheral neuropathy in patients with type 2 diabetes mellitus treated using metformin. North Clin Istanb 2017;4:233–6.

133. Abbas ZG, Swai ABM. Evaluation of the efficacy of thiamine and pyridoxine in the treatment of symptomatic diabetic peripheral neuropathy. East African Med J 1997;74:804-8.

134. Stracke H, Lindemann A, Federlin K. A benfotiamine-vitamin B combination in treatment of diabetic polyneuropathy. Exp Clin Endocrinol Diabetes 1996;104:311-6.

135. Kornerup T, Strom L. Vitamin B12 and retinopathy in juvenile diabetics. Acta Paediatr 1958:47:646-51.

136. Porter SR, Scully C, Flint S. Hematologic status in recurrent aphthous stomatitis compared to other oral disease. Oral Surg Oral Med Oral Pathol 1988;66:41-4.

137. Palopoli J, Waxman J. Recurrent aphthous stomatitis and vitamin B12 deficiency. South Med J 1990;83:475-7.

138. Wray D, Ferguson MM, Hutcheon WA, Dagg JH. Nutritional deficiencies in recurrent aphthae. J Oral Pathol 1978;7:418-23.

139. Barnadas MA, Remacha A, Condomines J, de Moragas JM. [Hematologic deficiencies in patients with recurrent oral aphthae]. Med Clin (Barc) 1997;109:85-7 [in Spanish].

140. Olson JA, Feinberg I, Silverman S, et al. Serum vitamin B12, folate, and iron levels in recurrent aphthous ulceration. Oral Surg Oral Med Oral Pathol 1982;54:517-20.

141. Weusten BL, van de Wiel A. Aphthous ulcers and vitamin B12 deficiency. Neth J Med 1998;53:172-5.

142. Porter S, Flint S, Scully C, Keith O. Recurrent aphthous stomatitis: the efficacy of replacement therapy in patients with underlying hematinic deficiencies. Ann Dent 1992;51:14-6.

143. Wray D, Ferguson MM, Mason DK, et al. Recurrent aphthae: treatment with vitamin B12, folic acid, and iron. Br Med J 1975;2(5969):490-3.

144. Volkov I, Rudoy I, Freud T, et al. Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: a randomized, double-blind, placebo-controlled trial.J Am Board Fam Med 2009;22:9-16.

145. Nolan A, McIntosh WB, Allam BF, Lamey PJ. Recurrent aphthous ulceration: vitamin B1, B2 and B6 status and response to replacement therapy. J Oral Pathol Med 1991;20:389-91.

146. Haisraeli-Shalish M, Livneh A, Katz J, et al. Recurrent aphthous stomatitis and thiamine deficiency. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1996;82:634-6.

147. Shemesh Z, Attias J, Ornan M, et al. Vitamin B12 deficiency in patients with chronic tinnitus and noise-induced hearing loss. Am J Otolaryngol 1993;14:94-9.

148. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988;318:1720-8.

149. Penninx BW, Guralnik JM, Ferrucci L, et al. Vitamin B(12) deficiency and depression in physically disabled older women: epidemiologic evidence from the Women's Health and Aging Study. Am J Psychiatry 2000;157:715-21.

150. Holmes JM. Cerebral manifestations of vitamin B12 deficiency. J Nutr Med 1991;2:89-90.

151. Ellis FR, Nasser S. A pilot study of vitamin B12 in the treatment of tiredness. Br J Nutr 1973;30:277-83.

152. Levine J, Stahl Z, Sela BA, et al. Homocysteine-reducing strategies improve symptoms in chronic schizophrenic patients with hyperhomocysteinemia. Biol Psychiatry 2006;60:265-9.

153. Montes LF, Diaz ML, Lajous J, Garcia NJ. Folic acid and vitamin B12 in vitiligo: a nutritional approach. Cutis 1992;50:39-42.

154. Juhlin L, Olsson MJ. Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure. Acta Derm Venereol 1997;77:460-2.

155. Rauma AL, Torronsen R, Hanninen O, Mykkanen H. Vitamin B12 status of long term adherents of a strict uncooked vegan diet (“living food diet”) is compromised. J Nutr 1995;125:2511-5.

156. Takenaka S, Sugiyama S, Ebara S, et al. Feeding dried purple laver (nori) to vitamin B12-deficient rats significantly improves vitamin B12 status. Br J Nutr 2001;85:699-703.

157. Gaby, AR. Nutritional Medicine. Concord, NH: Fritz Perlberg Publishing, 2011.

158. Goldberg TH. Oral vitamin B12 supplementation for elderly patients with B12 deficiency. J Am Geriatr Soc 1995;43:SA73 [abstr #P258].

159. Lederle FA. Oral cobalamin for pernicious anemia. Medicine's best kept secret? JAMA 1991;265(1):94-5.

160. Kondo H. Haematological effects of oral cobalamin preparations on patients with megaloblastic anemia. Acta Haematol 1998;99:200-5.

161. Waif SO, Jansen CJ, Crabtree RE, et al. Oral vitamin B12 without intrinsic factor in the treatment of pernicious anemia. Ann Intern Med 1963;58:810-7.

162. Crosby WH. Oral cyanocobalamin without intrinsic factor for pernicious anemia. Arch Intern Med 1980;140:1582.

163. Kaufman W. The use of vitamin therapy to reverse certain concomitants of aging. J Am Geriatr Soc 1955;3:927-36.

164. Lindenbaum J, Rosenberg IH, Wilson PWF, et al. Prevalence of cobalamin deficiency in the Framingham elderly population. Am J Clin Nutr 1994;60:2-11.

165. Verhaeverbeke I, Mets T, Mulkens K, Vandewoulde M. Normalization of low vitamin B12 serum levels in older people by oral treatment. J Am Geriatr Soc 1997;45:124-5 [letter].

166. Eussen SJ, de Groot LC, Clarke R, et al. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency: a dose-finding trial. Arch Intern Med 2005;165:1167-72.

167. Delpre G, Stark P, Niv Y. Sublingual therapy for cobalamin deficiency as an alternative to oral and parenteral cobalamin supplementation. Lancet 1999;354:740-1. [letter]

168. Snow CF. Laboratory diagnosis of vitamin B12 and folate deficiency. A Guide for the primary care physician. Arch Intern Med 1999;159:1289-98 [review].

169. Rana S, D'Amico F, Merenstein JH. Relationship of vitamin B12 deficiency with incontinence in older people. J Am Geriatr Soc 1998;46:931-2.

170. Houston DK, Johnson MA, Nozza RJ, et al. Age-related hearing loss, vitamin B-12, and folate in elderly women. Am J Clin Nutr 1999;69:564-71.

171. Kaptan K, Beyan C, Ural AU, et al. Helicobacter pylori—is it a novel causative agent in Vitamin B12 deficiency? Arch Intern Med 2000;160:1349-53.

172. Perez-Perez GI. Role of Helicobacter pylori infection in the development of pernicious anemia. Clin Infect Dis 1997;25:1020-2 [review].

173. Fong TL, Dooley CP, Dehesa M, et al. Helicobacter pylori infection in pernicious anemia: a prospective controlled study. Gastroenterology 1991;100:328-32.

174. Shemesh Z, Attias J, Ornan M, et al. Vitamin B12 deficiency in patients with chronic tinnitus and noise-induced hearing loss. Am J Otolaryngol 1993;14:94-9.

175. Remacha AF, Cadafalch J. Cobalamin deficiency in patients infected with the human immunodeficiency virus. Semin Hematol 1999;36:75-87.

176. Lindenbaum J, Healton EB, Savage DG, et al. Neuropsychiatric disorders caused by cobalamin deficiency in the absence of anemia or macrocytosis. N Engl J Med 1988;318:1720-8.

177. Penninx BW, Guralnik JM, Ferrucci L, et al. Vitamin B(12) deficiency and depression in physically disabled older women: epidemiologic evidence from the Women's Health and Aging Study. Am J Psychiatry 2000;157:715-21.

178. Wu K, Helzlsouer KJ, Comstock GW, et al. A prospective study on folate, B12, and pyridoxal 5'-phosphate (B6) and breast cancer. Cancer Epidemiol Biomarkers Prev 1999;8:209-17.

179. Kanazawa S, Herbert V. Total corrinoid, cobalamin (vitamin B12), and cobalamin analogue levels may be normal in serum despite cobalamin in liver depletion in patients with alcoholism. Lab Invest 1985;53:108-10.

180. Cravo ML, Camilo ME. Hyperhomocysteinemia in chronic alcoholism: relations to folic acid and vitamins B(6) and B(12) status. Nutrition 2000;16:296-302 [review].

181. Pardo J, Peled Y, Bar J, et al. Evaluation of low serum vitamin B(12) in the non-anaemic pregnant patient. Hum Reprod 2000;15:224-6.

182. Sauer SW, Keim ME. Hydroxocobalamin: improved public health readiness for cyanide disasters. Ann Emerg Med 2001;37:635-41.

183. Snowden JA, Chan-Lam D, Thomas SE, Ng JP. Oral or parenteral therapy for vitamin B12 deficiency. Lancet 1999;353:411 [letter].

184. Hovding G. Anaphylactic reaction after injection of vitamin B12. Br Med J 1968;3:102.

185. Moloney FJ, Hughes R, O'Shea D, Kirby B. Type I immediate hypersensitivity reaction to cyanocobalamin but not hydroxycobalamin. Clin Exp Dermatol 2008;33:412-4.

186. House AA, Eliasziw M, Cattran DC, et al. Effect of B-vitamin therapy on progression of diabetic nephropathy. A randomized controlled trial. JAMA 2010;303:1603-9.

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The information presented by TraceGains is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2020.

Copyright © 2020 TraceGains, Inc. All rights reserved.

The information presented by TraceGains is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. Self-treatment is not recommended for life-threatening conditions that require medical treatment under a doctor's care. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or pharmacist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires December 2020.