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    Vitamin B12

    Vitamin B12

    Uses

    What Are Star Ratings?

    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.

    3 Stars Reliable and relatively consistent scientific data showing a substantial health benefit.

    2 Stars Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit.

    1 Star For an herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support.

    This supplement has been used in connection with the following health conditions:

    Used for Why
    3 Stars
    Anemia and Vitamin B12 Deficiency
    600 to 1,000 mcg daily
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    Deficiencies of iron , vitamin B12 , and folic acid are the most common nutritional causes of anemia.1 Although rare, severe deficiencies of several other vitamins and minerals, including vitamin A ,2 , 3 vitamin B2 ,4 vitamin B6 ,5 , 6 vitamin C ,7 and copper ,8 , 9 can also cause anemia by various mechanisms. Rare genetic disorders can cause anemias that may improve with large amounts of supplements such as vitamin B1 .10 , 11

    3 Stars
    Depression and Vitamin B12 Deficiency
    See a doctor for evaluation
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    Deficiency of vitamin B12 can create disturbances in mood that respond to B12 supplementation.12 Significant vitamin B12 deficiency is associated with a doubled risk of severe depression, according to a study of physically disabled older women.13 Depression caused by vitamin B12 deficiency can occur even if there is no B12 deficiency-related anemia.14

    Mood has been reported to sometimes improve with high amounts of vitamin B12 (given by injection), even in the absence of a B12 deficiency.15 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 .

    3 Stars
    High Homocysteine (Vitamin B6, Folic Acid)
    400 to 1,000 mcg of folic acid daily, 10 to 50 mg of vitamin B6 daily, and 50 to 300 mcg of vitamin B12 daily
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    dd
    3 Stars
    Vitamin B12 Deficiency
    Consult a qualified healthcare practitioner
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    Normally, only 3 to 4 mcg per day of vitamin B12 is required to prevent dietary deficiency. If gastrointestinal function is normal, even these small amounts of vitamin B12 from oral supplementation can prevent deficiency in vegans.16 If a deficiency already exists, most doctors will recommend an initial vitamin B12 injection, then oral amounts ranging from 500 mcg to 1,000 mcg per day until symptoms subside; this is followed by a maintenance level of approximately 10 mcg per day to prevent future deficiencies.

    In a person with true PA, initial B12 supplementation should begin with an injection given by a qualified healthcare professional. After blood abnormalities are reversed, maintenance supplementation can be successfully accomplished with oral vitamin B12 at 1,000 to 2,000 mcg (1 to 2 mg) per day and does not require further injections.17 In a person lacking intrinsic factor, only about 1% of this oral amount (10-20 mcg) will be absorbed, but that amount is more than sufficient to prevent future vitamin B12 deficiency.18 , 19 Many physicians are unaware of this well-researched option and thus unnecessarily recommend lifelong B12 injections.20

    2 Stars
    Age-Related Cognitive Decline (Folic Acid)
    100 mcg per day of vitamin B12 and 400 mcg per day of folic acid
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    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.21
    2 Stars
    Age-Related Cognitive Decline (Vitamin B6, Folic Acid)
    Refer to label instructions
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    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.22
    2 Stars
    Age-Related Cognitive Decline and Vitamin B12 Deficiency
    Consult a qualified healthcare practitioner
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    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.23 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.24

    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.

    2 Stars
    Bell's Palsy
    Consult a qualified healthcare practitioner
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    Vitamin B12 deficiency can cause nerve degeneration,25 and both oral26 and injected27 , 28 vitamin B12 have been used to treat many types of nerve disorders.29 One older case report described successful treatment of chronic Bell's palsy with vitamin B12 injections of 500 to 1,000 mcg given every one to two days.30 A more recent trial compared the effect of 500 mcg of injected vitamin B12 (in the form of methylcobalamin) given three times weekly for at least eight weeks-steroid medication, or both. Researchers found significantly faster recovery in the groups given B12 injections with or without steroids, compared to those given steroids alone.31 These findings agree with earlier reports on the effectiveness of methylcobalamin injections for Bell's palsy.32 , 33 It is unlikely that oral vitamin B12 would be similarly effective. People seeking B12 injections should consult a physician.

    2 Stars
    Celiac Disease (Vitamin B6, Folic Acid)
    3 mg vitamin B6, 0.8 mg folic acid, and 0.5 mg vitamin B12
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    In one trial, 11 people with celiac disease suffered from persistent depression despite being on a gluten-free diet for more than two years. However, after supplementation with vitamin B6 (80 mg per day) for six months, the depression disappeared.34 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.35
    2 Stars
    Chronic Fatigue Syndrome
    Consult a qualified healthcare practitioner
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    Vitamin B12 deficiency may cause fatigue. However, some reports,36 even double-blind ones,37 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.38 Nonetheless, some doctors have continued to take the limited scientific support for B12 seriously.39 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.40 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.

    2 Stars
    Indigestion and Vitamin B12 Deficiency, Delayed Gastric Emptying, and Helicobacter Pylori Infection
    1,000 mcg daily
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    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.42

    2 Stars
    Low Back Pain (Vitamin B1, Vitamin B6)
    Take under medical supervision: 50 to 100 mg each of vitamins B1 and B6, and 250 to 500 mcg of vitamin B12, all taken three times per day
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    A combination of vitamin B1 , vitamin B6 , and vitamin B12 has proved useful for preventing a relapse of a common type of back pain linked to vertebral syndromes,43 as well as reducing the amount of anti-inflammatory medications needed to control back pain, according to double-blind trials.44 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.45 , 46 Such high amounts of vitamin B6 require supervision by a doctor.

    2 Stars
    Macular Degeneration (Vitamin B6, Folic Acid)
    2.5 mg folic acid, 50 mg vitamin B6, and 1 mg vitamin B12
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    In a double-blind study of female health professionals who had cardiovascular disease or cardiovascular disease risk factors, daily supplementation with folic acid (2.5 mg), vitamin B6 (50 mg), and vitamin B12 (1 mg) for 7.3 years significantly decreased the incidence of age-related macular degeneration.47 

     

    2 Stars
    Male Infertility
    1,500 mcg daily
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    Vitamin B12 is needed to maintain fertility. Vitamin B12 injections have increased sperm counts for men with low numbers of sperm.48 These results have been duplicated in double-blind research.49 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.50 However, controlled trials are needed to confirm these preliminary results. Men seeking vitamin B12 injections should consult a physician.

    2 Stars
    Migraine Headache
    1 mg daily
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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.51 A placebo-controlled study is needed to determine how much of this improvement was due to a placebo effect.

    2 Stars
    Osteoporosis and High Homocysteine
    1,500 mcg with 5 mg of folic acid daily
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    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.52 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.53 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.54 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.
    2 Stars
    Schizophrenia and High Homocysteine (Vitamin B6, Folic Acid)
    Take folic acid (2 mg), vitamin B6 (25 mg), and vitamin B12 (400 mcg) daily
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    In another double-blind study, daily supplementation with  folic acid  (2 mg),  vitamin B6  (25 mg), and  vitamin B12  (400 mcg) for three months improved symptoms of schizophrenia compared with a placebo.55 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.
    2 Stars
    Sickle Cell Anemia and Vitamin B12 Deficiency
    Consult a qualified healthcare practitioner
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    Sickle cell anemia may result in vitamin B12 deficiency. A study of children with sickle cell anemia found them to have a higher incidence of vitamin B12 deficiency than children without the disease.56 A study of 85 adults with sickle cell anemia showed more of them had vitamin B12 deficiency than did a group of healthy people.57 A subsequent preliminary trial demonstrated that for patients with low blood levels of vitamin B12, intramuscular injections of 1 mg of vitamin B12 weekly for 12 weeks led to a significant reduction in symptoms.58 Researchers do not know whether people with sickle cell anemia who are found to be deficient in vitamin B12 would benefit equally from taking vitamin B12 supplements orally.

    Preliminary research has found that patients with sickle cell anemia are more likely to have elevated blood levels of homocysteine compared to healthy people.59 , 60 Elevated homocysteine is recognized as a risk factor for cardiovascular disease .61 In particular, high levels of homocysteine in sickle cell anemia patients have been associated with a higher incidence of stroke .62 Deficiencies of vitamin B6 , vitamin B12, and folic acid occur more frequently in people with sickle cell anemia than in others63 , 64 , 65 and are a cause of high homocysteine levels.66 A controlled trial found homocysteine levels were reduced 53% in children with sickle cell anemia receiving a 2-4 mg supplement of folic acid per day, depending on age, but vitamin B6 or B12 had no effect on homocysteine levels.67 A double-blind trial of children with sickle cell anemia found that children given 5 mg of folic acid per day had less painful swelling of the hands and feet compared with those receiving placebo, but blood abnormalities and impaired growth rate associated with sickle cell anemia were not improved.68 In the treatment of sickle cell anemia, folic acid is typically supplemented in amounts of 1,000 mcg daily.69 Anyone taking this amount of folic acid should have vitamin B12 status assessed by a healthcare professional.

    2 Stars
    Thalassemia and Vitamin B12 Deficiency
    If deficient: 300 to1,000 mcg daily
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    Test tube studies have shown that propionyl-L-carnitine (a form of L-carnitine ) protects red blood cells of people with thalassemia against free radical damage.70 In a preliminary study, children with beta thalassemia major who took 100 mg of L-carnitine per 2.2 pounds of body weight per day for three months had a significantly decreased need for blood transfusions.71 Some studies have found people with thalassemia to be frequently deficient in folic acid , vitamin B12 ,72 and zinc .73 , 74 Researchers have reported improved growth rates in zinc-deficient thalassemic children who were given zinc supplements of 22.5 to 90 mg per day, depending on age.75 , 76 Magnesium has been reported to be low in thalassemia patients in some,77 , 78 but not all,79 studies. A small, preliminary study reported that oral supplements of magnesium, 7.2 mg per 2.2 pounds of body weight per day, improved some red blood cell abnormalities in thalassemia patients.80

    2 Stars
    Type 2 Diabetes and Diabetic Neuropathy (Vitamin B1)
    Refer to label instructions
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    A controlled trial in Africa found that supplementing with both vitamin B1 (25 mg per day) and vitamin B6 (50 mg per day) led to significant improvement of symptoms of diabetic neuropathy after four weeks.81 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.82 As a result, some doctors recommend that people with diabetic neuropathy supplement with vitamin B1, though the optimal level of intake remains unknown.
    2 Stars
    Type 2 Diabetes and Diabetic Neuropathy
    Consult a qualified healthcare practitioner
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    Vitamin B12 is needed for normal functioning of nerve cells. Vitamin B12 taken orally has reduced symptoms of nerve damage caused by diabetes in 39% of people studied; when given both intravenously and orally, two-thirds of people improved.83 In a preliminary trial, people with nerve damage due to kidney disease or to diabetes plus kidney disease received intravenous injections of 500 mcg of methylcobalamin (the main form of vitamin B12 found in the blood) three times a day for six months in addition to kidney dialysis. Nerve pain was significantly reduced and nerve function significantly improved in those who received the injections.84 Oral vitamin B12 up to 500 mcg three times per day is recommended by some practitioners.
    2 Stars
    Urinary Incontinence (if deficient )
    See a doctor to test for deficiency
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    Vitamin B12 deficency can cause urinary incontinence that can be cured with B12 supplementation.85 One preliminary study,86 but not others,87 , 88 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.
    2 Stars
    Vitiligo
    Refer to label instructions
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    A clinical report describes the use of vitamin supplements in the treatment of vitiligo.89 Folic 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.90 This combined regimen was more effective than either vitamin supplementation or sun exposure alone.

    1 Star
    Alzheimer's Disease
    Refer to label instructions
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    Some researchers have found an association between Alzheimer's disease and deficiencies of vitamin B12 and folic acid ;91 , 92 however, other researchers consider such deficiencies to be of only minor importance.93 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.94 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.

    1 Star
    Asthma
    Refer to label instructions
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    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.95 The trace mineral molybdenum also helps the body detoxify sulfites.96 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,97 and preliminary short-term trials have used supplemental amounts of 500 mcg per day.98 People who suspect sulfite-sensitive asthma should consult with a physician before taking molybdenum.

    1 Star
    Atherosclerosis
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    Blood levels of an amino acid called homocysteine have been linked to atherosclerosis and heart disease in most research,99 , 100 though uncertainty remains about whether elevated homocysteine actually causes heart disease.101 , 102 Although some reports have found associations between homocysteine levels and dietary factors, such as coffee and protein intakes,103 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 homocysteine104 and supplementing with these vitamins lowers homocysteine levels.105 , 106

    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.107 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).108 Similar results were seen in another study.109

    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.110 Of these four supplements, folic acid appears to be the most important.111 Attempts to lower homocysteine by simply changing the diet rather than by using vitamin supplements have not been successful.112

    1 Star
    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.113 , 114 There is some evidence that patients diagnosed with mania are also more likely to have folate deficiencies than healthy controls.115 Other studies, however, have found that folic acid deficiency was not more common in bipolar patients taking lithium than in healthy people.116 , 117 , 118 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.119 , 120 Not all studies have confirmed these findings, however.121 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.122

    There have been case reports of both mania and depression associated with vitamin B12 deficiency, and these symptoms cleared after treatment with injections of B12.123 , 124 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.

    1 Star
    Bursitis
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    In a preliminary study, intramuscular injections of vitamin B12 125 , 126 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.

    1 Star
    Canker Sores
    3 to 1,000 mcg daily
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    Several preliminary studies,127 , 128 , 129 , 130 though not all,131 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.132 , 133 , 134 In addition, a double-blind study found that supplementing with vitamin B12 prevented recurrences even in people who were not deficient in the vitamin.135 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.136 Thiamine (B1) deficiency specifically has been linked to an increased risk of canker sores.137 The right supplemental level of iron requires diagnosis of an iron deficiency by a healthcare professional using lab tests.

    1 Star
    Crohn's Disease
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    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.138 , 139 , 140 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.

    1 Star
    Dermatitis Herpetiformis and Vitamin B12 Deficiency
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    People with DH frequently have mild malabsorption (difficulty absorbing certain nutrients) associated with low stomach acid (hypochlorhydria) and inflammation of the stomach lining (atrophic gastritis).141 Mild malabsorption may result in anemia 142 and nutritional deficiencies of iron , folic acid ,143 , 144 vitamin B12 ,145 , 146 and zinc .147 , 148 , 149 More severe malabsorption may result in loss of bone mass.150 Additional subtle deficiencies of vitamins and minerals are possible, but have not been investigated. Therefore, some doctors recommend people with DH have their nutritional status checked regularly with laboratory studies. These doctors may also recommend multivitamin-mineral supplements and, to correct the low stomach acid, supplemental betaine HCl (a source of hydrochloric acid).

    1 Star
    Down's Syndrome
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    The red blood cells of people with Down's syndrome are unusual in ways that suggest either vitamin B12 or folic acid deficiency.151 , 152 , 153 However, folic acid levels have been found to be normal in each of these studies, and only one study has found lower levels of vitamin B12 in Down's syndrome as compared with healthy individuals.154 Intervention trials using either vitamin B12 or folic acid have not been done.

    1 Star
    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,155 , 156 , 157 , 158 though not all,159 , 160 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.161 Folic acid 162 , 163 and vitamins B6 and B12 are known to lower homocysteine.164

    There is a clear association between low blood levels of folate and increased risk of heart attacks in men.165 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.

    1 Star
    Hepatitis
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    Vitamin B12 (with or without folic acid ) has been reported in trials from the 1950s to help some people with hepatitis.166 , 167 Vitamin B12 injections are likely to be more beneficial than oral administration, though 1,000 mcg (taken orally) each day can also be supplemented.

    1 Star
    HIV and AIDS Support
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    In HIV-positive people with B-vitamin deficiency, the use of B-complex vitamin supplements appears to delay progression to and death from AIDS.168 Thiamine ( vitamin B1 ) deficiency has been identified in nearly one-quarter of people with AIDS.169 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.170 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.171 Low blood levels of folic acid and vitamin B12 are also common in HIV-positive people.172

    1 Star
    Hives
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    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.173 , 174 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.175 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.

    1 Star
    Immune Function
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    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.176 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.
    1 Star
    Insomnia
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    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).177 , 178

    1 Star
    Lung Cancer
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    Folic acid and vitamin B12 work together in the body to help cells replicate normally. In a double-blind trial, smokers with precancerous changes in the lungs were given a placebo or the combination of 10,000 mcg of folic acid and 500 mcg of vitamin B12 per day for four months.179 A significant reversal of precancerous changes occurred in those given vitamin supplements compared with those given the placebo.180
    1 Star
    Pain
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    Vitamin B12 has exhibited pain-killing properties in animal studies.181 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.182 Further studies are needed to confirm the efficacy of this treatment.

    1 Star
    Phenylketonuria and Vitamin B12 Deficiency
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    People with PKU may be deficient in several nutrients, due to the restricted diet which is low in protein and animal fat. Deficiencies of long-chain polyunsaturated fatty acids (LC-PUFAs),183 , 184 , 185 selenium ,186 , 187 , 188 , 189 vitamin B12 ,190 and vitamin K may develop on this diet.191

    Vitamin B12 is found almost exclusively in foods of animal origin, which are restricted on the PKU diet. People on the PKU diet who are inconsistent in their use of a vitamin B12 supplement may become deficient in this vitamin. In a survey of young adults with PKU, 32% were found to have low or low-normal blood levels of vitamin B12.192 Vitamin B12 deficiency can cause anemia and nerve problems.

    1 Star
    Pre- and Post-Surgery Health
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    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.193 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.194 However, no research has explored any other benefits of B vitamin supplementation in surgery patients.

    1 Star
    Retinopathy
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    One study investigated the effect of adding 100 mcg per day of vitamin B12 to the insulin injections of 15 children with diabetic retinopathy.195 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.

    1 Star
    Schizophrenia
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    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 B12.196 Some studies have reported finding lower levels of vitamin B12 in people with schizophrenia than in the general population,197 but others have found no difference.198 No trials of vitamin B12 supplementation in schizophrenic patients have been published.

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    Seborrheic Dermatitis in Adults
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    One physician reported that injections of B-complex vitamins were useful in the treatment of seborrheic dermatitis in infants.199 A preliminary trial found that 10 mg per day of folic acid was helpful in 17 of 20 cases of adult seborrheic dermatitis.200 However, this study also found that oral folic acid did not benefit infants with cradle cap. A preliminary study found that topical application of vitamin B6 ointment (containing 10 mg B6 per gram of ointment) to affected areas improved adult seborrheic dermatitis.201 However, oral vitamin B6 (up to 300 mg per day) was ineffective. Injections of vitamin B12 were reported to improve in 86% of adults with seborrheic dermatitis in a preliminary trial.202 Oral administration of vitamin B12 for seborrheic dermatitis has not been studied.

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    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.203 , 204 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.

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    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.205 , 206 , 207 Supplementation with folic acid , vitamin B6 , and vitamin B12 generally lowers homocysteine levels in humans.208 , 209 , 210 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%.211

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    Tinnitus
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    People exposed to loud noise on the job who develop tinnitus are commonly deficient in Vitamin B12 .212 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.

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    Type 1 Diabetes
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    is needed for normal functioning of nerve cells. Vitamin B12 taken orally has reduced symptoms of nerve damage caused by diabetes in 39% of people studied; when given both intravenously and orally, two-thirds of people improved. In a preliminary trial, people with nerve damage due to kidney disease or to diabetes plus kidney disease received intravenous injections of 500 mcg of methylcobalamin (the main form of vitamin B12 found in the blood) three times a day for six months in addition to kidney dialysis. Nerve pain was significantly reduced and nerve function significantly improved in those who received the injections. Oral vitamin B12 up to 500 mcg three times per day is recommended by some practitioners.

    How It Works

    How to Use It

    Most people do not require vitamin B12 supplements. However, vegans should supplement with at least 2 to 3 mcg per day.

    People with pernicious anemia are often treated with injections of vitamin B12. However, oral administration of 1,000 mcg per day can be used reliably as an alternative to vitamin B12 injections.213 , 214 , 215 , 216 , 217

    Absorption of vitamin B12 is reduced with increasing age. Some research suggests that elderly people may benefit from 10 to 25 mcg per day of vitamin B12.218 , 219 , 220 One study of elderly people with vitamin B12 deficiency suggested that as much as 500 to 1,000 mcg of vitamin B12 per day might be necessary to achieve optimal vitamin B12 status.221 Vitamin B12 status was measured in this study using a sensitive laboratory test (the plasma methylmalonic acid concentration).

    When vitamin B12 is used for therapeutic purposes other than correcting a deficiency, injections are usually necessary to achieve results.

    Sublingual forms of vitamin B12 are available,222 but there is no proof that they offer any advantage to oral supplements.

    Where to Find It

    Vitamin B12 is found in all foods of animal origin, including dairy, eggs, meat, poultry, and fish. According to one report, small, inconsistent amounts occur in seaweed (including nori and chlorella) and tempeh.223 Many researchers and healthcare professionals believe that people cannot rely on vegetarian sources to provide predictably sufficient quantities of vitamin B12. However, another study found substantial amounts of vitamin B12 in nori (at least 55 mcg per 100 grams of dry weight).224

    Possible Deficiencies

    Vegans (vegetarians who also avoid dairy and eggs) frequently become deficient, though the process often takes many years. People with malabsorption conditions, including those with tapeworm infestation and those with bacterial overgrowth in the intestines, often suffer from vitamin B12 deficiency. Malabsorption of vitamin B12 can also result from pancreatic disease, the effects of gastrointestinal surgery, or various prescription drugs.225

    Pernicious anemia is a special form of vitamin B12 malabsorption due to impaired ability of certain cells in the stomach to make intrinsic factor-a substance needed for normal absorption of vitamin B12. By definition, all people with pernicious anemia are vitamin B12-deficient. They require either vitamin B12 injections or oral supplementation with very high levels (1000 mcg per day) of vitamin B12.

    Older people with urinary incontinence226 and hearing loss227 have been reported to be at increased risk of B12 deficiency.

    Infection with Helicobacter pylori, a common cause of gastritis and ulcers , has been shown to cause or contribute to adult vitamin B12 deficiency. H. pylori has this effect by damaging cells in the stomach that make hydrochloric acid-which is needed for normal absorption of vitamin B12. In one trial, H. pylori was detected in 56% of people with anemia due to vitamin B12 deficiency. Successful eradication of H. pylori led to improved blood levels of B12 in 40% of those infected.228 Other studies have also suggested a link between H. pylori infection and vitamin B12 deficiency.229 , 230 Elimination of H. pylori infection does not always improve vitamin B12 status. People with H. pylori infections should have vitamin B12 status monitored.

    In a preliminary report, 47% of people with tinnitus and related disorders were found to have vitamin B12 deficiencies that may be helped by supplementation.231

    HIV -infected patients often have low blood levels of vitamin B12.232

    A disproportionately high amount of people with psychiatric disorders are deficient in B12.233 Significant vitamin B12 deficiency is associated with a doubled risk of severe depression , according to a study of physically disabled older women.234

    A preliminary study found that postmenopausal women who were in the lowest one-fifth of vitamin B12 consumption had an increased risk of developing breast cancer .235

    Although blood levels of vitamin B12 may be higher in alcoholics , actual body stores of vitamin B12 in the tissues (such as the liver) of alcoholics are frequently deficient.236 , 237

    Low blood levels of vitamin B12 are sometimes seen in pregnant women; however, this does not always indicate a vitamin B12 deficiency.238 The help of a healthcare professional is needed to determine when a true vitamin B12 deficiency exists in pregnant women with low blood levels of the vitamin.

    Hydroxocobalamin (a form of vitamin B12) has been recognized for more than 40 years as an effective antidote to cyanide poisoning. It is currently being used in France for that purpose. Because of its safety, hydroxocobalamin is considered by some researchers to be an ideal treatment for cyanide poisoning.239

    Interactions

    Interactions with Supplements, Foods, & Other Compounds

    If a person is deficient in vitamin B12 and takes 1,000 mcg or more of folic acid per day, the folic acid supplementation can improve the anemia caused by vitamin B12 deficiency . The effect of folic acid on vitamin B12 deficiency-induced anemia is not a folic acid toxicity. Rather, the folic acid supplementation is acting to correct one of the problems caused by B12 deficiency. The other problems caused by a lack of vitamin B12 (mostly neurological) do not improve with folic acid supplements, and can become irreversible if vitamin B12 is not provided to someone who is vitamin B12 deficient.

    Some doctors are unaware that vitamin B12 deficiencies often occur without anemia-even in people who do not take folic acid supplements. This lack of knowledge can delay diagnosis and treatment of people with vitamin B12 deficiencies. This can lead to permanent injury. When such a delayed diagnosis occurs in someone who inadvertently erased the anemia of vitamin B12 deficiency by taking folic acid supplements, the folic acid supplementation is often blamed for the missed diagnosis. This problem is rare and should not occur in people whose doctors understand that a lack of anemia does not rule out a vitamin B12 deficiency. Anyone supplementing 1,000 mcg or more per day of folic acid should be initially evaluated by a doctor before the folic acid can obscure a proper diagnosis of a possible B12 deficiency.

    Interactions with Medicines

    Certain medicines interact with this supplement.

    Types of interactions: Beneficial Adverse Check

    Replenish Depleted Nutrients

    • Aspirin

      In a study of people hospitalized with heart disease, those who had been taking aspirin were nearly twice as likely as nonusers to have a low or marginally low blood level of vitamin B12.240 That finding by itself does not prove that taking aspirin causes vitamin B12 deficiency. However, aspirin is known to damage the stomach in some cases, and the stomach plays a key role in vitamin B12 absorption (by secreting hydrochloric acid and intrinsic factor).

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • AZT

      Vitamin B12 deficiency in HIV infected persons may be more common in those taking AZT.241 HIV infected people with low vitamin B12 levels were shown in one study to be more likely to develop blood-related side effects (particularly anemia) from taking AZT.242

    • Carbamazepine

      Anemia is an uncommon side effect experienced by people taking anticonvulsant drugs. Though many researches believe that low blood levels of folic acid are involved, the effects might be caused by a vitamin B12 deficiency. Deficiencies of folic acid and vitamin B12 can lead to nerve and mental problems. One study revealed that individuals on long-term anticonvulsant therapy, despite having no laboratory signs of anemia, had dramatically lower levels of vitamin B12 in their cerebrospinal fluid (the fluid that bathes the brain) when compared with people who were not taking seizure medications. Improvement in mental status and nerve function was observed in a majority of symptomatic individuals after taking 30 mcg of vitamin B12 daily for a few days.243 Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12.244 The results of these two studies indicate that people taking anticonvulsant drugs might experience side effects of vitamin B12 deficiency, and that the deficiency is not easily detected by the usual blood tests. Therefore, individuals taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.

    • Cimetidine

      Hydrochloric acid is needed to release vitamin B12 from food so it can be absorbed by the body. Cimetidine, which reduces stomach acid, may decrease the amount of vitamin B12 available for the body to absorb.245 The vitamin B12 found in supplements is available to the body without the need for stomach acid. Lab tests can determine vitamin B12 levels in people.

    • Clofibrate

      Clofibrate has been reported to reduce absorption of vitamin B12.246

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Colchicine

      Colchicine may interfere with vitamin B12 in the body. Research is inconsistent. Both colchicine and vitamin B12 deficiency are reported to cause neuropathies (disorders of the nervous system), but it remains unclear whether neuropathies caused by colchicine could be due to vitamin B12 depletion.247 , 248

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Cycloserine

      Cycloserine may interfere with calcium and magnesium absorption.249 The clinical significance of these interactions is unclear.

      Cycloserine may interfere with the absorption and/or activity of folic acid, vitamin B6, and vitamin B12.250 , 251 The clinical importance of this interaction is unclear.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Desogestrel-Ethinyl Estradiol

      A review of literature suggests that women who use oral contraceptives may experience decreased vitamin B1 , B2 , B3 , B12 , C , and zinc levels.252 , 253 , 254 Oral contraceptive use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A .255 , 256 , 257 Oral contraceptives may interfere with manganese absorption.258 The clinical importance of these actions remains unclear.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Erythromycin

      Erythromycin may interfere with the absorption and/or activity of calcium , folic acid , magnesium , vitamin B6 and vitamin B12 ,259 which may cause problems, especially with long-term erythromycin treatment. Until more is known, it makes sense for people taking erythromycin for longer than two weeks to supplement with a daily multivitamin-multimineral .

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Ethinyl Estradiol and Levonorgestrel

      A review of literature suggests that women who use oral contraceptives may experience decreased vitamin B1 , B2 , B3 , B12 , C , and zinc levels.260 , 261 , 262 Oral contraceptive use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A .263 , 264 , 265 Oral contraceptives may interfere with manganese absorption.266 The clinical importance of these actions remains unclear.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Ethinyl Estradiol and Norethindrone

      A review of literature suggests that women who use OCs may experience decreased vitamin B1 , B2 , B3 , B12 , C , and zinc levels.267 , 268 , 269 OC use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A .270 , 271 , 272 OCs may interfere with manganese absorption.273 The clinical importance of these actions remains unclear.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Ethinyl Estradiol and Norgestimate

      A review of literature suggests that women who use OCs may experience decreased vitamin B1 , B2 , B3 , B12 , C , and zinc levels.274 , 275 , 276 OC use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A .277 , 278 , 279 OCs may interfere with manganese absorption.280 The clinical importance of these actions remains unclear.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Ethinyl Estradiol and Norgestrel

      A review of literature suggests that women who use oral contraceptives may experience decreased vitamin B1 , B2 , B3 , B12 , C , and zinc levels.281 , 282 , 283 Oral contraceptive use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A .284 , 285 , 286 Oral contraceptives may interfere with manganese absorption.287 The clinical importance of these actions remains unclear.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Famotidine

      Stomach acid is needed for the vitamin B12 in food to be absorbed. H-2 blocker drugs reduce stomach acid and may therefore inhibit absorption of the vitamin B12 naturally present in food. However, the vitamin B12 found in supplements does not depend on stomach acid for absorption.288 Lab tests can determine vitamin B12 levels in people.

    • Felbamate

      Anemia is an uncommon side effect experienced by people taking anticonvulsant drugs. Though many researches believe that low blood levels of folic acid are involved, the effects might be caused by a vitamin B12 deficiency. Deficiencies of folic acid and vitamin B12 can lead to nerve and mental problems. One study revealed that individuals on long-term anticonvulsant therapy, despite having no laboratory signs of anemia, had dramatically lower levels of vitamin B12 in their cerebrospinal fluid (the fluid that bathes the brain) when compared with people who were not taking seizure medications. Improvement in mental status and nerve function was observed in a majority of symptomatic individuals after taking 30 mcg of vitamin B12 daily for a few days.289 Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12.290 The results of these two studies indicate that people taking anticonvulsant drugs might experience side effects of vitamin B12 deficiency, and that the deficiency is not easily detected by the usual blood tests. Therefore, individuals taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.

    • Isoniazid

      Isoniazid may interfere with the activity of other nutrients, including vitamin B3 (niacin) , vitamin B12 , vitamin D , and vitamin E , folic acid , calcium , and magnesium .294 , 295 Supplementation with vitamin B6 is thought to help prevent isoniazid-induced niacin deficiency; however, small amounts of vitamin B6 (e.g. 10 mg per day) appear to be inadequate in some cases.296 People should consider using a daily multivitamin-mineral supplement during isoniazid therapy.

    • Lansoprazole

      Omeprazole, a drug closely related to lansoprazole, has interfered with the absorption of vitamin B12 from food (though not supplements) in some,297 , 298 but not all, studies.299 , 300 This interaction has not yet been reported with lansoprazole. However, a fall in vitamin B12 status may result from decreased stomach acid caused by acid blocking drugs, including lansoprazole.301

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Levetiracetam

      Anemia is an uncommon side effect experienced by people taking anticonvulsant drugs. Though many researches believe that low blood levels of folic acid are involved, the effects might be caused by a vitamin B12 deficiency. Deficiencies of folic acid and vitamin B12 can lead to nerve and mental problems. One study revealed that individuals on long-term anticonvulsant therapy, despite having no laboratory signs of anemia, had dramatically lower levels of vitamin B12 in their cerebrospinal fluid (the fluid that bathes the brain) when compared with people who were not taking seizure medications. Improvement in mental status and nerve function was observed in a majority of symptomatic individuals after taking 30 mcg of vitamin B12 daily for a few days.302 Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12.303 The results of these two studies indicate that people taking anticonvulsant drugs might experience side effects of vitamin B12 deficiency, and that the deficiency is not easily detected by the usual blood tests. Therefore, individuals taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.

    • Levonorgestrel

      A review of literature suggests that women who use oral contraceptives may experience decreased vitamin B1 , B2 , B3 , B12 , C , and zinc levels.304 , 305 , 306 Oral contraceptive use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A .307 , 308 , 309 Oral contraceptives may interfere with manganese absorption.310 The clinical importance of these actions remains unclear.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Levonorgestrel-Ethinyl Estrad

      A review of literature suggests that women who use oral contraceptives may experience decreased vitamin B1 , B2 , B3 , B12 , C , and zinc levels.311 , 312 , 313 Oral contraceptives use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A .314 , 315 , 316 Oral contraceptivess may interfere with manganese absorption.317 The clinical importance of these actions remains unclear.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Mestranol and Norethindrone

      A review of literature suggests that women who use oral contraceptives may experience decreased vitamin B1 , B2 , B3 , B12 , C , and zinc levels.318 , 319 , 320 Oral contraceptive use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A .321 , 322 , 323 Oral contraceptives may interfere with manganese absorption.324 The clinical importance of these actions remains unclear.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Metformin

      Metformin therapy has been shown to deplete vitamin B12,325 and sometimes, but not always,326 folic acid as well.327 This depletion occurs through the interruption of a calcium-dependent mechanism. Supplementation with calcium has reversed this effect in a clinical trial.328 People taking metformin should supplement vitamin B12 and folic acid or ask their doctor to monitor folic acid and vitamin B12 levels.

    • Methyldopa

      Methyldopa can decrease vitamin B12 levels, thus increasing the risk of vitamin B12 deficiency.329

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Neomycin

      Neomycin can decrease absorption or increase elimination of many nutrients, including calcium , carbohydrates, beta-carotene , fats, folic acid , iron , magnesium , potassium , sodium, and vitamin A , vitamin B12 , vitamin D , and vitamin K .330 , 331 Surgery preparation with oral neomycin is unlikely to lead to deficiencies. It makes sense for people taking neomycin for more than a few days to also take a multivitamin-mineral supplement.

    • Nizatidine

      Stomach acid is needed for vitamin B12 in food to be absorbed by the body. H-2 blocker drugs reduce stomach acid and may therefore inhibit absorption of the vitamin B12 naturally present in food. However, the vitamin B12 found in supplements does not depend on stomach acid for absorption.332 Lab tests can determine vitamin B12 levels in people.

    • Norgestimate-Ethinyl Estradiol

      A review of literature suggests that women who use oral contraceptives may experience decreased vitamin B1 , B2 , B3 , B12 , C , and zinc levels.333 , 334 , 335 Oral contraceptive use has been associated with increased absorption of calcium and copper and with increased blood levels of copper and vitamin A .336 , 337 , 338 Oral contraceptives may interfere with manganese absorption.339 The clinical importance of these actions remains unclear.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Omeprazole

      Omeprazole interferes with the absorption of vitamin B12 from food (though not from supplements) in some340 , 341 , 342 , 343 but not all344 , 345 studies. A true deficiency state, resulting in vitamin B12-deficiency anemia, has only been reported in one case.346 The fall in vitamin B12 status may result from the decrease in stomach acid required for vitamin B12 absorption from food caused by the drug.347 This problem may possibly be averted by drinking acidic juices when eating foods containing vitamin B12.348

      However, all people taking omeprazole need to either supplement with vitamin B12 or have their vitamin B12 status checked on a yearly basis. Even relatively small amounts of vitamin B12 such as 10-50 mcg per day, are likely to protect against drug induced vitamin depletion.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Oxcarbazepine

      Anemia is an uncommon side effect experienced by people taking anticonvulsant drugs. Though many researches believe that low blood levels of folic acid are involved, the effects might be caused by a vitamin B12 deficiency. Deficiencies of folic acid and vitamin B12 can lead to nerve and mental problems. One study revealed that individuals on long-term anticonvulsant therapy, despite having no laboratory signs of anemia, had dramatically lower levels of vitamin B12 in their cerebrospinal fluid (the fluid that bathes the brain) when compared with people who were not taking seizure medications. Improvement in mental status and nerve function was observed in a majority of symptomatic individuals after taking 30 mcg of vitamin B12 daily for a few days.349 Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12.350 The results of these two studies indicate that people taking anticonvulsant drugs might experience side effects of vitamin B12 deficiency, and that the deficiency is not easily detected by the usual blood tests. Therefore, individuals taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.

    • Phenobarbital

      Anemia is an uncommon side effect experienced by people taking anticonvulsant drugs. Though the cause may be folic acid deficiency in many cases, a deficiency of vitamin B12 may also be a factor in some instances. Deficiencies of folic acid and vitamin B12 can lead to nerve and mental problems. One study revealed that individuals on long-term anticonvulsant therapy, despite having no laboratory signs of anemia, had dramatically lower levels of vitamin B12 in their cerebrospinal fluid (the fluid that bathes the brain) when compared with people who were not taking seizure medications. Improvement in mental status and nerve function was observed in a majority of symptomatic individuals after taking 30 mcg of vitamin B12 daily for a few days.353 Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12.354 Despite these contradictory findings, people taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Primidone

      Anemia is an uncommon side effect experienced by people taking anticonvulsant drugs. Though many researches believe that low blood levels of folic acid are involved, the effects might be caused by a vitamin B12 deficiency. Deficiencies of folic acid and vitamin B12 can lead to nerve and mental problems. One study revealed that individuals on long-term anticonvulsant therapy, despite having no laboratory signs of anemia, had dramatically lower levels of vitamin B12 in their cerebrospinal fluid (the fluid that bathes the brain) when compared with people who were not taking seizure medications. Improvement in mental status and nerve function was observed in a majority of symptomatic individuals after taking 30 mcg of vitamin B12 daily for a few days.357 Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12.358 The results of these two studies indicate that people taking anticonvulsant drugs might experience side effects of vitamin B12 deficiency, and that the deficiency is not easily detected by the usual blood tests. Therefore, individuals taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.

    • Ranitidine

      Stomach acid is needed to release vitamin B12 from food so it can be absorbed by the body. H-2 blocker drugs reduce stomach acid and are associated with decreased dietary vitamin B12 absorption.359 The vitamin B12 found in supplements is available to the body without the need for stomach acid. Lab tests can determine vitamin B12 levels.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Sulfamethoxazole

      Sulfonamides, including sulfamethoxazole, can decrease absorption of calcium, magnesium, and vitamin B12.360 This is generally not a problem when taking sulfamethoxazole for two weeks or less. People taking sulfamethoxazole for longer than two weeks should ask their doctor about nutrient monitoring and supplementation.

      Note: Since sulfamethoxazole is often prescribed in combination with trimethoprim (for example, in Bactrim or Septra), it may be easy to associate this interaction with trimethoprim. However, this interaction is not known to occur with trimethoprim alone.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Tetracycline

      Tetracycline can interfere with the activity of folic acid , potassium , and vitamin B2 , vitamin B6 , vitamin B12 , vitamin C , and vitamin K .361 This is generally not a problem when taking tetracycline for two weeks or less. People taking tetracycline for longer than two weeks should ask their doctor about vitamin and mineral supplementation. Taking 500 mg vitamin C simultaneously with tetracycline was shown to increase blood levels of tetracycline in one study.362 The importance of this interaction is unknown.

    • Topiramate

      Anemia is an uncommon side effect experienced by people taking anticonvulsant drugs. Though many researches believe that low blood levels of folic acid are involved, the effects might be caused by a vitamin B12 deficiency. Deficiencies of folic acid and vitamin B12 can lead to nerve and mental problems. One study revealed that individuals on long-term anticonvulsant therapy, despite having no laboratory signs of anemia, had dramatically lower levels of vitamin B12 in their cerebrospinal fluid (the fluid that bathes the brain) when compared with people who were not taking seizure medications. Improvement in mental status and nerve function was observed in a majority of symptomatic individuals after taking 30 mcg of vitamin B12 daily for a few days.363 Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12.364 The results of these two studies indicate that people taking anticonvulsant drugs might experience side effects of vitamin B12 deficiency, and that the deficiency is not easily detected by the usual blood tests. Therefore, individuals taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.

    • Trimethoprim/ Sulfamethoxazole

      Sulfonamides, including sulfamethoxazole , can decrease absorption of calcium, magnesium, and vitamin B12.365 This is generally not a problem when taking sulfamethoxazole for two weeks or less. People taking sulfamethoxazole for longer than two weeks should ask their doctor about nutrient monitoring and supplementation.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Valproate

      Anemia is an uncommon side effect experienced by people taking anticonvulsant drugs. Though the cause may be folic acid deficiency in many cases, a deficiency of vitamin B12 may also be a factor in some cases. Deficiencies of folic acid and vitamin B12 can lead to nerve and mental problems. One study revealed that individuals on long-term anticonvulsant therapy had dramatically lower levels of vitamin B12 in their cerebrospinal fluid (the fluid that bathes the brain) when compared with people who were not taking seizure medications. Improvement in mental status and nerve function was observed in a majority of symptomatic individuals after taking 30 mcg of vitamin B12 daily for a few days.368 Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12.369 Despite these contradictory findings, people taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Zonisamide

      Anemia is an uncommon side effect experienced by people taking anticonvulsant drugs. Though many researches believe that low blood levels of folic acid are involved, the effects might be caused by a vitamin B12 deficiency. Deficiencies of folic acid and vitamin B12 can lead to nerve and mental problems. One study revealed that individuals on long-term anticonvulsant therapy, despite having no laboratory signs of anemia, had dramatically lower levels of vitamin B12 in their cerebrospinal fluid (the fluid that bathes the brain) when compared with people who were not taking seizure medications. Improvement in mental status and nerve function was observed in a majority of symptomatic individuals after taking 30 mcg of vitamin B12 daily for a few days.370 Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12.371 The results of these two studies indicate that people taking anticonvulsant drugs might experience side effects of vitamin B12 deficiency, and that the deficiency is not easily detected by the usual blood tests. Therefore, individuals taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.

    Reduce Side Effects

    • Fenofibrate

      Increased blood levels of homocysteine are associated with increased risk of atherosclerosis and heart disease . One study revealed that fenofibrate dramatically increases blood homocysteine levels, though blood levels of vitamins were not reduced.291 In one study, supplementation with 10 mg per day of folic acid prevented the increase in homocysteine levels resulting from fenofibrate therapy.292 Further research is needed to determine whether supplemental  vitamin B6 and vitamin B12, which are also capable of lowering homocysteine levels, might lower fenofibrate-induced elevations in homocysteine levels.

    • Gentamicin

      In a study of guinea pigs, a single intramuscular injection of methylcobalamin (a form of vitamin B12), in the amount of 125 mg per 2.2 pounds of body weight, given immediately after administration of gentamicin, prevented damage to the inner ear, which is a common side effect of gentamicin therapy.293 No studies have been done to determine whether the same protective effect would occur in humans.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Phenobarbital

      Anemia is an uncommon side effect experienced by people taking anticonvulsant drugs. Though the cause may be folic acid deficiency in many cases, a deficiency of vitamin B12 may also be a factor in some instances. Deficiencies of folic acid and vitamin B12 can lead to nerve and mental problems. One study revealed that individuals on long-term anticonvulsant therapy, despite having no laboratory signs of anemia, had dramatically lower levels of vitamin B12 in their cerebrospinal fluid (the fluid that bathes the brain) when compared with people who were not taking seizure medications. Improvement in mental status and nerve function was observed in a majority of symptomatic individuals after taking 30 mcg of vitamin B12 daily for a few days.351 Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12.352 Despite these contradictory findings, people taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Phenytoin

      Anemia is an uncommon side effect experienced by people taking anticonvulsant drugs. Though many researches believe that low blood levels of folic acid are involved, the effects might be caused by a vitamin B12 deficiency. Deficiencies of folic acid and vitamin B12 can lead to nerve and mental problems. One study revealed that individuals on long-term anticonvulsant therapy, despite having no laboratory signs of anemia, had dramatically lower levels of vitamin B12 in their cerebrospinal fluid (the fluid that bathes the brain) when compared with people who were not taking seizure medications. Improvement in mental status and nerve function was observed in a majority of symptomatic individuals after taking 30 mcg of vitamin B12 daily for a few days.355 Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12.356 The results of these two studies indicate that people taking anticonvulsant drugs might experience side effects of vitamin B12 deficiency, and that the deficiency is not easily detected by the usual blood tests. Therefore, individuals taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    • Valproate

      Anemia is an uncommon side effect experienced by people taking anticonvulsant drugs. Though the cause may be folic acid deficiency in many cases, a deficiency of vitamin B12 may also be a factor in some cases. Deficiencies of folic acid and vitamin B12 can lead to nerve and mental problems. One study revealed that individuals on long-term anticonvulsant therapy had dramatically lower levels of vitamin B12 in their cerebrospinal fluid (the fluid that bathes the brain) when compared with people who were not taking seizure medications. Improvement in mental status and nerve function was observed in a majority of symptomatic individuals after taking 30 mcg of vitamin B12 daily for a few days.366 Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12.367 Despite these contradictory findings, people taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.

    Support Medicine

    • none

    Reduces Effectiveness

    • none

    Potential Negative Interaction

    • none

    Explanation Required

    • Gabapentin

      Anemia is an uncommon side effect experienced by people taking anticonvulsant drugs. Though many researches believe that low blood levels of folic acid are involved, the effects might be caused by a vitamin B12 deficiency. Deficiencies of folic acid and vitamin B12 can lead to nerve and mental problems. One study revealed that individuals on long-term anticonvulsant therapy, despite having no laboratory signs of anemia, had dramatically lower levels of vitamin B12 in their cerebrospinal fluid (the fluid that bathes the brain) when compared with people who were not taking seizure medications. Improvement in mental status and nerve function was observed in a majority of symptomatic individuals after taking 30 mcg of vitamin B12 daily for a few days.372 Another study found that long-term anticonvulsant therapy had no effect on blood levels of vitamin B12.373 The results of these two studies indicate that people taking anticonvulsant drugs might experience side effects of vitamin B12 deficiency, and that the deficiency is not easily detected by the usual blood tests. Therefore, individuals taking anticonvulsant drugs for several months or years might prevent nerve and mental problems by supplementing with vitamin B12.

      The interaction is supported by preliminary, weak, fragmentary, and/or contradictory scientific evidence.
    The Drug-Nutrient Interactions table may not include every possible interaction. Taking medicines with meals, on an empty stomach, or with alcohol may influence their effects. For details, refer to the manufacturers' package information as these are not covered in this table. If you take medications, always discuss the potential risks and benefits of adding a supplement with your doctor or pharmacist.

    Side Effects

    Side Effects

    Oral vitamin B12 supplements are not generally associated with any side effects.

    Although quite rare, serious allergic reactions to injections of vitamin B12 (sometimes even life-threatening) have been reported.374 , 375 , 376 Whether these reactions are to the vitamin itself, or to preservatives or other substances in the injectable vitamin B12 solution, remains somewhat unclear. Most, but not all, injectable vitamin B12 contains preservatives.

    In a double-blind trial, people with diabetes who also had with kidney disease received a daily placebo or 2.5 mg of folic acid, 1 mg of vitamin B12, and 25 mg of vitamin B6 for three years. Compared with the placebo, vitamin supplementation accelerated the decline in kidney function and increased the incidence of cardiovascular events (such as heart attacks) and heart disease-related deaths.377 Based on this study, diabetics with kidney disease should not take these vitamins without a doctor's supervision.

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