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Supplement Forms/Alternate Names
• Cobalamin; Cyanocobalamin; Hydrocobalamin; Methylcobalamin
Principal Proposed Uses
• Correcting Deficiency
Other Proposed Uses
• Alzheimer's Disease; Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease); Asthma; Bell's Palsy; Depression; Diabetic Neuropathy; Eczema; HIV Support; Male Infertility; Multiple Sclerosis; Osteoporosis; Periodontal Disease; Recurrent Miscarriage; Restless Legs Syndrome; Tinnitus; Vitiligo
Vitamin B 12, an essential nutrient, is also known as cobalamin. The cobal in the name refers to the metal cobalt contained in B 12. Vitamin B 12 is required for the normal activity of nerve cells and works with folate and vitamin B 6 to lower blood levels of homocysteine, a chemical in the blood that might contribute to heart disease. B 12 also plays a role in the body's manufacture of S-adenosylmethionine (SAMe).
Anemia is usually (but not always) the first sign of B 12 deficiency. Earlier in this century, doctors coined the name "pernicious anemia" for a stubborn form of anemia that did not improve even when the patient was given iron supplements. Today we know that pernicious anemia comes about when the stomach fails to excrete a special substance called intrinsic factor. The body needs the intrinsic factor for efficient absorption of vitamin B 12. In 1948, vitamin B 12 was identified as the cure for pernicious anemia. B 12 deficiency also causes nerve damage, and this may, in some cases, occur without anemia first developing.
Vitamin B 12 has also been proposed as a treatment for numerous other conditions, but as yet there is no definitive evidence that it is effective for any purpose other than correcting deficiency.
Extraordinarily small amounts of vitamin B 12 suffice for daily nutritional needs. The official US and Canadian recommendations for daily intake are as follows:
Vitamin B 12 is available in three forms: cyanocobalamin, hydrocobalamin, and methylcobalamin. The first is the most widely available and least expensive, but some experts think that the other two forms are preferable.
Vitamin B 12 is found in most animal foods; it is also found only in animal food (unless otherwise fortified). Clams and beef liver have extremely high amounts of this vitamin. The National Institutes of Health's Office of Dietary Supplements offers this list of foods that are high in B 12:72
Vitamin B12 Deficiency
Vitamin B 12 deficiency is rare in the young, but it is not unusual in older people: Probably 10% to 20% of the elderly are deficient in B 12.1-4 This may be because older people have lower levels of stomach acid. The vitamin B 12 in our food comes attached to proteins and must be released by acid in the stomach in order to be absorbed. When stomach acid levels are low, we do not absorb as much vitamin B 12 from our food. Fortunately, vitamin B 12 supplements do not need acid for absorption and should, therefore, get around this problem. However, for reasons that are unclear, one study found that B 12 -deficient seniors need very high dosages of the supplements to normalize their levels, as high as 600 to 1,000 mcg daily.65
Similarly, people who take medications that greatly reduce stomach acid, such as omeprazole (Prilosec) or ranitidine (Zantac) also may have trouble absorbing B 12 from food and could benefit from supplementation.5-10
Stomach surgery and other conditions affecting the digestive tract can also lead to B 12 deficiency. Vitamin B 12 absorption or levels in the blood may also be impaired by colchicine (for gout), metformin and phenformin (for diabetes), and AZT (for AIDS).11,12,69 Exposure to nitrous oxide (such as may be experienced by dentists and dental hygienists) might cause B 12 deficiency, but studies disagree.14,15 Slow-release potassium supplements might impair B 12 absorption as well.17
Severe B 12 deficiency can cause anemia and, potentially, nerve damage. The latter may become permanent if the deficiency is not corrected in time. Anemia most often develops first, leading to treatment before permanent nerve damage develops. However, folate supplements can get in the way of this "early warning system." This is why people are cautioned against taking high doses of folate without medical supervision. When taken at a dosage higher than 400 mcg daily, folate can prevent anemia caused by B 12 deficiency, thereby allowing permanent nerve damage to develop without any warning. More mild deficiencies of vitamin B 12 may cause elevated levels of homocysteine in the blood, potentially increasing risk of heart disease. (See the Homocysteine article for more information.) Mild B 12 deficiency (too slight to cause anemia) may also impair brain function.24,25
Note: Total vegetarians (vegans) must take vitamin B 12 supplements or consume B 12 -fortified foods, or they will eventually become deficient.59,60 Contrary to some reports, seaweed and tempeh do not provide B 12. (Some forms of blue-green algae, such as spirulina, contain B 12, but it is not in an absorbable state.61 )
For correcting absorption problems caused by medications, taking vitamin B 12 at the level of dietary requirements should suffice.
For other purposes, enormously higher daily doses—ranging from 100 to 2,000 mcg—are sometimes recommended.
It appears that individuals who take medications that dramatically lower stomach acid, such as H2 blockers or proton pump inhibitors, would benefit by taking B 12 supplements.18-23 Other individuals likely to be deficient in B 12, such as the elderly, or those taking the medications listed in Requirements/Sources, might well benefit from a daily B 12 supplement to prevent B 12 deficiency.
For pernicious anemia, B 12 injections are traditionally used but research has shown that oral B 12 works just as well, provided you take enough of it (between 300 and 1,000 mcg daily).26-29
Weak evidence suggests that B 12 supplements may improve sperm activity and sperm count; on this basis, they could be useful for male infertility.30,31 Some cases of recurrent miscarriage might be due to vitamin B 12 deficiency.62
One placebo-controlled, double-blind study, enrolling 49 people with eczema, found benefit with a cream containing vitamin B 12 at a concentration of 0.07%.66 Topical B 12 is hypothesized to work for eczema by reducing local levels of the substance nitric oxide (not related to nitrous oxide).
On the basis of weak and sometimes contradictory evidence, vitamin B 12 has been suggested for HIV,33-37 amyotrophic lateral sclerosis,38 carpal tunnel syndrome,67 diabetic neuropathy,39,40 multiple sclerosis (MS),41-45 restless legs syndrome,46,47 and tinnitus.48
Some evidence suggests that people with vitiligo (splotchy loss of skin pigmentation) might be deficient in vitamin B 12, and supplementation along with folate may be helpful.52,53 However, the evidence is very weak and not all studies agree.54
Some alternative practitioners recommend the use of injected vitamin B 12 for Bell’s palsy. However, the only scientific support for this approach comes from one study that was not double-blind.63 (For information on the importance of a double-blind design, see Why Does This Database Rely on Double-blind Studies?)
Vitamin B 12 is also sometimes recommended for numerous other problems, including asthma, osteoporosis, periodontal disease, and depression. But, there is not a lot of evidence as yet that it really works.
A double-blind trial of vitamin B 12 for seasonal affective disorder (SAD—a type of depression related to lack of light during the winter) failed to find evidence of benefit.58 And, a randomized trial involving older adults with mild depression found that taking folate (400 mcg) and vitamin B 12 (100 mcg) daily for two years was no better than a placebo for reducing depressive symptoms.71
One double-blind, placebo-controlled study of 140 people with mildly low B 12 levels failed to find the supplement helpful for improving mental function and mood.68
Although vitamin B 12 has been proposed as a treatment for Alzheimer's disease, this recommendation is based solely on the results of one small, poorly designed study.49 More recent and better-designed studies found little to no benefit.50,51,70
What Is the Scientific Evidence for Vitamin B 12 ?
Vitamin B 12 deficiencies in men can lead to reduced sperm counts and lowered sperm mobility. For this reason, B 12 supplements have been tried for improving fertility in men with abnormal sperm production. In one double-blind study of 375 infertile men, supplementation with vitamin B 12 produced no benefits on average in the group as a whole.55 However, in a particular subgroup of men with sufficiently low sperm count and sperm motility, B 12 appeared to be helpful. Such "dredging" of the data is suspect from a scientific point of view, however, and this study cannot be taken as proof of effectiveness.
Vitamin B 12 appears to be extremely safe. However, in some cases very high doses of the vitamin can cause or worsen acne symptoms.56,57
Interactions You Should Know About
If you are taking:
Colchicine, AZT, medications that reduce stomach acid (such as the H2 blocker ranitidine [Zantac] or the proton pump inhibitor omeprazole [Prilosec], oral hypoglycemics (such as metformin or phenformin), slow-release potassium supplements, or if you are exposed to nitrous oxide anesthesia: You may need extra B 12. Another option is to take extra calcium, which may, in turn, improve B 12 absorption.
References [ + ]
1. Saltzman JR, Kemp JA, Golner BB, et al. Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B 12 absorption. J Am Coll Nutr. 1994;13:584-591.
2. van Goor L, Woiski MD, Lagaay AM, et al. Review: cobalamin deficiency and mental impairment in elderly people. Age Ageing. 1995;24:536-542.
3. Pennypacker LC, Allen RH, Kelly JP, et al. High prevalence of cobalamin deficiency in elderly outpatients. J Am Geriatr Soc. 1992;40:1197-1204.
4. Yao Y, Yao SL, Yao SS, et al. Prevalence of vitamin B 12 deficiency among geriatric outpatients. J Fam Pract. 1992;35:524-528.
5. Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin. Ann Intern Med. 1994;120:211-215.
6. Saltzman JR, Kemp JA, Golner BB, et al. Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B 12 absorption. J Am Coll Nutr. 1994;13:584-591.
7. Streeter AM, Goulston KJ, Bathur FA, et al. Cimetidine and malabsorption of cobalamin. Dig Dis Sci. 1982;27:13-16.
8. Aymard JP, Aymard B, Netter P, et al. Haematological adverse effects of histamine H 2 -receptor antagonists. Med Toxicol Adverse Drug Exp. 1988;3:430-448.
9. Salom IL, Silvis SE, Doscherholmen A. Effect of cimetidine on the absorption of vitamin B 12. Scand J Gastroenterol. 1982;17:129-131.
10. Belaiche J, Zittoun J, Marquet J, et al. Effect of ranitidine on gastric intrinsic factor and cobalamin (vitamin B 12) absorption [translated from French]. Gastroenterol Clin Biol. 1983;7:381-384.
11. Webb DI, Chodos RB, Mahar CQ, et al. Mechanism of vitamin B 12 malabsorption in patients receiving colchicine. N Engl J Med. 1968;279:845-850.
12. Adams JF, Clark JS, Ireland JT, et al. Malabsorption of vitamin B 12 and intrinsic factor secretion during biguanide therapy. Diabetologia. 1983;24:16-18.
13. Flippo TS, Holder WD Jr. Neurologic degeneration associated with nitrous oxide anesthesia in patients with vitamin B 12 deficiency. Arch Surg. 1993;128:1391-1395.
14. Baum MK, Javier JJ, Mantero-Atienza E, et al. Zidovudine-associated adverse reactions in a longitudinal study of asymptomatic HIV-1 infected homosexual males. J Acquir Immune Defic Syndr. 1991;4:1218-1226.
15. Deleu D, Louon A, Sivagnanam S, et al. Long-term effects of nitrous oxide anaesthesia on laboratory and clinical parameters in elderly Omani patients: a randomized double-blind study. J Clin Pharm Ther. 2000;25:271-277.
16. Bauman WA, Shaw S, Jayatilleke E, et al. Increased intake of calcium reverses vitamin B 12 malabsorption induced by metformin. Diabetes Care. 2000;23:1227-1231.
17. Drug Evaluations Annual. Vol. 3. Milwaukee, WI: American Medical Association; 1993.
18. Marcuard SP, Albernaz L, Khazanie PG. Omeprazole therapy causes malabsorption of cyanocobalamin. Ann Intern Med. 1994;120:211-215.
19. Saltzman JR, Kemp JA, Golner BB, et al. Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B 12 absorption. J Am Coll Nutr. 1994;13:584-591.
20. Streeter AM, Goulston KJ, Bathur FA, et al. Cimetidine and malabsorption of cobalamin. Dig Dis Sci. 1982;27:13-16.
21. Aymard JP, Aymard B, Netter P, et al. Haematological adverse effects of histamine H 2 -receptor antagonists. Med Toxicol Adverse Drug Exp. 1988;3:430-448.
22. Salom IL, Silvis SE, Doscherholmen A. Effect of cimetidine on the absorption of vitamin B 12. Scand J Gastroenterol. 1982;17:129-131.
23. Belaiche J, Zittoun J, Marquet J, et al. Effect of ranitidine on secretion of gastric intrinsic factor and absorption of vitamin B 12. Gastroenterol Clin Biol. 1983;7:381-384.
24. Carmel R, Gott P, Degiorgio C, et al. Abnormal P300 event-related potentials in mild, preclinical cobalamin deficiency [abstract]. Int J Hematol. 2000;72(suppl 1):207.
25. Louwman MW, van Dusseldorp M, van de Vijver FJ, et al. Signs of impaired cognitive function in adolescents with marginal cobalamin status. Am J Clin Nutr. 2000;72:762-769.
26. Elia M. Oral parenteral therapy for B 12 deficiency. Lancet. 1998;352:1721-1722.
27. McIntyre PA, Hahn R, Masters JM, et al. Treatment of pernicious anemia with orally administered cyanocobalamin (vitamin B 12). Arch Intern Med. 1960;106:280-292.
28. Waife SO, Jansen CJ Jr, Crabtree RE, et al. Oral vitamin B 12 without intrinsic factor in the treatment of pernicious anemia. Ann Intern Med. 1963;58:810-817.
29. Berlin H, Berlin R, Brante G. Oral treatment of pernicious anemia with high doses of vitamin B 12 without intrinsic factor. Acta Med Scand. 1968;184:247-258.
30. Kumamoto Y, Maruta H, Ishigami J, et al. Clinical efficacy of mecobalamin in treatment of oligozoospermia—results of double-blind comparative clinical study [in Japanese; English abstract]. Hinyokika Kiyo. 1988;34:1109-1132.
31. Sandler B, Faragher B. Treatment of oligospermia with vitamin B 12. Infertility. 1984;7:133-138.
32. Wright J. Vitamin B 12: Powerful protection against asthma. Int Clin Nutr Rev. 1989;9:185-188.
33. Rule SA, Hooker M, Costello C, et al. Serum vitamin B 12 and transcobalamin levels in early HIV disease. Am J Hematol. 1994;47:167-171.
34. Richman DD, Fischl MA, Grieco MH, et al. The toxicity of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. A double-blind, placebo-controlled trial. N Engl J Med. 1987;317:192-197.
35. Shor-Posner G, Morgan R, Wilkie F, et al. Plasma cobalamin levels affect information processing speed in a longitudinal study of HIV-1 disease. Arch Neurol. 1995;52:195-198.
36. Kieburtz KD, Giang DW, Schiffer RB, et al. Abnormal vitamin B 12 metabolism in human immunodeficiency virus infection. Association with neurological dysfunction. Arch Neurol. 1991;48:312-314.
37. Baum MK, Shor-Posner G, Lu Y, et al. Micronutrients and HIV-1 disease progression. AIDS. 1995;9:1051-1056.
38. Kaji R, Kodama M, Imamura A, et al. Effect of ultrahigh-dose methylcobalamin on compound muscle action potentials in amyotrophic lateral sclerosis: a double-blind controlled study. Muscle Nerve. 1998;21:1775-1778.
39. Ide H, Fujiya S, Asanuma Y, et al. Clinical usefulness of intrathecal injection of methylcobalamin in patients with diabetic neuropathy. Clin Ther. 1987;9:183-192.
40. Yaqub BA, Siddique A, Sulimani R. Effects of methylcobalamin on diabetic neuropathy. Clin Neurol Neurosurg. 1992;94:105-111.
41. Kira J, Tobimatsu S, Goto I. Vitamin B12 metabolism and massive-dose methyl vitamin B 12 therapy in Japanese patients with multiple sclerosis. Intern Med. 1994;33:82-86.
42. Goodkin DE, Jacobsen DW, Galvez N, et al. Serum cobalamin deficiency is uncommon in multiple sclerosis. Arch Neurol. 1994;51:1110-1114.
43. Baig SM, Qureshi GA, Minami M. The interrelation between the deficiency of vitamin B 12 and neurotoxicity of homocysteine with nitrite in some of neurologic disorders. Biogenic Amines. 1998;14:1-14.
44. Reynolds EH. Multiple sclerosis and vitamin B 12 metabolism. J Neuroimmunol. 1992;40:225-230.
45. Simpson CA, Newell DJ, Miller H. The treatment of multiple sclerosis with massive doses of hydroxocobalamin. Neurology. 1965;15:599-603.
46. O'Keeffe ST. Restless legs syndrome: a review. Arch Intern Med. 1996;156:243-248.
47. Silber MH. Restless legs syndrome. Mayo Clin Proc. 1997;72:261-264.
48. Shemesh Z, Attias J, Ornan M, et al. Vitamin B 12 deficiency in patients with chronic tinnitus and noise-induced hearing loss. Am J Otolarygol. 1993;14:94-99.
49. Martin DC, Francis J, Protetch J, et al. Time dependency of cognitive recovery with cobalamin replacement: Report of a pilot study. J Am Geriatr Soc. 1992;40:168-172.
50. Kwok T, Tang C, Woo J, et al. Randomized trial of the effect of supplementation on the cognitive function of older people with subnormal cobalamin levels. Int J Geriatr Psychiatry. 1998;13:611-616.
51. Teunisse S, Bollen AE, van Gool WA, et al. Dementia and subnormal levels of vitamin B 12: Effects of replacement therapy on dementia. J Neurol. 1996;243:522-529.
52. Montes LF, Diaz ML, Lajous J, et al. Folic acid and vitamin B 12 in vitiligo: a nutritional approach. Cutis. 1992;50:39-42.
53. Juhlin L, Olsson MJ. Improvement of vitiligo after oral treatment with vitamin B 12 and folic acid and the importance of sun exposure. Acta Derm Venereol (Stockh). 1997;77:460-462.
54. Kim SM, Kim YK, Hann S-K. Serum levels of folic acid and vitamin B 12 in Korean patients with vitiligo. Yonsei Med J. 1999;40:195-198.
55. Kumamoto Y, Maruta H, Ishigami J, et al. Clinical efficacy of mecobalamin in treatment of oligozoospermia--results of double-blind comparative clinical study [in Japanese; English abstract]. Hinyokika Kiyo. 1988;34:1109-1132.
56. Sheretz EF. Acneform eruption due to "megadose" vitamins B 6 and B 12. Cutis.. 1991;48:19-20.
57. Braun-Falco O, Lincke H. The problem of vitamin B6/B12 acne. A contribution on acne medicamentosa [in German; English abstract]. MMW Munch Med Wochenschr. 1976;118:155-160.
58. Oren DA, Teicher MH, Schwartz PJ, et al. A controlled trial of cyanocobalamin (vitamin B12) in the treatment of winter seasonal affective disorder. J Affect Disord. 1994;32:197-200.
59. Donaldson MS. Metabolic vitamin B12 status on a mostly raw vegan diet with follow-up using tablets, nutritional yeast, or probiotic supplements. Ann Nutr Metab. 2000;44:229-234.
60. Lightowler HJ, Davies GJ. Micronutrient intakes in a group of UK vegans and the contribution of self-selected dietary supplements. J R Soc Health. 2000;120:117-124.
61. Dagnelie P, van Staveren WA, van den Berg H. Vitamin B-12 from algae appears not to be bioavailable. Am J Clin Nutr. 1991;53:695-697.
62. Reznikoff-Etievant MF, Zittoun J, Vaylet C, et al. Low vitamin B(12) level as a risk factor for very early recurrent abortion. Eur J Obstet Gynecol Reprod Biol. 2002;104:156-159.
63. Jalaludin MA. Methylcobalamin treatment of Bell’s palsy. Methods Find Exp Clin Pharmaco. 1995;17:539-544.
64. Hvas AM, Juul S, Nexo E, et al. Vitamin B-12 treatment has limited effect on health-related quality of life among individuals with elevated plasma methylmalonic acid: a randomized placebo-controlled study. J Intern Med. 2003;253:146-152.
65. Seussen SJ, de Groot LC, Clarke R, et al. Oral cyanocobalamin supplementation in older people with vitamin B12 deficiency. Arch Intern Med. 2005;165:1167-72.
66. Stucker M, Pieck C, Stoerb C, et al. Topical vitamin B—a new therapeutic approach in atopic dermatitis—evaluation of efficacy and tolerability in a randomized placebo-controlled multicentre clinical trial. Br J Dermatol. 2004;150:977-83.
67. Sato Y, Honda Y, Iwamoto J, et al. Amelioration by mecobalamin of subclinical carpal tunnel syndrome involving unaffected limbs in stroke patients. J Neurol Sci. 2005;231:13-8.
68. Hvas AM, Juul S, Lauritzen L, et al. No effect of vitamin B-12 treatment on cognitive function and depression: a randomized placebo controlled study. J Affect Disord. 2004;81:269-273.
69. Ting RZ, Szeto CC, Chan MH, et al. Risk factors of vitamin B12 deficiency in patients receiving metformin. Arch Intern Med. 2006;166:1975-9.
70. Malouf R, Grimley Evans J. Folic acid with or without vitamin B12 for the prevention and treatment of healthy elderly and demented people. Cochrane Database Syst Rev. 2008;CD004514.
71. Walker JG, Mackinnon AJ, Batterham P, et al. Mental health literacy, folic acid and vitamin B12, and physical activity for the prevention of depression in older adults: randomised controlled trial. Br J Psychiatry. 2010;197(1):45-54.
72. Dietary supplement fact sheet: B12. Office of Dietary Supplements website. Available at: http://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/. Accessed September 10, 2012.
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