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Vitamin B12, an essential nutrient, is also known as cobalamin. The "cobal" in the name refers to the metal cobalt contained in B12. Vitamin B12 is required for the normal activity of nerve cells, and works with folate and vitamin B6 to lower blood levels of homocysteine, a chemical in the blood that is thought to contribute to heart disease. B12 also plays a role in the body's manufacture of S-adenosylmethionine, or SAMe.
Anemia is usually (but not always) the first sign of B12 deficiency. Earlier in this century, doctors coined the name "pernicious anemia" for a stubborn anemia that didn't improve even when the patient was given iron supplements. Today we know that pernicious anemia is usually caused by a condition in which the stomach fails to excrete a special substance called intrinsic factor. The body needs the intrinsic factor for efficient absorption of vitamin B12. In 1948, vitamin B12 was identified as the cure for pernicious anemia. B12 deficiency also causes nerve damage, and this may in some cases occur without anemia first developing.
Even in the absence of deficiency, B12 supplements might improve sperm count and mobility, possibly enhancing fertility. Vitamin B12 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.
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Requirements/Sources
Extraordinarily small amounts of vitamin B12 suffice for daily nutritional needs. The official U.S. and Canadian recommendations for daily intake are as follows:
Infants 0–6 months, 0.4 mcg
7–12 months, 0.5 mcg
Children 1–3 years, 0.9 mcg
4–8 years, 1.2 mcg
9–13 years, 1.8 mcg
Males and females 14 years and older, 2.4 mcg
Pregnant women, 2.6 mcg
Nursing women, 2.8 mcg
Vitamin B12 deficiency is rare in the young, but it's not unusual in older people: Probably 10 to 20% of the elderly are deficient in B12.1–4 This may be because older people have lower levels of stomach acid. The vitamin B12 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 don't absorb as much vitamin B12 from our food. Fortunately, vitamin B12 supplements don't need acid for absorption. For this reason, people who take medications that greatly reduce stomach acid, such as Prilosec (omeprazole) or Zantac (ranitidine), should probably also take B12 supplements.5–10
Stomach surgery and other conditions affecting the digestive tract can also lead to B12 deficiency. Vitamin B12 absorption or levels in the blood may also be impaired by colchicine (for gout), metformin and phenformin (for diabetes), AZT (for AIDS), and nitrous oxide,11–14 although one recent study found no effect from nitrous oxide.15 Interestingly, taking extra calcium may improve B12 absorption in individuals using metformin and possibly also in those using phenformin.16 Slow-release potassium supplements can impair B12 absorption as well.17
Vitamin B12 is found in most animal foods. Beef, liver, clams, and lamb provide a whopping 80 to 100 mcg of B12 per 3.5-ounce serving, at least 40 times the dietary requirement. Sardines, chicken liver, beef kidney, and calf liver are also good sources, providing between 25 and 60 mcg per serving. Trout, salmon, tuna, eggs, whey, and many cheeses provide at least the recommended daily intake. Nondairy, or total, vegetarians can eventually become B12-deficient, unless they take B12 supplements or eat B12-enriched yeast.
Vitamin B12 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.
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Therapeutic Dosages
For correcting absorption problems caused by medications, taking vitamin B12 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.
Because the B vitamins tend to work together, many nutritional experts recommend taking B12 with other B vitamins in the form of a B-complex supplement.
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Therapeutic Uses
It appears that individuals who take medications that dramatically lower stomach acid would profit by taking B12 supplements.18–23 Other individuals likely to be deficient in B12, such as the elderly, or those taking the medications listed in Requirements/Sources, might well benefit from a daily B12 supplement to prevent B12 deficiency.
Severe B12 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 B12 deficiency, thereby allowing permanent nerve damage to develop without any warning. Therefore, you should not take folate at high dosages without first getting a blood test to evaluate your B12 levels.)
Mild B12 deficiency (too slight to cause anemia) may impair brain function.24,25 A study evaluated 34 individuals over 60 years of age with evidence of marginal B12 status, along with 21 control participants with normal B12 levels. Careful measurement of brain function found evidence of impairment in 38.2% of the B12-deficient participants, but in only 9.5% of those with sufficient B12. In addition, treatment with B12 supplements restored normal brain function.
For pernicious anemia, B12 injections are traditionally used but research has shown that oral B12 works just as well, provided you take enough of it (between 300 and 1,000 mcg daily).26–29
Preliminary evidence suggests that B12 supplements may improve sperm activity and sperm count and perhaps treat male infertility.30,31
Vitamin B12 is widely recommended as a treatment for asthma,32 but there is little real evidence that it is effective. On the basis of weak and sometimes contradictory evidence, vitamin B12 has been suggested for HIV,33–37amyotrophic lateral sclerosis,38 diabetic neuropathy,39,40multiple sclerosis (MS),41–45restless legs syndrome,46,47 and tinnitus.48
Although vitamin B12 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
Some evidence suggests that people with vitiligo (splotchy loss of skin pigmentation) might be deficient in vitamin B12 and supplementation along with folate may be helpful.52,53 However, the evidence is very weak and not all studies agree.54 Vitamin B12 is also sometimes recommended for numerous other problems, including depression, osteoporosis, and periodontal disease, but there is little to no evidence as yet that it really works.
A double-blind trial of vitamin B12 for seasonal affective disorder (SAD-- a type of depression related to lack to lack of light during the winter) found no evidence of benefit.58
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What Is the Scientific Evidence for Vitamin B12?
Male Infertility
Vitamin B12 deficiencies in men can lead to reduced sperm counts and lowered sperm mobility. For this reason, B12 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 B12 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, B12 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.
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Safety Issues
Vitamin B12 appears to be extremely safe. However, in some cases very high doses of vitamin B12 can cause or worsen acne symptoms.56,57
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Interactions You Should Know About
If you are taking
Medications that reduce stomach acid such as H2 blockers—such as Zantac (ranitidine)—and proton pump inhibitors—such as Prilosec (omeprazole)—colchicine, AZT, or if you are exposed to nitrous oxide anesthesia: You may need extra B12.
Metformin or phenformin: You may need extra B12. Another option is to take extra calcium, which may in turn improve B12 absorption.
Potassium:You may need extra B12.
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References
1. Saltzman JR, Kemp JA, Golner BB, et al. Effect of hypochlorhydria due to omeprazole treatment or atrophic gastritis on protein-bound vitamin B12 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 B12 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 B12 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 H2-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 B12. 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 B12) absorption [translated from French]. Gastroenterol Clin Biol. 1983;7:381–384.
11. Webb DI, Chodos RB, Mahar CQ, et al. Mechanism of vitamin B12 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 B12 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 B12 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 B12 malabsorption induced by metformin. Diabetes Care. 2000;23:1227–1231.
17. Drug Evaluations Annual. Vol. 3. Milwaukee, Wis: 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 B12 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 H2-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 B12. 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 B12. 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 B12 deficiency. Lancet. 1998;352:1721–1722.
27. McIntyre PA, Hahn R, Masters JM, et al. Treatment of pernicious anemia with orally administered cyanocobalamin (vitamin B12). Arch Intern Med. 1960;106:280–292.
28. Waife SO, Jansen CJ Jr, Crabtree RE, et al. Oral vitamin B12 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 B12 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 B12. Infertility. 1984;7:133–138.
32. Wright J. Vitamin B12: Powerful protection against asthma. Int Clin Nutr Rev. 1989;9:185–188.
33. Rule SA, Hooker M, Costello C, et al. Serum vitamin B12 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 B12 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 B12 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 B12 and neurotoxicity of homocysteine with nitrite in some of neurologic disorders. Biogenic Amines. 1998;14:1–14.
44. Reynolds EH. Multiple sclerosis and vitamin B12 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 B12 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 B12: 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 B12 in vitiligo: a nutritional approach. Cutis. 1992;50:39–42.
53. Juhlin L, Olsson MJ. Improvement of vitiligo after oral treatment with vitamin B12 and folic acid and the importance of sun exposure. Acta Derm Venereol (Stockh). 1997;77:460–462.
54. Kim SM, Kim YK, Hann S-K. Serum levels of folic acid and vitamin B12 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 B6 and B12. 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.
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