Vitamin B12 (Cobalamin / Cyanocobalamin)
Description and function
Vitamin B12 is a water-soluble B complex vitamin that contains the mineral cobalt. It is required for amino-acid metabolism, synthesis of nucleic acid and for red blood cell formation. Vitamin B12 is also involved in the metabolism and regeneration of folic acid. Finally, Vitamin B12, with vitamin B9 (Folic Acid) and Vitamin B6 (Pyridoxine), plays a role in the regulation of the level of homocysteine. High levels of homocysteine are associated with the formation of atheromatous plaques and, as a consequence, with an increased risk for cardiovascular diseases such as stroke and coronary artery disease.
Absorption of vitamin B12 is a complex process. After ingestion, vitamin B12 binds to the “intrinsic factor” in the stomach and duodenum (proximal intestine). It is only under this complex form, cobalamin-intrinsic factor, that vitamin B12 can then be absorbed at the level of the terminal ileum (distal small intestine).
Deficiency
Vitamin B12 is stored in the liver. Reserves can be abundant and the apparition of symptoms of vitamin B12 deficiency may take a few years to develop in certain. Vitamin B12 deficiency may result from various reasons. The most common causes are:
- Gastric resection (surgical removal of the stomach)
- Gastric atrophy and “intrinsic factor” deficiency. Without intrinsic factor, vitamin B12 cannot be absorbed in the ileum.
- Resection of the ileum where the intrinsic factor-cobalamin complex is absorbed.
- Strict vegetarianism, including veganism, can lead to vitamin B12 deficiency, except, for instance, when food is contains fecal contaminants of animal origin.
Signs and symptoms of vitamin B12 deficiency include megaloblastic changes of the bone marrow, anemia, peripheral neuropathy (numbness and tingling in the hands and feet), poor balance, poor coordination, and dementia.
Because of the role of vitamin B12 in the metabolism of folic acid, a deficiency in vitamin B12 may lead to signs and symptoms associated with folic acid deficiency and may, at times, be difficult to distinguish from folic acid deficiency.
Finally, vitamin B12 deficiency may lead to higher blood levels of homocysteine, which is a risk factor of cardiovascular disease.
Sources
Vitamin B12 is not found in plants and is produced by micro-organisms. Consequently, dietary sources include meat and meat products, eggs, and dairy products. Because vitamin B12 is not found in plants, the only sure way for strict vegetarians and vegans to get vitamin B12 in sufficient amounts is through vitamin supplements.
Toxicity
No toxicity is reported, even with excessive excess.
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Scientific References
Books
Cobalamin (Vitamin B-12). Carmel R. In: Shils ME, Shike M, Ross AC, Caballero B, Cousins RJ, eds. Modern Nutrition in Health and Disease. Philadelphia: Lippincott Williams & Wilkins; 2006:482-497.
Folic acid, vitamin B-12, and vitamin B-6. Shane B. In: Stipanuk M, ed. Biochemical and Physiological Aspects of Human Nutrition. Philadelphia: W.B. Saunders Co.; 2000:483-518.
PDR for Nutritional Supplements. Hendler SS, Rorvik DR, eds. Montvale: Medical Economics Company, Inc; 2001
Vitamin B-12. Herbert V. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition. 7th ed. Washington D.C.: ILSI Press; 1996:191-205.
Nutritional Biochemistry. Brody T. 2nd ed. San Diego: Academic Press; 1999.
Food and Nutrition Board, Institute of Medicine. Vitamin B12. Dietary Reference Intakes: Thiamin, Riboflavin, Niacin, Vitamin B6, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington D.C.: National Academy Press; 1998:306-356. (National Academy Press)
Scientific articles
A controlled trial of homocysteine lowering and cognitive performance. McMahon JA, Green TJ, Skeaff CM, Knight RG, Mann JI, Williams SM. N Engl J Med. 2006;354(26):2764-2772.
[Abstract]
A prospective study on folate, B12, and pyridoxal 5'-phosphate (B6) and breast cancer. Wu K, Helzlsouer KJ, Comstock GW, Hoffman SC, Nadeau MR, Selhub J. Cancer Epidemiol Biomarkers Prev. 1999;8(3):209-217.
[Abstract]
Alzheimer disease: protective factors. Nourhashemi F, Gillette-Guyonnet S, Andrieu S, et al. Am J Clin Nutr. 2000;71(2):643S-649S.
[Abstract]
Dietary folate and vitamins B-12 and B-6 not associated with incident Alzheimer's disease. Morris MC, Evans DA, Schneider JA, Tangney CC, Bienias JL, Aggarwal NT. J Alzheimers Dis. 2006;9(4):435-443.
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Dietary folate intake and breast cancer risk: results from the Shanghai Breast Cancer Study. Shrubsole MJ, Jin F, Dai Q, et al. Cancer Res. 2001;61(19):7136-7141.
[Abstract]
Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. Termanini B, Gibril F, Sutliff VE, Yu F, Venzon DJ, Jensen RT. Am J Med. 1998;104(5):422-430.
[Abstract]
Effect of oral vitamin B-12 with or without folic acid on cognitive function in older people with mild vitamin B-12 deficiency: a randomized, placebo-controlled trial. Eussen SJ, de Groot LC, Joosten LW, et al. Am J Clin Nutr. 2006;84(2):361-370.
[Abstract]
Effective treatment of cobalamin deficiency with oral cobalamin. Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Blood. 1998;92(4):1191-1198.
[Abstract]
Effects of B-vitamins on plasma homocysteine concentrations and on risk of cardiovascular disease and dementia. Clarke R, Lewington S, Sherliker P, Armitage J. Curr Opin Clin Nutr Metab Care. 2007;10(1):32-39.
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Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4-butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Delle Chiaie R, Pancheri P, Scapicchio P. Am J Clin Nutr. 2002;76(5):1172S-1176S.
[Abstract]
Folate and cobalamin in psychiatric illness. Hutto BR. Compr Psychiatry. 1997;38(6):305-314.
[Abstract]
Folate, vitamin B(6), and vitamin B(12) intake and the risk of breast cancer among Mexican women. Lajous M, Lazcano-Ponce E, Hernandez-Avila M, Willett W, Romieu I. Cancer Epidemiol Biomarkers Prev. 2006;15(3):443-448.
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Folate, vitamin B12 and postmenopausal breast cancer in a prospective study of French women. Lajous M, Romieu I, Sabia S, Boutron-Ruault MC, Clavel-Chapelon F. Cancer Causes Control. 2006;17(9):1209-1213.
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Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM. Arch Neurol. 1998;55(11):1449-1455.
[Abstract]
Homocysteine and atherosclerosis. Gerhard GT, Duell PB. Curr Opin Lipidol. 1999;10(5):417-428.
[Abstract]
Homocysteine and cognitive function in healthy elderly community dwellers in Italy. Ravaglia G, Forti P, Maioli F, et al. Am J Clin Nutr. 2003;77(3):668-673.
[Abstract]
Homocysteine and folate as risk factors for dementia and Alzheimer disease. Ravaglia G, Forti P, Maioli F, et al. Am J Clin Nutr. 2005;82(3):636-643.
[Abstract]
Homocysteine and neural tube defects. Mills JL, Scott JM, Kirke PN, et al. J Nutr. 1996;126(3):756S-760S.
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Homocysteine Lowering Trialists' Collaboration. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration. BMJ. 1998;316(7135):894-898.
[Abstract]
Homocysteine-lowering trials for prevention of cardiovascular events: a review of the design and power of the large randomized trials. Am Heart J. 2006;151(2):282-287.
[Abstract]
Importance of both folic acid and vitamin B12 in reduction of risk of vascular disease. Quinlivan EP, McPartlin J, McNulty H, et al. Lancet. 2002;359(9302):227-228.
[Abstract]
Micronucleus frequency in human lymphocytes is related to plasma vitamin B12 and homocysteine. Fenech M. Mutat Res. 1999;428(1-2):299-304.
[Abstract]
Open or closed? A world of difference: a history of homocysteine research. Eskes TK. Nutr Rev. 1998;56(8):236-244.
[Abstract]
Oral cobalamin for pernicious anemia. Medicine's best kept secret? Lederle FA. JAMA. 1991;265(1):94-95.
Oral cobalamin for treatment of pernicious anemia? Hathcock JN, Troendle GJ. JAMA. 1991;265(1):96-97.
Oral or parenteral therapy for B12 deficiency. Elia M. Lancet. 1998;352(9142):1721-1722.
Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. Seshadri S, Beiser A, Selhub J, et al. N Engl J Med. 2002;346(7):476-483.
[Abstract]
Practitioners' guide to meeting the vitamin B-12 recommended dietary allowance for people aged 51 years and older. Ho C, Kauwell GP, Bailey LB. J Am Diet Assoc. 1999;99(6):725-727.
[Abstract]
Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Luchsinger JA, Tang MX, Miller J, Green R, Mayeux R. Arch Neurol. 2007;64(1):86-92.
[Abstract]
Relation of serum ascorbic acid to serum vitamin B12, serum ferritin, and kidney stones in US adults. Simon JA, Hudes ES. Arch Intern Med. 1999;159(6):619-624.
[Abstract]
Vitamin absorption in the elderly. Kasper H. Int J Vitam Nutr Res. 1999;69(3):169-172.
Vitamin B(12) and folate in relation to the development of Alzheimer's disease. Wang HX, Wahlin A, Basun H, Fastbom J, Winblad B, Fratiglioni L. Neurology. 2001;56(9):1188-1194.
[Abstract]
Vitamin B(12) deficiency and depression in physically disabled older women: epidemiologic evidence from the Women's Health and Aging Study. Penninx BW, Guralnik JM, Ferrucci L, Fried LP, Allen RH, Stabler SP. Am J Psychiatry. 2000;157(5):715-721.
[Abstract]
Vitamin B12 deficiency in the elderly. Baik HW, Russell RM. Annu Rev Nutr. 1999;19:357-377.
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Vitamin B-12 deficiency in the elderly: current dilemmas. Stabler SP, Lindenbaum J, Allen RH. Am J Clin Nutr. 1997;66(4):741-749.
[Abstract]
Vitamin B12, folate, and homocysteine in depression: the Rotterdam Study.Tiemeier H, van Tuijl HR, Hofman A, Meijer J, Kiliaan AJ, Breteler MM. Am J Psychiatry. 2002;159(12):2099-2101.
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