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Micronutrient Information Center

References: Vitamin B12


1.  Brody T. Nutritional Biochemistry. 2nd ed. San Diego: Academic Press; 1999.

2.  Carmel R. Cobalamin (Vitamin B-12). 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.

3.  Shane B. Folic acid, vitamin B-12, and vitamin B-6. In: Stipanuk M, ed. Biochemical and Physiological Aspects of Human Nutrition. Philadelphia: W.B. Saunders Co.; 2000:483-518.

4.  Carmel R. How I treat cobalamin (vitamin B12) deficiency. Blood. 2008;112(6):2214-2221.  (PubMed)

5.  Kozyraki R, Cases O. Vitamin B12 absorption: mammalian physiology and acquired and inherited disorders. Biochimie. 2013;95(5):1002-1007.  (PubMed)

6.  Baik HW, Russell RM. Vitamin B12 deficiency in the elderly. Annu Rev Nutr. 1999;19:357-377.  (PubMed)

7.  Neumann WL, Coss E, Rugge M, Genta RM. Autoimmune atrophic gastritis--pathogenesis, pathology and management. Nat Rev Gastroenterol Hepatol. 2013;10(9):529-541.  (PubMed)

8.  Lahner E, Persechino S, Annibale B. Micronutrients (Other than iron) and Helicobacter pylori infection: a systematic review. Helicobacter. 2012;17(1):1-15.  (PubMed)

9.  Carmel R. Megaloblastic anemias. Curr Opin Hematol. 1994;1(2):107-112.  (PubMed)

10.  Banka S, Ryan K, Thomson W, Newman WG. Pernicious anemia - genetic insights. Autoimmun Rev. 2011;10(8):455-459.  (PubMed)

11.  Lam-Tse WK, Batstra MR, Koeleman BP, et al. The association between autoimmune thyroiditis, autoimmune gastritis and type 1 diabetes. Pediatr Endocrinol Rev. 2003;1(1):22-37.  (PubMed)

12.  Checchi S, Montanaro A, Ciuoli C, et al. Prevalence of parietal cell antibodies in a large cohort of patients with autoimmune thyroiditis. Thyroid. 2010;20(12):1385-1389.  (PubMed)

13.  Ho C, Kauwell GP, Bailey LB. Practitioners' guide to meeting the vitamin B-12 recommended dietary allowance for people aged 51 years and older. J Am Diet Assoc. 1999;99(6):725-727.  (PubMed)

14.  Watkins D, Rosenblatt DS. Lessons in biology from patients with inborn errors of vitamin B12 metabolism. Biochimie. 2013;95(5):1019-1022.  (PubMed)

15.  Weir DG, Scott JM. Vitamin B12 "Cobalamin". In: Shils M, ed. Nutrition in Health and Disease. 9th ed. Baltimore: Williams & Wilkins; 1999:447-458.

16.  Herbert V. Vitamin B-12. In: Ziegler EE, Filer LJ, eds. Present Knowledge in Nutrition. 7th ed. Washington D.C.: ILSI Press; 1996:191-205.

17.  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)

18.  Scalabrino G. The multi-faceted basis of vitamin B12 (cobalamin) neurotrophism in adult central nervous system: Lessons learned from its deficiency. Prog Neurobiol. 2009;88(3):203-220.  (PubMed)

19.  Schottker B, Adamu MA, Weck MN, Muller H, Brenner H. Helicobacter pylori infection, chronic atrophic gastritis and major cardiovascular events: a population-based cohort study. Atherosclerosis. 2012;220(2):569-574.  (PubMed)

20.  Gerhard GT, Duell PB. Homocysteine and atherosclerosis. Curr Opin Lipidol. 1999;10(5):417-428.  (PubMed)

21.  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.  (PubMed)

22.  Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration. Bmj. 1998;316(7135):894-898.  (PubMed)

23.  Quinlivan EP, McPartlin J, McNulty H, et al. Importance of both folic acid and vitamin B12 in reduction of risk of vascular disease. Lancet. 2002;359(9302):227-228.  (PubMed)

24.  Stabler SP, Lindenbaum J, Allen RH. Vitamin B-12 deficiency in the elderly: current dilemmas. Am J Clin Nutr. 1997;66(4):741-749.  (PubMed)

25.  Marti-Carvajal AJ, Sola I, Lathyris D, Karakitsiou DE, Simancas-Racines D. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2013;1:CD006612.  (PubMed)

26.  Huang T, Chen Y, Yang B, Yang J, Wahlqvist ML, Li D. Meta-analysis of B vitamin supplementation on plasma homocysteine, cardiovascular and all-cause mortality. Clin Nutr. 2012;31(4):448-454.  (PubMed)

27.  Ji Y, Tan S, Xu Y, et al. Vitamin B supplementation, homocysteine levels, and the risk of cerebrovascular disease: A meta-analysis. Neurology. 2013;81(15):1298-1307.  (PubMed)

28.  Potter K, Hankey GJ, Green DJ, Eikelboom J, Jamrozik K, Arnolda LF. The effect of long-term homocysteine-lowering on carotid intima-media thickness and flow-mediated vasodilation in stroke patients: a randomized controlled trial and meta-analysis. BMC Cardiovasc Disord. 2008;8:24.  (PubMed)

29.  Qin X, Xu M, Zhang Y, et al. Effect of folic acid supplementation on the progression of carotid intima-media thickness: a meta-analysis of randomized controlled trials. Atherosclerosis. 2012;222(2):307-313.  (PubMed)

30.  Spence JD. B vitamin therapy for homocysteine: renal function and vitamin B12 determine cardiovascular outcomes. Clin Chem Lab Med. 2013;51(3):633-637.  (PubMed)

31.  Fenech M. Folate (vitamin B9) and vitamin B12 and their function in the maintenance of nuclear and mitochondrial genome integrity. Mutat Res. 2012;733(1-2):21-33.  (PubMed)

32.  Fenech M. Micronucleus frequency in human lymphocytes is related to plasma vitamin B12 and homocysteine. Mutat Res. 1999;428(1-2):299-304.  (PubMed)

33.  Wu K, Helzlsouer KJ, Comstock GW, Hoffman SC, Nadeau MR, Selhub J. A prospective study on folate, B12, and pyridoxal 5'-phosphate (B6) and breast cancer. Cancer Epidemiol Biomarkers Prev. 1999;8(3):209-217.  (PubMed)

34.  Wu W, Kang S, Zhang D. Association of vitamin B6, vitamin B12 and methionine with risk of breast cancer: a dose-response meta-analysis. Br J Cancer. 2013;109(7):1926-1944.  (PubMed)

35.  Lajous M, Lazcano-Ponce E, Hernandez-Avila M, Willett W, Romieu I. Folate, vitamin B(6), and vitamin B(12) intake and the risk of breast cancer among Mexican women. Cancer Epidemiol Biomarkers Prev. 2006;15(3):443-448.  (PubMed)

36.  Yang D, Baumgartner RN, Slattery ML, et al. Dietary intake of folate, B-vitamins and methionine and breast cancer risk among Hispanic and non-Hispanic white women. PLoS One. 2013;8(2):e54495.  (PubMed)

37.  Bassett JK, Baglietto L, Hodge AM, et al. Dietary intake of B vitamins and methionine and breast cancer risk. Cancer Causes Control. 2013;24(8):1555-1563.  (PubMed)

38.  Eskes TK. Open or closed? A world of difference: a history of homocysteine research. Nutr Rev. 1998;56(8):236-244.  (PubMed)

39.  Mills JL, Scott JM, Kirke PN, et al. Homocysteine and neural tube defects. J Nutr. 1996;126(3):756S-760S.  (PubMed)

40.  Imbard A, Benoist JF, Blom HJ. Neural tube defects, folic acid and methylation. Int J Environ Res Public Health. 2013;10(9):4352-4389.  (PubMed)

41.  Wang ZP, Shang XX, Zhao ZT. Low maternal vitamin B(12) is a risk factor for neural tube defects: a meta-analysis. J Matern Fetal Neonatal Med. 2012;25(4):389-394.  (PubMed)

42.  Dror DK, Allen LH. Interventions with vitamins B6, B12 and C in pregnancy. Paediatr Perinat Epidemiol. 2012;26 Suppl 1:55-74.  (PubMed)

43.  McCaddon A. Vitamin B12 in neurology and ageing; clinical and genetic aspects. Biochimie. 2013;95(5):1066-1076.  (PubMed)

44.  Nourhashemi F, Gillette-Guyonnet S, Andrieu S, et al. Alzheimer disease: protective factors. Am J Clin Nutr. 2000;71(2):643S-649S.  (PubMed)

45.  Smith AD. The worldwide challenge of the dementias: a role for B vitamins and homocysteine? Food Nutr Bull. 2008;29(2 Suppl):S143-172.  (PubMed)

46.  Clarke R, Smith AD, Jobst KA, Refsum H, Sutton L, Ueland PM. Folate, vitamin B12, and serum total homocysteine levels in confirmed Alzheimer disease. Arch Neurol. 1998;55(11):1449-1455.  (PubMed)

47.  Seshadri S, Beiser A, Selhub J, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N Engl J Med. 2002;346(7):476-483.  (PubMed)

48.  Ravaglia G, Forti P, Maioli F, et al. Homocysteine and cognitive function in healthy elderly community dwellers in Italy. Am J Clin Nutr. 2003;77(3):668-673.  (PubMed)

49.  Ravaglia G, Forti P, Maioli F, et al. Homocysteine and folate as risk factors for dementia and Alzheimer disease. Am J Clin Nutr. 2005;82(3):636-643.  (PubMed)

50.  O'Leary F, Allman-Farinelli M, Samman S. Vitamin B(1)(2) status, cognitive decline and dementia: a systematic review of prospective cohort studies. Br J Nutr. 2012;108(11):1948-1961.  (PubMed)

51.  Clarke R, Birks J, Nexo E, et al. Low vitamin B-12 status and risk of cognitive decline in older adults. Am J Clin Nutr. 2007;86(5):1384-1391.  (PubMed)

52.  Tangney CC, Tang Y, Evans DA, Morris MC. Biochemical indicators of vitamin B12 and folate insufficiency and cognitive decline. Neurology. 2009;72(4):361-367.  (PubMed)

53.  Kivipelto M, Annerbo S, Hultdin J, et al. Homocysteine and holo-transcobalamin and the risk of dementia and Alzheimers disease: a prospective study. Eur J Neurol. 2009;16(7):808-813.  (PubMed)

54.  Hooshmand B, Solomon A, Kareholt I, et al. Homocysteine and holotranscobalamin and the risk of Alzheimer disease: a longitudinal study. Neurology. 2010;75(16):1408-1414.  (PubMed)

55.  Hooshmand B, Solomon A, Kareholt I, et al. Associations between serum homocysteine, holotranscobalamin, folate and cognition in the elderly: a longitudinal study. J Intern Med. 2012;271(2):204-212.  (PubMed)

56.  Ford AH, Almeida OP. Effect of homocysteine lowering treatment on cognitive function: a systematic review and meta-analysis of randomized controlled trials. J Alzheimers Dis. 2012;29(1):133-149.  (PubMed)

57.  Walker JG, Batterham PJ, Mackinnon AJ, et al. Oral folic acid and vitamin B-12 supplementation to prevent cognitive decline in community-dwelling older adults with depressive symptoms--the Beyond Ageing Project: a randomized controlled trial. Am J Clin Nutr. 2012;95(1):194-203.  (PubMed)

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

59.  Douaud G, Refsum H, de Jager CA, et al. Preventing Alzheimer's disease-related gray matter atrophy by B-vitamin treatment. Proc Natl Acad Sci U S A. 2013;110(23):9523-9528.  (PubMed)

60.  Hankey GJ, Ford AH, Yi Q, et al. Effect of B vitamins and lowering homocysteine on cognitive impairment in patients with previous stroke or transient ischemic attack: a prespecified secondary analysis of a randomized, placebo-controlled trial and meta-analysis. Stroke. 2013;44(8):2232-2239.  (PubMed)

61.  Hutto BR. Folate and cobalamin in psychiatric illness. Compr Psychiatry. 1997;38(6):305-314.  (PubMed)

62.  Penninx BW, Guralnik JM, Ferrucci L, Fried LP, Allen RH, Stabler SP. Vitamin B(12) deficiency and depression in physically disabled older women: epidemiologic evidence from the Women's Health and Aging Study. Am J Psychiatry. 2000;157(5):715-721.  (PubMed)

63.  Tiemeier H, van Tuijl HR, Hofman A, Meijer J, Kiliaan AJ, Breteler MM. Vitamin B12, folate, and homocysteine in depression: the Rotterdam Study. Am J Psychiatry. 2002;159(12):2099-2101.  (PubMed)

64.  Mischoulon D, Fava M. Role of S-adenosyl-L-methionine in the treatment of depression: a review of the evidence. Am J Clin Nutr. 2002;76(5):1158S-1161S.  (PubMed)

65.  Fernandez-Roig S, Lai SC, Murphy MM, Fernandez-Ballart J, Quadros EV. Vitamin B12 deficiency in the brain leads to DNA hypomethylation in the TCblR/CD320 knockout mouse. Nutr Metab (Lond). 2012;9:41.  (PubMed)

66.  Bressa GM. S-adenosyl-l-methionine (SAMe) as antidepressant: meta-analysis of clinical studies. Acta Neurol Scand Suppl. 1994;154:7-14.  (PubMed)

67.  Bell KM, Plon L, Bunney WE, Jr., Potkin SG. S-adenosylmethionine treatment of depression: a controlled clinical trial. Am J Psychiatry. 1988;145(9):1110-1114.  (PubMed)

68.  Delle Chiaie R, Pancheri P, Scapicchio P. 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. Am J Clin Nutr. 2002;76(5):1172S-1176S.  (PubMed)

69.  Williams AL, Girard C, Jui D, Sabina A, Katz DL. S-adenosylmethionine (SAMe) as treatment for depression: a systematic review. Clin Invest Med. 2005;28(3):132-139.  (PubMed)

70.  Almeida OP, McCaul K, Hankey GJ, Norman P, Jamrozik K, Flicker L. Homocysteine and depression in later life. Arch Gen Psychiatry. 2008;65(11):1286-1294.  (PubMed)

71.  Moorthy D, Peter I, Scott TM, et al. Status of vitamins B-12 and B-6 but not of folate, homocysteine, and the methylenetetrahydrofolate reductase C677T polymorphism are associated with impaired cognition and depression in adults. J Nutr. 2012;142(8):1554-1560.  (PubMed)

72.  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.  (PubMed)

73.  Almeida OP, Marsh K, Alfonso H, Flicker L, Davis TM, Hankey GJ. B-vitamins reduce the long-term risk of depression after stroke: The VITATOPS-DEP trial. Ann Neurol. 2010;68(4):503-510.  (PubMed)

74.  Vacek TP, Kalani A, Voor MJ, Tyagi SC, Tyagi N. The role of homocysteine in bone remodeling. Clin Chem Lab Med. 2013;51(3):579-590.  (PubMed)

75.  van Wijngaarden JP, Doets EL, Szczecinska A, et al. Vitamin B12, folate, homocysteine, and bone health in adults and elderly people: a systematic review with meta-analyses. J Nutr Metab. 2013;2013:486186.  (PubMed)

76.  Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K. Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. JAMA. 2005;293(9):1082-1088.  (PubMed)

77.  Sawka AM, Ray JG, Yi Q, Josse RG, Lonn E. Randomized clinical trial of homocysteine level lowering therapy and fractures. Arch Intern Med. 2007;167(19):2136-2139.  (PubMed)

78.  Herrmann W, Kirsch SH, Kruse V, et al. One year B and D vitamins supplementation improves metabolic bone markers. Clin Chem Lab Med. 2013;51(3):639-647.  (PubMed)

79.  van Wijngaarden JP, Dhonukshe-Rutten RA, van Schoor NM, et al. Rationale and design of the B-PROOF study, a randomized controlled trial on the effect of supplemental intake of vitamin B12 and folic acid on fracture incidence. BMC Geriatr. 2011;11:80.  (PubMed)

80.  LeBlanc JG, Milani C, de Giori GS, Sesma F, van Sinderen D, Ventura M. Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr Opin Biotechnol. 2013;24(2):160-168.  (PubMed)

81.  Watanabe F, Yabuta Y, Tanioka Y, Bito T. Biologically active vitamin B12 compounds in foods for preventing deficiency among vegetarians and elderly subjects. J Agric Food Chem. 2013;61(28):6769-6775.  (PubMed)

82.  Pawlak R, Parrott SJ, Raj S, Cullum-Dugan D, Lucus D. How prevalent is vitamin B(12) deficiency among vegetarians? Nutr Rev. 2013;71(2):110-117.  (PubMed)

83.  Hendler SS, Rorvik DR, eds. PDR for Nutritional Supplements. Montvale: Medical Economics Company, Inc; 2001.

84.  Kuzminski AM, Del Giacco EJ, Allen RH, Stabler SP, Lindenbaum J. Effective treatment of cobalamin deficiency with oral cobalamin. Blood. 1998;92(4):1191-1198.  (PubMed)

85.  Dharmarajan TS, Kanagala MR, Murakonda P, Lebelt AS, Norkus EP. Do acid-lowering agents affect vitamin B12 status in older adults? J Am Med Dir Assoc. 2008;9(3):162-167.  (PubMed)

86.  Wilhelm SM, Rjater RG, Kale-Pradhan PB. Perils and pitfalls of long-term effects of proton pump inhibitors. Expert Rev Clin Pharmacol. 2013;6(4):443-451.  (PubMed)

87.  Valuck RJ, Ruscin JM. A case-control study on adverse effects: H2 blocker or proton pump inhibitor use and risk of vitamin B12 deficiency in older adults. J Clin Epidemiol. 2004;57(4):422-428.  (PubMed)

88. Termanini B, Gibril F, Sutliff VE, Yu F, Venzon DJ, Jensen RT. Effect of long-term gastric acid suppressive therapy on serum vitamin B12 levels in patients with Zollinger-Ellison syndrome. Am J Med. 1998;104(5):422-430.  (PubMed)

89.  Bauman WA, Shaw S, Jayatilleke E, Spungen AM, Herbert V. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care. 2000;23(9):1227-1231.  (PubMed)

90.  Obeid R. Metformin causing vitamin B12 deficiency: a guilty verdict without sufficient evidence. Diabetes Care. 2014;37(2):e22-23.  (PubMed)

91.  Mazokopakis EE, Starakis IK. Recommendations for diagnosis and management of metformin-induced vitamin B12 (Cbl) deficiency. Diabetes Res Clin Pract. 2012;97(3):359-367.  (PubMed)

92.  Simon JA, Hudes ES. Relation of serum ascorbic acid to serum vitamin B12, serum ferritin, and kidney stones in US adults. Arch Intern Med. 1999;159(6):619-624.  (PubMed)