Why Food Fortification with Vitamin B12 Is Needed?

  • Ilia Volkov
  • Victor R. PreedyEmail author
Part of the Nutrition and Health book series (NH)


There are many articles indicating the increasing prevalence of low vitamin B12 (also called cobalamin) status in different segments of the general population [1–7]. The early detection of vitamin B12 deficiency is essential in order to prescribe opportune treatments, and there is evidence that such deficiencies are more common than would be expected. Vitamin B12 deficiency frequently occurs in individuals with dietary patterns that exclude animal food products and patients who are unable to absorb vitamin B12. Vitamin B12 deficiency has many causes, and pernicious anemia has been described as a widespread cause of this. Recent studies on vitamin B12, including the description of novel etiologies of vitamin B12 deficiency, have added to our understanding of this essential dietary component. For example, vitamin B12 deficiency can arise not only from insufficient dietary intake [8] but also from food-cobalamin malabsorption syndrome [9]. The latter is characterized by the failure to release vitamin B12 from food or a deficiency of intestinal vitamin B12 transport proteins or both, due to chronic overgrowth of Helicobacter pylori [10] and intestinal microbial proliferation. Changes in gut flora can arise from antibiotic treatment, long-term ingestion of biguanides (metformin) [11, 12], and antacids, including H2-receptor antagonists and proton-pump inhibitors [13] (mainly among patients with Zollinger–Ellison syndrome [14]). There are also genetic vitamin B12 metabolism diseases as Imerslund–Grasbeck syndrome which is a selective vitamin B12 malabsorption with proteinuria [15]. Chronic alcoholism, surgery (e.g., bypass surgery for obesity), and partial pancreatic exocrine failure can also contribute to vitamin B12 deficiency. Overall, this demonstrates that new approaches to the identification and treatment of subjects with vitamin B12 deficiency may be needed.


Vitamin B12 Cobalamin Vitamin B12 deficiency Vitamin B12 routine fortification Malignancy and vitamin B12 Quality of life 



Magnetic resonance imaging


Recurrent aphthous stomatitis


  1. 1.
    Masalha R, Rudoy I, Volkov I, Yusuf N, Wirguin I, Herishana Y. Symptomatic dietary vitamin B12 deficiency in a nonvegetarian population. Am J Med. 2002;112:413–6.PubMedCrossRefGoogle Scholar
  2. 2.
    Stabler SP, Allen RH. Vitamin B12 deficiency as a worldwide problem. Annu Rev Nutr. 2004;24:299–326.PubMedCrossRefGoogle Scholar
  3. 3.
    Savage D, Gangaidzo I, Lindenbaum J, Kiire C, Mukiibi JM, Moyo A, et al. Vitamin B12 deficiency is the primary cause of megaloblastic anaemia in Zimbabwe. Br J Haematol. 1994;86(4):844–50.PubMedCrossRefGoogle Scholar
  4. 4.
    Allen LH. Folate and vitamin B12 status in the Americas. Nutr Rev. 2004;62(6 Pt 2):S29–33.PubMedCrossRefGoogle Scholar
  5. 5.
    Fora MA, Mohammad MA. High frequency of suboptimal serum vitamin B12 level in adults in Jordan. Saudi Med J. 2005;26(10):1591–5.PubMedGoogle Scholar
  6. 6.
    Dagnelie PC. Nutrition and health-potential health benefits and risks of vegetarianism and limited consumption of meat in the Netherlands. Ned Tijdschr Geneeskd. 2003;147(27):1308–13.PubMedGoogle Scholar
  7. 7.
    Volkov I, Rudoy I, Machagna M, Glezer I, Ganel U, Orenshtein A, et al. Modern society and prospects of low vitamin B12 intake. Ann Nutr Metab. 2007;51:468–70.PubMedCrossRefGoogle Scholar
  8. 8.
    Narayanan MN, Dawson DW, Lewis MJ. Dietary deficiency of vitamin B12 is associated with low serum cobalamin levels in non-vegetarians. Eur J Haematol. 1991;47(2):115–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Andres E, Loukili NH, Noel E, Kaltenbach G, Abdelgheni MB, Perrin AE, et al. Vitamin B12 (cobalamin) deficiency in elderly patients. CMAJ. 2004;171(3):251–9. Review.PubMedGoogle Scholar
  10. 10.
    Kaptan K, Beyan C, Ural AU, Cetin T, Avcu F, Gulsen M, et al. Helicobacter pylori—is it a novel causative agent in vitamin B12 deficiency? Arch Intern Med. 2000;160:1349–53.PubMedCrossRefGoogle Scholar
  11. 11.
    Bauman WA, Shaw S, Javatilleke E, Spungen AM, Herbert V. Increased intake of calcium reverses vitamin B12 malabsorption induced by metformin. Diabetes Care. 2000;23:1227–31.PubMedCrossRefGoogle Scholar
  12. 12.
    Andrès E, Noel E, Goichot B. Metformin-associated vitamin B12 deficiency. Arch Intern Med. 2002;162:2251–2.PubMedCrossRefGoogle Scholar
  13. 13.
    Howden CW. Vitamin B12 levels during prolonged treatment with proton pump inhibitors. J Clin Gastroenterol. 2000;30:29–33.PubMedCrossRefGoogle Scholar
  14. 14.
    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;104:422–30.PubMedCrossRefGoogle Scholar
  15. 15.
    Grasbeck R. Imerslund-Grasbeck syndrome (selective vitamin B12 malabsorption with proteinuria). Orphanet J Rare Dis. 2006;1:17.PubMedCrossRefGoogle Scholar
  16. 16.
    Smolka V, Bekarek V, Hlidkova E, et al. Metabolic complications and neurologic manifestations of vitamin B12 deficiency in children of vegetarian mothers. Cas Lek Cesk. 2001;140(23):732–5.PubMedGoogle Scholar
  17. 17.
    Muthayya S, Dwarkanath P, Mhaskar M, Mhaskar R, Thomas A, Duggan C, et al. The relationship of neonatal serum vitamin B12 status with birth weight. Asia Pac J Clin Nutr. 2006;15(4):538–43.PubMedGoogle Scholar
  18. 18.
    Brasseur D. Excessive dietetic restrictions in children. Rev Med Brux. 2000;21(4):A367–70.PubMedGoogle Scholar
  19. 19.
    Healton EB, Savage DG, Brust JC, Carett TJ, Lindenbaum J. Neurologic aspects of cobalamin deficiency. Medicine (Baltimore). 1991;70(4):229–45.PubMedGoogle Scholar
  20. 20.
    Miller A, Korem M, Almog R, Galboiz Y. Vitamin B12, demyelination, remyelination and repair in multiple sclerosis. J Neurol Sci. 2005;233(1–2):93–7. Review.PubMedCrossRefGoogle Scholar
  21. 21.
    Wolters M, Strohle A, Hahn A. Cobalamin: a critical vitamin in the elderly. Prev Med. 2004;39:1256–66.PubMedCrossRefGoogle Scholar
  22. 22.
    Masalha R, Chudakov B, Muhamad M, Rudoy I, Volkov I, Wirguin I. Cobalamin-responsive psychosis as the sole manifestation of vitamin B12 deficiency. Isr Med Assoc J. 2001;3:701–3.PubMedGoogle Scholar
  23. 23.
    Sachdev PS. Homocysteine and brain atrophy. Prog Neuropsychopharmacol Biol Psychiatry. 2005;29(7):1152–61. Review.PubMedCrossRefGoogle Scholar
  24. 24.
    Corder EH, Beaumont H. Susceptibility groups for Alzheimer’s disease (OPTIMA cohort): integration of gene variants and biochemical factors. Mech Ageing Dev. 2006;128(1):76–82.PubMedCrossRefGoogle Scholar
  25. 25.
    Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol. 2006;5(11):949–60. Review.PubMedCrossRefGoogle Scholar
  26. 26.
    Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke. JAMA. 2002;288:2015–22.CrossRefGoogle Scholar
  27. 27.
    Del Ser T, Barba R, Herranz AS, Seijas V, López-Manglano C, Domingo J, et al. Hyperhomocyst(e)inemia is a risk factor of secondary vascular events in stroke patients. Cerebrovasc Dis. 2001;12:91–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Boysen G, Brander T, Christensen H, Gideon R, Truelsen T. Homocysteine and risk of recurrent stroke. Stroke. 2003;34(5):1258–61.PubMedCrossRefGoogle Scholar
  29. 29.
    Stanger O, Herrmann W, Pietrzik K, Fowler B, Geisel J, Dierkes J, et al. DACH-LIGA homocystein (German, Austrian and Swiss Homocysteine Society): consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. Clin Chem Lab Med. 2003;41:1392–403.PubMedGoogle Scholar
  30. 30.
    Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;355(7):746. Erratum in: N Engl J Med. 2006;355(7):746.CrossRefGoogle Scholar
  31. 31.
    Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006;354(15):1578–88.PubMedCrossRefGoogle Scholar
  32. 32.
    Bazzano LA, Reynolds K, Holder KN, He J. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA. 2006;296(22):2720–6.PubMedCrossRefGoogle Scholar
  33. 33.
    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(2):82–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Wheatley C. A scarlet pimpernel for the resolution of inflammation? The role of supra-therapeutic doses of cobalamin, in the treatment of systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, and septic or traumatic shock. Med Hypotheses. 2006;67(1):124–42.PubMedCrossRefGoogle Scholar
  35. 35.
    Broderick KE, Feala J, McCulloch A, Paternostro G, Sharma VS, Pilz RB, et al. The nitric oxide scavenger cobinamide profoundly improves survival in Drosophila melanogaster model of bacterial sepsis. FASEB J. 2006;20(11):1865–73.PubMedCrossRefGoogle Scholar
  36. 36.
    Diamond AL. Vitamin B12-associated neurological diseases. Review, eMedicine Website. Last updated Nov.2004.Google Scholar
  37. 37.
    Solomon LR. Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing. Blood. 2005;105:978–85.PubMedCrossRefGoogle Scholar
  38. 38.
    Hash RB, Sargent MA, Katner H. Anemia secondary to combined deficiencies of iron and cobalamin. Arch Fam Med. 1996;5:585–8.PubMedCrossRefGoogle Scholar
  39. 39.
    Carmel R. Prevalence of undiagnosed pernicious anemia in the elderly. Arch Intern Med. 1996;156:1097–100.PubMedCrossRefGoogle Scholar
  40. 40.
    Herrmann W, Obeid R, Schorr H, Geisel J. Functional vitamin B12 deficiency and determination of holotranscobalamin in populations at risk. Clin Chem Lab Med. 2003;41(11):1478–88.PubMedGoogle Scholar
  41. 41.
    Volkov I, Rudoy I, Freud T, Sardal G, Naimer S, Peleg R, et al. Effectiveness of vitamin B12 in treating recurrent aphthous stomatitis: a randomized double blind placebo controlled trial. J Am Board Fam Med. 2009;22:9–16.PubMedCrossRefGoogle Scholar
  42. 42.
    Kumamoto Y, Maruta H, Ishigami J, Kamidono S, Orikasa S, Kimura M, et al. Clinical efficacy of mecobalamin in the treatment of oligozoospermia—results of double-blind comparative clinical study. Hinyokika Kiyo. 1988;34(6):1109–32.PubMedGoogle Scholar
  43. 43.
    Bennett M. Vitamin B12 deficiency, infertility and recurrent fetal loss. J Reprod Med. 2001;46(3):209–12.PubMedGoogle Scholar
  44. 44.
    Chatterjee S, Chowdhury RG, Khan B. Medical management of male infertility. J Indian Med Assoc. 2006;104(2):74, 76–7.Google Scholar
  45. 45.
    Reznikoff-Etievant MF, Zittoun J, Vaylet C, Pernet P, Milliez J. Low vitamin B(12) level as a risk factor for very early recurrent abortion. Eur J Obstet Gynecol Reprod Biol. 2002;104(2):156–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Herrmann M, Widmann T, Herrmann W. Homocysteine—a newly recognised risk factor for osteoporosis. Clin Chem Lab Med. 2005;43(10):1111–7. Review.PubMedGoogle Scholar
  47. 47.
    Bloom DE. 7 Billion and counting. Science. 2011;333:560–2.CrossRefGoogle Scholar
  48. 48.
    Sipponen P, Laxén F, Huotari K, Härkönen M. Prevalence of low vitamin B12 and high homocysteine in serum in an elderly male population: association with atrophic gastritis and Helicobacter pylori infection. Scand J Gastroenterol. 2003;38(12):1209–16.PubMedCrossRefGoogle Scholar
  49. 49.
    Andersen CB, Madsen M, Storm T, Moestrup SK, Andersen GR. Structural basis for receptor recognition of vitamin-B(12)-intrinsic factor complexes. Nature. 2010;464(7287):445–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Wang YH, Yan F, Zhang WB, Ye G, Zheng YY, Zhang XH, et al. An investigation of vitamin B12 deficiency in elderly inpatients in neurology department. Neurosci Bull. 2009;25(4):209–15.PubMedCrossRefGoogle Scholar
  51. 51.
    Bozoglu E, Isik AT, Doruk H, Kilic S. The effects of early vitamin B12 replacement therapy on the cognitive and functional status of elderly subjects. Bull Clin Psychopharmacol. 2010;20:120–4.Google Scholar
  52. 52.
    Watanabe F. Vitamin B12 sources and bioavailability. Exp Biol Med (Maywood). 2007;232(10):1266–74.CrossRefGoogle Scholar
  53. 53.
    Dangour AD, Allen E, Clarke R, Elbourne D, Fasey N, Fletcher AE, et al. A randomised controlled trial investigating the effect of vitamin B12 supplementation on neurological function in healthy older people: the Older People and Enhanced Neurological function (OPEN) study protocol [ISRCTN54195799]. Nutr J. 2011;10:22.PubMedCrossRefGoogle Scholar
  54. 54.
    Lin YT, Lin MH, Lai HY, Chen LK, Hwang SJ, Lan CF. Regular vitamin B12 supplementation among older Chinese men in a veterans care home in Taiwan. Arch Gerontol Geriatr. 2009;49(1):186–9.PubMedCrossRefGoogle Scholar
  55. 55.
    Selhub J, Paul L. Folic acid fortification: why not vitamin B12 also? Biofactors. 2011;37(4):269–71. doi: 10.1002/biof.173.PubMedCrossRefGoogle Scholar
  56. 56.
    Recommended Dietary Allowances: 10th edn. Retrieved 30 March 2011.
  57. 57.
    Bor MV, Lydeking-Olsen E, Moller J, Nexo E. A daily intake of approximately 6 micrograms of vitamin B-12 appears to saturate all the vitamin B-12-related variables in Danish postmenopausal women. Am J Clin Nutr. 2006;83:52–8.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Family Medicine, Siaal Research Center for Family Medicine and Primary CareBen-Gurion University of the Negev Beer-ShevaLehavimIsrael
  2. 2.Department of Nutrition and Dietetics, Diabetes and Nutritional Sciences, School of MedicineKing’s College LondonLondonUK

Personalised recommendations