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The Role of B-Vitamins in Nutritional Anemia

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Nutritional Anemia

Part of the book series: Nutrition and Health ((NH))

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Abstract

Severe deficiency of either folate or vitamin B12 leads to megaloblastic anemia which clinically manifests as fatigue, weakness, and shortness of breath owing to a low red blood cell count. Hematologically, megaloblastic anemia is characterized by the presence of large, immature, nucleated cells (megaloblasts) in the bone marrow and macrocytes in the peripheral blood. Folate deficiency typically arises when folate requirement is increased (e.g., in pregnancy) and/or when folate availability is reduced as a result of low dietary intakes or malabsorption (e.g., in celiac disease). Pernicious anemia, the clinical condition of severe deficiency of vitamin B12, arises from an autoimmune gastritis characterized by B12 malabsorption owing to loss of intrinsic factor. A more subtle depletion of vitamin B12 status can however arise from mild atrophic gastritis leading to reduced gastric acid production, thereby diminishing B12 absorption from food. Apart from folate and B12, riboflavin deficiency can also lead to nutritional anemia. There are consequences of B-vitamin deficiency throughout the lifecycle, adversely affecting metabolic functioning and contributing substantially to the global burden of disease. This chapter will consider the causes, detection, and consequences of B-vitamin deficiency, ranging from the anemia of clinical deficiency to other manifestations associated with less severe deficiency, and the potential for prevention through effective public health measures.

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References

  1. WHO Global Nutrition Targets 2025. Anaemia policy brief. Geneva: World Health Organization; 2014 (WHO/NMH/NHD/14.4). https://www.who.int/nutrition/publications/globaltargets2025_policybrief_anaemia/en/.

  2. Bailey LB, Stover PJ, McNulty H, et al. Biomarkers of nutrition for development—folate review. J Nutr. 2015;145:1636S–80S.

    Article  CAS  Google Scholar 

  3. McNulty H, Ward M, Hoey L, Hughes CF, Pentieva K. Addressing optimal folate and related B vitamin status through the lifecycle: health impacts and challenges. Proc Nutr Soc. 2019;78(3):449–62.

    Article  Google Scholar 

  4. Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. Washington (DC): National Academies Press (US); 1998.

    Google Scholar 

  5. European Food Safety Authority (EFSA) Panel on Dietetic Products, Nutrition and Allergies (NDA). Scientific opinion on dietary reference values for folate. EFSA J. 2014;12(11):3893.

    Google Scholar 

  6. Gibson RS. Assessment of folate and vitamin B12 status. In: Principles of nutritional assessment. 2nd ed. New York, NY: Oxford University Press; 2005. p. 595–640.

    Google Scholar 

  7. Refsum H, Smith AD, Ueland PM, et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem. 2004;50:3–32.

    Article  CAS  Google Scholar 

  8. Rogers LM, Cordero AM, Pfeiffer CM, et al. Global folate status in women of reproductive age: a systematic review with emphasis on methodological issues. Ann N Y Acad Sci. 2018;1431:35–57.

    Article  CAS  Google Scholar 

  9. McNulty B, McNulty H, Marshall B, et al. Impact of continuing folic acid after the first trimester of pregnancy: findings of a randomized trial of folic acid supplementation in the second and third trimesters. Am J Clin Nutr. 2013;98:92–8.

    Article  CAS  Google Scholar 

  10. Blot I, Papiernik E, Kaltwasser JP, et al. Influence of routine administration of folic acid and iron during pregnancy. Gynecol Obstet Investig. 1981;12:294–304.

    Article  CAS  Google Scholar 

  11. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Council Vitamin Study. Lancet. 1991;338:131–7.

    Article  Google Scholar 

  12. Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992;327:1832–5.

    Article  CAS  Google Scholar 

  13. Vollset E, Botto LD. Neural tube defects, other congenital malformations and single nucleotide polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene. In: Ueland P, Rozen R, editors. MTHFR polymorphisms and disease. Georgetown, TX: Landes Bioscience; 2004. p. 127–45.

    Google Scholar 

  14. Rothenberg SP, da Costa MP, Sequeira JM, et al. Autoantibodies against folate receptors in women with a pregnancy complicated by a neural-tube defect. N Engl J Med. 2004;350:134–42.

    Article  CAS  Google Scholar 

  15. Molloy AM, Kirke PN, Troendle JF, Burke H, Brody LC, Scott JM, Mills JL. Maternal vitamin B12 status and risk of neural tube defects in a population with high neural tube defects and no folic acid supplementation. Pediatrics. 2009;123:917–23.

    Article  Google Scholar 

  16. Van Beynum IM, Kapusta L, Bakker MK, et al. Protective effect of periconceptional folic acid supplements on the risk of congenital heart defects: a registry-based case-control study in the northern Netherlands. Eur Heart J. 2010;31:464–71.

    Article  Google Scholar 

  17. Psara E, Pentieva K, Ward M, McNulty H. Critical review of nutrition, blood pressure and risk of hypertension through the lifecycle: do B vitamins play a role? Biochimie. 2020;173:76–90.

    Article  CAS  Google Scholar 

  18. De Ocampo MPG, Araneta MRG, Macera CA, Alcaraz JE, Moore TRCC. Folic acid supplement use and the risk of gestational hypertension and preeclampsia. Women Birth. 2018;31:e77–83.

    Article  Google Scholar 

  19. Wen SW, White RR, Rybak N, Gaudet LM, et al. Effect of high dose folic acid supplementation in pregnancy on pre-eclampsia (FACT): double blind, phase III, randomised controlled, international, multicentre trial. BMJ. 2018;362:k3478.

    Article  Google Scholar 

  20. Caffrey A, McNulty H, Irwin RE, et al. Maternal folate nutrition and offspring health: evidence and current controversies. Proc Nutr Soc. 2019;78:208–20.

    Article  Google Scholar 

  21. James P, Sajjadi S, Tomar AS, et al. Candidate genes linking maternal nutrient exposure to offspring health via DNA methylation: a review of existing evidence in humans with specific focus on one-carbon metabolism. Int J Epidemiol. 2018;47(6):1910–37.

    Google Scholar 

  22. McNulty H, Strain JJ, Pentieva K, Ward M. One-carbon metabolism and CVD outcomes in older adults. Proc Nutr Soc. 2012;71:213–21.

    Article  CAS  Google Scholar 

  23. Wang X, Qin X, Demirtas H, et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet. 2007;369:1876–82.

    Article  CAS  Google Scholar 

  24. Yang Q, Botto LD, Erickson JD, et al. Improvement in stroke mortality in Canada and the United States, 1990 to 2002. Circulation. 2006;113:1335–43.

    Article  Google Scholar 

  25. Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354:1567–77.

    Article  CAS  Google Scholar 

  26. Saposnik G, Ray JG, Sheridan P, et al. the HOPE 2 Investigators. Homcysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke. 2009;40:1365–72.

    Article  CAS  Google Scholar 

  27. Rosenblatt DS. Inherited disorders of folate transport and metabolism. In: Scriver CR, Beaudet AL, Sly WS, et al., editors. The metabolic basis of inherited disease. New York: Mc Graw; 1995. p. 3111–28.

    Google Scholar 

  28. Porter K, Hoey L, Hughes CF, et al. Causes, consequences and public health implications of low B-vitamin status in ageing. Nutrients. 2016;8:1–29.

    Article  Google Scholar 

  29. 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:e12244.

    Article  Google Scholar 

  30. 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. 2013;110:9523–8.

    Article  CAS  Google Scholar 

  31. Reynolds E. Vitamin B12, folic acid, and the nervous system. Lancet Neurol. 2006;5:949–60.

    Article  CAS  Google Scholar 

  32. Gilbody S, Lightfoot T, Sheldon T. Is low folate a risk factor for depression? A meta-analysis and exploration of heterogeneity. J Epidemiol Comm Hlth. 2007;61:631–7.

    Article  Google Scholar 

  33. Moore K, Hughes CF, Hoey L, et al. B-vitamins in relation to depression in older adults over 60 years of age: the TUDA Cohort study. JAMDA. 2019;20(2):551–7.

    Google Scholar 

  34. Gjesdal CG, Vollset SE, Ueland PM, et al. Plasma homocysteine, folate, and vitamin B 12 and the risk of hip fracture: the Hordaland Homocysteine Study. J Bone Miner Res. 2007;22:747–56.

    Article  CAS  Google Scholar 

  35. van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med. 2004;350:2033–41.

    Article  Google Scholar 

  36. Kim Y-I. Folate and carcinogenesis: evidence, mechanisms, and implications. J Nutr Biochem. 1999;10:66–88.

    Article  CAS  Google Scholar 

  37. Blount BC, Mack MM, Wehr CM, et al. Folate deficiency causes uracil misincorporation into human DNA and chromosome breakage: implications for cancer and neuronal damage. Proc Natl Acad Sci U S A. 1997;94:3290–5.

    Article  CAS  Google Scholar 

  38. Cole BF, Baron JA, Sandler RS, et al. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007;297:2351–9.

    Article  CAS  Google Scholar 

  39. Allen LH, Miller JW, de Groot L, Rosenberg IH, Smith AD, Refsum H, Raiten DJ. Biomarkers of nutrition for development (BOND): vitamin B-12 review. J Nutr. 2018;148:1995S–2027S.

    Article  Google Scholar 

  40. Stabler SP. Vitamin B12 deficiency. New Engl J Med. 2013;368:2041–2.

    Article  CAS  Google Scholar 

  41. Carmel R. Diagnosis and management of clinical and subclinical cobalamin deficiencies: why controversies persist in the age of sensitive metabolic testing. Biochimie. 2013;95:1047–55.

    Article  CAS  Google Scholar 

  42. Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310:2435–42.

    Article  CAS  Google Scholar 

  43. Porter KM, Ward M, Hughes CF. Hyperglycemia and metformin use are associated with B vitamin deficiency and cognitive dysfunction in older adults. J Clin Endocrinol Metab. 2019;104:4837–47.

    Article  Google Scholar 

  44. Green R, Allen LH, Bjorke-Monsen AL, et al. Vitamin B12 deficiency. Nat Rev Dis Primers. 2017;3:17040.

    Article  Google Scholar 

  45. Hughes CF, McNulty. Assessing biomarker status of vitamin B12 in the laboratory: no simple solution. Ann Clin Biochem. 2018;55:188–9.

    Article  CAS  Google Scholar 

  46. Almeida OP, Ford AH, Flicker L. Systematic review and meta-analysis of randomized placebo-controlled trials of folate and vitamin B12 for depression. Int Psychogeriatr. 2015;27:727–37.

    Article  Google Scholar 

  47. Tucker KL, Hannan MT, Qiao N, et al. Low plasma vitamin B12 is associated with lower BMD: the Framingham Osteoporosis study. J Bone Miner Res. 2005;20:152–8.

    Article  CAS  Google Scholar 

  48. Morris M, Jacques P. Selhub J Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans. Bone. 2005;37:234–42.

    Article  CAS  Google Scholar 

  49. 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.

    Google Scholar 

  50. Carmel R, Lau K, Baylink D, et al. Cobalamin and osteoblast-specific proteins. N Engl J Med. 1988;319:70–5.

    Article  CAS  Google Scholar 

  51. Powers HJ, Hill MH, Mushtaq S, et al. Correcting a marginal riboflavin deficiency improves hematologic status in young women in the United Kingdom (RIBOFEM). Am J Clin Nutr. 2011;93:1274–84.

    Article  CAS  Google Scholar 

  52. Ma AG, Schouten EG, Zhang FZ, et al. Retinol and riboflavin supplementation decreases the prevalence of anemia in Chinese pregnant women taking iron and folic Acid supplements. J Nutr. 2008;138:1946–50.

    Article  CAS  Google Scholar 

  53. McNulty H, Strain JJ, Hughes CF, Pentieva K, Ward M. Evidence of a role for one-carbon metabolism in blood pressure: can B vitamin intervention address the genetic risk of hypertension owing to a common folate polymorphism. Curr Dev Nutr. 2020;4(1):nzz102.

    Article  CAS  Google Scholar 

  54. Ward M, Hughes C, Strain JJ, aI. Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project. BMC Med. 2020;18:318.

    Article  CAS  Google Scholar 

  55. Jungert A, McNulty H, Hoey L, et al. Riboflavin is an important determinant of vitamin B6 status in healthy adults. J Nutr. 2020;150:2699–706.

    Article  Google Scholar 

  56. Hopkins SM, Gibney MJ, Nugent AP, et al. Impact of voluntary fortification and supplement use on dietary intakes and biomarker status of folate and vitamin B12 in Irish adults. Am J Clin Nutr. 2015;101:1163–72.

    Article  CAS  Google Scholar 

  57. Khoshnood B, Loane M, Dolk H, et al. Long term trends in prevalence of neural tube defects in Europe: population based study. BMJ (Online). 2015;351:1–5.

    Google Scholar 

  58. Food Safety Authority of Ireland FSAI. Update report on folic acid and the prevention of birth defects in Ireland. 2016. https://www.fsai.ie/news_centre/press_releases/folic_acid_report_04052016.html.

  59. Scientific Advisory Committee on Nutrition (SACN) Folate and Disease Prevention Report (2006) and Folic acid updated SACN recommendations (2017). Available at https://www.gov.uk/government/publications/sacn-folate-and-disease-prevention-report https://www.gov.uk/government/publications/folic-acid-updated-sacn-recommendations.

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Authors and Affiliations

  1. Nutrition Innovation Centre for Food and Health (NICHE), Ulster University, Coleraine, Northern Ireland, UK

    Helene McNulty

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  1. Helene McNulty
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Correspondence to Helene McNulty .

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Editors and Affiliations

  1. Human Nutrition, The University of British Columbia, Vancouver, BC, Canada

    Crystal D. Karakochuk

  2. Institute of Food Nutrition and Health, ETH Zurich, Zürich, Zürich, Switzerland

    Michael B. Zimmermann

  3. Department of Health, University of Applied Sciences of South Switzerland (SUPSI) and Swiss Distance University of Applied Sciences (FFHS), Zürich, Zürich, Switzerland

    Diego Moretti

  4. International Health, Sight and Life Foundation and Johns Hopkins School of Public Health, Basel, Switzerland

    Klaus Kraemer

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McNulty, H. (2022). The Role of B-Vitamins in Nutritional Anemia. In: Karakochuk, C.D., Zimmermann, M.B., Moretti, D., Kraemer, K. (eds) Nutritional Anemia. Nutrition and Health. Springer, Cham. https://doi.org/10.1007/978-3-031-14521-6_13

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  • DOI: https://doi.org/10.1007/978-3-031-14521-6_13

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