Ukr.Biochem.J. 2022; Volume 94, Issue 1, Jan-Feb, pp. 5-13


Pyridoxine, folate, and cobalamin and the condition of the innate and acquired immunity

M. I. Kinash, O. R. Boyarchuk

Ivan Horbachevsky Ternopil National Medical University, Ukraine;

Received: 23 September 2021; Accepted: 21 January 2022

The immune response to the pathogen depends on the state and coordinated activity of innate and acquired immunity. To date, the positive role of many micronutrients (vitamins and minerals) in maintaining homeostasis of the human immune system has been proven. The aim of the review was to analyze the main manifestations of vitamins B6, B9, B12 influence on the state of innate and adaptive immunity. These vitamins play an important role in the synthesis of DNA and RNA, cytokines and immunoglobulins, thus maintaining the proper state of the immune system. The functioning of the main links of specific and nonspecific immunity at the normal vitamin status and at pyridoxine, folate and cobalamin deficiency is compared.

Keywords: , , ,


  1. The 2020 Global Nutrition Report in the Context of COVID-19. 168 p.
  2. Global Report on Food Crises 2021. Regime of access :
  3. Mertens E, Peñalvo JL. The Burden of Malnutrition and Fatal COVID-19: A Global Burden of Disease Analysis. Front Nutr. 2021;7:619850.  PubMed, PubMedCentral, CrossRef
  4. Katona P, Katona-Apte J. The interaction between nutrition and infection. Clin Infect Dis. 2008;46(10):1582-1588. PubMed, CrossRef
  5. Cunningham-Rundles S, McNeeley DF, Moon A. Mechanisms of nutrient modulation of the immune response. J Allergy Clin Immunol. 2005;115(6):1119-1128. PubMed, CrossRef
  6. Haryanto B, Suksmasari T, Wintergerst E, Maggini S. Multivitamin Supplementation Supports Immune Function and Ameliorates Conditions Triggered by Reduced Air Quality. Vitam Miner. 2015;4(2):1-15. CrossRef
  7. Maggini S, Beveridge S, Sorbara PJ, Senatore G. Feeding the immune system: The role of micronutrients in restoring resistance to infections. CAB Reviews. 2008;3(098):1-21. CrossRef
  8. Albers R, Bourdet-Sicard R, Braun D, Calder PC, Herz U, Lambert C, Lenoir-Wijnkoop I, Méheust A, Ouwehand A, Phothirath P, Sako T, Salminen S, Siemensma A, van Loveren H, Sack U. Monitoring immune modulation by nutrition in the general population: identifying and substantiating effects on human health. Br J Nutr. 2013;110(Suppl 2):S1-S30. PubMed, CrossRef
  9. Calder PC, Kew S. The immune system: a target for functional foods? Br J Nutr. 2002;88(Suppl 2):S165-S177. PubMed, CrossRef
  10.  Field CJ, Johnson IR, Schley PD. Nutrients and their role in host resistance to infection. J Leukoc Biol. 2002;71(1):16-32. PubMed
  11. Bhaskaram P. Micronutrient malnutrition, infection, and immunity: an overview. Nutr Rev. 2002;60(5 Pt 2):S40-S45. PubMed, CrossRef
  12. Kinash MI, Boyarchuk OR. Fat-soluble vitamins and immunodeficiency: mechanisms of influence and opportunities for use. Vopr Pitan. 2020;89(3):22-32. (In Russian). PubMed, CrossRef
  13. Boyarchuk OR, Dobrovolska LI, Kinash MI, Shulhai OM, Hlushko KT, Horishnyi IM. Survey assesment of vitamin D and calcium dietary intake in children with somatic pathology. Vopr Pitan. 2019;88(5):53-62. (In Russian). PubMed, CrossRef
  14. Maggini S, Pierre A, Calder PC. Immune Function and Micronutrient Requirements Change over the Life Course. Nutrients. 2018;10(10):1531. PubMed, PubMedCentral, CrossRef
  15. Selhub J. Folate, vitamin B12 and vitamin B6 and one carbon metabolism. J Nutr Health Aging. 2002;6(1):39-42. PubMed
  16. Kinash M, Boyarchuk O, Shulhai O, Boyko Y, Hariyan T. Prіmary immunodeficiencies associated with DNA damage response: complexities of the diagnosis. Arch Balk Med Union. 2020; 55(3): 510-517. CrossRef
  17. Wintergerst ES, Maggini S, Hornig DH. Contribution of selected vitamins and trace elements to immune function. Ann Nutr Metab. 2007;51(4):301-323. PubMed, CrossRef
  18. Gombart AF, Pierre A, Maggini S. A Review of Micronutrients and the Immune System-Working in Harmony to Reduce the Risk of Infection. Nutrients. 2020;12(1):236. PubMed, PubMedCentral, CrossRef
  19. Goldman L, Schafer AI. The innate and adaptive immune systems, Cecil Medicine (24thedn.) Elsevier, Philadelphia, 2011.
  20. Maggini S, Wintergerst ES, Beveridge S, Hornig DH. Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses. Br J Nutr. 2007;98(Suppl 1):S29-S35. PubMed, CrossRef
  21. Knight JA. Review: Free radicals, antioxidants, and the immune system. Ann Clin Lab Sci. 2000;30(2):145-158. PubMed
  22. Pecora F, Persico F, Argentiero A, Neglia C, Esposito S. The Role of Micronutrients in Support of the Immune Response against Viral Infections. Nutrients. 2020;12(10):3198. PubMed, PubMedCentral, CrossRef
  23. Saeed F, Nadeem M, Ahmed RS, Nadeem MT, Arshad MS, Ullah A. Studying the impact of nutritional immunology underlying the modulation of immune responses by nutritional compounds – a review. Food Agric Immunol. 2016; 27(2):205-229. CrossRef
  24.  Troen AM, Mitchell B, Sorensen B, Wener MH, Johnston A, Wood B, Selhub J, McTiernan A, Yasui Y, Oral E, Potter JD, Ulrich CM. Unmetabolized folic acid in plasma is associated with reduced natural killer cell cytotoxicity among postmenopausal women. J Nutr. 2006;136(1):189-194. PubMed, CrossRef
  25. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. Molecular Biology of the Cell (4th Ed.). NY: Garland Science, 2002. 1616 p.
  26. Ekkens MJ, Shedlock DJ, Jung E, Troy A, Pearce EL, Shen H, Pearce EJ. Th1 and Th2 cells help CD8 T-cell responses. Infect Immun. 2007;75(5):2291-2296. PubMed, PubMedCentral, CrossRef
  27. Kondĕlková K, Vokurková D, Krejsek J, Borská L, Fiala Z, Ctirad A. Regulatory T cells (TREG) and their roles in immune system with respect to immunopathological disorders. Acta Medica (Hradec Kralove). 2010;53(2):73-77. PubMed, CrossRef
  28. Yoshii K, Hosomi K, Sawane K, Kunisawa J. Metabolism of Dietary and Microbial Vitamin B Family in the Regulation of Host Immunity. Front Nutr. 2019;6:48. PubMed, PubMedCentral, CrossRef
  29. Courtemanche C, Elson-Schwab I, Mashiyama ST, Kerry N, Ames BN. Folate deficiency inhibits the proliferation of primary human CD8+ T lymphocytes in vitro. J Immunol. 2004;173(5):3186-3192. PubMed,CrossRef
  30. Calder P, Prescott S, Caplan M. Scientific Review: The Role of Nutrients in Immune Function of Infants and Young Children Emerging Evidence for Long-Chain Polyunsaturated Fatty Acids. Mead Johnson & Company; Glenview, IL, USA: 2007.
  31. Micronutrient Information Center Immunity in Depth. [(accessed on 10 May 2019)]; 2016 Linus Pauling Institute. Available online:
  32. Sakakeeny L, Roubenoff R, Obin M, Fontes JD, Benjamin EJ, Bujanover Y,F Jacques P, Selhub J. Plasma pyridoxal-5-phosphate is inversely associated with systemic markers of inflammation in a population of U.S. adults. J Nutr. 2012;142(7):1280-1285. PubMed, PubMedCentral, CrossRef
  33. Peterson CT, Rodionov DA, Osterman AL, Peterson SN. B Vitamins and Their Role in Immune Regulation and Cancer. Nutrients. 2020;12(11):3380. PubMed, PubMedCentral, CrossRef
  34. Ueland PM, McCann A, Midttun Ø, Ulvik A. Inflammation, vitamin B6 and related pathways. Mol Aspects Med. 2017;53:10-27. PubMed, CrossRef
  35. Julier Z, Park AJ, Briquez PS, Martino MM. Promoting tissue regeneration by modulating the immune system. Acta Biomater. 2017;53:13-28. PubMed, CrossRef
  36. Tamura J, Kubota K, Murakami H, Sawamura M, Matsushima T, Tamura T, Saitoh T, Kurabayshi H, Naruse T. Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment. Clin Exp Immunol. 1999;116(1):28-32. PubMed, PubMedCentral, CrossRef
  37. Biesalski HK. Nutrition meets the microbiome: micronutrients and the microbiota. Ann N Y Acad Sci. 2016;1372(1):53-64. PubMed, CrossRef
  38. Qian B, Shen S, Zhang J, Jing P. Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations. J Immunol Res. 2017;2017:2197975. PubMed, PubMedCentral, CrossRef
  39. Rowland I, Gibson G, Heinken A, Scott K, Swann J, Thiele I, Tuohy K. Gut microbiota functions: metabolism of nutrients and other food components. Eur J Nutr. 2018;57(1):1-24. PubMed, PubMedCentral, CrossRef
  40. Kelly FJ. Oxidative stress: its role in air pollution and adverse health effects. Occup Environ Med. 2003;60(8):612-616. PubMed, PubMedCentral, CrossRef
  41. Evans P, Halliwell B. Micronutrients: oxidant/antioxidant status. Br J Nutr. 2001;85(Suppl 2):S67-S74. PubMed, CrossRef
  42. Calder PC, Jackson AA. Undernutrition, infection and immune function. Nutr Res Rev. 2000;13(1):3-29. PubMed, PubMedCentral, CrossRef
  43. Schaible UE, Kaufmann SHE. Malnutrition and infection: complex mechanisms and global impacts. PLoS Med. 2007;4(5):e115. PubMed, PubMedCentral, CrossRef
  44. Boyarchuk O, Dmytrash L. Clinical Manifestations in the Patients with Primary Immunodeficiencies: Data from One Regional Center. Turk J Immunol. 2019;7(3):113-119. CrossRef
  45. Boyarchuk O, Volokha A, Hariyan T, Kinash M, Volyanska L, Birchenko I, Habor H, Korda M. The impact of combining educational program with the improving of infrastructure to diagnose on early detection of primary immunodeficiencies in children. Immunol Res. 2019;67(4-5):390-397. PubMed, CrossRef
  46. Watkins D, Rosenblatt DS. Immunodeficiency and inborn disorders of vitamin B12 and folate metabolism. Curr Opin Clin Nutr Metab Care. 2020;23(4):241-246. PubMed, CrossRef

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.