Exploration of Immunology

Table 1. One-carbon metabolism and immune regulation [2, 3, 5, 6, 8, 13, 14].

Component	Role	Immune relevance	Effect of vitamin B12 deficiency	References
Vitamin B12 (cobalamin)	Cofactor for methionine synthase	Maintains DNA synthesis, methylation, and energy metabolism	↓ SAM formation, DNA hypomethylation, impaired lymphocyte proliferation	[2, 3, 6, 8]
Methionine	Amino acid; precursor of SAM	Required for methylation of DNA, RNA, and proteins	↓ Methionine → defective methylation and altered gene transcription	[5, 8, 13]
S-adenosylmethionine (SAM)	Universal methyl donor	Regulates cytokine expression and T cell differentiation via epigenetic mechanisms	↓ SAM → dysregulated cytokine expression, potential alteration of cytokine programs	[2, 3, 8]
Folate	Cofactor in one-carbon metabolism	Supports nucleotide synthesis and cell division	Deficiency → similar functional consequences as vitamin B12 deficiency	[3, 13, 14]

Return to article view

Overview of biochemical roles of vitamin B12 (cobalamin) in one-carbon metabolism, energy production, and redox regulation.

Declarations

Acknowledgments

AI-Assisted Work Statement: During the preparation of this work, author(s) used ChatGPT for assistance in generating Figure 1. After using the tool, author(s) reviewed and edited the content as needed and take(s) full responsibility for the content of the publication.

The authors wish to sincerely thank the patients and clinicians of the Strasbourg B12 research group (CARE B12) at the Hôpitaux Universitaires de Strasbourg (HUS, France) for their invaluable contributions to this study.

Author contributions

EA: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. NLV: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. TL: Validation, Writing—review & editing, Supervision. All authors read and approved the submitted version.

Conflicts of interest

The authors declare no conflict of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

Publisher’s note

Open Exploration maintains a neutral stance on jurisdictional claims in published institutional affiliations and maps. All opinions expressed in this article are the personal views of the author(s) and do not represent the stance of the editorial team or the publisher.

References

O’Leary F, Samman S. Vitamin B12 in health and disease. Nutrients. 2010;2:299–316. [DOI] [PubMed] [PMC]

Scalabrino G, Peracchi M. New insights into the pathophysiology of cobalamin deficiency. Trends Mol Med. 2006;12:247–54. [DOI] [PubMed]

Green R, Allen LH, Bjørke-Monsen AL, Brito A, Guéant JL, Miller JW, et al. Vitamin B₁₂ deficiency. Nat Rev Dis Primers. 2017;3:17040. [DOI] [PubMed]

Halczuk K, Kaźmierczak-Barańska J, Karwowski BT, Karmańska A, Cieślak M. Vitamin B12-Multifaceted In Vivo Functions and In Vitro Applications. Nutrients. 2023;15:2734. [DOI] [PubMed] [PMC]

Allen LH. Causes of vitamin B12 and folate deficiency. Food Nutr Bull. 2008;29:S20–34. [DOI] [PubMed]

Quadros EV. Advances in the understanding of cobalamin assimilation and metabolism. Br J Haematol. 2010;148:195–204. [DOI] [PubMed] [PMC]

Ohkura N, Kitagawa Y, Sakaguchi S. Development and maintenance of regulatory T cells. Immunity. 2013;38:414–23. [DOI] [PubMed]

Nielsen MJ, Rasmussen MR, Andersen CB, Nexø E, Moestrup SK. Vitamin B12 transport from food to the body's cells--a sophisticated, multistep pathway. Nat Rev Gastroenterol Hepatol. 2012;9:345–54. [DOI] [PubMed]

O'Neill LA, Kishton RJ, Rathmell J. A guide to immunometabolism for immunologists. Nat Rev Immunol. 2016;16:553–65. [DOI] [PubMed] [PMC]

10.

Pearce EL, Pearce EJ. Metabolic pathways in immune cell activation and quiescence. Immunity. 2013;38:633–43. [DOI] [PubMed] [PMC]

11.

van de Lagemaat EE, de Groot LCPGM, van den Heuvel EGHM. Vitamin B₁₂ in Relation to Oxidative Stress: A Systematic Review. Nutrients. 2019;11:482. [DOI] [PubMed] [PMC]

12.

Weinberg JB, Chen Y, Jiang N, Beasley BE, Salerno JC, Ghosh DK. Inhibition of nitric oxide synthase by cobalamins and cobinamides. Free Radic Biol Med. 2009;46:1626–32. [DOI] [PubMed] [PMC]

13.

Quadros EV, Sequeira JM. Cellular uptake of cobalamin: transcobalamin and the TCblR/CD320 receptor. Biochimie. 2013;95:1008–18. [DOI] [PubMed] [PMC]

14.

Obeid R, Herrmann W. Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett. 2006;580:2994–3005. [DOI] [PubMed]

15.

Tamura J, Kubota K, Murakami H, Sawamura M, Matsushima T, et al. 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;116:28–32. [DOI] [PubMed] [PMC]

16.

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;12:236. [DOI] [PubMed] [PMC]

17.

Obeid R, Andrès E, Češka R, Hooshmand B, Guéant-Rodriguez RM, Prada GI, et al.; The Vitamin B Consensus Panelists Group. Diagnosis, Treatment and Long-Term Management of Vitamin B12 Deficiency in Adults: A Delphi Expert Consensus. J Clin Med. 2024;13:2176. [DOI] [PubMed] [PMC]

18.

Sakaguchi S, Yamaguchi T, Nomura T, Ono M. Regulatory T cells and immune tolerance. Cell. 2008;133:775–87. [DOI] [PubMed]

19.

Degnan PH, Barry NA, Mok KC, Taga ME, Goodman AL. Human gut microbes use multiple transporters to distinguish vitamin B₁₂ analogs and compete in the gut. Cell Host Microbe. 2014;15:47–57. [DOI] [PubMed] [PMC]

20.

Lurz E, Horne RG, Määttänen P, Wu RY, Botts SR, Li B, et al. Vitamin B12 Deficiency Alters the Gut Microbiota in a Murine Model of Colitis. Front Nutr. 2020;7:83. [DOI] [PubMed] [PMC]

21.

Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F. From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell. 2016;165:1332–45. [DOI] [PubMed]

22.

Liu B, Li A, Liu Y, Zhou X, Xu J, Zuo X, et al. Transcobalamin 2 orchestrates monocyte proliferation and TLR4-driven inflammation in systemic lupus erythematosus via folate one-carbon metabolism. Front Immunol. 2024;15:1339680. [DOI] [PubMed] [PMC]

23.

Cassiano LMG, Cavalcante-Silva V, Oliveira MS, Prado BVO, Cardoso CG, Salim ACM, et al. Vitamin B12 attenuates leukocyte inflammatory signature in COVID-19 via methyl-dependent changes in epigenetic markings. Front Immunol. 2023;14:1048790. [DOI] [PubMed] [PMC]

24.

Nikolich-Žugich J. The twilight of immunity: emerging concepts in aging of the immune system. Nat Immunol. 2018;19:10–9. [DOI]

25.

Simonenko SY, Bogdanova DA, Kuldyushev NA. Emerging Roles of Vitamin B12 in Aging and Inflammation. Int J Mol Sci. 2024;25:5044. [DOI] [PubMed] [PMC]

26.

Jiang L, Yan T, Zhang X, Liu C, Yan Q, Chai Y, et al. Association between low vitamin B-12 status and latent tuberculosis infection among adults. Asia Pac J Clin Nutr. 2025;34:627–35. [DOI] [PubMed] [PMC]

27.

Scalabrino G. Vitamin-regulated cytokines and growth factors in the CNS and elsewhere. J Neurochem. 2009;111:1309–26. [DOI] [PubMed]

28.

Tejero JD, Hesterberg RS, Drapela S, Ilter D, Raizada D, Lazure F, et al. Methylmalonic acid induces metabolic abnormalities and exhaustion in CD8+ T cells to suppress anti-tumor immunity. Oncogene. 2025;44:105–14. [DOI] [PubMed] [PMC]