{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:18:36Z","timestamp":1785403116341,"version":"3.56.0"},"reference-count":83,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Renal Association"},{"id":[{"id":"https:\/\/ror.org\/00e9kx775","id-type":"ROR","asserted-by":"publisher"}]},{"name":"ERA4Health Joint Transnational Call 2024"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vitamin B12 supplementation among people without proven deficiency has become popularized, driven by perceptions of (i) frequent underdiagnosis of deficiency, (ii) promotion as a natural enhancer of well-being, and (iii) a favourable safety profile. Here, we examine whether these claims align with current evidence. We present guidance from major health authorities, which advises against routine testing in asymptomatic individuals without risk factors. The prevalence of B12 deficiency varies greatly, mainly because definitions of B12 deficiency are not standardized and may include clinical, biochemical, or functional criteria. Biochemical deficiency (typically serum B12 &lt; 148 pmol\/L) is the predominant definition in epidemiological and clinical research studies. Using this criterion, deficiency appears uncommon in general populations of high-income countries (~2%), but substantially more frequent in settings with limited access to animal-source foods or B12-fortified products (up to 69%). Studying the effects of supplementation is also challenged by variation in the regimens used, which range from 0.02 to 1 mg\/day orally and from 1 to 5 mg\/week intramuscularly, with durations spanning ~4 weeks to ~7 years. This limits cross-study comparability. Overall, supplementation has not shown consistent benefits in populations without overt clinical or biochemical B12 deficiency, with no clear improvements in fatigue, mood, cognition, or cardiovascular outcomes. Benefits, when reported, appear confined to selected subgroups (e.g., hyperhomocysteinemia or low\u2013normal B12 status). B12 supplementation is generally well tolerated. There are rare reports of acneiform and hypersensitivity responses, although these cannot be completely distinguished from reactions to, e.g., excipients. Observational studies associate B12 supplementation and higher circulating B12 levels with increased risks of malignancy. However, these findings are inconsistent, and current evidence is insufficient to establish causality, as potential reverse causation remains a major concern.<\/jats:p>","DOI":"10.3390\/nu18101597","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T08:56:27Z","timestamp":1779094587000},"page":"1597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Vitamin B12 Supplementation: Is More Always Better?"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4693-5974","authenticated-orcid":false,"given":"Manuela","family":"Yepes-Calder\u00f3n","sequence":"first","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caecilia S. E.","family":"Doorenbos","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariken E.","family":"Stegmann","sequence":"additional","affiliation":[{"name":"Department of Primary and Longterm Care, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1429-4789","authenticated-orcid":false,"given":"Daan J.","family":"Touw","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2725-6148","authenticated-orcid":false,"given":"Hermie J. M.","family":"Harmsen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3477-0770","authenticated-orcid":false,"given":"M. Rebecca","family":"Heiner-Fokkema","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolic Diseases, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3773-1929","authenticated-orcid":false,"given":"Francjan J.","family":"van Spronsen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Metabolic Diseases, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2974-3305","authenticated-orcid":false,"given":"Eva","family":"Corpeleijn","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3356-6791","authenticated-orcid":false,"given":"Stephan J. L.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","unstructured":"Sloan, J.L., Carrillo, N., Adams, D., and Venditti, C.P. (1993). Disorders of Intracellular Cobalamin Metabolism, University of Washington."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s10545-016-9991-4","article-title":"Guidelines for Diagnosis and Management of the Cobalamin-Related Remethylation Disorders CblC, CblD, CblE, CblF, CblG, CblJ and MTHFR Deficiency","volume":"40","author":"Huemer","year":"2017","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_3","unstructured":"National Institute for Health and Care Excellence (2024). 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