Vitamin B₁₂ Supplementation: Is More Always Better?

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 < 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-normal 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.