B vitamins and metabolic dysfunction-associated steatotic liver disease (MASLD): a systematic review of observational...

B vitamins are crucial cofactors in metabolic regulation; however, their role in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. Evidence for individual B vitamins is often contradictory. This systematic review evaluated the findings of observational studies examining the association between B vitamin intake and MASLD risk, severity, and outcomes.

A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar for studies published up to January 2026, adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All included studies were observational in design, encompassing cross-sectional, case-control, cohort, and Mendelian randomization (MR) studies that assessed dietary, supplemental, or biological B-vitamin status in relation to MASLD diagnoses. Study quality was evaluated using the Newcastle-Ottawa scale (NOS). No quantitative meta-analysis was performed and the evidence was narratively synthesized.

Fifty-nine studies were included (38 cross-sectional, 13 case-control, 6 cohort, and 2 MR studies). Folate has been extensively studied, with most evidence suggesting a protective role for serum folate and 5-mTHF against MASLD and fibrosis. However, this was contradicted by positive associations for RBC folate and unmetabolized folic acid (UMFA). Cohort studies have linked higher folate status to reduced all-cause mortality. Vitamin B12 findings were highly controversial, with studies reporting protective, detrimental, and null associations; MR studies suggested a positive causal link with MASLD risk. Choline intake was inversely associated with steatosis but positively correlated with fibrosis in specific subgroups, including men and postmenopausal women. Evidence for niacin and pyridoxine was inconsistent, though often suggesting an inverse relationship with MASLD.

Observational evidence suggests significant, albeit contradictory, associations between specific B-vitamins (particularly folate and B12), choline, and MASLD progression. However, given the massive methodological heterogeneity and heavy reliance on cross-sectional data, the certainty of these findings is very low. The inherent uncertainty of these associations rather than concluding a probable clinical benefit should also be emphasized. Rigorous prospective cohorts and randomized controlled trials are required to establish causality and clarify the true clinical utility of B-vitamin status in MASLD.

Not applicable.