Dietary one-carbon metabolism nutrients and risk of MASLD progression: a prospective cohort study.

BACKGROUND/OBJECTIVES: The relationship between one-carbon metabolism (OCM) nutrients (methionine, folate, vitamin B2, vitamin B6, and vitamin B12) and metabolic dysfunction-associated steatotic liver disease (MASLD) remains uncertain. This study aimed to examine the association of dietary intake OCM nutrients intake with liver-related events (LRE) and mortality among individuals with MASLD. METHODS: This prospective cohort study analyzed data from 46,800 participants in the UK Biobank. MASLD was defined using a validated Fatty Liver Index (FLI) ≥ 60. Dietary intake was assessed using a web-based 24-hour dietary recall tool. Participants with a history of cancer or LRE at baseline were excluded. Multivariable Cox proportional hazard models and restricted cubic splines (RCS) were employed to estimate hazard ratios (HRs) and evaluate dose-response relationships. RESULTS: During a median follow-up of 13.3 years, 291 incident LRE cases and 3547 deaths occurred. Higher dietary intakes of several OCM nutrients were associated with lower risks of LRE and mortality, with the strongest evidence observed for vitamin B6. The HRs and 95% CIs of LRE comparing the highest with lowest intake categories were 0.74 (0.53, 1.04) for methionine, 0.66 (0.48, 0.92) for vitamin B6, 0.78 (0.56, 1.08) for vitamin B2, 0.71 (0.51, 0.99) for vitamin B12, and 0.72 (0.52, 1.00) for folate. Similar inverse associations were observed for mortality. RCS analyses indicated an approximately linear dose-response relationship with LRE incidence, whereas the associations with mortality appeared non-linear. CONCLUSIONS: Higher dietary intake of OCM nutrients is associated with lower risks of LRE and mortality in populations with MASLD.