Dietary folate intake and metabolic dysfunction-associated steatotic liver disease: a prospective cohort study

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic disease, but it remains unclear whether it is related to dietary folate. This research sought to investigate the association between dietary folate and MASLD.

This cohort study utilized the UK Biobank (UKB) database (N = 58,047). Dietary folate intake was assessed using an online dietary questionnaire, and MASLD was ascertained through International Classification of Diseases, Tenth Revision (ICD-10). Cox proportional hazard regression, mediation analysis and restricted cubic splines (RCS) were employed to investigate the association and dose-response relationship between dietary and MASLD. The stability of findings was verified by stratified analyses and sensitivity analyses.

Dietary folate intake was observed to be negatively associated with MASLD in cohort studies. During a median follow-up of 12.18 years, 691 cases of MASLD occurred. The risk of MASLD decreased by 24% (HR = 0.76, 95% CI: 0.59-0.97) among the participants in the highest dietary folate intake relative to lowest quartile. The protective effect was more pronounced in participants aged < 60 years (HR = 0.63, 95% CI: 0.45-0.89), male (HR = 0.63, 95% CI: 0.44-0.89), and obese participants (HR = 0.68, 95% CI: 0.48-0.95). The research results remained robust in the sensitivity analyses that excluded participants with ≤ 2 years of follow-up time, extremely folate intake, and other conditions. C-reactive protein (CRP) explained 6.56% of the association between dietary folate and MASLD. The dietary folate intake had an L-shaped relationship with the risk of MASLD (P for nonlinearity = 0.003).

Moderate folate intake (approximately 300 µg) may reduce the risk of MASLD, suggesting that promoting folate-rich diets may be a viable and cost-effective strategy for MASLD prevention.