Associations of different serum folate forms with indices of nonalcoholic fatty liver disease and advanced fibrosis

Abstract

Objective: We aim to examine the associations of different serum folate forms (total folate, 5-methyltetrahydrofolate [5-mTHF] and unmetabolized folic acid [UMFA]), with the prevalence of nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis.

Methods: This cross-sectional analysis was conducted in 6610 participants aged ≥ 18 years from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) database. NAFLD was defined as a United States fatty liver index (USFLI) ≥ 30. Advanced fibrosis was defined as a Fibrosis-4 score (FIB-4) > 3.25, a NAFLD Fibrosis Score (NFS) > 0.676, and a Hepamet Fibrosis Score (HFS) ≥ 0.47, respectively.

Results: The prevalence of NAFLD was 34.5%. Overall, serum total folate and 5-mTHF were inversely associated with the prevalence of NAFLD (both P for trend across quartiles <0.001). A similar trend was found for advanced fibrosis based on NFS and HFS (both P for trend across quartiles <0.05). However, a higher concentration of UMFA was significantly related to a higher prevalence of NAFLD (P for trend across quartiles =0.004). A similar relation was found for advanced fibrosis based on NFS (P for trend across quartiles =0.024).

Conclusions: Higher concentrations of serum total folate and 5-mTHF were associated with a lower prevalence of NAFLD and advanced fibrosis, while a higher concentration of UMFA was related to a higher prevalence of NAFLD.

Keywords: 5-methyltetrahydrofolate; Advanced fibrosis; Nonalcoholic fatty liver disease; Total folate; Unmetabolized folic acid.