Serum folate associated with nonalcoholic fatty liver disease and advanced hepatic fibrosis

Abstract

The role played by serum folate in the progression of nonalcoholic fatty liver disease (NAFLD) remains controversial. The purpose of this study was to investigate the association of serum folate with NAFLD and advanced liver fibrosis (AHF). We conducted a cross-sectional study with 5417 participants using 2011–2018 NHANES data. Multiple logistic regression analysis and propensity score matching analysis were used to investigate the association of serum folate with NAFLD and AHF. In the completely adjusted model, participants in the high serum folate group had a 27% (OR 0.73, 95% CI 0.62, 0.87, p = 0.0003) and 53% (OR 0.47, 95% CI 0.35, 0.63, p < 0.0001) lower odds of suffering from NAFLD and AHF, respectively, compared to the low serum folate group. The similar results in propensity score matching further validated the above association. Stratified analysis showed that the negative correlation of serum folate with NAFLD and AHF demonstrated a broad consistency across populations. The results of this study indicate that higher serum folate level was associated with lower odds of NAFLD and AHF among US adults. Further prospective studies are necessary due to the limitations of cross-sectional studies.

The association between diverse serum folate with MAFLD and liver fibrosis based on NHANES 2017–2020

“…These observations align with antecedent investigations in the domain and retain their robustness even following adjustments for diverse potential confounding factors, encompassing sociodemographic characteristics, lifestyle elements, hypertension, and diabetes ( 14 , 25 ). Nevertheless, our subgroup analyses revealed no significant distinctions in variables, a finding that aligns with previous studies ( 14 , 16 ).…”

“…To the best of our knowledge, prior investigations examining the association between various serum folate levels and NAFLD and liver fibrosis have utilized diverse analytical approaches. These analyses primarily relied on blood biomarker indicators, such as the United States Fatty Liver Index (USFLI), Fatty Liver Index (FLI), Fibrosis-4 score (FIB-4), and NAFLD Fibrosis Score (NFS) (14)(15)(16). Earlier studies have also explored the impact of serum total folate on MAFLD using Vibration-Controlled Transient Elastography (VCTE).…”

Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective

“…However, epidemiologic evidence also suggests a positive correlation between vitamin B6 intake levels and the degree of hepatic steatosis in patients with MAFLD [169]. Recent studies revealed that elevated circulating homocysteine levels and reduced vitamin B9 levels are risk factors for MAFLD [170,171]. Vitamin B 9 , also known as folate, is mainly involved in one-carbon metabolism in biochemical reactions such as nucleic acid synthesis, methylation reactions, and sulfur-containing amino acid metabolism, and insufficient intake or metabolic disorders of folate may promote MAFLD progression [172,173].…”

Evaluation of In Vivo Folic Acid Bioavailability in Different Mouse Strains Using Enzymatic Digestion Combined with Ultra Performance Liquid Chromatography

“…5 Additionally, in patients with type 2 diabetes mellitus, it is possible that a deficiency in folic acid could potentially heighten the likelihood of elevated TSH levels, 6 and low serum folate levels have been associated with nonalcoholic fatty liver disease and advanced hepatic fibrosis. 7 At the same time, folic acid induces acute kidney injury (AKI), which is widely used in medicine as a reproducible model of AKI. 8 Consequently, ensuring adequate folic acid supplementation is of utmost importance to promote proper development, growth, and overall well-being among various individuals, particularly pregnant women, infants, and the elderly.…”

“…Timely supplementation of folic acid during pregnancy can reduce the risk of congenital malformations, particularly heart defects . Additionally, in patients with type 2 diabetes mellitus, it is possible that a deficiency in folic acid could potentially heighten the likelihood of elevated TSH levels, and low serum folate levels have been associated with nonalcoholic fatty liver disease and advanced hepatic fibrosis . At the same time, folic acid induces acute kidney injury (AKI), which is widely used in medicine as a reproducible model of AKI .…”