The Association Between Dietary Acid Load and Non-Alcoholic Fatty Liver Disease

The global prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing in parallel with obesity and metabolic disorders. Recent evidence suggests that diet-induced low-grade metabolic acidosis, quantified by dietary acid load (DAL) indices such as potential renal acid load (PRAL) and net endogenous acid production (NEAP), may contribute to the pathogenesis of NAFLD. However, existing findings are inconsistent. This systematic review aimed to evaluate the association between dietary acid load and the risk of NAFLD in adult populations. We conducted a comprehensive search of PubMed, Web of Science, and Scopus databases from inception to January 2025. Observational studies examining the association between DAL and NAFLD in adults were included. Two reviewers independently screened and extracted data, and the methodological quality was assessed using the AXIS tool for cross-sectional studies and the Newcastle-Ottawa Scale for case-control studies. A narrative synthesis approach was adopted due to heterogeneity in outcome measurements. Of 809 records identified, five studies (four cross-sectional and one case-control), published between 2015 and 2023 and conducted in Iran, the United States, the Netherlands, and China, met the inclusion criteria. DAL was primarily assessed using PRAL and NEAP, while NAFLD was diagnosed using imaging techniques or validated non-invasive indices. Three studies reported positive associations between higher DAL and NAFLD, with adjusted odds ratios generally ranging from approximately 1.3 to 2.2 for higher versus lower DAL categories, particularly for PRAL or NEAP. One study reported no significant association after adjustment for confounders, and one case-control study identified a modest U-shaped relationship, with moderate PRAL levels inversely associated with NAFLD odds (adjusted OR ≈fsn371597-bib-00180.46; 95% CI, 0.24-0.89), while higher PRAL levels were not significantly associated. Current evidence suggests a possible association between higher dietary acid load and increased risk of NAFLD, although findings remain inconsistent. Further well-designed longitudinal studies are warranted to clarify this relationship and determine causality.