Diet-Dependent Acid Load - The Missing Link between an Animal Protein-Rich Diet and Nonalcoholic Fatty Liver Disease?

Objective: Our group recently showed that animal protein was independently associated with nonalcoholic fatty liver disease (NAFLD). We hypothesize that this may be explained by a high diet-dependent acid load [dietary acid load (DAL)]. Methods: This cross-sectional study is embedded in a prospective population-based cohort. We estimated DAL proxies via food-frequency questionnaires using potential renal acid load (PRAL; using dietary protein, phosphorus, potassium, calcium, and magnesium intake), net endogenous acid production (NEAP; using protein and potassium intake), and the animal protein-to-potassium ratio (A:P). We defined NAFLD using ultrasound after excluding secondary steatogenic causes. We used logistic regression models - adjusted for sociodemographic, lifestyle, and metabolic traits - on categorized [quartile (Q)1 to 4] and continuous DAL proxies (allowing for nonlinearity) and NAFLD. Results: We included 3882 participants, of which 1337 had NAFLD. All DAL proxies were higher, meaning more acidic, in individuals with NAFLD (PRAL, -2.9 vs -5.5 mEq/d; NEAP, 37.0 vs 35.1 mEq/d; and A:P, 13.3 vs 12.4; all P < 0.001). The highest Q of DAL proxies was associated with NAFLD independent of sociodemographic and lifestyle confounders, but significance dissipated after correction for metabolic confounders and multiple testing. However, the P value for nonlinearity was significant in all DAL proxies (P < 0.001). Natural cubic splines performed better with than without DAL proxies in the fully adjusted model (all P ≤ 0.038). The highest probability of NAFLD was found for an acidic diet. Conclusions: This study showed an independent nonlinear association between an acidic diet and NAFLD. Further studies with acid-base biomarkers are needed, but our findings might provide a mechanistic explanation for the harmful association between an animal protein-rich diet and NAFLD.