Diet-dependent acid load - the missing link between an animal protein-rich diet and non-alcoholic fatty liver disease?

Alferink, Louise J M; Kiefte-de Jong, Jessica C; Erler, Nicole S; de Knegt, Robert J; Hoorn, Ewout J; Ikram, M Arfan; Janssen, Harry L A; Metselaar, Herold J; Franco, Oscar H; Murad, Sarwa Darwish (2019). Diet-dependent acid load - the missing link between an animal protein-rich diet and non-alcoholic fatty liver disease? The Journal of clinical endocrinology and metabolism, 104(12), pp. 6325-6337. The Endocrine Society 10.1210/jc.2018-02792

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OBJECTIVE

Our group recently showed that animal protein was independently associated with non-alcoholic fatty liver disease (NAFLD). We hypothesize that this may be explained by a high diet-dependent 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 animal-protein-to-potassium-ratio (A:P). We defined NAFLD using ultrasound after excluding secondary steatogenic causes. We used logistic regression models -adjusted for socio-demographic, lifestyle, and metabolic traits- on categorized (Q1-Q4) and continuous DAL-proxies (allowing for non-linearity) 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 -5.5mEq/day; NEAP: 37.0 vs 35.1mEq/day, and AP:13.3 vs 12.4; all P<0.001). The highest quartile of DAL-proxies was associated with NAFLD independent of socio-demographic and lifestyle confounders, but significance dissipated after correction for metabolic confounders and multiple testing. However, the P-value for non-linearity 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 non-linear 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.

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