Differential Effects of Low or High-Fat Dairy and Fat Derived from Dairy Products on MASLD

Background & Aims Metabolic dysfunction-associated steatotic liver disease (MASLD) is strongly related to nutrition. However, only a few human and animal studies tested MASLD's association with dairy consumption and the effect of milk fat on liver damage. Therefore, we aimed to test the association of dairy product consumption with MASLD incidence and fibrosis markers in humans, and the effect of milk fat versus other fats in animal studies. Methods A prospective 7-year follow-up cohort study. MASLD was determined by ultrasonography or controlled attenuation parameter (CAP), and liver fibrosis by FibroTest or Fibroscan. C57BL/6j male mice 6 weeks old were fed for 12 weeks with high-fat diets based on lard, soybean oil, and milk fat. Metabolic impairment was assessed during the experiment, serum advanced glycation end-products (AGEs) and liver damage were evaluated. Results In the cohort, 316 subjects were included. In multivariable analysis, high consumption of low-medium fat low-sugar dairy products (g/d above the baseline gender-specific median) was associated with a lower risk for MASLD incidence (OR=0.42, 0.18-0.95, P=0.037) or incidence/persistence at follow-up (OR=0.58, 0.34-0.97, P=0.039). Constantly high consumption of high-fat low-sugar dairy products was associated with greater odds for new onset/persistence of MASLD. Neither low-medium nor high-fat dairy consumption was related to fibrosis markers. In mice, all high-fat diets induced similar weight gain and steatosis and did not affect liver enzymes. Milk fat increases serum cholesterol and AGEs levels more than lard or soybean oil. Conclusion Low-medium fat low-sugar dairy products may be protective and should be preferred over high-fat dairy to prevent MASLD. High-fat diets from different fat sources with a wide spectrum of fatty acid saturation content are equally deleterious. Impact and implications • MASLD is related to nutrition, but evidence of an association between high and low-fat dairy products is lacking, therefore, we elaborated on this association by performing mice and human studies.• For MASLD prevention, a differential effect of types of dairy products should be considered: low-medium fat low-sugar dairy products were found to be protective, in contrast to high-fat dairy and generally high-fat diets which may be harmful.• It may be advised to prefer low-fat low-sugar dairy products and minimize high-fat dairy products, but more evidence is needed to allow generalizability of our findings.