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 have tested the association between MASLD and dairy consumption and the effect of milk fat on liver damage. Therefore, we aimed at testing the association between consumption of dairy product and the incidence of MASLD and fibrosis markers in humans, and the effect of milk fat vs. other fats on MASLD in animal studies.

Methods: A prospective 7-year follow-up cohort study was performed including baseline and follow-up fasting blood tests, liver evaluation and a face-to-face interview on health status and behaviour using structured questionnaires. MASLD was determined by ultrasonography or by controlled attenuation parameter (CAP), and liver fibrosis by FibroTest™ or FibroScan®. An animal study was performed in which 6-week-old C57BL/6j male mice were fed a high-fat diet (HFD) consisting of lard, soybean oil, and milk fat for 12 weeks. Metabolic impairment was assessed during the animal experiment, and serum advanced glycation end-products (AGEs) and liver damage were evaluated.

Results: A total of 316 patients were included in the prospective cohort. In multivariable analysis, high consumption of low-medium fat low-sugar dairy products (g/day above the baseline sex-specific median) was associated with a lower risk for MASLD incidence (OR 0.42, 95% CI 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 HFDs 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.

Conclusions: Low-medium fat low-sugar dairy products may be protective and should be preferred over high-fat dairy to prevent MASLD. HFDs 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-fat and low-fat dairy products is lacking, therefore, we evaluated this association by performing experimental studies in mice and an observational human study. For MASLD prevention, a differential effect based on the type of dairy products should be considered: low-medium fat low-sugar dairy products were found to be protective, in contrast high-fat dairy and generally high-fat diets may be harmful. It would be advisable to prefer low-fat low-sugar dairy products and minimise intake of high-fat dairy products; however, additional evidence is needed to allow generalisability of our findings.