Increased vitamin D may prevent NAFLD in patients with European ancestry

Increased levels of vitamin D may prevent nonalcoholic fatty liver disease among European populations, according to research published in Clinical Gastroenterology and Hepatology.

“Vitamin D has been revealed to modulate liver inflammation and fibrogenesis and to improve hepatic response to insulin in animal studies. Furthermore, an inverse association between serum 25-hydroxyvitamin D (S-25(OH)D), a clinical marker of vitamin D status, and NAFLD has been observed in several cross-sectional and case-control studies, although not all,” Shuai Yuan, BMed, MMedSc, of the Institute of Environmental Medicine at the Karolinska Institutet in Stockholm, and colleagues wrote. “These inconsistent findings and possible effects of reverse causality and residual confounding on the associations in the observational studies hinder the causal inference in the association between vitamin D and NAFLD.”

In a bidirectional Mendelian randomization study, researchers aimed to determine the association between S-25(OH)D and NAFLD using summary-level data from the SUNLIGHT consortium (79,366 individuals), a genome-wide association meta-analysis (1,483 cases and 17,781 controls), the FinnGen consortium (894 cases and 217,898 controls) and the UK Biobank study (275 cases and 360,919 controls). They used seven and six independent genetic variants associated with S-25(OH)D and NAFLD at the genome-wide level, respectively, as instrumental variables.

Researchers observed genetic correlations between S-25(OH)D with NAFLD and certain liver enzymes with genetically predicted higher levels of vitamin D associated with a decreased risk for NAFLD. Further, for one standard deviation increase in genetically predicted S-25(OH)D levels, the combined OR of NAFLD was 0.78 (95% CI, 0.69-0.89).

When analyzing liver enzymes, researchers found S-25(OH)D inversely correlated with alkaline phosphatase (P = 0.03) but not alanine aminotransferase (P = 0.301) and aspartate aminotransferase (P = 0.835).

Genetic predisposition to NAFLD did not associate with S-25(OH)D levels (95% CI, –0.26-0.3).

“This study found inverse genetic correlations of S-25(OH)D with NAFLD and certain liver enzymes and an inverse association of genetically predicted S-25(OH)D with risk of NAFLD in European individuals. These findings have clinical implications as they suggest that vitamin D may play a role in NAFLD prevention,” Yuan and colleagues concluded. “Whether NAFLD has a causal effect on lowering S-25(OH)D levels warrants more study.”