Association between Vitamin D Levels and Nonalcoholic Fatty Liver Disease: Potential Confounding Variables

Nonalcoholic fatty liver disease (NAFLD), historically considered to be the hepatic componentof the metabolic syndrome, is a spectrum of fat-associated liver conditions, in the absence of secondarycauses, that may progress to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Diseaseprogression is closely associated with body weight or fatness, dyslipidemia, insulin resistance,oxidative stress, and inflammation. Recently, vitamin D deficiency has been linked to the pathogenesisand severity of NAFLD because of vitamin D “pleiotropic” functions, with roles in immune modulation,cell differentiation and proliferation, and regulation of inflammation. Indeed, several studies havereported an association between vitamin D and NAFLD/NASH. However, other studies have failed tofind an association. Therefore, we sought to critically review the current evidence on the associationbetween vitamin D deficiency and NAFLD/NASH, and to analyze and discuss some key variables thatmay interfere with this evaluation, such as host-, environment-, and heritability-related factors regulatingvitamin D synthesis and metabolism; definitions of deficient or optimal vitamin D status with respectto skeletal and nonskeletal outcomes including NAFLD/NASH; methods of measuring 25(OH)D;and methods of diagnosing NAFLD as well as quantifying adiposity, the cardinal link between vitaminD deficiency and NAFLD.