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

Nonalcoholic fatty liver disease (NAFLD), historically considered as the hepatic component of the metabolic syndrome, is a spectrum of fat-associated liver conditions in the absence of secondary causes that may progress to nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. Disease progression is closely associated with body weight or fatness, dyslipidemia, insulin resistance, oxidative stress, and inflammation. Recently, there has been a significant scientific interest into the relationship between vitamin D status and NAFLD. Because oxidative stress and inflammation might act as the common pathogenic mechanisms of NAFLD and vitamin D deficiency, and as both diseases are associated with insulin resistance, type 2 diabetes and cardiovascular disease, several studies have investigated the association between vitamin D deficiency and NAFLD/NASH, but with conflicting findings. Therefore, we sought to critically review the current evidence on the association between vitamin D deficiency and NAFLD/NASH, and to analyze and discuss some key variables that may interfere with this evaluation, such as host-, environment-, and heritability-related factors regulating vitamin D synthesis and metabolism; definitions of deficient or optimal vitamin D status with respect to skeletal and nonskeletal outcomes including NAFLD/NASH; methods of measuring 25(OH)D; and methods of diagnosing NAFLD as well as quantifying adiposity, e.g. the cardinal link between vitamin D deficiency and NAFLD.