Serum vitamin D and lean non-alcoholic fatty liver disease: a nonlinear ‘L-shaped’ association in a national cross-sectional study

While the association between vitamin D and non-alcoholic fatty liver disease (NAFLD) is well-established in obese populations, its role in lean NAFLD remains controversial. This study aimed to investigate the potential nonlinear dose-response relationship between serum 25-hydroxyvitamin D [25(OH)D] concentrations and lean NAFLD by leveraging large-scale data from the National Health and Nutrition Examination Survey (NHANES). We conducted a cross-sectional analysis of 4,201 adults with BMI < 25 kg/m2. Lean NAFLD was defined using the US Fatty Liver Index (USFLI). The association between serum vitamin D and lean NAFLD was assessed employing multivariable logistic regression models, alongside more advanced techniques including restricted cubic splines (RCS) and generalized additive models (GAM) to capture potential nonlinearity. Initial linear models revealed no significant association. However, subsequent nonlinear analyses uncovered a pronounced ‘L-shaped’ curve relationship (P-nonlinear < 0.05). A segmented regression approach identified an inflection point at 60.3 nmol/L. Notably, at serum vitamin D levels below this threshold, concentrations were significantly inversely associated with lean NAFLD risk (Odds Ratio [OR] = 0.71, 95% Confidence Interval [CI]: 0.57–0.89). Conversely, above this inflection point, the inverse association attenuated and plateaued. The robustness of this nonlinear association was corroborated by the GAM analysis. This large-scale study is the first to identify a significant ‘L-shaped’ nonlinear association between serum vitamin D and lean NAFLD, wherein the association is most potent at concentrations below approximately 60 nmol/L. This finding highlights an epidemiological inflection point and underscores the need for nonlinear approaches in future research.