Abstract
Background: The association of vitamin D with metabolic dysfunction-associated fatty liver disease (MAFLD) remained unclear. This study aimed to examine the relationships of total 25-hydroxyvitamin D [25(OH)D, the sum of 25(OH)D(2) and 25(OH)D(3)], 25(OH)D(3), and epi-25(OH)D(3) with MAFLD. Methods: We used the National Health and Nutrition Examination Survey of the 2017-2018 cycle for our present analysis. Binary logistic regression analyses were conducted to explore the associations of total 25(OH)D, 25(OH)D(3), and epi-25(OH)D(3) with MAFLD after adjusting for confounders. Interaction tests were conducted to compare the association between 25(OH)D and MAFLD in subgroups. Results: The final analysis included 4605 subjects. After adjustment for confounders, the odds of MAFLD decreased with increasing concentrations of total 25(OH)D (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.29-0.68; p for trend < 0.001). Serum 25(OH)D(3) showed a strong inverse association with MAFLD (OR, 0.39; 95% CI, 0.25-0.59; p for trend < 0.001). In addition, participants with lower epi-25(OH)D(3) levels had a higher likelihood of MAFLD, as demonstrated in both quartile and continuous models (OR, 0.77; 95% CI, 0.60-0.99; p=0.041). After stratification by lipid status, inverse associations of total 25(OH)D and 25(OH)D(3) with MAFLD were found only in dyslipidemic participants (p for interaction < 0.001). A sex-specific interaction was also noted for 25(OH)D(3), showing stronger effects in women than in men (p=0.036). Conclusions: Low serum total 25(OH)D, 25(OH)D(3), and epi-25(OH)D(3) were significantly associated with a higher prevalence of MAFLD. These associations showed nonlinear patterns and were particularly evident among participants with dyslipidemia, with 25(OH)D(3) demonstrating stronger protective effects in women than in men. Given the cross-sectional design, causality cannot be inferred, and further prospective studies are required to confirm these findings.