Association of 25‐Hydroxyvitamin D With Metabolic Dysfunction‐Associated Fatty Liver Disease: Results From NHANES 2017–2018

<b>Background:</b> 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)D₂ and 25(OH)D₃], 25(OH)D₃, and epi-25(OH)D₃ with MAFLD. <b>Methods:</b> 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)D₃, and epi-25(OH)D₃ with MAFLD after adjusting for confounders. Interaction tests were conducted to compare the association between 25(OH)D and MAFLD in subgroups. <b>Results:</b> 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; <i>p</i> for trend < 0.001). Serum 25(OH)D₃ showed a strong inverse association with MAFLD (OR, 0.39; 95% CI, 0.25-0.59; <i>p</i> for trend < 0.001). In addition, participants with lower epi-25(OH)D₃ levels had a higher likelihood of MAFLD, as demonstrated in both quartile and continuous models (OR, 0.77; 95% CI, 0.60-0.99; <i>p</i>=0.041). After stratification by lipid status, inverse associations of total 25(OH)D and 25(OH)D₃ with MAFLD were found only in dyslipidemic participants (<i>p</i> for interaction < 0.001). A sex-specific interaction was also noted for 25(OH)D₃, showing stronger effects in women than in men (<i>p</i>=0.036). <b>Conclusions:</b> Low serum total 25(OH)D, 25(OH)D₃, and epi-25(OH)D₃ 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)D₃ 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.