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

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)D₂ and 25(OH)D₃], 25(OH)D₃, and epi-25(OH)D₃ 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)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. 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)D₃ 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)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; p=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 (p for interaction < 0.001). A sex-specific interaction was also noted for 25(OH)D₃, showing stronger effects in women than in men (p=0.036). Conclusions: 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.