Antioxidants and the risk of metabolic dysfunction-associated steatotic liver disease: results of National Health and Nutrition Examination Survey and two-sample Mendelian randomization analyses

BACKGROUND: The link between antioxidants and metabolic dysfunction-associated steatotic liver disease (MASLD) is a topic of considerable discussion in the field of observational studies, with the exact causal connections still being unclear. METHODS: In this investigation, a cohort consisting of 17 061 participants from the National Health and Nutrition Examination Surveys was studied. Initially, a cross-sectional analysis was carried out to examine the relationship between the CDAI and MASLD. Further, Mendelian randomization (MR) was utilized to assess the possible causal links between antioxidant levels in the bloodstream and MASLD. RESULTS: The association between the CDAI and MASLD was found to be significant in the fully adjusted logistic regression model, showing an OR of 0.95 [95% confidence interval (CI): 0.94-0.97; P < 0.001]. The use of restricted cubic spline regression revealed no significant nonlinear association between the CDAI and the occurrence of MASLD ( Pnonlinearity = 0.321). Additionally, MR findings did not suggest any causal connections between circulating levels of various antioxidants and MASLD. These antioxidants included vitamin A (retinol) (IVW: OR: 0.67, 95% CI: 0.33-1.36, P = 0.272), vitamin C (ascorbate) (IVW: OR: 0.61, 95% CI: 0.34-1.09, P = 0.094), vitamin E (α-tocopherol) (IVW: OR: 0.55, 95% CI: 0.13-2.25, P = 0.407), vitamin E (γ-tocopherol) (IVW: OR: 0.89, 95% CI: 0.36-2.23, P = 0.806), zinc (IVW: OR: 0.95, 95% CI: 0.82-1.09, P = 0.449), selenium (IVW: OR: 0.98, 95% CI: 0.84-1.16, P = 0.855), and carotene (IVW: OR: 0.80, 95% CI: 0.36-1.81, P = 0.596). CONCLUSION: The findings highlight a significant negative linear relationship between CDAI and MASLD prevalence in the observational component of the study. However, the MR analysis did not indicate any causal effects of circulating antioxidant levels on MASLD.