Synergistic Effects of Dietary Protein and Vitamin E Intake on Reducing Metabolic-Associated Fatty Liver Disease Risk: Insights From NHANES [2017-2023] and Mendelian Randomization Study.

Nutritional intervention plays a pivotal role in managing metabolic-associated fatty liver disease (MAFLD), but the combined effect of protein and vitamin E on MAFLD remains indistinct. This study sought to evaluate the synergistic effects of these nutrients on MAFLD. This study enrolled 14,489 participants from the NHANES database. MAFLD was defined by liver fat accumulation and metabolic syndrome components. Multivariable logistic regression, restricted cubic spline modeling, and internal validation were applied to assess the dose-response and joint effects of protein and vitamin E, with gender stratification to explore effect heterogeneity. A Mendelian randomization (MR) approach was utilized to probe the causality between α-tocopherol and protein intake with MAFLD. Intake levels of protein and vitamin E were significantly reduced in individuals with MAFLD compared to the non-MAFLD group (All p < 0.001). Multivariable logistic regression analysis indicated that combined intake of high protein (> 0.82 g/kg/d) and vitamin E (> 0.140 mg/kg/d) significantly reduced the risk of MAFLD by 72% (OR = 0.280, 95% CI: 0.244-0.320, p < 0.001), outperforming the high intake of either nutrient alone; internal validation further confirmed the robustness of the model. Sex-stratified analysis indicated that elevated intake of protein and vitamin E was associated with a significantly decreased risk of MAFLD in both males and females. MR analysis confirmed that high α-tocopherol was causally related to a lower risk of MAFLD (IVW OR = 0.871, 95% CI: 0.780-0.973, p = 0.015). Although the causality between protein intake and MAFLD was not statistically significant, further analysis indicated that protein intake-associated genetic variants may influence MAFLD through the regulation of carbonic anhydrase 11 expression. This study revealed that combined intake of protein and vitamin E exerts a synergistic protective effect against MAFLD, with gender-specific effects. It provides translational medical evidence for developing nutrient-combination-based therapeutic strategies for MAFLD.