Association between vitamin A intake and depression: A cross-sectional study of NHANES from 2005 to 2020 and Mendelian randomization analysis

Background: The association of vitamin A intake with depression remains unclear. This study combined observational research and Mendelian randomization (MR) analysis to explore the relationship between vitamin A intake and depression. Methods: First, we performed a cross-sectional study utilizing the National Health and Nutrition Examination Survey (NHANES) data from 2005 to 2020. Weighted multivariable logistic regressions and restricted cubic spline (RCS) regression were applied to explore the association between vitamin A intake and depression. We also conducted stratified and sensitivity analyses to assess the robustness of the results. Second, we conducted a MR analysis to assess the causal association between vitamin A and depression risk using the publicly available Genome-Wide Association Studies (GWAS) database. The inverse-variance weighted (IVW) method was our primary method for MR analysis. In addition, we performed multiple sensitivity analyses to evaluate the reliability of the results, including Cochran’s Q test, MR-Egger intercept regression, MR-Pleiotropy Residual Sum and Outlier (MR-PRESSO), and leave-one-out analysis. Results: In the cross-sectional study, a total of 38,157 individuals were enrolled. The vitamin A intake was negatively associated with depression after adjusting for all covariates (OR=0.92, 95%CI: 0.88-0.97, P =0.001). Similar inverse associations were observed when vitamin A intake was converted into categorical variables. The RCS analysis found an L-shaped nonlinear relationship between dietary vitamin A intake and depression ( P for non-linearity=0.010) after adjusting for all covariates. Vitamin A consumption was inversely associated with depression (OR=0.999, 95% CI: 0.999-1.000, P =0.002) for intakes below 492.00 μg. In contrast, no association was found between dietary vitamin A intake and depression ( P =0.656) for intakes of 492.00 μg or higher. Furthermore, The inverse relationship between vitamin A intake and depression remained robust in both stratified and sensitivity analyses. In the MR analysis, a total of 15 single-nucleotide polymorphisms (SNPs) were identified as instrumental variables (IVs). The IVW method found no significant causal relationship between vitamin A and the risk of depression (OR=0.39, 95%CI: 0.10-1.58, P =0.188). Similar results were found in MR-Egger method, weighted median method, simple mode method, and weighted mode method. Sensitivity analyses confirmed the reliability of these results. Conclusions: The observational study found that vitamin A intake was inversely associated with depression, regardless of whether vitamin A was measured as a continuous or categorical variable. However, findings from the MR analysis did not indicate a causal relationship between vitamin A and depression risk.