Abstract
We aimed to explore the associations between diet-derived antioxidants and kidney stone disease (KSD) risk in this study. We performed weighted multivariable-adjusted logistic regression to assess the associations between the six main diet-derived antioxidants and the risk of KSD by using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Then, we used the Mendelian randomization (MR) approach to verify the causal relationships between circulating antioxidants levels and KSD risk. Genetic tools were extracted from published genome-wide association studies (GWAS). Summary data for KSD was from the FinnGen study and UK biobank. Inverse variance weighted (IVW) was the primary analysis. The 26,438 participants, including 2,543 stone formers, were included for analyses. There were no significant associations between retinol, vitamin B6, vitamin C, vitamin E, and lycopene intake with the risk of KSD across all the quartile categories. Similarly, pooled odds ratio (OR) for KSD risk in genetically predicted per unit change were 1.25 (95% CI: 0.39, 4.02; p = 0.712), 1.14 (95% CI: 0.84, 1.53; p = 0.400), 0.75 (95% CI: 0.52, 1.10; p = 0.141), 1.66 (95% CI: 0.80, 3.46; p = 0.178), 1.27 (95% CI: 0.29, 5.62; p = 0.756), and 0.92 (95% CI: 0.76, 1.12; p = 0.417) for retinol, β-carotene, vitamin B6, vitamin C, α-tocopherol, and lycopene, respectively. The above estimates were replicated in the secondary analyses using UK biobank data. Our study did not support a causal association between circulating antioxidants levels and KSD risk. However, these findings should be verified in larger sample-size MR due to the pleiotropy and other limitations.