Analysis of dietary vitamin C intake levels and the risk of hyperuricemia and gout based on cross-sectional studies and bi-directional Mendelian randomisation

Abstract

AbstractBackgroundVitamin C, a common antioxidant, may be useful for treating hyperuricemia and gout. The aim of this study was to investigate the risk association between dietary vitamin C intake and hyperuricemia/gout and to test for causality using the bi-directional Mendelian randomisation method.MethodsCross-sectional studies were selected from the National Health and Nutrition Examination Survey from 2007–2018 to assess the association between dietary vitamin C intake and the risk of hyperuricemia/gout, according to multivariate logistic regression modelling. Bi-directional Mendelian randomisation studies were conducted using genetic data from large-scale genome-wide association surveys of supplemental vitamin C, pharmacological vitamin C, and ascorbic acid intake and hyperuricemia/gout; these aimed to infer causal relationships between vitamin C and hyperuricemia/gout. Inverse variance weighting was used as the primary method of Mendelian randomisation analysis. A series of sensitivity analyses were used to assess multiplicity.ResultsThe cross-sectional study included 17.52% and 82.48% patients with and without hyperuricemia, respectively, as well as 2.67% and 97.33% patients with and without gout, respectively. In the model correcting for all covariates, the association between vitamin C intake and the risk of hyperuricemia/gout was stable, and the risk of hyperuricemia was generally lower in patients who consumed >111.75 mg vitamin C than in other patients when comparing three models with different moderators. Restricted cubic spline scores indicated that vitamin C intake recommendations of 75–525 mg and 75–225 mg were effective for targeting hyperuricemia and gout, respectively. In inverse variance weighting in the Mendelian randomisation analysis, the amount of vitamin C absorbed was negatively associated with hyperuricemia (OR = 0.985, 95% CI = 0.973–0.997, p = 0.015), and supplemental vitamin C was negatively associated with gout (OR = 0.857, 95% CI = 0.797–0.921, p < 0.001); sensitivity analysis yielded consistent results. Reverse Mendelian randomisation analysis showed that vitamin C had no reverse causal relationship with hyperuricemia and gout.ConclusionWe hypothesise that a dietary vitamin C intake of 75–525 mg or 75–225 mg may reduce the risk of hyperuricemia and gout, respectively. Further research with larger samples is required to confirm this.