The Association Between Magnesium Levels and Gout: Evidence from Mendelian Randomization, a Chinese Cross-Sectional Study, and NHANES Analysis

Congcong Jiao¹Yang Shao²Yuxin Zhao¹Ruichao Feng¹Xiangfei Cui³Junjun Luan¹Xiangnan Hao¹Cong Ma¹Haoshen Feng^4*Xu Yang^1*Zhou Hua^1*

• ¹Department of Nephrology, Shengjing Hospital of China Medical University, Shenyang, China
• ²Department of Rehabilitation Medicine, The First Hospital of China Medical University, Shenyang, China
• ³Department of Nephrology, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, China
• ⁴Department of Pulmonary and Critical Care Medicine, Shengjing Hospital of China Medical University, Shenyang, China

Although the roles of micronutrients in human health are widely acknowledged, their specific associations with gout remain inadequately explored. This study integrates evidence from Mendelian randomization (MR), Chinese cross-sectional, and NHANES analyses to comprehensively investigate. First, the MR analysis was used to evaluate the potential causal associations between 15 trace elements (copper, calcium, iron, magnesium, potassium, selenium, zinc, carotenoids, folate, vitamin A, vitamin B12, vitamin B6, vitamin C, vitamin D, and vitamin E) and gout risk from the FinnGen database (n = 327,457). Calcium, magnesium, and vitamin B6 were screened out (Inverse Variance Weighted: P < 0.05). Multivariable MR indicated that higher magnesium reduced gout risk (OR = 0.630, 95% CI: 0.400 - 0.992, P = 0.046). Subsequently, logistic regression analysis of Chinese clinical data (n = 4,359) supported that high serum magnesium levels (Q4) were associated with lower gout risk (OR = 0.546, 95% CI: 0.319–0.933, P = 0.027) than the lowest magnesium levels (Q1). Finally, the NHANES (2011-2018, n = 13,902) analysis indicated that higher dietary magnesium intake was associated with lower gout risk (OR = 0.738, 95% CI: 0.550– 0.989, P = 0.049). Additionally, the restricted cubic spline (RCS) found that the OR began below 1 when the dietary magnesium intake exceeded 0.27 g/day. This multifaceted study provides novel evidence supporting a protective role of magnesium against gout. The underlying mechanism may involve magnesium's influence on uric acid or its anti-inflammatory effects. These hypotheses need to be clarified by further experimental and clinical studies.