Association Between Circulating Zinc Levels and Risk Factors of Metabolic Syndrome: Insights from a Bi-directional Mendelian Randomization Analysis and Cross-Sectional Study

Previous studies on the relationship between zinc and metabolic syndrome (MetS) have yielded inconsistent results. This comprehensive study aimed to elaborately explore the impact of zinc on MetS risk factors. The bi-directional Mendelian randomization (MR) analyses were performed to estimate the causal relationship between zinc and MetS risk factors. Additionally, a retrospective cross-sectional study incorporated 4389 subjects to provide a broader perspective in conjunction with the MR analyses. In the MR analyses, genetically instrumented zinc was positively associated with five of the MetS components in Europeans, including BMI, FBG, HbA1c, TC, and LDL-c (β (95%CI) = 0.023 (0.019–0.027), 0.019 (0.013–0.025), 0.041 (0.022–0.060), 0.027 (0.013–0.042), and 0.018 (0.010–0.026), respectively). In the cross-sectional study, higher concentration of zinc was strongly associated with increased BMI, LDL-c, and UA (β (95%CI) = 0.040 (0.010–0.085), 0.026 (0.018–0.035), and 1.529 (0.614–2.445), respectively). Moreover, these unfavorable associations were more obvious in women compared to men, with a borderline significant interaction effect for BMI (P=0.051). Our study showed that higher blood concentration of zinc, an essential trace element, was associated with unfavorable changes of the component metabolic risk factors of MetS, especially with BMI and LDL-c. Notably, these associations seemed to be more pronounced in women rather than in men. Further studies are warranted to elucidate the role of zinc status in the underlying mechanisms of MetS.