Enhancing antioxidant capacity and reducing asthma risk: the impact of zinc and iron on molecular pathways

Asthma is a complex chronic inflammatory disease with unclear causal links to micronutrients such as zinc and iron. Two-sample Mendelian randomization (MR) analyses, integrated with bioinformatics, were conducted to assess the associations of circulating zinc and iron levels with asthma risk. Analysis of data from Open GWAS and FinnGen demonstrated that each 1-SD increase in circulating zinc levels was associated with a modest reduction in asthma risk (OR = 0.947, 95% CI = 0.902–0.994, p = 0.029), while each 1-SD increase in circulating iron levels was similarly associated with lower risk (OR = 0.782, 95% CI = 0.652–0.937, p = 0.008). Multivariable MR confirmed a statistically significant but limited protective association for zinc (OR = 0.944, p = 0.039), whereas the association for iron was not significant (OR = 0.776, p = 0.227). Bioinformatic analyses indicated that key genes in the NRF2/HO-1 and NF-κB pathways are linked to asthma severity, suggesting potential molecular mechanisms underlying trace metal effects. Collectively, these findings support a potential causal role of zinc and iron in asthma and motivate targeted mechanistic and clinical trials. Protective Mechanism of Zinc and Iron in Asthma via NRF2/HO-1 and NF-κB Pathway Regulation of Inflammation and Oxidative Stress