UNRAVELING THE LINK BETWEEN ANTI-INFLAMMATORY DIET, ZINC, AND CADMIUM TOXICITY IN INFLAMMATION REGULATION AMONG CHILDREN AND ADOLESCENTS

Abstract

Zinc (Zn) possesses antioxidant and anti-inflammatory properties essential for regulating the body’s inflammatory response. However, the interplay between diet, heavy metal toxicity, and Zn status in influencing inflammation in children remains poorly understood. This study examined the associations among diet, Zn levels, cadmium (Cd) toxicity, and inflammation, using high-sensitivity C-reactive protein (hsCRP) and white blood cell count (WBCs) as biomarkers. Data from the 2015-2016 National Health and Nutrition Examination Survey (NHANES), comprising 3,507 U.S. children aged 2–19 years, were analyzed. Linear regression models assessed the relationships between serum Zn, the Anti-inflammatory Diet Score (ADS), Cd levels, and inflammatory markers. Of the participants, 49.4% were male and 50.6% female. Serum Zn was inversely associated with inflammation (β = -0.236, p = 0.008 for WBCs; β = -0.223, p = 0.035 for hsCRP) after adjusting for covariates. Although ADS showed an inverse relationship with inflammation, the associations were not statistically significant. Blood Cd levels were positively associated with WBCs (β = 0.436, p = 0.008), but not hsCRP. Interestingly, adjusting for Zn reversed the association between Cd and inflammation, though the results were not significant, suggesting Zn may counteract Cd’s pro-inflammatory effects. Complementary studies in C. elegans were conducted to further explore these findings. Survival assays showed that Cd exposure significantly reduced worm survival, whereas co-incubation with equal concentrations of Zn (100 µM) mitigated this toxic effect, as demonstrated by two-way ANOVA and Tukey tests. Overall, this study highlights that serum Zn is a more reliable marker of inflammation than dietary Zn intake in children. Zn appears to partially neutralize Cd's toxic effects, with findings supported by both epidemiological data and experimental models. Maintaining adequate Zn levels may reduce inflammation and counteract Cd toxicity. These results underscore the importance of dietary strategies to enhance Zn status, potentially mitigating the adverse health effects of environmental Cd exposure in children.