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

Abstract

Zinc (Zn) is known for its antioxidant and anti-inflammatory properties and is important in regulating the body’s inflammatory response. However, there is limited evidence on how factors such as diet and heavy metal toxicity contribute to inflammation in children, and whether these effects are influenced by Zn status. This study aimed to investigate the links between diet, Zn, and cadmium (Cd) toxicity with inflammation, using high-sensitivity C-reactive protein (hsCRP) and white blood cell count (WBCs) as biomarkers. Using data from the 2015-2016 National Health and Nutrition Examination Survey (NHANES), which included 3,507 children in the U.S. aged 2-19 years, we explored the associations between the main exposure variables (Zn, Anti-inflammatory Diet Score (ADS), and Cd) and inflammatory biomarkers. Statistical analysis was conducted using a linear regression model. Of the participants, 49.4% were male and 50.6% female. We observed an inverse relationship between serum Zn and inflammation (β = -.236, p = .008 for WBCs, and β = -.223, p = .035 for hsCRP) after adjusting covariates. Although ADS was inversely associated with inflammation, the relationship was not significant (β = -.006, p = .186 for WBCs, and β = -.003, p = .210 for hsCRP). Significant associations were found between blood Cd and WBCs (β = .436, p = .008), but not for hsCRP. After adjusting for Zn, the relationship between Cd and inflammation became inversely associated (β = -.083 for WBCs, β = -.099 for hsCRP), although these results were not significant, suggesting that Zn may mitigate Cd’s inflammatory effects. To further support the epidemiological findings, we conducted studies using young C. elegans. The experiment consisted of two studies analyzing the effects of Zn and Cd on the survival of the worms using two-way ANOVA and Tukey tests. The results showed that Cd treatment significantly decreased the survival of worms; however, co-incubation with Zn attenuated this effect when the concentration of Cd and Zn were equal (100 µM). In conclusion, the epidemiological data indicate that serum Zn is a more reliable indicator of inflammation in children than Zn intake. The study also suggests zinc status neutralizes Cd's pro-inflammatory effects on inflammatory biomarkers. Additionally, C. elegans model demonstrated that Zn supplementation mitigated Cd-induced toxicity. These findings highlight the importance of maintaining adequate Zn status to mitigate the harmful effects of Cd exposure in children. Therefore, dietary interventions that improve Zn status could potentially reduce inflammation and counteract the adverse impact of Cd exposure on a population level.