Abstract
PURPOSE OF REVIEW: Zinc is an essential micronutrient with a myriad of key roles in human health. This review summarizes mechanistic data supporting the protective effects of zinc on metal toxicity and discusses the framework for an interventional clinical trial of zinc supplementation within a metal exposed Native American community. RECENT FINDINGS: Many metals have common underlying mechanisms of toxicity that contribute to adverse human health effects. Studies demonstrate that multiple aspects of metal toxicity can be attributed to disruption of essential zinc-dependent functions. Multiple lines of evidence suggest that zinc may confer protection against metal toxicity in human populations with mixed-metal exposures. Thinking Zinc is a mechanism-informed intervention study of zinc supplementation to test the potential benefits of zinc while maintaining a culturally responsive research approach. The current knowledge of diverse metal and zinc interactions, coupled with strong mechanistic evidence for zinc benefits in the context of toxic metal exposures, supports the hypothesis that zinc supplementation may mitigate the impact of toxic metals exposures in populations with chronic mixed metal exposures and in populations with low zinc status.