Gene-diet interaction amplifies toxic cadmium and lead burdens in Asian populations

Cadmium (Cd) is a toxic heavy metal and one of the top ten chemicals of public health concern globally. For most people, dietary intake is the primary source of Cd exposure because crops such as rice readily accumulate Cd from contaminated soils. Yet some populations carry disproportionately high Cd burdens relative to exposure, raising concerns about environmental health equity. Here, we integrated global dietary intake and human biomonitoring data with United States health survey analyses, population transcriptomics, and a controlled mouse experiment to investigate why people of Asian ancestry show elevated Cd and lead (Pb) burdens. We found that Asian populations had markedly higher urinary Cd relative to estimated dietary Cd intake than other populations; Asian Americans, likewise, showed significantly higher blood and urinary Cd, as well as elevated Pb, than other ethnic groups in NHANES. Transcriptomic analyses revealed higher expression of the metal transporter gene SLC11A2 ( DMT1 ) in East Asian populations. In mice, rice-based, micronutrient-poor diets upregulated intestinal DMT1 and increased Cd and Pb accumulation compared with nutritionally balanced diets. Together, these findings support a gene-diet interaction in which dietary structure and enhanced intestinal metal transport jointly contribute to elevated toxic metal burdens in Asian populations. Our results identify Cd as an environmental health inequity shaped by both diet and biology and suggest that diet diversification, iron and zinc fortification of staple foods, and stricter control of Cd in staple crops may help reduce Cd and Pb exposure in vulnerable populations.