Metal and metal mixture biomarkers across three U.S. cohorts: MASALA, MESA-LA, and Strong Heart Family Study

Low-dose metal exposure contributes to chronic disease, yet differences in metal exposure and metabolism across diverse U.S. populations remain poorly characterized. Geographic location, drinking-water sources, diet, lifestyle, and culturally specific product use may shape multi-metal exposure. To characterize urinary multi-metal biomarkers among Asian Indian adults, compare them with profiles with other western U.S. populations, and evaluate serum–urine relationships for these metals among Asian Indian adults to distinguish metal clearance from physiological regulation. We measured 19 urinary metals by inductively coupled plasma mass spectrometry (ICP-MS) in harmonized subsamples of Asian Indians in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) pilot study (San Francisco Bay Area, 2010–2013; n = 111), White, Black, Hispanic/Latino, and Chinese in the Multi-Ethnic Study of Atherosclerosis, Los Angeles (MESA-LA, 2010–2012; n = 444), and American Indians in the Strong Heart Family Study (SHFS, 2006–2009; n = 111). Metals were creatinine-corrected and reported as µg/g creatinine. In MASALA, the same 19-metal panel was measured in serum. Median age (years)/percent female were 56/50% (MASALA), 62/49% (MESA-LA), and 56/49% (SHFS). Compared with MESA-LA and SHFS, MASALA participants had the lowest urinary Zn (354 µg/g) and Mn (0.11 µg/g), and the highest Mo (66.5 µg/g) and Tl (0.26 µg/g). Median urinary Cs in MASALA (8.55 µg/g) was comparable to MESA-LA Chinese (9.38 µg/g), while Ba was highest in MASALA (2.57 µg/g) relative to both MESA-LA and SHFS. MASALA participants had higher As, Pb, and Cd than SHFS (As 7.60 vs 5.08 µg/g; Pb 0.88 vs 0.59 µg/g; Cd 0.51 vs 0.47 µg/g), but lower levels than MESA-LA Chinese (As 43.9 µg/g; Pb 1.12 µg/g; Cd 0.81 µg/g). In MASALA, serum–urine correlations were strongest for Mo ( r = 0.83), As ( r = 0.79), Co ( r = 0.76), and Cs ( r = 0.67); Zn, Cu, and Mn were weakly correlated. Multi-metal biomarker patterns differed across study populations, influencing exposure assessment and biomonitoring interpretation. Serum–urine analyses distinguish elements reflecting recent exposure versus physiological regulation and support population-specific metal mixtures linked to chronic disease risk. Harmonized multi-metal biomarker data across diverse U.S. populations remain limited, which constrains interpretation of exposure patterns in epidemiologic research. This study provides one of the first cross-cohort comparisons of urinary metal profiles across diverse study populations in the western United States and includes paired urine–serum measurements for a broad 19-metal panel in MASALA adults, a population with elevated cardiometabolic disease risk but limited metal exposure data. The results support population-specific biomonitoring approaches and future studies evaluating metal mixtures and chronic disease.