Researchers compared metal biomarkers across six diverse US populations to investigate why exposure patterns can vary so markedly between communities.

Study: Metal and metal mixture biomarkers across three U.S. cohorts: MASALA, MESA-LA, and Strong Heart Family Study. Image Credit: Francesco Scatena / Shutterstock

In a recent study published in the Journal of Exposure Science & Environmental Epidemiology, researchers evaluated urinary multi-metal biomarker distributions across diverse ethnic populations in the western United States (US) to assess how environmental, dietary, and geographic factors may shape urinary metal profiles.

The study specifically compared the concentrations of a broad panel of up to 19 trace elements across harmonized subsamples of Asian Indian, White, Black, Hispanic, Chinese American, and American Indian adults.

The analyses identified substantial differences in urinary metal concentrations between cohorts and further suggested that dietary patterns, drinking-water sources and hydrogeology, urban-rural differences, smoking, and other social and behavioral factors may help explain these differences.

Background

Extensive research across global cohorts has established chronic low-dose exposure to metals as one of the leading modifiable chemical contributors to the global disease burden. Previous research has estimated that metals account for more disability-adjusted life years (DALYs) than other toxic chemicals, while the study authors note that their burden also exceeds that attributed to lifestyle factors such as alcohol use or physical inactivity.

These alarming findings have been attributed to the widespread presence of these contaminants across the environment (e.g., air and water) and consumer products (e.g., foods and housing), which can lead to chronic low-dose exposure to non-essential trace metals such as lead (Pb), cadmium (Cd), and arsenic (As).

Notably, metal exposure, including exposure to Pb, Cd, and As, has been associated with cardiovascular disease (CVD), chronic kidney disease (CKD), and diabetes. Furthermore, while essential in moderation, elevated concentrations of essential micronutrients (e.g., zinc [Zn] and copper [Cu]) can also be harmful and have been associated with metabolic dysregulation.

Unfortunately, despite this knowledge, few studies in the United States (US) have compared multi-metal profiles across diverse racial and ethnic groups using harmonized analytical methods. For example, South Asian Americans are known to face elevated cardiometabolic risk compared to other ethnic groups within the country. However, metal exposure profiles in these populations remain comparatively understudied.

About the study

The present study aimed to address these empirical gaps and inform future biomonitoring approaches by characterizing multi-metal biomarker patterns across three western United States cohorts: 1. The Mediators of Atherosclerosis in South Asians Living in America (MASALA) pilot study in the San Francisco Bay Area (n = 111), 2. The Multi-Ethnic Study of Atherosclerosis, Los Angeles center (MESA-LA; n = 444), and 3. The Strong Heart Family Study (SHFS; n = 111).

The combined sample dataset comprised six demographic subpopulations: 1. Asian Indian, 2. White, 3. Black, 4. Hispanic, 5. Chinese American, and 6. American Indian. The study’s statistical analyses evaluated harmonized subsamples of 111 participants from each of the demographic groups (n = 666; median age = 56 for MASALA and SHFS, 62 for MESA-LA; \~50% female).

Urine samples from all three cohorts were analyzed using inductively coupled plasma mass spectrometry (ICP-MS), thereby enabling quantification of a broad panel of trace elements. Urinary concentrations were subsequently normalized to creatinine (micrograms per gram, µg/g). In the MASALA cohort, the same broad metal panel was also measured in serum, enabling paired serum-urine comparisons. Nickel, lithium, antimony, and vanadium were not measured in MESA-LA.

Study findings

The study’s analyses revealed that MASALA participants exhibited the highest urinary concentrations of molybdenum (Mo; median = 66.5 µg/g) and thallium (Tl; median = 0.26 µg/g) but also depicted the lowest concentrations of zinc (354 µg/g) and manganese (Mn; median = 0.11 µg/g). The authors suggested that these patterns may partly reflect dietary patterns previously reported among Asian Indian populations, including higher legume and lower red and processed meat intake, as legumes are recognized sources of molybdenum, whereas red meat is a source of zinc and selenium.

Conversely, Chinese MESA-LA participants demonstrated the highest total urinary arsenic concentration (43.9 µg/g), nearly sixfold higher than MASALA (7.60 µg/g) and eightfold higher than SHFS (5.08 µg/g), which the authors suggested may partly reflect greater rice and seafood intake. Because total urinary arsenic can include relatively low-toxicity seafood-derived compounds, arsenic speciation, which distinguishes different chemical forms of arsenic, would be needed to clarify the sources and toxicological significance of this difference.

Urinary lead concentrations were higher in MASALA and several MESA-LA groups than in the predominantly rural SHFS cohort, including 1.12 µg/g among MESA-LA Chinese participants and 0.88 µg/g in MASALA, compared with 0.59 µg/g in SHFS. The authors suggested this pattern may reflect legacy traffic and industrial emissions, older housing, and differences in smoking prevalence. They also noted that urinary lead is not considered a sensitive biomarker.

Geographic differences in water sources and regional hydrogeology were similarly reflected in participants’ uranium concentrations, which were lower in San Francisco’s MASALA cohort (0.008 µg/g; surface water) than in MESA-LA (0.019 µg/g) and SHFS (0.016 µg/g), consistent with the San Francisco Bay Area’s reliance on surface water, whereas MESA-LA and SHFS include regions with greater reliance on groundwater or mixed supplies.

Finally, paired serum-urine evaluations demonstrated strong correlations for several renally cleared elements, including molybdenum (r = 0.83), arsenic (r = 0.79), cobalt (Co; r = 0.76), and cesium (Cs; r = 0.67), whereas tightly regulated essential elements such as zinc, copper, and manganese showed weak correlations. Molybdenum and cobalt were notable exceptions among essential elements because of their rapid renal clearance.

Conclusions

This study provides one of the first cross-cohort comparisons of urinary metal profiles across diverse study populations in the western United States and suggests that intersecting dietary patterns, hydrogeology, urban-rural conditions, and other demographic and behavioral factors may contribute to distinct population-specific exposure profiles. Strong agreement in barium-strontium (Ba-Sr) and cesium-thallium (Cs-Tl) clustering was consistent with common exposure sources and shared transport or metabolic pathways across populations.

The authors cautioned that serum measurements were available only for MASALA and that unmeasured environmental and lifestyle factors, including industrial and agricultural emissions, supplements, traditional medicines, and consumer-product use, may also have contributed to differences between cohorts.

These findings support population-specific biomonitoring approaches in the US. The study also provides a basis for future research evaluating how these exposure patterns relate to chronic disease risk.