Associations of Arsenic Exposure, Arsenic Metabolism, and Cadmium Exposure with Body Composition: Evidence from the Multi-Ethnic Study of Atherosclerosis

Exposures to arsenic (As) and cadmium (Cd) in drinking water and food pose significant environmental health problems with increased risk of cardiovascular and metabolic (cardiometabolic) diseases worldwide. However, pathogenic mechanisms that underlie these disease burden from environmental contaminants remain unresolved. Body composition changes have been associated with elevated cardiometabolic disease risks. Thus, there is a need to investigate whether exposure to environmental metals is associated with altered body composition and subsequent cardiometabolic health risks. We hypothesized that As and Cd exposure are associated with lower abdominal skeletal muscle quality with greater fat infiltration, and greater abdominal fat. We designed a cross-sectional study using urinary metals and body composition measures in 283 participants (age 45-80) enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). Body composition was measured with abdominal CT scan. Body mass index (BMI) and waist circumference were also included as anthropometric measurements. We evaluated the health effects of total urinary Cd, total urinary arsenicals (ΣAs), and the proportion of each As metabolite [monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)] over ΣAs separately. We built linear regression models for each body composition indicator with urinary As and Cd adjusted for age, sex, race, exam region, and urinary creatinine. We found that when treated as categorical variable, ΣAs was positively associated with BMI. In continuous As metabolite models, urinary MMA% was inversely associated with abdominal fat area and abdominal muscle area, but not with muscle density. In contrast to MMA%, urinary DMA% was positively associated with all studied body composition endpoints. Categorical urinary Cd was only observed to be associated with decreased density and increased fat accumulation in abdominal stabilization muscles. The data suggest that poor As metabolism (high MMA% and low DMA% in the urine) may underlie a trend in altered body composition that can consequently increase the risk of cardiometabolic diseases. The effects of Cd's impacts on body composition appear to be more subtle and might limit to specific muscle groups. This study provides evidence for further investigating that changes in muscle and body composition might be an underlying mechanism for cardiometabolic disease risk from environmental exposures