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Background: Chronic stress, characterized by sustained activation of physiological stress response systems, is a key risk factor for numerous health conditions. Allostatic load (AL), a biomarker of cumulative physiological stress, offers a quantitative measure of this burden. Lifestyle habits such as alcohol consumption and smoking, alongside environmental exposures to toxic metals like lead, cadmium, and mercury, were individually implicated in increasing AL. However, the combined impact of these lifestyle habits and environmental factors remains underexplored, particularly in populations facing co-occurring exposures. This study aims to investigate the joint effects of lifestyle habits and environmental factors on AL, using data from the NHANES 2017–2018 cycle. By employing linear regression and Bayesian Kernel Machine Regression (BKMR), we identify key predictors and explore interaction effects, providing new insights into how cumulative exposures contribute to chronic stress. Results from BKMR analysis underscore the importance of addressing combined exposures, particularly the synergistic effects of cadmium and alcohol consumption, in managing physiological stress. Methods: Descriptive statistics were calculated to summarize the dataset, and multivariate linear regression was performed to assess associations between exposures and AL. BKMR was employed to estimate exposure–response functions and posterior inclusion probabilities (PIPs), focusing on identifying key predictors of AL. Results: Descriptive analysis indicated that the mean levels of lead, cadmium, and mercury were 1.23 µg/dL, 0.49 µg/dL, and 1.37 µg/L, respectively. The mean allostatic load was 3.57. Linear regression indicated that alcohol consumption was significantly associated with increased AL (β = 0.0933; 95% CI [0.0369, 0.1497]; p = 0.001). Other exposures, including lead (β = −0.1056; 95% CI [−0.2518 to 0.0408]; p = 0.157), cadmium (β = −0.0001, 95% CI [−0.2037 to 0.2036], p = 0.999), mercury (β = −0.0149; 95% CI [−0.1175 to 0.0877]; p = 0.773), and smoking (β = 0.0129; 95% CI [−0.0086 to 0.0345]; p = 0.508), were not significant. BKMR analysis confirmed alcohol’s strong importance for AL, with a PIP of 0.9996, and highlighted a non-linear effect of cadmium (PIP = 0.7526). The interaction between alcohol and cadmium showed a stronger effect on AL at higher exposure levels. In contrast, lead, mercury, and smoking demonstrated minimal effects on AL. Conclusions: Alcohol consumption and cadmium exposure were identified as key contributors to increased allostatic load, while other exposures showed no significant associations. These findings emphasize the importance of addressing lifestyle habits and environmental factors in managing physiological stress.more » « lessFree, publicly-accessible full text available February 1, 2026
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