Is Acrylamide a Hidden Threat to Muscle Health? Integrative Evidence From Epidemiological and Mechanistic...

Acrylamide is an environmental toxicant widely found in processed foods and tobacco smoke. While its neurotoxic and carcinogenic effects are well established, its impact on skeletal muscle health remains poorly understood. This study aimed to investigate the association between acrylamide exposure and muscle mass using epidemiological data and to explore potential mechanisms through bioinformatic analyses. We analyzed data from 1443 adults participating in the 2013-2016 National Health and Nutrition Examination Survey. Hemoglobin adducts of acrylamide (HbAA), glycidamide (HbGA), and their ratio (HbGA/HbAA) were used as biomarkers of exposure. Multivariable linear regression models were applied to examine associations with muscle mass index, with results reported as beta coefficients and 95% confidence intervals (CIs). Restricted cubic spline (RCS) models assessed dose-response relationships. Mediation analyses explored the roles of potential mediators. Network-based bioinformatic analyses were performed to identify molecular targets and pathways. Higher HbAA levels were significantly associated with lower muscle mass index (β = -0.331, 95% CI: -0.543 to -0.118, p = 0.006), while the HbGA/HbAA ratio showed a positive association (β = 1.029, 95% CI: 0.702 to 1.356, p < 0.001). RCS further confirmed linear relationships. Mediation analyses indicated that biomarkers of inflammation and oxidative stress partially mediated these associations (mediated proportions: 5.93% to 31.39%). Bioinformatic analysis identified 346 shared genes enriched in apoptosis and inflammatory pathways. This study provides the first integrative epidemiologic and mechanistic evidence linking acrylamide exposure to reduced muscle mass. These findings highlight the potential role of inflammation and apoptosis, underscoring the importance of environmental risk factors in muscle health.