Association between acrylamide hemoglobin adduct levels and rheumatoid arthritis: A NHANES analysis

Acrylamide is a widespread environmental and dietary contaminant, and hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA) serve as objective biomarkers of internal exposure. However, the association between acrylamide exposure and rheumatoid arthritis (RA) has not been well characterized at the population level. We analyzed data from 4 cycles of the US National Health and Nutrition Examination Survey (2003-2006 and 2013-2016), including 1972 adults aged ≥20 years with complete information on RA status and acrylamide hemoglobin adduct measurements. Multivariable logistic regression models accounting for the complex survey design were used to examine associations between HbAA, HbGA, total adducts (HbAA + HbGA), the metabolic ratio (HbGA/HbAA), and RA prevalence. Restricted cubic spline models were applied to explore potential nonlinear exposure-response relationships. Nonlinear associations were observed between acrylamide-related hemoglobin adducts and the prevalence of RA. HbAA exhibited a J-shaped association, with higher odds observed at intermediate exposure levels. In contrast, HbGA and total adduct concentrations showed increasing associations across higher exposure ranges. The HbGA/HbAA ratio was positively associated with RA prevalence. Restricted cubic spline analyses supported these non-monotonic exposure-response patterns. Subgroup analyses showed variability in point estimates across behavioral and clinical strata, but estimates were often imprecise and should be interpreted as exploratory. In this nationally representative cross-sectional study, HbAA was nonlinearly associated with the prevalence of RA among US adults. These findings support an epidemiological association between internal biomarkers of acrylamide exposure and RA. Prospective studies with repeated exposure assessment and mechanistic measurements are needed to clarify temporal relationships and underlying biological pathways.