Association of acrylamide exposure with markers of systemic inflammation and serum alpha-klotho concentrations in middle-late adulthood

BACKGROUND: Acrylamide (AA) is a ubiquitous environmental contaminant linked to systemic inflammation and oxidative stress in animal studies; however, the epidemiological evidence is still lacking. This study aimed to evaluate the association of AA exposure with markers of systemic inflammation and serum concentrations of an anti-aging protein, α-klotho. METHODS: The study used data of 1,545 adults aged 40-79 years from the National Health and Nutrition Examination Survey (NHANES) 2013-2016. Internal AA exposure was assessed using hemoglobin adducts of acrylamide and glycidamide (HbAA and HbGA, respectively), the sum of HbAA and HbGA (HbAA + HbGA), and the ratio of HbGA and HbAA (HbGA/HbAA). Two novel indicators, systemic immune-inflammation index (SII) and system inflammation response index (SIRI), were calculated using the lymphocyte, platelet, neutrophil, and monocyte counts. The serum concentration of soluble α-klotho was measured using enzyme-linked immunosorbent assay. Multivariable linear regression models were used to estimate the associations of AA hemoglobin biomarkers with systemic inflammation indicators and serum concentration of α-klotho. RESULTS: Each one-unit increase in ln-transformed HbAA, HbGA, and HbAA+HbGA was associated with an increase in SII in models adjusted for age, sex, and race/ethnicity [regression coefficient (β) = 32.16, 95% confidence interval (CI): 3.59, 60.73; β =36.37, 95% CI: 5.59, 67.15; and β = 37.17, 95% CI: 6.79, 67.55, respectively]. However, the associations were no longer significant after additional adjustment for lifestyle factors. Higher HbAA and HbAA+HbGA predicted lower serum α-klotho concentrations (β = -35.76 pg./mL, 95% CI: -63.27, -8.25; β = -33.82 pg./mL, 95% CI: -62.68, -4.96, respectively). CONCLUSION: The hemoglobin adducts of AA parameters, as biomarkers of internal AA exposure, were associated with reduced serum concentrations of α-klotho among the United States population in their middle-late adulthood. The findings indicated that exposure to AA may have impacts on the molecular pathways of aging and related diseases by influencing α-klotho concentrations.