Racial disparities in systemic inflammation: The mediating role of diet and physical activity in α-1-acid glycoprotein levels in the U.S. population

Racial and ethnic disparities in systemic inflammation contribute to differences in chronic disease risk. α-1-acid glycoprotein (AAG), an acute-phase inflammatory marker, has been associated with metabolic dysfunction and cardiovascular risk. Despite known racial differences in inflammatory biomarkers, the role of diet and physical activity as mediators of racial disparities in AAG levels remains unclear. This study investigates whether racial disparities in AAG are mediated by diet quality and physical activity in a nationally representative U.S. sample. We conducted a cross-sectional mediation analysis using National Health and Nutrition Examination Survey (NHANES) data (2011-2022), including 2451 participants. AAG levels were measured via serum assays. Diet quality was assessed using the healthy eating index (HEI-2015), while physical activity was quantified using metabolic equivalent of task (MET) minutes per week. Mediation analysis was performed using causal mediation models, adjusting for age, sex, body mass index (BMI), socioeconomic status (SES), and other covariates. Moderated mediation models assessed whether the mediation effect varied by gender, BMI, income, and age. Significant racial disparities in AAG were observed, with Non-Hispanic Black participants exhibiting higher AAG levels than Non-Hispanic Whites and Mexican Americans (P < .001). Diet quality significantly mediated the association between Race and AAG. However, physical activity was not a significant mediator in most racial comparisons, except for a minor effect in the Other/Multi-Racial group. Moderated mediation analysis revealed that the diet-AAG mediation effect was stronger among females, individuals with lower BMI, and those with lower income levels (P < .01). Racial disparities in AAG are partially explained by differences in diet quality, suggesting that nutritional interventions targeting racial/ethnic disparities may help reduce systemic inflammation. However, physical activity did not significantly mediate AAG disparities, indicating that other structural or behavioral factors may contribute. Future longitudinal studies are needed to confirm these relationships and explore additional mediators of inflammation-related health disparities.