This study aims to further validate the association of serum albumin and obesity in a larger population and explore potential underlying mediating factors. Our study utilized data from 5881 participants in the National Health and Nutrition Examination Survey (NHANES 1999–2004). Multivariable weighted logistic regression analyses were conducted to assess the association between serum albumin and obesity, while evaluating the potential mediating effects of extracellular fluid (ECF), percentage body fat (PFAT), and C-reactive protein (CRP). Secondary analyses encompassed restricted cubic splines (RCS) and subgroup analyses. Every 1 g/L increase in serum albumin concentration was associated with a 17% reduction in obesity prevalence (adjusted odds ratio = 0.83; 95% confidence interval (CI): 0.79–0.87; P < .001), after adjusting for age, sex, race/ethnicity, smoking status, drinking status, physical activity, hypertension, diabetes, calorie consumption, protein consumption, insulin, glycohemoglobin, TG, creatinine, ALT, and NHANES cycle. RCS analysis revealed no evidence of a nonlinear relationship ( P for nonlinearity = .983). ECF mediated 66.3% (95% CI: 53.1–81.6), PFAT 31.7% (95% CI: 23.4–41.3), and CRP 11.1% (95% CI: 7.1–17.4) of the relationship (all P < .001). Sensitivity analyses revealed robust findings. Serum albumin levels demonstrated an inverse association with obesity odds. Mediation analyses confirmed mediating effects of ECF, PFAT and CRP, suggesting serum albumin may be associated with obesity through these mediators.
Wang et al. (2026) studied this question.