The association between albumin, globulin, and hyperhomocysteinemia in Chinese adults: a cross-sectional study based on a hospital-based health examination database

Albumin (ALB) and globulin (GLB) are key liver function parameters. While hyperhomocysteinemia (HHcy) is a known risk factor for various diseases, population-based evidence linking these markers to HHcy remains limited. This study investigated the associations between ALB, GLB, and HHcy. A cross-sectional analysis of triennial health examination data (2020, 2021, 2023) enrolled 1,050 eligible participants. Restricted cubic splines (RCS) examined nonlinear associations, while multivariate logistic regression and subgroup analyses assessed relationships. Random forest and Boruta algorithms validated predictive power. Among 1050 participants, 764 had HHcy. The HHcy group showed significantly higher ALB but lower GLB levels. In adjusted models, each 1-g/L ALB increase was associated with a 13% higher likelihood of HHcy (OR = 1.13; 95% CI 1.05–1.21; P < 0.001), while each 1-g/L GLB increase correlated with a6% reduction in the odds of HHcy (OR = 0.94; 95% CI 0.89–0.98; P = 0.006). RCS confirmed linear associations for both markers. Subgroup analyses demonstrated robust associations across sex, age, BMI, and metabolic syndrome components (all interaction P > 0.05). Machine learning identified ALB and GLB as informative predictors, with logistic regression achieving the highest AUC among ten models (AUC = 0.798), although discrimination was modest and external validation is still required. Elevated ALB and reduced GLB are independently associated with increased HHcy likelihood in this cross-sectional sample, suggesting their potential as candidate biomarkers that require validation in prospective studies before clinical implementation.