ArticleCurrent developments in nutrition2026
The Potential Mediating Role of HDL-Cholesterol Concentrations in the Association between Physical Activity and Depression: A Nationwide Population-Based Study.
Article in Current developments in nutrition, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Depression is a leading cause of global disability. Physical activity (PA) has been found to be associated with lower risk of depression, but the underlying biological mediating factors remain understudied. HDL cholesterol (HDL-C) is an important biomarker with neuroprotective properties, however, its potential mediating role in the relationship between PA and depression has not been explored. Objectives: Our study aimed to investigate the role of HDL cholesterol in the association between PA and depressive symptoms. Methods: A total of 16,535 adults from the NHANES (2009-2016) were analyzed. Depression was assessed with the Patient Health Questionnaire-9, and data on PA and HDL-C were collected for each participant. Multivariate logistic regressions, subgroup analysis, mediation analysis, and sensitivity analysis were performed. Results: After adjusting for covariates, individuals with sufficient PA had 57% lower prevalence of depression [odds ratio (OR): 0.43; 95% confidence interval (CI): 0.35, 0.53] compared with those reporting insufficient PA. Of note, each unit increase in HDL-C associated with 23% lower odds of depression (OR: 0.77; 95% CI: 0.65, 0.90). Mediation analysis suggested a small but statistically significant indirect effect of HDL-C in the association between PA and depressive symptoms (indirect effect: -0.03; 95% CI: -0.04, -0.01), accounting for 3.3% of the total effect. Conclusions: PA showed a protective association with depression through mediation of HDL-C, highlighting a metabolic pathway in the association between PA and mental health. Promoting PA and optimizing HDL-C concentration may help prevent depression at population levels.
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