The cross-sectional relationship among omega-3 fatty acid levels, cardiorespiratory fitness, and depressive symptoms from the Cooper Center Longitudinal Study

Objective: Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are implicated in numerous illnesses including depression. The literature is mixed regarding the relationship between n-3 PUFA levels and depression, and studies based on self-reported dietary n-3 PUFA intake may not accurately reflect in vivo levels. Method: The current cross-sectional analysis examined the relationship between erythrocyte levels (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and depressive symptoms (Center for Epidemiologic Studies Depression Scale; CES[sbnd]D), adjusting for health-related factors and omega-3 supplement use in 16,398 adults assessed at the Cooper Clinic in Dallas, Texas for preventative medical examinations between April 6, 2009, and September 1, 2020. A three-stage hierarchical linear regression was conducted to examine the EPA and DHA levels on CES-D before and after inclusion of cardiorespiratory fitness (CRF) and high sensitivity C-reactive protein (hs-CRP) in the model. Results: DHA level, but not EPA level, was significantly associated with CES-D scores. Taking omega-3 supplements was associated with lower CES-D scores even when adjusting for CRF, while hs-CRP was non-significantly associated with CES-D scores. These findings suggest that DHA levels are related to depressive symptom severity. Omega-3 PUFA supplement use was associated with lower CES-D scores when controlling for EPA and DHA levels. Conclusion: The findings from this cross-sectional study suggest that lifestyle and/or other contextual factors unrelated to EPA and DHA levels may also be associated with depressive symptom severity. Longitudinal studies are needed to evaluate the role of health-related mediators among these relationships.