No Effects of Omega-3 Supplementation on Kynurenine Pathway, Inflammation, Depressive Symptoms, and Stress Response in Males: A Placebo-Controlled Trial

<b>Background:</b> Increased inflammation and heightened physiological stress reactivity have been associated with pathophysiology of depressive symptoms. The underlying biological mechanisms by which inflammation and stress may influence neurogenesis are changes in the kynurenine (KYN) pathway, which is activated under stress. Supplementation with <i>n</i>-3 polyunsaturated fatty acids (<i>n</i>-3 PUFAs) has anti-inflammatory properties and can increase stress resilience. Whether <i>n</i>-3 PUFAs alter KYN stress response is unknown. <b>Objectives:</b> This placebo-controlled study investigated the effect of <i>n</i>-3 PUFAs on KYN metabolism, inflammation, depressive symptoms, and mood. Moreover, stress-induced changes following a laboratory stressor have been assessed. <b>Methods:</b> In this placebo-controlled study, 47 healthy male adults received either 4 g <i>n</i>-3 PUFAs per day (Omega-3 group) or a placebo (Placebo group) for 12 weeks. <b>Results:</b> A significant group-by-time interaction was found for the inflammatory markers gp130 (F = 7.07, <i>p</i> = 0.011), IL-6R alpha (F = 10.33, <i>p</i> = 0.003), and TNF_RI (F= 10.92, <i>p</i> = 0.002). No significant group-by-time interactions were found for KYN metabolites, depressive symptoms, and mood (except for Hedonic tone (F = 6.50, <i>p</i> = 0.014)), nor for stress-induced changes in KYN metabolites and mood following a laboratory stressor. <b>Conclusions:</b> Overall, increased <i>n</i>-3 PUFA levels in healthy men ameliorate inflammatory markers but do not ameliorate KYN metabolism, depressive symptoms, mood, or KYN metabolism and mood following a stress induction. This study was registered at ClinicalTrials.gov with the identifier NCT05520437 (30/08/2022 first trial registration).