Regulation of inflammation by omega-3 and omega-6 fatty acids: a meta-analysis of randomized trials

This study quantitatively compared the anti-inflammatory effects of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs) across different populations via meta-analysis. A systematic search of six major databases identified nine randomized controlled trials (RCTs) involving 504 participants. Data on inflammatory markers, including interleukin-6 (IL-6), C-reactive protein (CRP), interleukin-1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α) were extracted, and subgroup analyses were performed based on fatty acid type, population health status, and intervention duration. Effect sizes were synthesized using random/fixed effect models. Overall, omega-3/6 supplementation showed no significant effects on IL-6, CRP, and TNF-α ( p > 0.05). However, IL-1β levels were significantly reduced in the intervention group (MD = −0.04, 95% CI: −0.07 to −0.01, p = 0.02), with a more pronounced effect observed in the omega-6 subgroup (MD = −0.05, p = 0.03). No significant differences in IL-6 or TNF-α were observed between healthy individuals and patients following omega-3/6 intervention. Additionally, omega-3 supplementation did not improve IL-6 levels in Metabolic dysfunction-associated steatotic liver disease (MASLD) patients (MD = 0.00, p > 0.05). Short-term interventions (10–12 weeks) did not significantly alter IL-6 (omega-6) or TNF-α (omega-3) levels. These findings suggest that omega-6 PUFAs may inhibit IL-1β release via specific pathways, while both omega-3 and omega-6 exert limited effects on most inflammatory markers.