Effect of Fish-Derived Lipids on Inflammation Status and Health-Related Quality of Life in Women with Endometriosis

Background: Endometriosis is a chronic, estrogen-dependent inflammatory disorder associated with pain and immune dysregulation. Omega-3 (n-3) fatty acids and fish-derived bioactive lipids may modulate inflammation and metabolism. This study investigated whether adding fish-derived lipids (FDLs) to a Healthy Eating Plate diet improves inflammatory markers, gut inflammation, pain, and quality of life in women with endometriosis. Methods: In this 12-week randomized controlled trial, 46 women with confirmed endometriosis were assigned to either a Healthy Eating Plate diet alone (control group, CG) or the same diet plus FDLs (intervention group, IG). Primary outcomes included serum cytokine concentrations (interleukin [IL]-1β, IL-6, IL-8, IL-10, and tumor necrosis factor-alpha [TNF-α]) and fecal calprotectin (CAL). Secondary outcomes included pain intensity measured using the visual analog scale (VAS) and health-related quality of life assessed with the Endometriosis Health Profile-30 (EHP-30). Results: IL-10 levels (pg/mL) increased in the IG (32.5 ± 51.5 to 265 ± 508; p = 0.024) with a significant adjusted effect (ANCOVA: 5.07 [95% CI: 1.32–19.48], p = 0.019). Other cytokines showed heterogeneous responses, and CAL levels remained unchanged. EHP-30 Pain scores improved within both groups (CG p = 0.016; IG p = 0.002) without significant between-group change or adjusted effects (all p > 0.05). VAS scores decreased within the IG (5.0 ± 2.1 to 4.3 ± 2.1; p = 0.011), although there were no between-group differences in change and ANCOVA (all p > 0.05). However, ≥1-point responder rates were higher in the IG vs. CG (73.9% vs. 34.8%): adjusted RR = 2.11 (95% CI: 1.16; 3.89; p = 0.014). Conclusions: Overall, FDL supplementation was associated with a selected regulatory immune signal, reflected mainly by the IL-10 response, while most inflammatory, pain-related, and quality-of-life outcomes did not show consistent significant between-group effects. The observed greater likelihood of pain reduction in the FDL-supplemented group of women with endometriosis, along with the IL-10 response, should be interpreted with caution and confirmed in larger studies with longer follow-up/intervention time, taking into account the potential mechanisms of biological response.