DHA-Rich n-3 PUFA Supplementation Improves Morning Stiffness and Quality of Life in Patients with Rheumatoid Arthritis and Downregulates TNF-α Expression in PBMCs

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease associated with joint pain, stiffness, functional impairment, and reduced quality of life. Omega-3 (n-3) polyunsaturated fatty acids (PUFAs) have been proposed as adjunctive therapies for RA due to their anti-inflammatory and pro-resolving properties; however, evidence regarding high-dose docosahexaenoic acid (DHA) supplementation remains inconclusive. This exploratory study investigated the effects of 16 weeks of DHA-rich PUFA supplementation (2.5 g/d DHA and 0.5 g/d EPA) on clinical, functional, and inflammatory outcomes in individuals with moderate RA. A modest sample size of thirteen women (23–61 y) were randomized to receive either n-3 PUFA (n = 7) or placebo (n = 6). Clinical outcomes, quality of life, functional performance, cardiometabolic parameters, and systemic inflammatory markers were assessed before and after the intervention. Additionally, the inflammatory response of peripheral blood mononuclear cells (PBMCs) exposed to patient serum collected before and after supplementation, with and without the n-3 PUFA mediator resolvin D1 (RvD1), was evaluated. DHA-rich PUFA supplementation significantly reduced morning stiffness duration and improved RA-specific quality of life scores, without affecting systemic inflammatory or cardiometabolic markers. Serum obtained after supplementation attenuated TNF-α expression in PBMCs and produced effects comparable to RvD1 treatment. These findings suggest that DHA-rich PUFA supplementation improves clinically relevant outcomes in RA, potentially through local pro-resolving mechanisms.