Effects of Omega-3 fatty acids on chronic pain: a systematic review and meta-analysis

LEI XIE^1,2Xin Wang^2,3JUNYANG CHU^1,2XINYAO HE^1,2JINGTING BAO^1,2YAZHI XI^1,2XUELIAN WEI^1,2QINGHE ZHOU^4*

• ¹Zhejiang Chinese Medical University, Hangzhou, China
• ²First Hospital of Jiaxing, Jiaxing, China
• ³Soochow University, Suzhou, China
• ⁴The Second Affiliated Hospital of Jiaxing University, Jiaxing, China

Background: Chronic pain afflicts approximately 20% of the global adult population and is frequently undertreated, with available pharmacologic options often associated with significant long-term adverse effects. Although omega-3 fatty acids are known for their anti-inflammatory and immunomodulatory effects, current clinical evidence regarding their efficacy in pain management remains inconclusive. Objective: To determine how well omega-3 fatty acids reduce chronic pain, and to investigate how factors like disease type, dosage, treatment duration, and study design influence their effectiveness. Methods: We searched four databases (PubMed, Embase, Cochrane Library, and Web of Science) from inception to 14 February 2025 with no language restrictions. Forty-one randomised controlled trials (RCTs; n = 3759) met predefined criteria. Risk of bias was assessed with RoB 2. Pooled standardised mean differences (SMDs) for pain intensity were obtained through random-effects meta-analyses. Subgroup, sensitivity, and publication-bias analyses were also conducted. Results: Omega-3 fatty acids showed a moderate, statistically and clinically significant reduction in pain intensity with a standardized mean difference (SMD) of –0.55 (95% CI –0.76 to –0.34; I² = 87%). The relief was noticeable at 1 month (SMD = –0.27) and improved by 6 months (SMD = –0.83). Lower doses (≤1.35 g/day) were more effective (SMD = –0.60) compared to higher doses (>1.35 g; SMD = –0.53). The benefits were significant for rheumatoid arthritis, migraine, and other mixed chronic pain conditions, but not for osteoarthritis or mastalgia. There was minimal publication bias according to trim-and-fill adjustment, and leave-one-out tests confirmed robust results. Conclusion: Omega-3 fatty acid supplementation offers a clinically meaningful and time-dependent reduction in chronic pain, particularly at moderate doses and in certain disease contexts. Standardization of outcome measures, dose optimization, and long-term trials are needed to better define its role in pain management. Trial registration: CRD420251035960