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

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.

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.

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 = 3,759) 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.

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; I ² = 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.

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.

https://www.crd.york.ac.uk/PROSPERO/view/CRD420251035960, Identifier CRD420251035960.