The omega-3 fatty acids EPA and DHA are essential, meaning the body cannot synthesise them in adequate quantities and must obtain them from diet or supplementation. Their roles include cell membrane fluidity, eicosanoid synthesis, gene expression regulation, and anti-inflammatory signalling. The evidence for omega-3 supplementation has had a turbulent history in clinical research, with initial enthusiasm followed by several negative trials, and then by the recognition that dose, baseline status, and the specific outcome measured all substantially affect whether a benefit is detectable.
Triglycerides: The Strongest Evidence
The evidence for omega-3 reduction of serum triglycerides is consistent and clinically significant. High-dose EPA and DHA, typically 2 to 4g per day, reduces triglycerides by 20 to 30 percent in adults with elevated levels. A prescription-strength omega-3 preparation, icosapentaenoic acid at 4g daily, was trialled in the REDUCE-IT study involving over 8000 adults with elevated cardiovascular risk and elevated triglycerides. The trial found a 25 percent reduction in major cardiovascular events, including heart attack and stroke, which represents one of the most clinically significant results in cardiovascular supplementation research.
Inflammation and Joint Health
EPA and DHA are converted in the body to anti-inflammatory resolvins and protectins that actively resolve inflammatory processes. A meta-analysis of omega-3 supplementation in rheumatoid arthritis found significant reductions in joint pain, morning stiffness, and NSAID use. The effect size was clinically meaningful: participants consumed on average 2.7g per day of combined EPA and DHA. For athletes and adults with musculoskeletal pain, 2 to 3g per day of combined EPA and DHA is a reasonable evidence-based target.
Mental Health Applications
The brain is approximately 60 percent fat by dry weight, and DHA is the dominant structural fatty acid in neuronal cell membranes. Prospective cohort studies consistently find inverse associations between omega-3 intake and depression risk. A meta-analysis by Mocking et al. of 13 randomised controlled trials found that omega-3 supplementation produced significant reductions in depressive symptoms, with EPA appearing more important than DHA for antidepressant effects. Formulations containing more than 60 percent EPA appear to be the most effective for mood applications.
- For general anti-inflammatory benefit: 1 to 2g per day of combined EPA and DHA from quality fish oil or algae oil
- For triglyceride reduction or cardiovascular risk: 2 to 4g per day, ideally with medical supervision
- For depression: EPA-dominant preparations with at least 60 percent EPA, 1 to 2g EPA daily
- Algae-derived DHA and EPA are appropriate for vegans and have equivalent efficacy to fish oil
- Store fish oil in the refrigerator: oxidised oil has the opposite of the intended anti-inflammatory effect
Sources
- Bhatt, D.L., et al. (2019). Cardiovascular risk reduction with icosapentaenoic acid for hypertriglyceridemia. New England Journal of Medicine, 380(1), 11-22.
- Mocking, R.J.T., et al. (2016). Meta-analysis and meta-regression of omega-3 polyunsaturated fatty acid supplementation for major depressive disorder. Translational Psychiatry, 6, e756.