Omega-3 fatty acids from fish oil were once expected to prevent heart disease broadly. Three large trials have now tested them. Their results separate a general fish-oil supplement from a purified prescription EPA product, and that separation is the main point of this article.
VITAL: the general-population trial
VITAL enrolled about 25,000 adults and tested 1 g of marine omega-3 a day against placebo, factorially with vitamin D, for a median of 5.3 years. Neither major cardiovascular events nor invasive cancer were significantly reduced. An exploratory heart-attack signal was reported in analyses that were not prespecified, and the investigators treated it as hypothesis-generating.
REDUCE-IT: a purified EPA product
REDUCE-IT randomized 8,179 statin-treated adults with elevated triglycerides to icosapent ethyl 4 g a day or mineral oil placebo. The primary composite was lower with icosapent ethyl (17.2% vs 22%), and triglycerides fell on the drug. The trial used a purified EPA ethyl ester, not the fish oil in capsules, and it was funded by the manufacturer.
STRENGTH: a second null result
STRENGTH compared a high-dose omega-3 carboxylic acid preparation (EPA and DHA) with corn oil in patients at high cardiovascular risk. It was stopped early after an independent monitoring committee judged that a benefit was unlikely. The primary composite was essentially the same in both groups (hazard ratio 0.99).
What the three trials together mean
The general-population and high-risk trials with ordinary omega-3 preparations did not show fewer cardiovascular events. The one positive result was with a purified EPA product at a high dose. The two findings are not in conflict, and neither supports a broad claim that fish oil capsules prevent heart disease.
What this does not say
- The positive REDUCE-IT result is for icosapent ethyl at 4 g a day. It is not a result for standard capsules at lower doses.
- The VITAL heart-attack finding was not prespecified and needs confirmation in a trial designed to test it.
- The trials measured cardiovascular events in specific populations; they do not address other possible uses.
How we use this
If your physician recommends a purified EPA product, we explain the difference between that product and fish oil capsules, and the trial behind each. We do not present fish oil capsules as a prevention for heart disease.
Your triglyceride and LDL levels and your risk determine whether any omega-3 product has a place in your plan.
Explore weight loss treatmentsSources
- 1.Manson JE et al. Marine n-3 fatty acids and prevention of cardiovascular disease and cancer. N Engl J Med 2019;380:23-32. NEJM
- 2.Bhatt DL et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia (REDUCE-IT). N Engl J Med 2019;380:11-22. NEJM
- 3.Nicholls SJ et al. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events (STRENGTH). JAMA 2020. JAMA
- 4.Hahn J et al. Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial. BMJ 2022;376:e066452. BMJ