Omega-3 fatty acids, specifically docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), are renowned for their therapeutic benefits for a broad range of bodily systems. Modern-day research has focused on some key health areas where supplementation can play a role, perhaps none larger than cardiovascular health.
Omega-3 fatty acids support the heart in numerous ways. First, these fatty acids are preferentially incorporated into cell membrane phospholipids, where they both influence signaling across membranes and preserve membrane fluidity. Omega-3s are also able to modulate the function of calcium and sodium membrane channels, and in doing so, promote anti-arrhythmic effects.
Omega-3 fatty acids also support heart health on several anti-inflammatory fronts, which means they may potentially prevent vascular damage that leads to atherosclerosis and endothelial dysfunction.1 For instance, omega-3s prevent the conversion of the omega-6 fatty acid, arachidonic acid, into pro-inflammatory eicosanoids. By substituting for arachidonic acid in cyclooxygenase (COX) and lipoxygenase (LOX) enzymes, omega-3s therefore decrease inflammation. In addition, omega-3s further promote anti-inflammation, including in vascular walls, by leading to the production of lipid mediators known as resolvins and protectins.
The Negative Current
Given these important attributes, it’s easy to see how DHA and EPA became broadly known as useful contributors to heart health. Yet, despite the fact that several published intervention studies and meta-analyses back the positive effects of omega-3 fats on cardiovascular health, controversy remains about their true value. Mainstream publications, including The New York Times2 and The Washington Post3, have questioned the science behind omega-3s, basing their questions on recent reviews and meta-analyses showing neutral effects of omega-3s on cardiovascular disease prevention.
A recent report published by the Agency for Healthcare Research and Quality (a division of the U.S. Department of Health and Human Services) evaluated the effects of, and associations between, omega-3 fatty acid intake and cardiovascular disease outcomes, looking at factors such as blood lipids, blood pressure, risk of cardiovascular mortality, and development of cardiovascular events.4 The reviewers searched for published studies between 2002 and 2015 and chose 61 randomized controlled trials and 37 longitudinal observational studies to include in the analysis. While the researchers concluded that there was evidence of a benefit of omega-3 fats for raising HDL cholesterol, lowering triglycerides, and lowering the total cholesterol:HDL ratio, they also said there was weak evidence to show that omega-3s help to reduce all-cause mortality, blood pressure, and myocardial infarct. They also noted that higher marine omega-3 intake was associated with a small but significant increase in LDL (bad) cholesterol levels. In addition, in terms of stroke prevention and cardiovascular death, the randomized controlled trials found no protective effect of omega-3s. (Evidence from observational studies, however, did indicate potential benefits of omega-3 intake.)
Additionally, in a recent observational study led by Jinnie Rhee of the Harvard T.H. Chan School of Public Health (Boston, MA), researchers assessed the association between consumption of fish and long-chain omega-3 polyunsaturated fatty acids (PUFA), including α-linolenic acid and marine omega-3 fatty acids, and the incidence of cardiovascular disease in healthy women who were enrolled in the Women’s Health Study.5 This analysis included 22 years of follow-up data from 38,392 women without a prior history of cardiovascular disease. Researchers found no association between the intake of fish, α-linolenic acid, or marine fatty acids and the risk of major cardiovascular disease, nor any association with individual cardiovascular events such as myocardial infarction, stroke, and cardiovascular death in this cohort.
Furthermore, a Canadian review looking at the evidence from randomized controlled trials on the primary and secondary prevention of cardiovascular disease was also not wholly supportive of omega-3s. The review included eight intervention studies (enrolling more than 1,000 patients with at least a one-year follow-up), as well as two published meta-analyses of randomized controlled trials.6 In the five trials including patients with preexisting cardiovascular disease, the reviewers found that only one trial demonstrated a reduction in the incidence of cardiovascular events; in the three trials looking at primary prevention with omega-3 fatty acids, only one trial demonstrated a minor reduction in major coronary events. Similarly, the two meta-analyses, which looked at secondary prevention in patients who have had a heart attack, concluded that omega-3 fatty acids do not further reduce the incidence of cardiovascular events as an adjunct to standard drug therapy. Based on their review, the authors concluded that there is currently a lack of evidence supporting routine omega-3 supplementation for either primary or secondary prevention of cardiovascular disease.
Evidence in Favor of Omega-3s
Juxtaposing these negative results, however, is a slew of positive research attesting to the benefits of omega-3 supplements for cardiovascular risk reduction.
For example, in a study led by Liana Del Gobbo from Stanford University School of Medicine (Stanford, CA), researchers pooled evidence from 19 cohort studies (17 of which were prospective trials) from 16 countries to assess the benefits of omega-3 fatty acids on coronary heart disease.7 The pooled analysis included 45,637 individuals without prevalent coronary heart disease, and the researchers analyzed the correlation of circulating and tissue biomarkers of omega-3 status with the incidence of total coronary heart disease, fatal coronary heart disease, and non-fatal myocardial infarction. They found that each standard deviation increase in the individual levels of EPA, DHA, and DPA (docosapentaenoic acid; another marine-derived omega-3 fatty acid) was associated with an approximately 9% lower risk of fatal coronary heart disease, while the sum of all three led to an 11% lower risk of fatal coronary heart disease. Furthermore, DPA levels (but not DHA or EPA levels) were associated with a significantly lower risk in the incidence of total coronary heart disease.
- Endo J et al., “Cardioprotective mechanism of omega-3 polyunsaturated fatty acids,” Journal of Cardiology, vol. 67, no. 1 (January 2016): 22–27
- O’Connor, Anahad, “Fish Oil Claims Not Supported by Research,” The New York Times, March 30, 2015. Available at http://well.blogs.nytimes.com/2015/03/30/fish-oil-claims-not-supported-by-research/?_r=1. Accessed October 17, 2016.
- Whoriskey, Peter, “Fish Oil Pills: A $1.2 Billion Industry Built, So Far, on Empty Promises,” The Washington Post, July 8, 2015. Available at https://www.washingtonpost.com/business/economy/claims-that-fish-oil-boosts-health-linger-despite-science-saying-the-opposite/2015/07/08/db7567d2-1848-11e5-bd7f-4611a60dd8e5_story.html. Accessed October 17, 2016.
- Agency for Healthcare Research and Quality. “Omega-3 Fatty Acids and Cardiovascular Disease: An Updated Systematic Review—Research Report—Final | AHRQ Effective Health Care Program.” Available at https://effectivehealthcare.ahrq.gov/search-for-guides-reviews-and-reports/?pageaction=displayproduct&productID=2262. Accessed October 17, 2016.
- Rhee JJ et al., “Fish consumption, omega-3 fatty acids, and risk of cardiovascular disease,” American Journal of Preventive Medicine. Published online September 16, 2016.
- Walz CP et al., “Omega-3 polyunsaturated fatty acid supplementation in the prevention of cardiovascular disease,” Canadian Pharmacists Journal, vol. 149, no. 3 (May 2016): 166–173
- Del Gobbo LC et al., “Ω3 polyunsaturated fatty acid biomarkers and coronary heart disease: pooling project of 19 cohort studies,” JAMA Internal Medicine, vol. 176, no. 8 (August 1, 2016): 1155–1166
- Casula M et al., “Long-term effect of high dose omega-3 fatty acid supplementation for secondary prevention of cardiovascular outcomes: a meta-analysis of randomized, placebo controlled trials [corrected],” Atherosclerosis, vol. 14, no. 2 (August 2013): 243–251
- Djoussé L et al., “Fish consumption, omega-3 fatty acids and risk of heart failure: a meta-analysis,” Clinical Nutrition, vol. 31, no. 6 (December 2012): 846–853
- Global Organization for EPA and DHA Issues Statement Reiterating Heart Health Benefits of Omega-3s | Business Wire. Available at http://www.businesswire.com/news/home/20150403005150/en/Global-Organization-EPA-DHA-Issues-Statement-Reiterating#.VR7UZvnF91Z. Accessed October 17, 2016.
- Ito MK, “Long-chain omega-3 fatty acids, fibrates and niacin as therapeutic options in the treatment of hypertriglyceridemia: a review of the literature,” Atherosclerosis, vol. 242, no. 2 (October 2015): 647–656
- Maki KC et al., “Triglyceride-lowering therapies reduce cardiovascular disease event risk in subjects with hypertriglyceridemia,” Journal of Clinical Lipidology, vol. 10, no. 4 (July–August 2016): 905–914
- Minihane AM et al., “Consumption of fish oil providing amounts of eicosapentaenoic acid and docosahexaenoic acid that can be obtained from the diet reduces blood pressure in adults with systolic hypertension: a retrospective analysis,” The Journal of Nutrition, vol. 146, no. 3 (March 2016): 516–523
- Yang B et al., “Fish, long-chain n-3 PUFA and incidence of elevated blood pressure: a meta-analysis of prospective cohort studies,” Nutrients, vol. 8, no. 1 (January 21, 2016)
- Miller PE et al., “Long-chain omega-3 fatty acids eicosapentaenoic acid and docosahexaenoic acid and blood pressure: a meta-analysis of randomized controlled trials,” American Journal of Hypertension, vol. 27, no. 7 (July 2014): 885–896
- Stroke and High Blood Pressure. Available at http://www.heart.org/HEARTORG/Conditions/HighBloodPressure/WhyBloodPressureMatters/Stroke-and-High-Blood-Pressure_UCM_301824_Article.jsp#.WAQaocnG-mp. Accessed October 17, 2016.
- Sekikawa A et al., “Recent findings of long-chain n-3 polyunsaturated fatty acids (LCn-3 PUFAs) on atherosclerosis and coronary heart disease (CHD) contrasting studies in Western countries to Japan,” Trends in Cardiovascular Medicine, vol. 25, no. 8 (November 2015): 717–723
- von Schacky C et al., “Omega-3 fatty acids in cardiovascular disease—an uphill battle,” Prostaglandins Leukotrienes, and Essential Fatty Acids, vol. 92 (January 2015): 41–47
- Wu JHY et al., “Ω-3 fatty acids, atherosclerosis progression and cardiovascular outcomes in recent trials: new pieces in a complex puzzle,” Heart, vol. 100, no. 7 (April 2014): 530–533