Differences in study populations certainly may play a role. Factors—including genetics, ethnicity, and background dietary intake of omega-3 fatty acids—all may have an impact on findings. In comparing the results of long-term clinical trials of omega-3s in western countries (which have often had neutral findings) to results from Japanese trials (which generally have positive findings), Akira Sekikawa of the University of Pittsburgh (Pittsburgh, PA) postulated that the doses used in the studies played a significant part and, importantly, that higher doses may be needed to ensure the greatest cardio-protective benefits. For example, the author, pointed out, dosages administered in the Japanese trials were generally higher than those in the western trials. In a recent trial in Japan showing a cardiovascular risk reduction of 19% with omega-3 fatty acid supplementation, the dose of omega-3 fatty acids given in the study was 1800 mg/day—this is in addition to the relatively high omega-3 dietary intake in the Japanese population of greater than 1,000 mg/day.17 By comparison, in western studies, the dose range was generally 300-900 mg of omega-3s per day, and the intake of omega-3s in western populations is generally less than 300 mg/day.
In recent intervention studies that have had neutral findings, another reason there may have been unfavorable results may be due to bioavailability issues associated with when the omega-3 supplements were administered. In a commentary on the discrepancies between recent intervention trials looking at cardiovascular risk reduction versus positive findings from epidemiologic studies, Clemens von Schacky from Ludwig-Maximilians-University (Munich, Germany) suggested that many of the intervention trials advised participants to consume their supplements with breakfast, which is often a low-fat meal.18 This could have significant impacts on omega-3 bioavailability because omega-3 absorption is dependent on the fat contained in foods and could partially explain the neutral findings. He advocated for new intervention trials to assess the real effect of omega-3s, keeping in mind the issue of bioavailability as well as controlling for the background dietary intake of study populations.
Jason Wu and Dariush Mozaffarian of the Harvard School of Public Health (Boston, MA) further speculated that another likely reason for neutral findings in recent studies versus older, positive trials may be the aggressive use of antihypertensive, lipid-lowering, and antiplatelet medications in later trials.19 Since many of the risk factors addressed overlap between the effects of these medications and the effects of omega-3 fatty acids (reduction of blood pressure, blood lipids, and circulation benefits), any additional effects of omega-3 fatty acids could have been masked by drug therapy. Researchers in the field should take these and other factors into account as they design further intervention trials assessing the benefits of omega-3s for cardiovascular health.
Plenty of Promise
In spite of the mixed findings of some recent trials, omega-3 fatty acids clearly play a role in cardiovascular wellness due to their mechanism of action on cardiovascular health parameters. Epidemiological studies consistently have shown positive associations with omega-3 supplementation, and clinical trial evidence from studies conducted around the world speaks to the impressive effects of omega-3 fatty acids on heart and vascular health.
Additional research will continue to provide specific evidence to assess the magnitude of omega-3’s true benefits. In the meantime, as supplement users consider the low risk associated with omega-3 supplementation and the potential upside of promoting heart health, increasing dietary and supplemental intake should make sense. These important nutrients remain a prudent choice for improving health and well-being.
- 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