Italian researchers similarly found significant benefits in a meta-analysis of randomized placebo-controlled trials involving 11 studies administering at least 1 g/day of omega-3 fatty acids for one year or more to patients with existing cardiovascular disease.8 Overall, the trials included 15,348 individuals with a history of cardiovascular disease. While no statistically significant effects were seen for all-cause mortality or stroke incidence, the meta-analysis revealed strong protection against cardiac death, sudden death, and myocardial infarction, indicating that daily doses of omega-3 fatty acids above 1 g may be increasingly beneficial.
Furthermore, in a meta-analysis led by Luc Djoussé from Brigham and Women’s Hospital (Boston, MA), researchers looked at seven prospective studies to assess the impact of fish intake and omega-3 fatty acid intake relative to the incidence of heart failure.9 After analyzing the data from the identified studies (which in total included 176,441 individuals), the authors concluded that higher marine omega-3 intakes were associated with a significantly lower risk of heart failure.
Given positive evidence like this, in April 2015 the association the Global Organization for EPA and DHA Omega-3s (GOED; Salt Lake City) issued a statement summarizing the fact that 10 meta-analyses of gold-standard, randomized clinical trials published between 2006 and 2014 all showed significant effects of omega-3 consumption for reduced cardiac death risk.10 The range of risk reduction was impressive, varying between 9%–35%.
Of course, omega-3 fatty acids have been found to reduce additional risk factors for cardiovascular disease as well, including triglyceride levels and blood pressure.
With regard to triglyceride reduction, a recent review indicated that omega-3 fatty acids (average dose of 4 g/day) consistently lowered triglycerides by a range of 25%-34% in placebo-controlled clinical trials.11
In the United States, approximately 33% of the population has elevated triglyceride levels, which is considered an independent risk factor for cardiovascular disease. A current meta-analysis evaluated the effects of triglyceride-lowering on cardiovascular disease risk and found that lowered triglycerides are consistently associated with cardiovascular risk reductions, indicating a protective effect against cardiovascular events.12
Blood Pressure Reduction
In terms of blood pressure, Anne Minihane and colleagues in the United Kingdom recently conducted a retrospective analysis of data from a multicenter, placebo-controlled randomized clinical trial.13 During the trial, healthy men and women consumed fish oil containing 0.7 g or 1.8 g of EPA plus DHA daily for eight weeks. In those adults with isolated systolic hypertension, the 0.7-g dose led to clinically meaningful reductions in blood pressure averaging 5 mm Hg. The authors indicated that this magnitude of blood pressure reduction in middle-aged individuals is associated with an approximate 20% reduction in the risk of cardiovascular disease.
Bo Yang and colleagues from Zhejiang University (Hangzhou, China) conducted a meta-analysis of eight prospective cohort studies involving 56,204 adults and found that higher circulating levels of long-chain omega-3 fatty acids (and DHA in particular) were significantly associated with a lower risk of elevated blood pressure, indicating that optimal intake of omega-3s could potentially serve as a primary means of preventing hypertension.14
These findings are buttressed by an earlier meta-analysis of 70 randomized controlled trials, which indicated that supplementation with EPA and DHA led to significant reductions of systolic blood pressure, while higher doses (more than 2 g/day) also significantly reduced diastolic blood pressure.15
High blood pressure is a leading cause of stroke16, and decreases associated with consuming omega-3s could lead to clinically meaningful risk reductions in this area.
Reconciling Current Findings
Research supports the benefits of omega-3 fatty acids for reducing several risk factors associated with cardiovascular disease. Why, then, do some researchers find potential discrepancies when analyzing the data, and, more importantly, how does one go about reconciling the divergence between positive and negative findings? Some experts have postulated several reasons for the seemingly disparate results.
- 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