Omega-3 fatty acids and cardiovascular health

By: Dr. Kevin C. Maki, Chief Scientist and Dr. Mary R. Dicklin, Senior Scientist, Midwest Biomedical Research Center for Metabolic and Cardiovascular Health

Summary

• A large number of studies have been conducted on the effects of omega-3 supplementation in supporting cardiovascular health, but seemingly conflicting results have left many confused.
• There is a continuing need for new science to inform future omega-3 intake and dosing guidelines. 
• A new study has suggested an association between high fish and omega-3 intake and a lower risk of mortality.

Hitting the headlines

Omega-3 fatty acids have been in the news as of late. Just last month, researchers reported that those who were the biggest consumers of omega-3s had a 15 to 18% lower risk of death from cardiovascular diseases, such as heart attack and stroke, compared to those who consumed lower amounts of omega-3s. Being in the top 20% of fish intake, compared with the lowest 20%, was also associated with a 10% lower risk for death from cardiovascular causes.1 The findings were based on the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study that included more than 420,000 men and women, followed for an average of 16 years.

These results were reported very shortly after the authors of a well-publicized review of clinical trials had concluded that there was little evidence for cardiovascular benefits of omega-3 supplementation.2 The duelling headlines have created some confusion over what the scientific evidence really shows regarding dietary omega-3 fatty acids and cardiovascular health. This blog post is intended to explain why the experts have drawn different conclusions and provide perspective regarding the strengths and weaknesses in the available evidence.

Dietary recommendations

Dietary recommendations frequently emphasize regular consumption of fish and seafood, because higher intakes have been associated with lower risks for various adverse outcomes, particularly cardiovascular diseases. For example, a recent advisory from the American Heart Association recommended inclusion of 1-2 seafood meals per week in the diet. However, average dietary intakes of omega-3 fatty acid levels are well below the recommended levels around the globe, including in developed countries.

Diets high in long-chain omega-3 fatty acids have been more strongly associated with a lower risk of cardiac death compared to other types of cardiovascular events, such as non-fatal heart attacks and strokes. Higher dietary intake of omega-3 fatty acids and higher blood levels have consistently been linked with lower risk for cardiac death (i.e., death from heart attack, abnormal heart rhythm or heart failure), but not for non-fatal heart attacks and strokes. The process that triggers death during a heart attack or in heart failure is often an abnormal heart rhythm, resulting in uncoordinated contractions that are ineffective at pumping blood.

Limitations of the available evidence

Much of the evidence for the benefits of higher omega-3 fatty acid intake comes from observational studies. In this type of study, dietary intakes and/or blood levels are measured, after which participants are followed over time to see if there are relationships between the measurements and the occurrence of cardiovascular events. This type of study can be very useful, but is always limited by the possibility that high and low consumers of omega-3 fatty acids may be different in other ways. For example, high fish consumers may be more health conscious and therefore have other characteristics that could influence cardiovascular risk, such as exercising more, a generally healthier diet, or smoking less.

Intervention studies, known as randomized controlled trials (RCTs), are generally considered more reliable for evaluating the influence of a dietary intervention or treatment on a disease risk. With this type of study, participants are assigned at random to receive one intervention or another, for instance an omega-3 supplement or an inactive placebo. There have been a large number of such studies conducted to assess the effects of omega-3 (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)supplements on cardiovascular disease risk, as well as other diseases and risk factors. As noted above, a recent review of these trials did not produce clear evidence of a benefit. However, many of those studies had a number of serious limitations, adding to the confusion. The two main limitations of the intervention studies conducted to date have been the use of low dosages of EPA + DHA and a focus on composite outcomes that include several types of cardiovascular events. In fact, cardiac death is the outcome for which both the observational studies and RCTs suggest the greatest likelihood of benefit.

Exploring omega-3s further

Last year, a study published by our group in the Journal of Clinical Lipidology explored the available RCT data on omega-3 supplementation and the risk for cardiac death.3 Fourteen clinical trials with over 71,000 subjects were identified for the primary evaluation and meta-analysis, to compare cumulative frequencies of cardiac death events between those taking omega-3 fatty acids and control groups. This showed an 8% lower risk of cardiac death in subjects taking omega-3s. Notably, when the analysis was limited to studies in which the dosage used was >1 g/d of EPA + DHA, the results suggested a larger reduction in cardiac death of 29%.

This year, we published a commentary emphasizing the importance of further trials with higher EPA + DHA dosages (over 2 g/day).4 Results from biomarker studies in which levels of EPA + DHA have been measured in blood suggest a relationship between higher blood omega 3 levels and lower risk for cardiac death. Each 1-unit (standard deviation) increase in blood omega-3 biomarker level has been associated with a reduction of about 12 to 15% in cardiac death. Most of the clinical trials completed to date have used a dosage that would be expected to raise the blood level by just one-half unit. This would be expected to produce a very modest effect on cardiac death of around 6 to 8%, which is in line with what the reviews of RCT evidence have shown. This suggests the need for more studies using higher dosages. These findings also emphasize the importance of measuring blood levels of omega-3 fatty acids to confirm compliance and ensure that the intervention group is showing a sufficiently large increase compared with the control group to expect a benefit. Future studies should aim for an increase in the active group compared with the control group.

It is also important to note that there are differences between the three main omega-3 fatty acids – EPA, DHA and alpha-linolenic acid (ALA). EPA and DHA, known as long-chain omega-3s, are widely recognized as having the greatest functional importance throughout the body. The beneficial roles of EPA and DHA are illustrated by a recent announcement from the European Food Safety Authority that there is a “positive relationship between EPA and DHA on cardiac function.” ALA is a building block for EPA and DHA but, in humans, this conversion happens in very limited amounts. Therefore, preformed EPA and DHA – found in fish and other seafood, along with omega 3 dietary supplements – is preferred to ensure adequate amounts of EPA and DHA are regularly consumed.

The omega-3s EPA and DHA are the most studied nutrients, with more than 34,000 published papers and 3,300 human clinical trials to date.