Omega-3 and Heart Health

(Image source: https://www.heartuk.org.uk/)

Longer chain omega-3 fatty acids from fish sources include eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The early scientific literature suggested a role of omega-3 fatty acids supplementation for maintenance of cardiovascular health among healthy individuals and those with existing cardiovascular disease. Their effect on cardiovascular outcomes may be due to their ability to lower triglyceride levels, decrease platelet aggregation, and lower blood pressure. Nevertheless, recent meta-analyses and randomised controlled trials (RCTs) have not confirmed the beneficial effect of interventions with omega-3 fatty acids supplementation on heart health. The most recent study suggested the cardio protective effect of omega-3 only were only seen in populations with low fish intake.

Some background knowledge

Cardiovascular diseases (CVDs) are disorders of the heart and blood vessels. They include cerebrovascular disease (including stroke and transient ischemic attack), coronary heart disease (CHD) (including myocardial infarction and angina), and peripheral arterial disease, among others (1). The scientific literature suggests a role of omega-3 fatty acids, such as EPA and DHA, for maintenance of cardiovascular health.

EPA and DHA are long-chain polyunsaturated fatty acids (PUFA) for which the main dietary sources are marine foods, especially oily fish and fish oil supplements. Except from a limited endogenous synthesis of EPA and DHA from α-Linolenic acid (ALA) which is found in plants, mammals are dependent on dietary intake of EPA and DHA to cover the need of these omega-3 fatty acids (2).

The mechanisms linking EPA and DHA fatty acids to heart health are complex as they affect various targets across multiple organs. Overall, EPA and DHA are either incorporated into cell membranes thereby affecting cell signaling and membrane fluidity. They can also act directly as free fatty acids in low concentrations by modulating potassium, sodium, and calcium channels. Proposed mechanisms for the protective role of omega-3 fatty acids against CVD include lowering blood pressure, altering lipid profile, especially reduce serum triglycerides concentration, producing anti-inflammatory and anti-arrhythmic effects, improving vascular endothelial function and insulin sensitivity, and increasing plaque stability (2-5).

... So let's look at the scientific evidence

Studies done in the 1990s, demonstrated that omega 3 supplements can reduce the risk of developing heart diseases. For instance, the JELIS study involving 18,645 hypercholesterolaemic participants resulted in 19% reduction in major coronary events (6). GISSI study with a total of 11,324 patients also indicated 20% reduction in total death and a 30% reduction in CVD deaths (7). However, recent studies indicated conflicting evidence.

A Cochrane systematic review published in 2018 examined the effects of omega-3 fatty acids supplementation on all-cause mortality and CVDs from 79 RCTs (n=112,059) with a 12 to 72 months’ duration that included adults at varying cardiovascular risk. Increasing EPA and DHA has little or no effect on mortality or cardiovascular health but there was a reduction in serum triglyceride in a dose dependent manner and also a slight increase in HDL level (8). Another meta-analysis published in 2018 assessing 10 RCTs (n=77,917) on high-risk individuals also showed no significant associations between the use of omega-3 supplements with CHD mortality or any CHD events (9).

The most recent study (VITAL study) was published this year, involving 25,871 participants with different ethnic backgrounds concluded that supplementation with omega−3 fatty acids did not result in a lower incidence of major cardiovascular events than placebo. However, the subgroup analysis of the study provided an interesting finding. There was possible risk reduction of 19% on major cardiovascular events among participants with low fish intake (<1.5 serving/ week)(10). This indicates that omega-3 supplementation does not provide additional protection for those who have consumed enough omega-3 from their food intake but may be beneficial for those with low fish intake.

Conclusive Summary

Results from early studies had demonstrated a cardioprotective effect of long-chain omega-3 fatty acids supplementation. In contrast, recent meta-analyses of RCT have suggested a lack of effect. The most recent RCT showed minimal effect of omega-3 supplementation on the general population but indicated its beneficial effect for those with low fish intake.

Literature cited

1. WHO. Cardiovascular disease 2016 [Available from: http://www.who.int/cardiovascular_diseases/en/.
2. De Caterina R. n–3 Fatty Acids in Cardiovascular Disease. New England Journal of Medicine. 2011;364(25):2439-50.
3. Mozaffarian D, Wu JH. Omega-3 fatty acids and cardiovascular disease: effects on risk factors, molecular pathways, and clinical events. J Am Coll Cardiol. 2011;58(20):2047-67.
4. Mollace V, Gliozzi M, Carresi C, Musolino V, Oppedisano F. Re-assessing the mechanism of action of n− 3 PUFAs. International journal of cardiology. 2013;170(2):S8-S11.
5. Chang CL, Deckelbaum RJ. Omega-3 fatty acids: mechanisms underlying 'protective effects' in atherosclerosis. Current opinion in lipidology. 2013;24(4):345-50.
6. Yokoyama, M., Origasa, H., Matsuzaki, M., Matsuzawa, Y., Saito, Y., Ishikawa, Y.,. . . Shirato, K. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): A randomized open-label, blinded endpoint analysis. Lancet, 2007;369(9567):1090-1098.
7. GISSI-Prevenzione Investigators. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: Results of the GISSI-prevenzione trial. Lancet, 2007;354(9177): 447-55.
8. Abdelhamid AS, Brown TJ, Brainard JS, Biswas P, Thorpe GC, Moore HJ, et al. Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Systematic Reviews. 2018(7).
9. Aung T, Halsey J, Kromhout D, Gerstein HC, Marchioli R, Tavazzi L, et al. Associations of Omega-3 Fatty Acid Supplement Use With Cardiovascular Disease Risks: Meta-analysis of 10 Trials Involving 77917 Individuals. JAMA cardiology. 2018;3(3):225-34.
10. Manson, J., Cook, N., Lee, I., Christen, W., Bassuk, S., Mora, S., . . . Buring, J. Marine n−3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer. The New England Journal of Medicine, 2019;380(1):23-32.