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Omega-3 helps the heart, AHA class II recommendation, more than 1 gm may be needed – March 2018

Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health: A Comprehensive Review

Progress in Cardiovascular Diseases, online 20 March 2018
Andrew Elagizia, Carl J. Lavieb, , , Keri Marshallc, James J. DiNicolantoniod, James H. O'Keefed, Richard V. Milanib


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Omega-3 and Cardiovascular (items in both categories)

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The potential cardiovascular (CV) disease (CVD) benefits of Omega-3 Polyunsaturated Fatty Acids (OM3) have been intensely studied and debated for decades. Initial trials were performed in patients with low use of maximal medical therapy for CVD, and reported significant mortality benefits with the use of 1 g/day OM3 intervention following myocardial infarction (MI). More recent studies, including cohorts of patients receiving modern guideline directed medical therapy for CVD, have often not shown similar benefits with OM3 use. We conducted a literature review using PubMed, professional society guidelines, specific journal databases including New England Journal of Medicine and Journal of the American College of Cardiology from January 1, 2007 to December 31, 2017. References from selected articles were also reviewed, as well as key articles outside of the selected time-frame for their important findings or historical perspectives.

Currently, there are no Class I recommendations from the American Heart Association (AHA) for the use of OM3, however, considering the safety of this therapy and beneficial findings of some modern studies (including patients with current maximal medical therapy for CVD), the AHA has recently expanded their list of Class II recommendations, in which treatment with OM3 for CVD benefit is reasonable. This review discusses the current state of the evidence, summarizes current professional recommendations, and provides recommendations for future research.

AF, Atrial Fibrillation; AHA, American Heart Association; AHRQ, Agency of Healthcare Research and Quality; ALA, Alpha-linoleic Acid; ASA, Aspirin; BP, Blood Pressure; CHD, Coronary Heart Disease; CKD, Chronic Kidney Disease; CV, Cardiovascular; CVD, Cardiovascular Disease; DHA, Docosahexaenoic Acid; DPA, Docosapentaenoic Acid; DM, Diabetes Mellitus; EPA, Eicosapentaenoic Acid; FDA, Food and Drug Administration; HF, Heart Failure; HFrEF, Heart Failure with Reduced Ejection Fraction; LDL-C, Low-density Lipoprotein Cholesterol; LVSVI, Left Ventricular Systolic Volume Index; MACE, Major Adverse Cardiovascular Events; MI, Myocardial Infarction; OM3, Omega-3 Polyunsaturated Fatty Acid; OM6, Omega-6 Polyunsaturated Fatty Acid; RCT, Randomized Controlled Trial; RLP, Remnant Lipoprotein; SCD, Sudden Cardiac Death; SDA, Stearidonic Acid; TG, Triglyceride

Conclusion (from PDF)

While dietary intake of oily fish is currently recommended, fish oil supplementation is certainly a safe and reasonable alternative. There is no convincing evidence that OM3 increases risk of malignancy, and may in fact be protective. While OM6 has been associated with increased inflammation and pathogenesis of various disease processes, the AHA currently recommends an OM6 intake of at least 5-10% of total energy, which would seem to lower CHD risk.
Favorable CV effects found in older studies, such as GISSI-P, have been difficult to replicate in modern trials, likely due to the use of modern maximal medical therapy for CVD. Also, the use of 1 gram/day OM3 intervention in early landmark trials is often still used in current trials, despite possibly being an insufficient dose. We recommend that future research (I) focus on higher dose interventions using OM3 (II) in patients already receiving maximal medical therapy for CVD, (III) incorporate an objective measure of OM3 status, such as the OM3 index, to assess treatment efficacy and aid in the comparison of future trials, and (IV) implement early intervention following events such as MI or cardiac transplantation.
OM3 promote a favorable lipid profile that reduces levels of RLP, possibly reducing atherogenicity of LDL-C. OM3 may consequently prevent plaque development and contribute to plaque stabilization, and therefore may be beneficial when added to standard lipid-lowering therapy. We look forward to the results of the ongoing REDUCE-IT trial.
Resistance to antiplatelet agents is associated with increased risk of CHD events, and although this resistance may be reduced by: (I) triple therapy with ASA + clopidogrel + cilostazol, (II) high-dose ASA use, or (III) OM3 supplementation, the use of OM3 may be the safer option. OM3 does not seem to increase risk of bleeding.
The best evidence for the use of OM3 and CV health is for CHD mortality, SCD, post-MI and HFrEF. The AHA now recommends treatment for patients with HFrEF with OM3 to reduce mortality and hospitalizations.4 Some of these studies have shown favorable results with higher OM3 dosage (4 grams/day) and treatment early following MI or heart transplant, despite being used in patients receiving optimal medical therapy. OM3 use is reasonable for patients with CHD, such as recent MI, according to the AHA.4
There is insufficient evidence for recommendations regarding ischemic stroke and peripheral arterial disease, although there has been some evidence of benefit for secondary prevention of ischemic stroke with the use of OM3 in the JELIS trial. Currently, OM3 appear to play no role in the prevention of new or recurrent AF.

According to the AHA, the evidence does not support the use of OM3 supplementation in the general population who are not at high CVD risk, and there was a lack of consensus about the treatment of those at high risk.4
Treatment is also considered reasonable for secondary prevention of CHD death, and does not appear to have any role in treatment or prevention of AF.
The AHA has no class I recommendations for the use of OM3, and our findings indicate that there is currently insufficient evidence for OM3 use in the primary prevention of CVD in general, which is in agreement with recommendations from the AHA and National Institute of Health.4,6
A recurring argument for proponents of OM3 use is that even modest reduced risk of CVD or CV events should encourage the use of a largely innocuous therapy. Although the majority of authors from the AHA concluded that treatment with OM3 is not indicated for patients at high CVD risk, the AHA concluded that a potential reduction of CHD death by 10% would justify the use of OM3. 4 The AHA acknowledges that the lack of evidence of benefit differs from evidence of a lack of effect,4 however, the magnitude of benefit from OM3 for CV health remains largely undetermined. However, in patients with even moderately elevated LDL-C and /or TGs, this therapy could be strongly considered based on potential benefits and low cost and toxicity.


4) Siscovick DS, Barringer TA, Fretts AM, et al. Omega-3 Polyunsaturated Fatty Acid (Fish Oil) Supplementation and the Prevention of Clinical Cardiovascular Disease: A Science Advisory From the American Heart Association. Circulation. 2017;135(15):e867-e884. doi:10.1161/cir.0000000000000482.

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