Your Weekly Checkup: Good News about Fish Oil Supplements

Past research has provided disappointing results about the benefits of fish oil, but a new study’s findings are promising.

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“Your Weekly Checkup” is our online column by Dr. Douglas Zipes, an internationally acclaimed cardiologist, professor, author, inventor, and authority on pacing and electrophysiology. Dr. Zipes is also a contributor to The Saturday Evening Post print magazine. Subscribe to receive thoughtful articles, new fiction, health and wellness advice, and gems from our archive. 

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Previous information about fish oil supplementation has been disappointing, showing conflicting or no cardiovascular benefits. However, results from a recently published study are going to upend that conclusion.

The New England Journal of Medicine published a study of a randomized trial of more than 8,000 patients that tested a proprietary fish oil compound called icosapent ethyl (Vascepa). Icosapent ethyl is a highly concentrated preparation of eicosapentaenoic acid, the critical omega-3 fatty acid ingredient in fish oil.

Enrolled patients were 45 years of age or older and had established cardiovascular disease, or were 50 years or older and had diabetes mellitus and at least one additional risk factor. They had a mean age of 64 years, almost 30 percent were women, and all had been receiving statin therapy, so they had a normal low-density lipoprotein (LDL or “bad” cholesterol) of 41 to 100 mg per deciliter.

However, they had an elevated fasting triglyceride level (135 to 499 mg per deciliter), which is a known independent risk factor for heart attacks and strokes.

Icosapent ethyl versus placebo significantly reduced major adverse cardiovascular (CV) events, including cardiovascular death, nonfatal heart attack, nonfatal stroke, coronary revascularization, or unstable angina, by 25%, over a median of almost five years. The risk of CV death alone was reduced by 20 percent. Triglycerides were reduced by almost 20 percent.

Several factors make this trial notable. Patients were already taking a statin and had LDL controlled, yet still had a significant reduction in CV events. The daily dose of icosapent ethyl was 4 grams, considerably more of the highly purified omega-3 formulation than in previous trials, which may account for differences from previous trials. Clear benefits took about a year to become evident and were present despite an increase in LDL from 76 to 84 mg/dL over 1 year. Finally, despite the reduction in CV events, the incidence of atrial fibrillation rose, and patients experienced slightly more bleeding events. Heart failure did not change.

The significantly lower risk of major adverse CV events with icosapent ethyl appeared to occur regardless of the patients’ triglyceride levels at 1 year. Therefore, the benefits of icosapent ethyl may not just be due to a reduction in triglycerides. Icosapent ethyl may also have anti-inflammatory, antioxidative, plaque-stabilizing properties.

The results of the study, called “Cardiovascular Risk Reduction with Icosapent Ethyl for Hypertriglyceridemia” (REDUCE-IT) should not be generalized to other fish oil preparations, especially those containing omega-3 fatty acid mixtures, which are variable and unregulated, and which have not been shown to have clinical benefit. Over-the-counter fish oil products generally contain 1,000 or 1,200 mg of fish oil but only about 300 mg that is actually eicosapentaenoic acid.

Two other recent omega-3 studies using a lower dose failed to reduce CV outcomes. In a study called “The Vitamin D and Omega-3 Trial” (VITAL) in which patients were given omega-3 fatty acid at a dose of 1 gram/day, the fish oil supplementation did not reduce the incidence of major CV events. Similarly, the “Effects of n-3 Fatty Acid Supplements in Diabetes Mellitus” (ASCEND) trial of 1 gram/day of omega-3 fatty acid in 15,480 patients with diabetes without evidence of cardiovascular disease found no significant difference in the risk of serious vascular events between those who were assigned to receive omega-3 fatty acid supplementation and those who were assigned to receive a placebo.

Therefore, it is quite clear that the dose of omega-3 fatty acid is important, and that 4 grams/day has pronounced CV benefit, while 1 gram/day does not. It is exciting to think that a dietary supplement may be able to add CV benefits to statin drugs. Which patients, in addition to those with elevated triglyceride levels, should receive this new drug awaits further testing.

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