Your Weekly Checkup: Good News about Fish Oil Supplements

“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.

Your Weekly Checkup: Should You Take Vitamin and Mineral Supplements?

“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.  

Order Dr. Zipes’ new book, Damn the Naysayers: A Doctor’s Memoir.


For many years I began each day ingesting fish oil, adding my contribution to the $30 billion industry of dietary supplementation. I stopped when the available evidence did not support its benefits for people not at high risk for cardiovascular disease. (Fish oil supplements may be reasonable for some people after a heart attack.)

Half of American adults consume at least one dietary supplement daily, 48% swallowing vitamins and 39% ingesting minerals, hoping to maintain health and ward off disease. Many do so because their daily pressures prevent them from eating a healthful and balanced diet, and they rationalize that the supplements will provide nutrition absent from their fast food regimen.

But is that true? Most randomized clinical trials of vitamin and mineral supplements have not demonstrated clear benefits in preventing chronic diseases unrelated to nutritional deficiency. In fact, ingesting vitamins and minerals in amounts exceeding the recommended daily allowance may actually be harmful, increasing mortality, cancer, and strokes. Some supplements can counteract the beneficial action of specific medications. In most cases, dietary supplements provide little if any benefit beyond that obtained in a nutritious diet.

Also, the nutrients in food usually are better absorbed by the body, are associated with fewer potential adverse effects, and provide optimal and balanced amounts as opposed to ingesting isolated compounds in highly concentrated form. Positive health outcomes are more strongly related to dietary patterns and foods than to individual supplements.

It’s also important to remember that the Food and Drug Administration does not review dietary supplements for safety and efficacy and, while manufacturers must adhere to Good Manufacturing Practice regulations, compliance monitoring may be less than optimal. A good practice is to choose a supplement certified by an independent tester who verifies that the supplement contains the labeled doses and is not contaminated with microbes, heavy metals or other toxins. Check the website of the Office of Dietary Supplements of the National Institutes of Health for accurate information.

While routine supplementation is not recommended for the general public, diet alone may not provide the necessary nutritional requirements in some groups. Pregnant women need higher amounts of folic acid and prenatal vitamins, and some mid-life and older adults require supplemental vitamin B12 and vitamin D. Calcium is best obtained by calcium-rich foods, with calcium supplements used only if the daily goal is not met. A recent analysis of multiple randomized trials found that supplements that included calcium, vitamin D, or both compared with placebo or no treatment was not associated with a lower risk of fractures among community-dwelling older adults. I have often joked that the urine of many Americans has the highest concentration of vitamins found anywhere, since multivitamin/multimineral supplementation is not recommended for generally healthy adults and the excess is just excreted.

A final word: be sure to tell your doctor about any dietary supplement you are taking to be certain it is compatible with your other medications and overall medical condition.

Pass the Fish Tacos, Please


There’s solid proof that omega-3s support cardiovascular, cognitive, and joint health. But an important question lingers in the air: Do seafood and fish oil supplements offer equal protection?

“Fish oil supplement is not the same as eating whole fish. In fact, recent research found that omega-3s in capsule form may not provide any actual benefits to your heart health. That’s why I recommend my patients follow the Dietary Guidelines for Americans and consume 2 to 3 servings (8 to 12 ounces) of seafood each week,” says Dr. Lori Mosca, Professor of Medicine at Columbia University Medical Center and Director of Preventive Cardiology at New York-Presbyterian Hospital.

Interestingly, both women and men need the same amount of fish each week to support heart health and reduce heart disease risk. One serving is about the size of the palm of your hand, says Dr. Mosca who offers these simple ideas for powering family meals with omega-3s by replacing your usual protein with fish:

Breakfast option: Top a multigrain bagel with canned tuna.

Lunch option: Fill tacos with fish, or add fish to a green salad.

Dinner option: Grill salmon, or stir fish into a pasta sauce.

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