In case you are wondering what all the recent headlines about fish oil and omega-3 fatty acids are about, here is a breakdown.
There were 2 large randomized controlled trials evaluating the role of fish oil supplementation for prevention of heart disease that were presented at the American Heart Association meeting in Chicago on November 10, 2018. Results were published by the New England Journal of Medicine simultaneously as they were presented in the meeting.
What is the verdict?
The VITAL trial – showed that fish oil taken by healthy people without prior known heart disease, at a dose found in many supplements (1g/day), showed no clear ability to lower heart disease risks.
The REDUCE-IT trial – on the other hand, showed that higher amounts of a purified, prescription fish oil decreased heart problems and heart-related deaths among people with high triglycerides, a type of fat in the blood, and known heart disease or risk for heart disease.
What the fish?
Fish oil supplements and claims of their heart protective effects have been wrapped in controversy since time immemorial. Believers have rooted for consumption of omega 3 fatty acid supplements and non-believers have pointed out to several randomized controlled trials and meta-analyses that have demonstrated no improvement in rates of heart attacks or strokes or cardiovascular deaths in for patients who do take these supplements.
Probably the first report of fish consumption as a medical therapy is found in the Old Testament book of Tobias, “Then the angel said to him: Take out the entrails of the fish, and lay up his heart, and his gall, and his liver for thee; for these are necessary for useful medicines.” Large studies such as the Swedish Mammography cohort of 36,234 women followed for 8 years suggests moderate consumption of fatty fish is associated with a lower risk for heart failure hospitalization. However, as opposed to self-reported fish consumption in this study, clinical trials of dietary modification or fish oil supplements have not consistently reported significant reduction of cardiovascular events. Part of the confusion surrounding the different conclusions of these studies involves the assessment of the effect of either a fixed daily dose of omega-3, or the measurement of omega-3 blood levels achieved in each patient. In response to a fixed dose of fish oil, some patients may achieve a therapeutic level while others may not.
Patients with high risk of heart disease or known heart disease are placed on statins that act by lowering LDL cholesterol and some other effects like reducing inflammation. Prior studies have attempted to reduce the residual risk of heart disease by lowering triglycerides using niacin or fibrates, and these were unsuccessful.
Fish oils, also called omega-3 fatty acids, are found in salmon, tuna, and other fish. They are of different types including EPA and DHA. These also reduce triglycerides and inflammation and may have other effects.
REDUCE-IT, sponsored by Amarin Corp., tested prescription of 4g/day of purified EPA (Vascepa) in more than 8,000 patients with high triglycerides and a greater risk of heart problems for various reasons. All were already taking a statin such as Lipitor or Zocor to lower cholesterol. Patients were randomized to Vascepa or mineral oil placebo capsule. After five years, about 17 percent of those on Vascepa had suffered one of these problems — a heart attack, stroke, heart-related death or need to open clogged arteries supplying the heart. This translated into a 25% relative risk reduction of these events. Even when these end-points were examined individually, they were all significantly lower in the group on Vascepa.
The VITAL study on the other hand, tested a lower 1g/day dose of a different type of fish oil — an EPA/DHA combo sold as Lovaza or Omacor and in generic form — in 26,000 people with no prior heart problems. After about five years, rates of a combined measure of heart attacks, strokes and other problems were similar for fish oil users and the comparison group.
It is possible that these differential results are secondary to different patient populations tested and different omega-3 blood levels achieved in these patients given different compounds and doses tested. Regardless, for patients with heart disease or high risk of heart disease who have high triglycerides despite statin therapy, Vascepa may further help lower their risk.
Some things that were fishy…
In the REDUCE-IT trial, the comparison group was given mineral oil placebo. Mineral oil can reduce the absorption of statins and may have made the comparison group look worse as a result of that. But it is probably unlikely to have accounted for a 25% reduction in events, as agreed to by leaders of both studies. Another thing to note is that patients on Vascepa had higher rates of irregular rhythm called atrial fibrillation.
Regardless, results of the REDUCE-IT trial were met with cheers and enthusiasm in a packed auditorium at the McCormick place in Chicago, as Dr. Deepak Bhatt from the Brigham and Women’s Hospital in Boston presented the main results. Vascepa costs around $280 a month; many insurers cover it.
If you have any questions about cholesterol or heart disease, please ask us.