Prescription omega-3 fatty acid medication reduces triglyceride levels by 20-30% among the majority of people who require treatment for high triglyceride levels, according to a science advisory from the American Heart Association. “From our review of the evidence from 17 randomised, controlled clinical trials on high triglyceride levels, we concluded that treatment with 4 grams daily of any of the available prescription choices is effective and can be used safely in conjunction with statin medicines that lower cholesterol,” said Dr Ann Skulas-Ray, an author of the new science advisory.
There are two prescription omega-3 fatty acid medications available. One combines two types of fatty acids, EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid). The other medication provides EPA only. Since there have been no head-to-head comparisons of the two different formulations at prescription dosing, the advisory does not recommend one over the other.
Triglycerides are fats that circulate in the blood. Some studies have shown that elevated levels of triglycerides (above 200 mg/dL) can lead to atherosclerosis (narrowing of the arteries) which increases the risk of heart attack and stroke. In addition to cardiovascular risk, very high levels of triglycerides (above 500 mg/dL) can also cause pancreatitis, an inflammation of the pancreas.
Skulas-Ray points out that people with high triglyceride levels should not try to treat the condition themselves with non-prescription, omega-3 fatty acid fish oil supplements. “Dietary supplements containing omega-3 fatty acids are not regulated by the FDA. They should not be used in place of prescription medication for the long-term management of high triglycerides,” said Skulas-Ray, who is an assistant professor in the department of nutritional sciences at the University of Arizona in Tucson.
In a 2017 science advisory, the American Heart Association noted that there is a lack of scientific research to support clinical use of omega-3 fatty acid supplements to prevent heart disease in the general population. The effective dose for prescription omega-3 fatty acids is four grams per day taken with food. Currently, the FDA has approved prescription omega-3 fatty acid medications only for treating very high triglyceride levels above 500 mg/dL.
Healthy lifestyle choices, such as getting regular physical activity, losing weight, avoiding sugar and refined carbohydrates, limiting alcohol as well as choosing healthier fats from plants in place of saturated fats can help reduce triglycerides. It is also important to treat or eliminate conditions such as poorly controlled type 2 diabetes, hypothyroidism and obesity that may contribute to high triglyceride levels before turning to medication.
Fish is a good source of omega-3 fatty acids, and the American Heart Association recommends eating fatty fish – such as salmon, mackerel, herring and albacore tuna – at least two times per week.
In analysing the current scientific data, the advisory panel found:
For most people with high triglycerides (200 to 499 mg/dL), prescription doses of omega-3 fatty acids using drugs with either EPA+DHA or EPA alone can reduce triglyceride by 20 to 30%.
Contrary to common perception, the formula that contains both EPA and DHA does not increase the “bad” form of cholesterol (LDL-C) among most people with high triglyceride levels (200-499 mg/dL). However, when the drug is given to people with very high triglyceride levels at 500 mg/dL or greater, LDL-C may increase.
The panel’s review found that the prescription omega-3 drugs are effective in reducing triglyceride levels regardless of whether people are on statin therapy.
In a recent large, randomised placebo-controlled study called REDUCE-IT, researchers found that the EPA-only medication combined with statin medication resulted in a 25% reduction in major cardiovascular events (heart attack, stroke and cardiovascular death) among people with high triglycerides.
Elevated triglycerides are relatively common among people in the US, and the prevalence is increasing due to growing rates of obesity and diabetes. Both of those conditions raise triglyceride levels. About 25% of adults in the US have a triglyceride level above 150 mg/dL, which is considered borderline high.
Hypertriglyceridemia (triglycerides 200–499 mg/dL) is relatively common in the United States, whereas more severe triglyceride elevations (very high triglycerides, ≥500 mg/dL) are far less frequently observed. Both are becoming increasingly prevalent in the United States and elsewhere, likely driven in large part by growing rates of obesity and diabetes mellitus. In a 2002 American Heart Association scientific statement, the omega-3 fatty acids (n-3 FAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were recommended (at a dose of 2–4 g/d) for reducing triglycerides in patients with elevated triglycerides. Since 2002, prescription agents containing EPA+DHA or EPA alone have been approved by the US Food and Drug Administration for treating very high triglycerides; these agents are also widely used for hypertriglyceridemia. The purpose of this advisory is to summarize the lipid and lipoprotein effects resulting from pharmacological doses of n-3 FAs (>3 g/d total EPA+DHA) on the basis of new scientific data and availability of n-3 FA agents. In treatment of very high triglycerides with 4 g/d, EPA+DHA agents reduce triglycerides by ≥30% with concurrent increases in low-density lipoprotein cholesterol, whereas EPA-only did not raise low-density lipoprotein cholesterol in very high triglycerides. When used to treat hypertriglyceridemia, n-3 FAs with EPA+DHA or with EPA-only appear roughly comparable for triglyceride lowering and do not increase low-density lipoprotein cholesterol when used as monotherapy or in combination with a statin. In the largest trials of 4 g/d prescription n-3 FA, non–high-density lipoprotein cholesterol and apolipoprotein B were modestly decreased, indicating reductions in total atherogenic lipoproteins. The use of n-3 FA (4 g/d) for improving atherosclerotic cardiovascular disease risk in patients with hypertriglyceridemia is supported by a 25% reduction in major adverse cardiovascular events in REDUCE-IT (Reduction of Cardiovascular Events With EPA Intervention Trial), a randomized placebo-controlled trial of EPA-only in high-risk patients treated with a statin. The results of a trial of 4 g/d prescription EPA+DHA in hypertriglyceridemia are anticipated in 2020. We conclude that prescription n-3 FAs (EPA+DHA or EPA-only) at a dose of 4 g/d (>3 g/d total EPA+DHA) are an effective and safe option for reducing triglycerides as monotherapy or as an adjunct to other lipid-lowering agents.
Ann C Skulas-Ray, Peter WF Wilson, William S Harris, Eliot A Brinton, Penny M Kris-Etherton, Chesney K Richter, Terry A Jacobson, Mary B Engler, Michael Miller, Jennifer G Robinson, Conrad B Blum, Delfin Rodriguez-Leyva, Sarah D de Ferranti, Francine K Welty