On August 19th, the American Heart Association (AHA) released a new advisory about omega-3s and high triglycerides. Based on recent clinical trial evidence, it said prescription omega-3 fatty acid medication reduces triglyceride levels by 20-30% among the majority of people who require treatment for high triglyceride levels.
“From our review of the evidence from 17 randomized, 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 Ann Skulas-Ray, Ph.D., the lead author of the new science advisory published in the AHA’s journal Circulation.
The AHA Advisory authors summarized the lipid and lipoprotein effects resulting from pharmacological doses of omega-3s EPA and DHA (at 3 grams or greater per day of EPA+DHA) on the basis of new scientific data and availability of prescription omega-3 preparations. OmegaQuant’s Dr. Bill Harris is also an author on this 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.
FDA-approved prescription omega-3 fatty acid products include Lovaza and its generic (omega-3 fatty acid ethyl esters — EPA 0.465 mg and DHA 0.375 mg/capsule), Omtryg (a similar product but not clinically available), Vascepa (an ethyl ester product consisting of EPA only, chemical term “icosapent ethyl” — EPA 0.98 g/capsule), and Epanova (omega-3 carboxylic acid — EPA 0.55 g and DHA 0.2 g/capsule, not clinically available).
About 25% of adults in the U.S. have a triglyceride level above 150 mg/dL, which is considered borderline high. According to the AHA advisory, 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, however, which researchers believe is likely driven in large part by growing rates of obesity and diabetes mellitus.
In a 2002 AHA scientific statement, the omega-3s EPA and DHA were recommended (at a dose of 2-4 grams per day) for reducing triglycerides in patients with elevated triglycerides. Since 2002, prescription medicines containing EPA+DHA or EPA alone have been approved by FDA for treating very high triglycerides; these agents are also widely used for hypertriglyceridemia.
Triglycerides are fats that circulate in the blood. The authors of the AHA advisory say 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.
When used to treat hypertriglyceridemia, the AHA advisory said omega-3 fatty acids 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 that administered 4 grams per day of prescription omega-3, non–high-density lipoprotein cholesterol and apolipoprotein B were modestly decreased, indicating reductions in total atherogenic lipoproteins. The use of Vascepa 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 grams per day of prescription Epanova on hypertriglyceridemia are anticipated in 2020. The authors of the AHA advisory believe 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. Elevated plasma triglycerides are the result of an excess of triglyceride-rich lipoproteins of several different types, most commonly very-low-density
Results from the STRENGTH trial, a randomized placebo-controlled cardiovascular outcomes trial of 4 g/d prescription EPA+DHA in patients with HTG and low HDL-C on statins, are anticipated in 2020. We conclude that prescription omega-3 fatty acids, whether EPA+DHA or EPA-only, at a dose of 4 g/d, are clinically useful for reducing triglycerides, after any underlying causes are addressed and diet and lifestyle strategies are implemented, either as monotherapy or as an adjunct to other triglyceride-lowering therapies.
Other Recent Developments with Omega-3s and Heart Health
America’s “stroke belt” refers to a group of southeastern states that have much higher rates of heart attacks and strokes compared to the rest of the country. A new study published in Prostanglandins, Leukotrienes and Essential Fatty Acids shows that people living in these states also have remarkably low omega-3 levels as measured by the Omega-3 Index.
The people who participated in this study had their Omega-3 Index tested in free health screens across seven cities in the stroke belt region, including: Charleston, WV; Jacksonville, FL; Indianapolis, IN; Lexington, KY; Memphis, TN; Oklahoma City, OK; and Toledo, OH.
The screenings took place at church health fairs, malls, Departments of Public Health, medical clinics, and other public settings from October 2014 to November 2015. This project was organized by the Seafood Nutrition Partnership (SNP) in cooperation with local health partners, such as health insurance providers, schools of public health, local health clinics and centers.
In all, 2177 people had their Omega-3 Index measured. A startling 42% of those tested had an Omega-3 Index below 4%, which puts them at a 90% higher risk of sudden cardiac death. Only about 1% of those tested had an Omega-3 Index of 8% or above.
OmegaQuant’s Dr. Bill Harris, who was the lead author on this study, said “Since in other settings, a low Omega-3 Index is associated with increased risk for cardiovascular disease (CVD), this may be one factor contributing to the higher risk for CVD in this region of the US.”
In other omega-3 developments, in June, the agency approved a qualified health claim linking EPA and DHA omega-3s to a reduction in blood pressure. A long time in the making, the process was originally initiated by the Global Organization for EPA and DHA Omega-3s (GOED), which submitted a health claim petition almost five years ago.
And while this signifies a step in the right direction for omega-3s, the messaging that manufacturers are allowed to use on product packaging and marketing is somewhat bulky when you consider the “qualifying” language that accompanies the actual claim.
The qualified claims are permissible in the labeling of conventional foods and dietary supplements consistent with requirements in FDA’s letter of enforcement discretion, which specifically requires that conventional foods or dietary supplements using one of the claims contain at least 0.8 grams/serving of both EPA and DHA.
The approved claims include the following:
- “Consuming EPA and DHA combined may help lower blood pressure in the general population and reduce the risk of hypertension. However, FDA has concluded that the evidence is inconsistent and inconclusive. One serving of [name of the food or dietary supplement] provides [ ] gram(s) of EPA and DHA.”
- “Consuming EPA and DHA combined may reduce blood pressure and reduce the risk of hypertension, a risk factor for CHD (coronary heart disease). However, FDA has concluded that the evidence is inconsistent and inconclusive. One serving of [name of the food or dietary supplement] provides [ ] gram(s) of EPA and DHA.”
- “Consuming EPA and DHA combined may reduce the risk of CHD (coronary heart disease) by lowering blood pressure. However, FDA has concluded that the evidence is inconsistent and inconclusive. One serving of [name of the food or dietary supplement] provides [ ] gram(s) of EPA and DHA.”
- “Consuming EPA and DHA combined may reduce the risk of CHD (coronary heart disease) by reducing the risk of hypertension. However, FDA has concluded that the evidence is inconsistent and inconclusive. One serving of [name of the food or dietary supplement] provides [ ] gram(s) of EPA and DHA.”
- “Research shows that consuming EPA and DHA combined may be beneficial for moderating blood pressure, a risk factor for CHD (coronary heart disease). However, FDA has concluded that the evidence is inconsistent and inconclusive. One serving of [name of the food or dietary supplement] provides [ ] gram(s) of EPA and DHA.”
OmegaQuant’s Dr. Bill Harris was interviewed for a story discussing these new claims. Overall, he said he’s optimistic about the FDA’s acknowledgement of the benefits of omega-3s for maintaining healthy blood pressure.
“At least FDA is willing to acknowledge that there is something there. I think the approval of the health claims is a welcome step forward in the recognition of the multiple benefits of omega-3s,” OmegaQuant’s Dr. Harris said. “It’s not just about blood lipids, like triglycerides. They affect other risk factors like blood pressure and endothelial function.”
Earlier this year, Japanese researchers examined the association between omega-3s and measures of atherosclerosis in the general population in a study published in Nutrition, Metabolism & Cardiovascular Diseases.
Aortic calcification is a situation where calcium builds up on the aortic valve of the heart. The aortic valve’s role is to hold oxygen-rich blood before it is pumped out to the body. If there is a significant build-up of calcium, then it can impact the flow of blood to the rest of the body.
In this multiethnic population-based study of 1033 asymptomatic men aged 40-49 years (300 US-White, 101 US-Black, 287 Japanese American, and 310 Japanese in Japan), researchers investigated the relationship of omega-3s and aortic calcification measured by electron-beam computed tomography-EBCT-and quantified using the Agatston method, using Tobit regression and ordinal logistic regression after adjusting for potential confounders.
EBCT is a method of measuring calcium deposits in the arteries using a form of CT scanning. The Agatston score is a semi-automated tool used to calculate a score based on the extent of coronary artery calcification detected by an unenhanced low-dose CT scan, which is routinely performed in patients undergoing cardiac CT.
The study showed that there is a significant inverse association of omega-3s EPA and DHA with aortic calcification independent of conventional cardiovascular risk factors among men in the general population, an association that appeared to be driven by DHA but not EPA.
INFOGRAPHIC: How Omega-3s Landed on the Scientific Map