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Not All Omega-3 Fatty Acids Have the Same Effects on Lipids

Value-Based Care in Cardiometabolic Health Dec 2012, Vol 1, No 3

Boston, MA—The amount and the type of omega-3 fatty acids are important for triglyceride lowering. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are distinct omega-3 polyunsaturated fatty acids, but only EPA has been shown to lower triglyceride levels, without increasing low-density lipoprotein cholesterol (LDL-C) in patients with very high triglycerides levels, said Harold Bays, MD, Medical Director and President, Louisville Metabolic and Atherosclerosis Research Center, KY, at the 2012 Cardiometabolic Health Congress.

Although fibrates and EPA/DHA agents decrease triglycerides, LDL-C levels can increase. In patients with very high triglycerides who are at risk for pancreatitis, “we would like to have as clean of an effect upon their lipid levels as possible,” noted Dr Bays.

Triglycerides are mainly found in chylomicrons and in very-low-density lipoprotein (VLDL) particles. Other lipoproteins, such as intermediate-density lipoprotein particles, carry triglycerides as well. Triglyceride-rich lipoprotein remnants can promote atherogenesis.

Apolipoprotein (apo) B is found on atherogenic lipoprotein particles. “There is one molecule of apo B on every atherogenic lipoprotein. That means if your apo B levels are elevated, it suggests an increase in the number of atherogenic lipoprotein particles,” Dr Bays explained. “It’s the increase in lipoprotein particles that is thought to increase the risk for atherosclerotic cardiovascular disease.”

Primary causes of hypertriglyceridemia include genetic disorders, such as lipoprotein lipase deficiency, familial combined hyperlipidemia, and familial hypertriglyceridemia. Secondary causes include many lifestyle factors, such as diets with a high saturated fat content or a high glycemic index content, adiposopathy (adipocyte hypertrophy), uncontrolled diabetes, medications, and acute alcohol consumption with fatty liver.

High triglyceride levels respond to lifestyle changes more than other lipids, said Dr Bays. “Any treatment for hypertriglyceridemia should involve aggressive nutritional intervention and increasing physical activity,” he said. Patients should also be advised to limit ethanol consumption to no more than 2 U daily.

The guidelines for treating severe hypertriglyceridemia (triglyceride level ≥500 mg/dL) recommend targeting triglycerides to prevent acute pancreatitis. If the cause of hypertriglyceridemia is primary, the triglyceride level should be lowered to reduce the risk of acute pancreatitis using a very-low-fat diet, weight reduction, modification of alcohol intake, and polyunsaturated fatty acids or a fibrate. If the cause is secondary, guidelines recommend targeting LDL-C with a statin.

The 2 classes of essential fatty acids are omega-6 (primarily vegetable oils) and omega-3 (ie, alpha linolenic acid, DHA, and EPA). EPA comes specifically from marine sources (eg, fish and fish oils); “these lower the triglyceride levels,” said Dr Bays. “Omega-3 fatty acids that aren’t marine do not demonstrate significant triglyceride lowering.”

In 2011, the American Heart Association (AHA) recommended that when omega-3 fatty acids are used to lower triglycerides, they should be exclusively marine-derived EPA and/or DHA. The AHA recommended 2 g to 4 g daily of omega-3 EPA/DHA in capsule form for patients who need to lower their triglyceride levels, and noted a dose response between marine-derived omega-3 fatty acids and triglyceride lowering, with a 5% to 10% reduction in triglycerides for every 1 g of EPA/DHA consumed.

The content of EPA/DHA per capsule varies widely, from 300 mg to approximately 850 mg, noted Dr Bays.
EPA and DHA have different effects on lipids, he said. Although both lower triglyceride levels, DHA also increases levels of LDL-C by as much as 45%, whereas EPA has no effect on LDL-C levels.

In the randomized, double-blind MARINE trial (Bays HE, et al. Am J Cardiol. 2011;108:682-690), 4 g daily of an EPA ethyl ester (icosapent ethyl; Vascepa) that contained no DHA improved multiple lipid parameters in patients with fasting triglyceride levels of ≥500 mg/dL. The placebo-adjusted decrease in triglyceride levels with the EPA ethyl ester was 33% (2 g daily) and 45% (4 g daily) with significant declines in apo B, VLDL cholesterol, non–high-density lipoprotein cholesterol, and total cholesterol.

Proposed mechanisms for the lipid effects of EPA ethyl ester are reduced hepatic secretion of VLDL particles and enhanced triglyceride clearance from circulating VLDL particles, Dr Bays explained.

Last modified: August 30, 2021