will fish oil lower triglycerides?

Prescription omega-3 fatty acids are an "effective and safe option" to cut down triglycerides, according to a science advisory released by the American Heart Association (AHA).

However, over-the-counter omega-3 supplements are not reviewed or approved by the FDA and should not be used in place of prescription medication for the long-term management of high triglycerides, cautioned writing group chair Ann Skulas-Ray, PhD, of the University of Arizona, Tucson, in a press release.

Prescription omega-3 fatty acids "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," her group concluded.

Fish oil products containing eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA) taken at that dose have been shown to reduce triglyceride levels by at least 30% in patients with triglycerides of 500 mg/dL or greater, according to the statement published online in Circulation.

EPA-only formulations did not raise LDL cholesterol in this group, whereas combination EPA-DHA did, authors noted.

Among people with hypertriglyceridemia in the 200-499 mg/dL range, the 4-g/day dose of prescription omega-3 fatty acids lowered triglycerides by 20% to 30% without significantly increasing LDL cholesterol.

Nevertheless, these supplements may be accompanied by mild gastrointestinal complaints or nausea, so the AHA document recommended taking them with meals.

Available prescription omega-3 fatty acids include Lovaza (EPA+DHA) and Vascepa (EPA only), the latter of which was shown to reduce major adverse cardiovascular events by 25% over 5 years among statin-takers in the REDUCE-IT trial.

Next year, the STRENGTH trial is expected to shed light on the cardiovascular outcomes of prescription EPA+DHA in patients with high triglycerides and low HDL cholesterol on statins, Skulas-Ray's group noted.

Another question is whether omega-3 fatty acid supplementation works in children and adolescents: Negative findings have been reported from trials using lower doses or including smaller samples that in some cases included minors with only mildly elevated triglycerides.

The AHA statement said the supplements are "apparently safe," but larger trials testing at least 3 g/d EPA+DHA in children with 200–499 mg/dL triglycerides are needed to better establish efficacy, safety, and tolerability in this population.

Before omega-3 fatty acids are prescribed, however, physicians should first address any potential secondary causes of high triglycerides, such as hyperthyroidism or poorly managed type 2 diabetes, as well as implement a strategy to modify diet and lifestyle.

“If these changes are not possible or not effective, initiating triglyceride-lowering pharmacotherapy may be required,” write Ann Skulas-Ray, PhD (University of Arizona, Tucson), and colleagues in a paper published online August 19, 2019, in Circulation.

The science advisory updates prior AHA documents focused on omega-3 fatty acids, dating back to 2002 and 2011, that predate the advent of purified, prescription-strength formulations. The document also focuses specifically on their effects on hypertriglyceridemia, rather than atherosclerotic vascular disease.

To TCTMD, Skulas-Ray stressed that the degree of treatment response to omega-3 prescriptions is determined by the severity of an individual’s triglyceride levels prior to treatment. She also noted that levels are highly variable day-to-day, so the determination of response shouldn’t be based on a single triglyceride measurement.

For managing hypertriglyceridemia (200-499 mg/dL), the AHA experts state that prescription-strength omega-3 fatty acids, either with eicosapentaenoic acid (EPA) or EPA plus docosapentaenoic acid (DHA), would be expected to yield a 20% to 30% reduction in triglycerides without any increase in LDL cholesterol. For individuals with severe hypertriglyceridemia, 4 g/day of omega-3 fatty acids will reduce triglycerides by more than 30%, but LDL cholesterol may increase in agents that contain DHA. The goal for patients with severe hypertriglyceridemia is to reduce decrease triglycerides to less than 500 mg/dL and decrease the risk of pancreatitis.

“One of the surprising findings of this analysis is that the prescription omega-3 fatty acids containing DHA did not increase LDL cholesterol in studies of people with triglycerides less than 500 mg/dL,” said Skulas-Ray. In prior studies suggesting that DHA-containing agents may increase LDL cholesterol, researchers did not stratify by patient populations, such as those with and without severe hypertriglyceridemia. “The results we reviewed suggest to me that LDL increases proportionally to the degree of triglyceride reduction, not as a result of the prescription agent containing DHA,” she said.

Since 2004, several types of prescription-strength omega-3 fatty acid products have been approved by the FDA for lowering triglycerides, including Vascepa (Amarin), Lovaza (GlaxoSmithKline), Epanova (AstraZeneca), and two generic products. Their use in the treatment of high triglycerides recently received a massive boost with the publication of REDUCE-IT, a 2018 study testing 4 g/day of Amarin’s icosapent ethyl, a highly purified EPA ethyl ester. In that trial of patients with high triglycerides (135 to 499 mg/dL) also at high risk for cardiovascular disease, the addition of the omega-3 fatty acid on top of statin therapy reduced major adverse cardiovascular events by 25%.

“When we began writing this advisory, the results of REDUCE-IT were not yet available,” Skulas-Ray told TCTMD. “We delayed publication in order to include results of this trial. Omega-3 fatty acids are not always part of the discussion regarding triglyceride management, and this was likely due to the lack of studies evaluating effects prescription dosing of omega-3 fatty acids on hard endpoints in a population with elevated triglycerides. The results of REDUCE-IT changed that.”

But even when dangerous cholesterol particles are controlled, another lipid called triglycerides can block blood flow to the heart or brain.

Conventional medicine defines elevated triglycerides when blood levels exceed 149 mg/dL.1

Life Extension has long advocated that the reference range for optimal triglyceride levels should be less than 100 mg/dL.

Omega-3 fatty acids can lower triglycerides by as much as 50%.2

A recent meta-analysis found that EPA and DHA intake was associated with a 35% reduced risk of fatal heart attacks.3

Triglycerides consist of three (“tri”) fatty acids attached to a glycerol (sugar alcohol) backbone. They are in food and in our body fat.4,5

After eating, your body converts some calories it doesn’t need to triglycerides that are stored in fat cells. Triglycerides are released from fat storage for energy production between meals. Your body also makes triglycerides.

High triglyceride levels are strongly associated with metabolic disturbances that increase heart attack and ischemic stroke risk.6

Elevated levels are also associated with dangerous small-dense LDL particles,7 very low-density lipoproteins (VLDL),8 and cholesterol-enriched remnant lipoprotein particles.9 These are all known promoters of atherosclerosis.10-12

Life Extension considers optimal fasting triglyceride levels to be below 100 mg/dL. Individuals at high risk for cardiovascular events should strive for even lower levels.

Oral intake of fish oil containing the omega-3 fatty acids EPA and DHA is a proven way to bring triglycerides down.

Fish oil lowers triglycerides by:13-17

Scientists reviewed 22 clinical trials of EPA and/or DHA use in 1,637 healthy adults with normal or borderline-high triglycerides.18

In studies ranging from two weeks to a year, daily oral intake of 300-4,900 mg of omega-3s reduced fasting triglyceride levels by 4%-51%.18

Higher doses and longer time periods of taking fish oil generally produced greater benefits.18

A recent meta-analysis of 40 clinical trials found that EPA and DHA intake was associated with significant reductions in the risk for cardiovascular disease death.3

Specifically, this study found that EPA and DHA supplementation is associated with a reduced risk of:

The study, published in the Mayo Clinic Proceedings, concluded that supplementation with EPA and DHA reduced the risk of coronary heart disease, including heart attack.

Triglycerides tend to rise with increasing body weight. Fish oil helps combat this.

When 210 overweight or obese adults supplemented with 3,000 mg of omega-3 daily for six weeks, fasting triglycerides decreased by 15% in men and 17% in women.19

In a longer, 16-week placebo-controlled trial of 152 overweight or obese older adults, daily oral intake of fish oil reduced triglycerides by 24%.20

In these studies, fish oil helped bring triglycerides closer to optimal levels.

High triglycerides are often related to type II diabetes and non-alcoholic fatty liver disease.

Insulin resistance, which contributes to diabetes, is associated with an increase in the liver’s secretion of triglycerides. Clearance of triglycerides from the circulation tends to be slower in people with insulin resistance.21

In a three-month trial of 64 overweight/obese adults at increased risk for type II diabetes, oral intake of 2,000 mg fish oil daily led to a 16.54% decrease in fasting triglyceride levels.21

Excess fat buildup in the liver, such as in non-alcoholic fatty liver disease, is associated with an increased incidence of cardiovascular disease.22

Recently, scientists reviewed 18 placebo-controlled trials of fish oil in individuals with non-alcoholic fatty liver disease. Fish oil significantly lowered triglycerides in an impressive 89% of the trials.23

Some drugs that lower LDL cholesterol also decrease triglycerides. But they may not do enough.17,24,25

About one-third of all patients taking statin medications still have fasting triglyceride levels over 150 mg/dL. This leaves them vulnerable to cardiovascular problems.26

Fish oil has proven to be effective for reducing major adverse cardiovascular events.27

A major trial called REDUCE-IT included 8,179 high-risk heart patients who had LDL cholesterol controlled by statins yet still had elevated triglycerides. They were given 4,000 mg of a prescription EPA-only fish oil or a placebo daily for about five years.28

The fish oil group had a median reduction from baseline in fasting triglycerides of 19.7% within one year compared to placebo. The placebo group had a slight increase in triglycerides.

The fish oil group also had a 25% reduction in the risk of major cardiovascular events (beyond that provided by statin treatment), compared to the placebo group.

Elevated triglycerides increase risk of heart attack and stroke.

Fish oil containing the omega-3 fatty acids EPA and DHA can significantly lower triglycerides when consumed in sufficient amounts.

To promote healthy triglyceride levels, Life Extension suggests daily consumption of at least 2,000 mg of EPA/DHA from high-quality fish oil and/or regular consumption of cold-water fish.

There's strong evidence that omega-3 fatty acids can significantly reduce blood triglyceride levels. There also appears to be a slight improvement in high-density lipoprotein (HDL, or "good") cholesterol, although an increase in levels of low-density lipoprotein (LDL, or "bad") cholesterol also was observed.