Success of pharma firm’s studies let it “own” a known fish oil benefit
This is a good news story — albeit one with an unfortunate twist.
Last Friday, the Food & Drug Administration (FDA) approved Vascepa-brand pharmaceutical omega-3 fish oil as a drug to lower “high” triglyceride levels of 150 mg/dL or higher in certain heart and diabetes patients.
The FDA had previously approved the use of Vascepa and the several other prescription fish oils for lowering triglyceride levels above 500 mg/dL, which are classified as “very high”.
There’s ample evidence that regular, non-prescription fish oil lowers triglyceride levels — which is why the American Heart Association (AHA) has long recommended taking 2-4 grams of seafood-source omega-3s daily to lower high triglyceride levels.
Last August, the AHA published their review of the evidence from 17 randomized, placebo-controlled clinical trials, and concluded that 4 grams daily of any of the currently available prescription fish oils lowered triglyceride levels by 20-30% among most trial participants.
The FDA approved medical prescription of Vascepa only to the estimated five to eight million Americans who meet three criteria:
- Diagnosed with cardiovascular disease or diabetes.
- Triglyceride levels of 150 milligrams per deciliter (mg/dL) or higher.
- Display two or more additional risk factors for cardiovascular disease.
Some observers — no doubt including the makers of Vascepa fish oil — hoped or expected the FDA to approve its use for people with “borderline high” triglyceride levels (150 to 199 mg/dL), which would’ve expanded the prescription-eligible population to about 40 million people.
Two kinds of fish oil: Regular DHA + EPA and modified EPA-only
Fish and fish oil naturally contain two major omega-3s — DHA and EPA — which bring overlapping cardiovascular, immune, brain, and vision benefits.
The body can use the omega-3 found in certain plant foods, called ALA, to make small, conditionally adequate, amounts of DHA and EPA, which are the only omega-3s it needs to survive and thrive. For more about the different omega-3s from plants and seafood, see our Omega-3 Facts & Sources page.
Vascepa is simply a fish oil modified to contain only omega-3 EPA — a decision by its maker that seems to lack a strong scientific justification. Indeed, the AHA notes that EPA + DHA fish oils don’t raise LDL cholesterol levels in most people with high triglyceride levels (200-499 mg/dL). For more on this topic, see the section titled “Why is Vascepa EPA-only?” in Omega-3s’ Heart Value Vindicated in Long, Large Clinical Trial.
In contrast, like standard non-prescription fish oils, the three other FDA-approved prescription fish oils (Lovaza, Omtryg, and Epanova) contain both EPA and DHA. There haven’t been any clinical trials comparing the cardiovascular health effects of EPA-only Vascepa fish oil to EPA+DHA prescription fish oils, so the AHA’s scientific panel didn’t recommend one kind over the other in its recent evidence review.
Before we get to the downside of the FDA’s decision to approve Vascepa — and the three other pharmaceutical fish oils — as prescription drugs, let’s quickly review what causes high triglyceride levels, which rival unhealthful cholesterol profiles as a major cardiovascular risk factor.
High triglycerides harm heart health, and carbs are the main cause
High blood levels of triglyceride-type fats — the condition called hypertriglyceridemia — are linked to higher risks for heart disease and its adverse outcomes, including heart attacks.
This is how triglyceride levels are classified for the purpose of gauging cardiovascular and other risks:
- Normal — Below 150 mg/dL
- Borderline high — 150 to 199 mg/dL
- High — 200 to 499 mg/dL
- Very high — 500 mg/dL or above
Most of the available evidence shows that “high” triglyceride levels (i.e., at or above 200 mg/dL) can lead to atherosclerosis (narrowing of the arteries), which raises the risk of heart attack and stroke.
Triglycerides are the most common form of body fat, and when you consume more calories — especially calories from refined carbohydrates (i.e., sugars and starches) — than your body immediately needs, it typically converts them into triglycerides and stores them in your fat cells. Should you need energy between meals, your body uses hormones to make your stored triglycerides available to burn for energy.
High-carb/low-fiber diets, such as the standard American diet, raise blood triglyceride levels. Fructose — which constitutes half of the sucrose in fruits and refined white sugar and about half of most high fructose corn syrups — raises triglyceride levels more than other sugars, including glucose.
Carb-heavy, low-fiber diets also generate higher blood levels of small-dense LDL cholesterol particles, which are much more dangerous than the large, fluffy LDL particles associated with diets high in saturated fats.
Successful clinical trials prompted the FDA’s action
Amarin, the Irish pharma company that makes Vascepa, funded the clinical trial called REDUCE-IT that gained FDA approval of Vascepa as a triglyceride-lowering drug.
The REDUCE-IT trial involved 8,179 people who were already taking cholesterol-lowering or anti-diabetes drugs.
Compared with the trial participants who took placebo (mineral oil) capsules, those who added Vascepa fish oil to their heart or diabetes medicines were 20% less likely to die during the trial and 25% less likely to suffer a non-fatal heart attack or stroke, coronary artery bypass surgery, or unstable angina requiring hospitalization.
The positive results of the large, lengthy REDUCE-IT trial and two other, smaller Amarin-funded clinical trials — and a very large academic clinical trial called VITAL — were especially welcome because they followed a series of negative, and highly misleading, evidence reviews and media stories that questioned the cardiovascular benefits of omega-3 fish oil.
(We summarized the results of the Amarin-funded trials in High-Dose Omega-3s Score Twin Heart-Health Wins and Omega-3s’ Heart Value Vindicated in Long, Large Clinical Trial, and we reported the positive results of the VITAL trial in Omega-3s Score 2nd Big Heart Win.)
Downside of the FDA’s action: Private ownership of a fish oil benefit
To date, The FDA has approved two qualified health claims regarding omega-3 EPA and DHA, which can be made by any fish oil, whether prescription or non-prescription:
- Supportive but not conclusive research shows that consumption of EPA and DHA omega-3 fatty acids may reduce the risk of coronary heart disease.
- 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.
The bad side of today's news is that Vascepa — a proprietary prescription-only product — is now one of only four fish oils that can legally make a triglyceride-lowering health claim and be marketed and medically prescribed for that purpose.
If, instead of pharmaceutical companies, the federal government had directly funded appropriate clinical trials and — as seems highly likely — they’d produced similarly positive results, any fish oil could have borne and advertised the heart -related health claims justified by those trials’ outcomes.
This distinction matters because the list price for a month’s supply of the approved, risk-reducing 4-gram daily dose of Vascepa fish oil will be about $303 per month, which is comparable to the cost of other prescription fish oils. (Some of that cost may be covered by some public and private insurance policies.)
By comparison, the cost of a one-month supply of a daily 4-gram dose of omega-3 EPA from a typical non-prescription, lab-certified-pure fish oil that provides both DHA and EPA is about 61% lower than the list price for Vascepa.
Importantly, any fish oil that provides both DHA and EPA will certainly be more broadly healthful than an EPA-only fish oil like Vascepa. That’s because DHA delivers health benefits distinct from those associated with EPA, while there don’t appear to be any real drawbacks to fish oils that include both DHA and EPA.
Although DHA can raise LDL cholesterol levels slightly, and its anti-inflammatory effects in the vascular system may or may not be as strong as EPA’s, there isn’t any proven or likely downside to taking a stand DHA + EPA fish oil for cardiovascular health.
And DHA delivers distinct cardiovascular benefits, along with distinct brain and vision benefits. For more on this topic, see the section of Omega-3s’ Heart Value Vindicated in Long, Large Clinical Trial titled “Why is Vascepa EPA-only?”
- American Heart Association (AHA). Prescription omega-3 fatty acid medications effectively lower high triglycerides. August 19, 2019. Accessed at https://newsroom.heart.org/news/prescription-omega-3-fatty-acid-medications-effectively-lower-high-triglycerides
- Chong MF, Fielding BA, Frayn KN. Metabolic interaction of dietary sugars and plasma lipids with a focus on mechanisms and de novo lipogenesis. Proc Nutr Soc. 2007 Feb;66(1):52-9. Review.