FDA Suffers Major Legal Defeat In Federal Court

The FDA strictly regulates what drug makers are permitted to say about their products. Until lately, what could be said was limited to what the FDA allowed.

Recent federal court decisions involving the FDA have ruled against speech prohibition.

The latest victory over FDA censorship occurred when a maker of prescription drug fish oil sued the FDA to make a health claim about fish oil’s potential to reduce cardiovascular disease risk.¹

The FDA insisted it was illegal for the maker of this fish oil drug to state a coronary disease prevention claim until the FDA said so.

Fish oil has long been known to lower blood triglyceride levels. The FDA does not dispute this. What the FDA questions is whether persistently elevated triglyceride levels increase heart attack risk.

This article explores the FDA’s defeat in federal court and provides startling revelations as to why the FDA is not convinced of the vascular dangers posed by elevated blood triglycerides.

What may surprise you is how backward thinking the agency responsible for regulating our health care has become.

What I’ve done here is weave the science behind heart disease and triglycerides together with the FDA’s archaic interpretation of this data and the federal court’s final decision.

You’re going to read how an independent party (a federal judge) saw through the FDA’s charade and ruled against the agency based on scientific and Constitutional grounds.

Triglycerides are a type of fat that can be measured in blood.

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.

Triglycerides themselves are not a component of atherosclerotic plaque. High triglyceride levels, however, create metabolic disturbances that increase heart attack and ischemic stroke risk.²

The FDA acknowledges that triglyceride levels over 500 mg/dL are dangerous. The FDA allows a claim that fish oil drugs can reduce heart attack risk in people with triglycerides over 500 mg/dL.

The scientific argument the FDA lost in federal court is whether persistently high triglyceride levels between 200 to 499 mg/dL are a vascular risk factor.

What Are Optimal Triglyceride Readings?

Life Extension^® has argued for the past 36 years that optimal triglyceride levels are below 100 mg/dL. The American Heart Association concurs with Life Extension^®’s position on what ideal triglyceride levels should be.³

To keep score, the box below shows the upper-limit triglyceride numbers being debated by various groups:

As you can see, there is quite a difference of opinion on this issue.

Fortunately, a federal judge ruled unconstitutional the FDA’s position that a claim cannot be made for a health benefit when lowering triglyceride levels already below 500 mg/dL.

One of the judge’s reasons for this favorable ruling is that the evidence supporting the triglyceride-lowering effect of fish oil is truthful and non-misleading,^4-6 as is the totality of scientific evidence that reduction in triglycerides can reduce vascular disease risk.^7-9

It helped that the FDA itself admitted these benefits of fish oil in the court proceedings. The agency nonetheless clung to its antiquated argument that it retained arbitrary power to censor the health claim, whether it is truthful or not! The judge disagreed that the FDA could prohibit truthful speech.

FDA argued that they could deny this health claim for fish oil because “ …recent scientific studies have left it unclear whether reducing the triglyceride levels of persons with persistently high triglycerides reduces cardiovascular risk.” ¹⁰

The judge respectfully disagreed with the FDA’s interpretation of the scientific literature.

Why the Debate over Triglycerides?

In 1980, the New England Journal of Medicine published an article stating the evidence that triglycerides were an independent causative factor in vascular disease risk was “meager.”¹¹ We at Life Extension^® vehemently disagreed, but our organization was so tiny back then that no one paid any attention.

Despite several decades of research, there is still a controversy as to whether persistently elevated triglycerides by themselves (independently) increase heart attack/stroke risk.

It has been challenging to pinpoint the exact lethality of high triglycerides. One reason is that people with elevated triglycerides often present with low HDL, insulin resistance, obesity, and type II diabetes.^12-15 HDL beneficially removes cholesterol from arterial walls, while obesity and poor glycemic control are proven vascular risk factors.^16-20

So the question arises, if an obese and diabetic individual with low HDL suffers a heart attack and also has high triglycerides, was it the triglycerides or other factors that caused it? A quick answer in most cases is it was all of the above, plus other artery-clogging influences like chronic inflammation.

To further obscure the issue, high triglycerides are associated with dangerous small-dense LDL particles,²¹ very low-density lipoproteins (VLDL),²² and cholesterol-enriched remnant lipoprotein particles.²³ These are all known promoters of atherosclerosis.^24-26

These and other confounding factors have made it challenging for the scientific community to agree on what triglyceride level predisposes people to cardiovascular diseases.

Life Extension^® takes a rather simplistic view of this. We have tested the blood of thousands of younger individuals. If they are normal weight, their triglyceride levels are often below 70 mg/dL. These young adults don’t yet suffer outward vascular problems and are full of vitality. So why would anyone view triglyceride readings of 200 to 499 mg/dL in older persons as acceptable?

We at Life Extension^® want blood profiles to resemble healthy young people, not older individuals who often suffer from systemic atherosclerosis.

Human Data Reveals Dangers of High Triglycerides

Solid evidence about the dangers of triglycerides came from an analysis of a large and respected study (National Health and Nutrition Examination Survey, NHANES), that looked at all five components of metabolic syndrome, which include:

• Hypertension
• Insulin resistance
• Abdominal obesity
• Low HDL
• Elevated triglycerides

The results of the NHANES study showed that cardiovascular risk was most strongly associated with elevated triglycerides.² This finding, however, does not itself prove triglycerides are an independent vascular risk factor because other components of metabolic syndrome also inflict arterial damage.

More persuasive evidence comes from a meta-analysis that found for each 88.5 mg/dL increase in triglycerides in men, there was a 32% higher risk of cardiovascular disease. After adjusting for HDL, there was still a 14% higher cardiovascular disease risk for each 88.5 mg/dL increase in triglycerides.²⁷

In women, the dangers of higher triglycerides were more pronounced. For each 88.5 mg/dL increase in triglycerides, there was a 76% increased cardiovascular risk and 37% increased risk after adjusting for HDL.²⁷

To put this data in perspective, the FDA says there is insufficient evidence to prove that triglyceride levels up to 499 mg/dL are dangerous. Based on findings uncovered by the first meta-analysis, waiting for triglycerides to reach the 499 mg/dL level poses an increased risk for cardiovascular disease of 63% in men and 167% in women.²⁷

A second large meta-analysis (over 262,000 people) found a 72% increased risk of cardiovascular disease in those in the upper third triglyceride blood level compared to the lowest.⁸ This study further discredits the FDA’s argument that up to 499 mg/dL of triglycerides has not been proven hazardous, especially in light of Life Extension^® and American Heart Association positions that optimal triglyceride levels are below 100 mg/dL.

Based on this large study, the 5-fold difference of opinion over what are safe upper-limit triglyceride levels means that those who choose to follow the FDA’s recommendations may be at a 72% increased risk of today’s leading cause of death.

Perhaps the strongest triglyceride data comes from a study involving 13,953 men aged 26 to 45 who were followed up for 10.5 years. Baseline triglyceride levels in the top quintile were associated with a 4-fold increased risk of cardiovascular disease compared with the lowest triglyceride quintile, even after adjustment for other risk factors, including HDL. An evaluation of the change in triglyceride levels over the first five years of this study and cardiovascular disease in the next five years found a direct correlation between increases in triglyceride levels and cardiovascular incidences.²⁸

In world regions with lower cardiovascular risk (e.g., Spain, Japan, and Africa) triglyceride levels below 100mg/dL are commonly found.^29-31 Clinical trials consistently demonstrate the lowest risk of cardiovascular disease to be associated with the lowest fasting triglyceride levels.^28,32,33

To make matters worse, as Americans accumulate more body fat, average triglycerides have been steadily increasing. Overall, 31% of adult Americans have triglyceride levels over 150 mg/dL, a number that even standard reference labs say is too high.³

This data about the dangers of elevated triglycerides was argued for years in the federal court proceeding whereby the FDA threatened to bring criminal charges against the maker of a fish oil drug.

The judge ruled against the FDA on scientific grounds, which I find rather bizarre. Why are federal judges put in the position of making medical decisions like this? Isn’t that what physicians are trained to do?

How Triglycerides Accelerate Atherosclerosis

Triglycerides are a form of fat in the blood that are either used for cellular energy production or stored as body fat. Triglycerides are not part of human atherosclerotic lesions.

What happens when triglycerides are persistently elevated is they can contribute to deadly low HDL and impede the ability of HDL to remove cholesterol from arterial walls.^12,34

Elevated triglycerides also promote the formation of byproducts that are highly atherogenic.^21-23,35

These triglyceride byproducts promote arterial inflammation and abnormal arterial blood clotting while impairing endothelial function and insulin sensitivity.^3,36-39 Triglycerides also have a deadly impact that contribute to foam cells accumulating in atherosclerosis lesions.⁴⁰

This is why Life Extension^® and the American Heart Association advise that triglyceride levels should ideally be below 100 mg/dL.

It took a federal judge’s order to prevent the FDA from bringing criminal charges against a company that wanted to promote its fish oil drug for use in people with triglyceride readings in the 200 to 499 mg/dL range.

What Causes Elevated Triglycerides?

Factors that elevate blood triglyceride levels include a sedentary lifestyle, excess body weight (especially in the abdomen), unhealthy dietary patterns, and low intake of marine-derived omega-3 fatty acids.^3,41

What the FDA fails to understand is the association between triglyceride elevation and the aging process. For example, only 9.5% of people aged 20 to 29 have triglyceride levels over 200 mg/dL, whereas the number jumps to 22.6% in persons 60 to 69 years.³

Higher triglycerides have been observed in type I and type II diabetics.^42-44 In type I diabetes, higher triglyceride levels correlate with poor glycemic control.⁴² Elevated triglycerides predict progression towards type II diabetes in nondiabetics.⁴⁵

In people of all ages, insufficient intake of omega-3 fatty acids contributes to higher triglyceride levels.⁴⁶ Fortunately, quality fish oil supplements are available with or without a prescription.

Various genetic defects can lead to very high triglyceride levels,⁴⁷ and in these instances, everyone (including the FDA) agrees that fish oil supplementation is essential to protect against heart attack,^48-51 ischemic stroke,^51-53 and lesser-known problems caused by elevated triglycerides like pancreatitis.^54-56

An absurd argument the FDA made in the federal court case was that if a fish oil drug were allowed to be promoted to people with triglyceride levels between 200 to 499 mg/dL, then healthy lifestyle/dietary changes would not be made, since patients would see their triglycerides drop in response to fish oil.

The court rejected the FDA’s argument that sought to circumvent the First Amendment. The federal judge ruled that the maker of this fish oil drug had a free speech right to convey factual information without having to fear FDA prosecution.

Dietary Factors Affecting Triglyceride Blood Levels

Huge numbers of clinical trials have been conducted to ascertain what components of the human diet elevate or reduce blood triglyceride levels.

Data from these studies show how one’s triglyceride level can be modestly lowered by reducing the type and amount of unhealthy dietary fats, cholesterol-rich foods, and trans fats.

In a meta-analysis of 30 controlled feeding studies, a moderate-fat diet decreased triglycerides by 9.4 mg/mL, whereas type II diabetics consuming this same modest-fat diet showed a striking 24.8 mg/dL decrease in triglycerides.⁵⁷

This data indicates how dangerous it is for diabetics to excessively eat the wrong fats. Diabetics suffer multiple metabolic disturbances that preclude them from safely burning/storing dangerous fats that wind up in their bloodstream as triglycerides.

To help lower triglycerides while boosting beneficial HDL, all aging individuals should avoid added sugars and restrict total carbohydrate consumption to below 60% of one’s diet.

To demonstrate the danger of fast foods, a feeding study found that consuming a meal with 15 grams of fat boosted postprandial (after-meal) triglyceride levels by a modest 20%, whereas high-fat meals (50 grams of fat), including those served in popular fast-food restaurants, increased triglyceride levels by at least 50% beyond fasting levels.⁵⁸

While standard blood tests are usually done in the fasting state, a number of recent studies show that chronically high-after- meal blood levels of triglycerides and glucose are particularly dangerous.^59-61 This data adds to the growing body of evidence showing marked reductions in disease risk by following healthier eating patterns.^62-64

Adherence to a Mediterranean-style diet lowers triglycerides 10% to 15% more than a strict low-fat diet.^65,66 Yet triglyceride reductions in response to dietary changes are not always as substantial as many aging people require.

In response to reduced calorie intake, there are consistent reductions in body fat and blood triglyceride levels. The more body weight shed, the greater the decline in blood triglycerides. The percent reduction, however, does not always result in people achieving optimal triglyceride levels, which is why fish oil is so important.

Most Direct Way of Slashing Triglycerides

Consumption of omega-3 fatty acids has shown the most robust and consistent reductions in blood triglyceride levels.^6,67

A comprehensive review of human studies showed that triglyceride levels dropped 25% to 30% in response to daily ingestion of 4,000 mg of marine-derived omega-3s.⁵

This study found a dose-response relationship, with each 1,000 mg of EPA/DHA producing a 5% to 10% reduction in blood triglyceride readings. The effects of fish oil in lowering triglycerides are more pronounced for individuals with higher beginning triglyceride levels.

Studies on plant sources of omega-3s have not produced consistent triglyceride-lowering effects. That’s because plant-derived omega-3 comes in the form of alpha linolenic acid that requires an enzyme (delta-5-desaturase) to convert alpha linolenic acid to EPA/DHA in the body.⁶⁸

Activity of the delta-5-desaturase enzyme diminishes with aging.⁶⁹ Plant-based chia, flaxseed, and walnuts are healthy to eat, but don’t expect them to lower triglycerides the same as cold-water fish.

When one ingests marine omega-3s, EPA and DHA are obtained directly without the need of enzymatic conversion. For the purpose of lowering triglycerides, omega-3s should come from marine-derived EPA and/or DHA, i.e. fish oil concentrates.

The American Heart Association recommends 2,000 to 4,000 mg EPA/DHA a day to lower triglycerides, providing that the capsules are taken under a physician’s care. This recommendation is based on a large body of evidence showing triglyceride-lowering effects of marine-derived omega-3.^70-73

A person with blood triglyceride levels above 100 mg/dL can usually determine an appropriate omega-3 dose. Life Extension^® recommends a Mediterranean-type diet and supplementation with about 2,400 mg of EPA/DHA for overall health, which includes maintaining triglyceride levels in optimal ranges.

If triglycerides remain stubbornly high, then increase the amount of fish oil capsules and try to make healthier dietary and lifestyle choices.

The Prescription Fish Oil Drug

The name of the drug the FDA lost its legal case on is Vascepa^®.

Unlike fish oil dietary supplements that contain EPA and DHA, Vascepa^® contains only EPA. The reason for this is that while EPA and DHA both lower triglycerides, DHA omega-3 can slightly increase cholesterol.

Since cardiac patients often have cholesterol issues, a company obtained approval from the FDA to market EPA-only fish oil as an expensive prescription drug.

The FDA approved Vascepa^® only in people with very high triglycerides (over 500 mg/dL). When the company promoted Vascepa^® to doctors for use in patients with triglyceride levels between 200 to 499 mg/dL, the FDA threatened criminal charges because according to the FDA, there was insufficient evidence that lowering persistently elevated triglycerides (200 to 499 mg/dL) would produce a benefit to patients with coronary artery disease.

In response to exercising their First Amendment right to inform doctors of the benefit in lowering-persistently elevated triglycerides, the FDA mystically transformed Vascepa^® (EPA-fish oil) into a misbranded drug that subjected the company and its employees to criminal charges.

The company making Vascepa^® filed a lawsuit against the FDA stating their claims were truthful and non-misleading. According to the company, the FDA was chilling free speech by claiming the company’s promotion of Vascepa^® for use in people whose triglycerides were 200 to 499 mg/dL was illegal.

Recall that the American Heart Association and Life Extension^® believe that optimal triglyceride levels for protecting cardiovascular health are under 100 mg/dL. The FDA views are diametrically opposite to what is near consensus in the medical community, i.e. triglycerides levels should be no higher than 100 to 150 mg/dL of blood.

What’s Good and Bad about Vascepa®

Vascepa^® is marketed to doctors as a fish oil drug that lowers triglycerides without raising LDL cholesterol levels.

To the physician, this may sound appealing compared to a competitive fish oil drug called Lovaza^®, which contains EPA and DHA.

If you chose to use an expensive fish oil drug, Lovaza^® might be the better choice. That’s because of peer-reviewed findings showing Lovaza^® lowered triglycerides by a median of 51.6%, whereas Vascepa^® lowered triglycerides by a median of 33.1%, compared to placebo in both cases. Therefore, the studies examined found Lovaza ^® to be about 56% more effective than Vascepa^® at triglyceride lowering when comparing median percent changes.⁷⁴ The one benefit that Vascepa^® has as stated on their website is:

“Vascepa^®, EPA only, has been shown to lower triglycerides without raising LDL (bad) cholesterol. ” ⁷⁵

What doctors may not take the time to comprehend is that there is far more to consider than simply LDL cholesterol levels when comparing Vascepa^® (EPA only) with Lovaza^® (EPA+DHA).

Five direct-comparison studies from a large meta-analysis found DHA was more effective in reducing triglycerides than EPA. The same analysis also found DHA led to a 4.49 mg/dL increase in HDL-C, while EPA did not. ⁷⁶

Although LDL cholesterol may rise to some extent with EPA plus DHA supplementation, a shortcoming of relying on EPA alone is that DHA may reduce the atherogenicity of LDL. This is because DHA has been shown to significantly increase the size of LDL particles compared with EPA.⁷⁷ Larger, more buoyant LDL particles are less likely to clog arteries with deadly plaque.⁷⁸

In a large trial comparing EPA (Vascepa^®) plus statin therapy to statins alone, rates of sudden cardiac death and coronary death were not reduced by EPA.⁷⁹

In a separate large trial in which subjects were given EPA plus DHA (Lovaza^®), a 45% reduction in risk of sudden death was observed, along with a 20% reduced risk of death from any cause.⁸⁰ However, not all trials of omega-3 fatty acids have shown these robust effects.^81,82

International cardiovascular professional societies support the use of fish oil supplements.^3,83,84 The American Heart Association recommends 2 to 4 grams of marine EPA plus DHA daily for high triglycerides.³

Dangers of a DHA Deficit

What we at Life Extension^® are most troubled by is the fact that patients taking Vascepa^® are unlikely to take other fish oil supplements, and therefore suffer a deficiency of the DHA component of the omega-3 family.

How important is DHA? To start with, it forms the major structural component of brain cell membranes. When looking at the overall health benefits of DHA compared to EPA, the clear winner is DHA. Some respected sources have even written that most people could derive virtually all of fish oil’s benefits by taking only the DHA fraction.^76,85,86

The cost for a one-month supply of Vascepa^® is around $250. Lovaza^® costs around $300 a month. The same amounts of omega-3s can be obtained from high-quality dietary supplements for a fraction of these prices.

Even those with health insurance generous enough to cover prescription fish oil drugs will often find the copays for omega-3 prescription drugs exceed the low free-market price of high-quality fish oil supplements. Some insurance companies refuse to cover prescription drug fish oils and tell their policyholders to buy their fish oil from a dietary supplement company.

With the federal government committing billions of dollars a year to cover the full retail prices of prescription drugs for lower income individuals, we suspect that this is where many of the sales for Lovaza^® and Vascepa^® will come from. As a taxpayer, you should be outraged.

Become an Empowered Patient

Doctors are so inundated with new findings and suffocating bureaucracy that they cannot keep up with every aspect of medicine.

A growing shortage of practicing physicians mandates consumers take partial charge of their health care. When it comes to many of the known cardiovascular risk factors, taking charge is not difficult.

As it relates to triglycerides, you want your blood levels to be under 100 mg/dL. The comprehensive Male and Female Blood Test Panels offered by Life Extension^® include a host of vascular disease markers, including triglycerides.

If your triglyceride result comes back over 100 mg/dL, you are welcome to bring this to the attention of your physician. You may also want to take some action on your own, such as increasing your intake of omega-3s and making lifestyle changes to safely push triglycerides (and other vascular risk markers) down. You can then proudly show your physician what you accomplished and spare his/her time for more important treatment issues you may face.

Annual Blood Test Super Sale

Most Americans delay getting lab tests until after outward symptoms of disease develop.

The reasons for deferring blood testing includes not knowing which tests to order, difficulty in finding a physician to prescribe proper blood tests, inability to access results, and lack of affordability.

Life Extension^® resolved these problems 20 years ago by offering comprehensive blood test panels direct to health-conscious consumers at low prices with quick turnaround times, free access to health advisors to review results, and convenient drawing time usually with no appointment needed.

Every year, we announce our Blood Test Super Sale that slashes the price of our comprehensive panels.

This annual event prompts health-conscious consumers to order our Male or Female Blood Test Panels to identify health problems in time to take corrective actions.

A complete description of our popular Male and Female Blood Test Panels appears on the next page. These panels provide comprehensive assessments of heart attack/stroke risk factors by measuring total cholesterol, LDL and HDL,glucose, C-reactive protein, homocysteine, hormones, and triglycerides.

When you request these tests, we send you a pre-paid requisition receipt and a list of drawing stations in your area. You can then take the requisition to the nearest drawing station at your convenience.

To order the Male and/or Female Blood Test Panel, or any of the specialized tests Life Extension^® offers at huge savings, call 1-800-208-3444 or log on to LifeExtension.comhttps://www.lifeextension.com/lpages/labtest2019

For longer life,

William Faloon

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