Blurry Line Between Supplements and Drugs
25 August 2000
Wyn Snow, Managing Editor

Say goodbye to Cholestin -- a dietary supplement that has been proven to lower cholesterol and is made from red yeast. A US Court of Appeals recently upheld the FDA's ban on importing red yeast rice powder -- agreeing with the agency's argument that it is legally a drug rather than a food or dietary supplement.

What is red yeast?

Red yeast is a nutritional yeast -- used both in Chinese cooking as a spice and by traditional Chinese medical practitioners "to improve blood flow." It is grown on rice by fermentation, and is the main ingredient in Cholestin, a dietary supplement manufactured by Pharmanex. Pharmanex has conducted scientific research that demonstrates Cholestin's effectiveness in lowering cholesterol.

FDA claims that Cholestin is actually a drug

Red yeast is a complex substance. One component (called mevinolin) is chemically identical to lovastatin, the synthetic compound in Mevacor, Merck's cholesterol-lowering drug. Red yeast contains a relatively low amount of mevinolin -- but also contains other similar compounds, all of which appear to work together in reducing the body's production of cholesterol. However, the FDA claims that by manufacturing Cholestin, Pharmanex is actually manufacturing and marketing lovastatin.

Supplements not allowed to be "natural equivalents" of drugs

DSHEA says that substances that have been approved as drugs cannot be marketed as dietary supplements. Congress wanted to prevent drug manufacturers from evading the FDA's drug-approval process by finding naturally occuring equivalents to approved drugs and marketing them as dietary supplements.

However, a substance that has already been marketed as a dietary supplement or a food is exempt. It does not lose its status as a food if the FDA later approves that substance for use as an active ingredient in a new drug.

Even though red yeast has been used as a spice and dietary supplement for centuries by the Chinese and for decades in the US, neither mevinolin nor lovastatin had been marketed as a dietary supplement or as a food prior to lovastatin's approval as a new drug in 1987.

Question before the court: What is a drug?

The issue addressed by the Court of Appeals had to do with whether this exclusion and exemption in the language of DSHEA applied to lovastatin as an active ingredient in an approved drug -- or whether the term "new drug" meant only the finished product as a whole (namely Mevacor).

Essentially, unless the language in a law makes Congressional intent unambiguously clear, government agencies have wide latitude to interpret and enforce the terms of a law pretty much as they see fit -- unless that interpretation and enforcement is "arbitrary and capricious". In this case, the Court of Appeals held that the FDA's interpretation was reasonable -- and that a single active ingredient qualifies for protection under this exclusion.

Thus, the Court allowed the FDA's assertion that Cholestin is a drug because it contains mevinolin, which is chemically identical to lovastatin. The Court of Appeals did not address other issues in the original suit because the lower court had not addressed them either. The decision remanded the case back to the lower court for consideration of these other issues.

Implications: When is a tomato not a tomato?

Let's suppose that a company creates "Lycodin", a product based on lycopene, which is an antioxidant found in tomatoes and certain other red-colored fruits and vegetables. (Research indicates that lycopene may lower the risk of cancer and heart disease.) Let's suppose further that Lycodin gains FDA approval as a new drug -- and in the meantime, no one markets lycopene itself as a dietary supplement. According to this court decision, the FDA could then claim that tomato powder is a drug because it contains lycopene, an active ingredient in this fictional drug Lycodin.

Sounds ludicrous, doesn't it? But taking this hypothetical case one step further, let's suppose another company creates "Tomatesso", a lycopene-enhanced tomato-based powder, and sells it either as a food or a supplement -- after Lycodin's approval as a drug. The FDA could remove Tomatesso from the market, ruling that it was an unapproved drug because it contains lycopene, the active ingredient in Lycodin.

This is exactly what is happening to Cholestin.

Does it really matter if Cholestin disappears?

A reasonable person might wonder whether it matters if we eat red yeast, take Cholestin, or get a prescription for Mevacor. Isn't the end result "mostly the same"?

No. Prescription drugs are expensive and often have unwelcome side effects. The toll on our economy and on public health is unacceptably high. We need alternatives -- the kinds of alternatives that researchers are discovering among dietary supplements.

Could Cholestin apply for approval as a new drug?

Of course -- but this process takes years (usually 8-10 years), hundreds of millions of dollars (typically $300-$500 million), and the production of enough pieces of paper to fill a railroad car. And the end result would be another expensive product that we'd need a prescription to buy.

Surely it makes more sense to go ahead and use the knowledge that is already available from centuries of use in Chinese medicine, knowledge that includes how to use this substance safely and effectively -- and add to that knowledge with Western scientific inquiry. The American public is entitled to choose from among a wide array of health products -- including dietary supplements.

Penny wise, pound foolish

The FDA is charged by the Food, Drug, and Cosmetic Act with protecting public health and preventing consumer fraud. Yet its action against Cholestin accomplishes neither of these goals. Public health is improved rather than threatened by Cholestin. Also, research has demonstrated that Cholestin is effective, so there is no question of fraud. The main result of the FDA's action here is to protect Merck from a competing food-based product.

Public health is best served by an FDA that focuses less on restricting beneficial dietary supplements and focuses more on identifying and weeding out the harmful or ineffective ones.

Centuries ago, the Greek physician Galen (AD 130-200, the founder of Western medicine) used foods to treat disease, just as we now use drugs. In the intervening years, healers in all cultures used both foods and medicinal plants. Science gradually learned how to identify and isolate specific compounds to treat disease. Researchers are now investigating the ways in which complex groupings of chemicals in foods and other botanical resources act to promote health and fight disease.

We are now gaining scientific knowledge of a continuum of substances ranging from food (tomatoes, oats, soy, broccoli, red yeast) through supplements (Cholestin) to drugs (Mevacor). It is time to recognize that all three have valuable and interdependent rather than separate roles to play in human health -- and to preserve and expand our freedom to use these substances.