Therapeutic Dose: Nutraceuticals: Another Insurmountable Opportunity for FDA

The Dietary Supplement Health and Education Act (DSHEA) became law in 1994, amending the Federal Food, Drug and Cosmetic Act of 1938 (FDCA). It defines how dietary supplements are regulated and labeled. This was put into action this past June for larger nutraceutical firms and takes effect in June 2009 for smaller firms. The aim is to bring into play (albeit late in the game, and slowly) cGMPs for the “dietary supplement” industry.

The situation is like a “good news/bad news” joke. Now, the FDA can work towards making nutraceuticals safer and more reproducible, but where are they going to get the extra inspectors and lab personnel? The green light to add 1,300 new employees this year was welcome news, bringing Agency staffing levels closer to what they were before the Reagan years. However, these additions were meant to address the extra burden of overseas outsourcing and the spate of new generics at home and abroad. One might ask: Is there also room for inspections of natural products manufacturers?

On the Web, dietary supplement backers freely bash ethical pharmaceutical companies and FDA for “picking on” the nutraceutical industry. They gloat about ephedra, a “harmless, natural” material being allowed in diet preparations by court order. They claim that it was only banned because the FDA was “in the hip pocket” of Big Pharma. (I can just hear a number of my friends in Pharma saying, “If only!”) The mantra seems to be that these materials are “natural,” thus safe. That part made me shudder, because natural does not mean safe.

Plants, the source of most nutraceuticals, have only one defense: chemical substances. They can’t run away from predators; they don’t have claws or fangs to fight potential munchers, either. They can only produce poisons. Some of these poisons are, indeed,
safe and beneficial to humans. We get many vitamins and medicines from plants. We also get nicotine from tobacco plants, urushiol from poison ivy (oak and sumac), and a bunch of alkaloids from molds. Most are not something we want in everyday life.

To be fair, a huge number of vitamins and natural biologics are beneficial. But (always a “but” isn’t there?), even pure vitamins can and do have toxic levels. For many “folk medicines,” we don’t even know which of the hundreds of components present is/are
indeed the active ingredient(s).

In the early 1980s, Ex-Lax was owned by a large Pharma company. When the white phenolphthalein was shown to be around 97% pure, it was recrystallized to ~100% purity. The only problem was that the product was no longer effective; its impurities made the laxative work. [It now labels senna root rather than phenolphthalein as the active ingredient; now, all we have to do is find which ingredient in senna is the active.]

When the actives are known, the nature of deriving the chemicals from roots and leaves makes batch-to-batch quality control problematic. With no patents on things
like ginseng, a large number of companies sell versions (guess God never filed a patent for his plants) of these food supplements. That ensures a lower profit margin
than, say, Lipitor or Viagra. Lower profits mean little money for overhead and frills . . . like QC labs and chemists.

The variability from lot to lot alone makes nutraceuticals potentially dangerous. Vitamins, such as D and A, may have serious side effects in large doses. When the “active” ingredient in a nutraceutical is not known, possibilities of overdoses are quite likely.

Even in “safe” doses, natural products can interfere with prescription medicines. St. John’s wort has been known to interfere with birth control tablets and immune-suppressant drugs. The resulting pregnancies or organ rejections are not “minor” side-effects of a nutraceutical. Without formal clinical tests and identification of the moieties in nutraceuticals, potentially serious interactions with other drugs are a constant possibility.

The current FDA regulations are a wonderful first step in making widely used substances safe (and effective?), but much more work needs to be done to first understand, then to regulate, nutraceuticals. First, safety must be established— if only to uphold the Hippocratic Oath’s commandment to “First, do no harm.” I’m hopeful that there are truly some great drugs in the local health food store; we just have to use
modern tools to identify them.