Dietary Supplements: Shifting the Burden to Create a Pathway for Fraud week I have spent a significant time around a lot of people who have colds. This is a really bad week for me to be sick so I am thus currently very interested in preventative measures. I mentioned this to numerous people and was told by a few different folks that I should try taking Airborne, a dietary supplement that was developed by a former schoolteacher to help boost the immune system and prevent the onset of illness. I did, of course, express immediate skepticism that a dietary supplement, which is nothing more than a vitamin tablet, would keep me from getting sick. In fact, just a little digging showed that in 2008 the makers of Airborne agreed to pay $23 million to settle a class action false-advertising lawsuit. Based on my own experience this didn’t surprise me at all, however the conversation piqued my interest as to why so many folks feel better taking dietary supplements than medications. The answer to this question was not hard to find. Many people prefer supplements over drugs because they simply don’t trust the pharmaceutical industry. Between several largely publicized cases of unethical behavior and the laundry list of potential side-effects we are inundated with at the end of most drug commercials (which are required by the FDA to be listed) many people feel like drugs and medications are not worth the risk. The pharmaceutical industry is far more scientific than the dietary and nutritional supplement industry; however I am no pharmaceutical apologist. That is an industry that has done a lot to earn our mistrust (more in a later post about this topic). The point I want to make in this post is that the nutritional supplement industry does not deserve our trust either. Current regulations in the U.S. allow supplement manufacturers to make basically any claim without any verification of the efficacy of that claim. Further, the tactics the supplement industry uses to market their products are extremely misleading.

According to the Food, Drug, and Cosmetic Act the term ”drug” can mean any substance recognized in the official United States Pharmacopoeia and/or substances that are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in humans or other animals. It can also refer to any substance other than food that is intended to affect the structure or any function of the body of humans or other animals.

A dietary supplement has a somewhat different definition. In 1994 the Dietary Supplement and Health Education Act (DSHEA) was passed by congress. Under the DSHEA a dietary supplement is defined as:

“a ‘dietary ingredient’ intended to supplement the diet. The ‘dietary ingredients’ in these products may include: vitamins, minerals, herbs or other botanicals, amino acids, and substances such as enzymes, organ tissues, glandulars, and metabolites. Dietary supplements can also be extracts or concentrates, and may be found in many forms such as tablets, capsules, softgels, gelcaps, liquids, or powders. They can also be in other forms, such as a bar, but if they are, information on their label must not represent the product as a conventional food or a sole item of a meal or diet. Whatever their form may be, DSHEA places dietary supplements in a special category under the general umbrella of ‘foods,’ not drugs, and requires that every supplement be labeled a dietary supplement.”

So the difference between a drug and a supplement lies in the fact that their purported intentions are different: drugs can treat disease and supplements augment the diet. In reality, the line distinguishing the two has become very blurry in recent years; supplements are now being advertised in the same way drugs are and for the same types of things. I cite Airborne’s claim that it increases the immune response and prevents colds as a perfect example of this.

The most significant difference between drugs and dietary supplements, however, lies in the way they are developed and approved. In the U.S. the drug approval process stipulates that the manufacturer of a drug provide the FDA with evidence that the compound is biologically active, and reasonably safe for initial administration to humans. Once this requirement has been met, there are three phases of further research to determine the efficacy and safety of the drug. Finally, if it makes it this far, meetings are held in order to uncover any unresolved problems or issues, and then the drug and research is subjected to review by outside sources and advisors before any approval is made by the FDA. The process of drug approval is not without controversy and corruption but it is at least scientific.

Dietary supplements on the other hand are subjected to far less scrutiny than drugs, due in large part to the DSHEA. The intentions behind the DSHEA were to help increase the availability of certain nutrients to consumers, but it also led to a boom in the marketing of unsubstantiated claims. Before the bill was signed into law, dietary supplements were subject to regulation by the FDA. Now, however, it is the manufacturer who is responsible for determining that a given dietary supplement is safe and that any representations or claims made about it are substantiated by adequate evidence to show that they are not false or misleading. This means that dietary supplements do not need approval from FDA before they are marketed and that a manufacturer does not have to provide FDA with evidence to substantiate safety or effectiveness to market its products.

The problem inherent in the DSHEA is that it puts the burden of proof in the wrong place. Those who stand to make a great deal of money from a product need, from a scientific standpoint, to be the ones who are responsible to demonstrate that it is safe and effective before they market it, the DSHEA however, relieves them of that responsibility. The Federal Trade Commission (FTC) deals with false advertising claims, but as long as the manufacturers remain clever there is little the FTC can do.

Scientific research is eventually conducted on many supplements and there are several that have been shown to be effective for their intended purpose. However it is wise to remember is that even when supplements are effective, they are ultimately limited in their scope. The problem is that many of the more profitable supplements are on the market long before there is enough evidence to support their efficacy and safety, so it is often a crapshoot as to whether one will turn out to work. Furthermore, there is also the bigger problem of manufacturers simply misrepresenting the evidence.

xenadrineMy first experience as a research assistant made me acutely aware of this problem. In 2000 I was a research assistant at Eastern Michigan University where we examined the effect of the product Xenadrine RFA-1, which was a nutritional supplement that was ephedrine based and was purported to aid in weight loss. Ephedrine is currently banned from use in dietary supplements in the U.S., but at the time it was one of the hottest weight loss products available. During the study, which was funded by Cytodyne Technologies (the supplement manufacturers) we had subjects take either the supplement or a placebo and walk six miles per week to see if the supplement led to greater weight loss than the placebo. What we found was that the supplement group lost a little more weight than the placebo group, but that the difference was not statistically significant, meaning that the difference in our study was due to chance.

The actual amount of weight lost for the supplement group was 3.19 pounds. The representative for the company, however, told the principal investigator that we should report our findings by saying that the supplement group lost 759% more weight than the placebo group who actually had an average weight gain of just less than half a pound. Reporting the numbers this way would have been mathematically accurate but very misleading. The principal investigator, being an ethical researcher, refused to do this after which the company threatened legal action. The legal action didn’t get anywhere but, not to be thwarted, Cytodyne later ran a magazine advertisement in which they blatantly misrepresented the results of our research. This garnered the attention of Dr. Robert Robergs, the editor of the Journal of Exercise Physiology Online, which is where we published our original findings, who had this to say in an editorial that appeared in the May, 2002 issue of the journal:

The authors of this study presented their data in an ethical fashion.  However, subsequent use of the study findings for marketing of the product revealed claims that were not substantiated by the research published in our journal. Subsequent discussions by the managing editor of the journal, myself and the ASEP [American Society of Exercise Physiologists] president revealed frustration for this occurrence, as well as an apparent inability to require the company to withdraw marketing claims due to the lack of regulations requiring companies to adhere to the stringent criteria used in scientific research… It needs to be made clear that in no way does ASEP support or condone the use of any commercial product that is the focus of research published in any of its journals.

In a related article that appeared in the journal, Professionalization of Exercise Physiology Online, editor Tommy Boone describes how the company used an ad which appeared in an issue of Muscular Development to misrepresent our research.

As an example, the paid advertisement states that “…resting energy expenditure was greatly increased for the Xenadrine group.  This means that the Xenadrine subjects were burning far more calories without even exercising.”  Wrong!  The actual finding, as reported by the authors, is that “…resting energy expenditure…did not increase during the supplementation period….”  The authors did not report a statistically significant increase in resting energy expenditure.  The advertisement is nothing more than consumer fraud. . . the authors reported that “Analysis of…HDL cholesterol and LDL cholesterol revealed no effect of supplementation”.  In contrast, though, note the content of the advertisement published in May 2002 issue of Muscular Development – “…the placebo group in the Eastern Michigan study actually experienced lower ‘good’ HDL cholesterol…than the Xenadrine group [that] experienced lower ‘bad’ cholesterol than the placebo group…subjects who took Xenadrine improved their good cholesterol and lowered their bad.”  Quite stunning! Right.  The truth of the matter is none of the content is true.  Again, the authors reported no significant differences.

Even when research is conducted in a responsible fashion, there is not really anything to stop manufacturers from using the findings in any way they can to sell their products. The tactics of Cytodyne Technologies eventually landed them in a class-action lawsuit in California where they were ultimately forced to pay $12.5 million dollars in damages. In 2003 the New York Times reported some of the information that came out during the trial:

… an e-mail message in the Cytodyne lawsuit shows how the company tried to influence one researcher.

The researcher, Jeffrey Armstrong of Eastern Michigan University, had refused to rewrite a journal abstract the way the company wanted, according to testimony, and Tim Ziegenfuss, the consultant who commissioned the study on behalf of the company, said he would try to change Dr. Armstrong’s mind.

”As far as rewriting the abstract, since I am not recognized as a co-author on the study I am not allowed to do it,” Dr. Ziegenfuss said on November 2000 in an e-mail message to a company official. He added, ”In this case the best I can do is try to carefully nudge his interpretation/writing in Cytodyne’s favor.”

Cytodyne was unable to budge Dr. Armstrong — ”I will not be intimidated,” he said in an e-mail message after being told that the company was threatening to sue him. But in another message, Dr. Ziegenfuss suggested that the study could still be marketed.

”Let Jeff do his hum-drum ‘science’ thing,” he said.

”This will portray Cytodyne in an objective, favorable manner to the scientific community,” he added. ”This is particularly important now considering the recent bad press on ephedrine. And then since Jeff has no control over the use of data in ads, use percentage changes there to impress consumers.”

Manufacturers are not interested in “hum-drum” scientific findings that don’t support their claims and will often blatantly misrepresent themselves. This situation is not unique to Cytodyne and is certainly not likely to change in the near future. This means that the burden rests on consumers to evaluate the information for ourselves. I was a research assistant on this project and was not directly involved in any of the above events, but rather witnessed them from the sidelines. Looking back I have to admit that I find it rather amusing, in a sardonic sort of way, to think that I learned much more about commercial research from the drama that surrounded that project than I did working on the research itself.