Pharmacologists warn that the combining of many ingredients in popular weight-loss supplements increases the likelihood that unforeseen interactions can occur with medicines or foods.
And then there is the problem of assuming the safety or effectiveness of a "proprietary formula" when only its individual components have been studied.
Supplement manufacturers usually claim that mixing ingredients enhances the effects that each individual ingredient may have. But those claims are unproved, and just as likely, say experts, the ingredients can clash with each other.
In fact, dietary supplement makers seldom test the safety and effectiveness of their distinctive blend of ingredients -- their actual product -- on a large group of subjects for more than eight weeks -- or if they do, they don't publish those trials in scientific journals, says pharmacologist and research physician Arthur Grollman of the State University of New York at Stony Brook. And they virtually never compare a formulation's effect to that of a placebo, as is required to establish the risks and benefits of drugs under FDA rules.
Finally, there is the problem of establishing safety and effectiveness when doses vary and shift. This is one of the daunting challenges the FDA faces in its search for the ingredient, or combination of ingredients, in Hydroxycut that may have caused consumers harm.
Since last year, the largest supplement makers have come under new rules and inspection procedures governing "good manufacturing practices" -- a set of rules that should ensure more uniform quality in the purity and potency of dietary supplements. Mid-sized companies don't come under those regulations until next month, and the smallest supplement companies have another year to comply with the new rules.
"There are mechanisms in place to hold these companies accountable to make sure they are using the proper doses," says Dr. Andrew Shao, vice president for scientific and regulatory affairs at the Council for Responsible Nutrition, a group that represents dietary supplement makers. In an interview, Shao said the FDA's new manufacturing regulations mark a sharp departure from pre-2007 standards, when the manufacture of dietary supplements was held to the same standards as food.
Meanwhile, researchers and regulators have warned for years that many dietary supplements contain ingredients -- and contaminants -- not listed on labels, and dosages weaker or stronger than those advertised. A November 2005 report by New York-based ConsumerLab for instance, found that, of 11 weight-loss dietary supplements it tested, only six contained the ingredients in the strength advertised on their labels. One of those -- a product whose principal ingredient is hydroxycitric acid -- was found to be contaminated with five times the lead allowed by the state of California without a warning label.
Finally, supplement makers also respond to consumers' shifting whims by changing their formulations frequently. This week, safflower oil extract -- a source of polyunsaturated fat -- may be in; next week it might be replaced with chitosan, a lipid-absorbing powder derived from crustaceans.
For researchers or investigators, the shifting ingredients can be a serious obstacle to distinguishing between a product that's safe and a product that's a waste of money or -- worse -- a danger to consumers.
"I believe we need product-specific studies," says Dr. David B. Allison, director of the University of Alabama's Clinical Nutrition Research Center. "They market and patent these products on the basis of their unique formulation. But when the safety or effectiveness of the formulation is questioned, they fall back on claiming the safety and effectiveness of individual ingredients."