Phenylethylamines, or PEAs, are a category of amphetamine-like compounds reportedly found in small amounts in many botanical sources. Examples of PEAs or associated compounds that have been used in sports nutrition pre workout products include DMAA, alleged to be an extract of geranium, DMBA, purported to come from dendrobium, an orchid species, and BMPEA, whose claimed origin is in Acacia rigidula, a species of shrub native to Texas and Mexico. The Food and Drug Administration has taken the view that these ingredients, whether derived from plants or chemically synthesized, are New Dietary Ingredients and should have notifications on file. FDA has stated further in several cases that these ingredients are in fact synthetic versions of botanical constituents and therefore do not qualify as legal dietary ingredients under its thinking on that subject as outlined in the updated NDI Draft Guidance.
The fact that these ingredients have frequently appeared, and continue to appear, in dietary supplements has been a lightning rod for critics of the industry. DMAA has been associated with the deaths of two soldiers who used products containing the ingredient while exercising. FDA subsequently moved to remove the ingredient from the market, though it is still being sold by Hi Tech Pharmaceuticals while the lawsuit that company brought against the agency makes its way through the courts. DMBA products were removed from military commissary shelves after a study conducted by Dr. Pieter Cohen of Harvard Medical School that found the ingredient had marked similarities to DMAA. Dr. Cohen has been a vocal and prolific critic of the dietary supplement industry. Dr. Cohen conducted another study on BMPEA, this one in collaboration with Dr. Ikhlas Khan of the National Center for Natural Products Research, in which they said, “Consumers of Acacia rigidula supplements may be exposed to pharmacological dosages of an amphetamine isomer that lacks evidence of safety in humans. The FDA should immediately warn consumers about BMPEA and take aggressive enforcement action to eliminate BMPEA in dietary supplements.”
There was a similar clamor several years ago about the existence of so-called ‘designer steroids’ in sports nutrition products. These ingredients differed in detail, but not in general pharmacology, from those steroids that were already on the list of controlled substances maintained by the Drug Enforcement Agency. Chemists had found ways to tweak the chemistry to make similar, but not identical, ingredients to those banned substances. Those tweaks including altering those steroids to become a class of chemicals known as ‘pro hormones.’ Those ingredients were covered by the Designer Anabolic Steroid Control Act of 2014 (DASCA), which had broad support within the dietary supplement industry.
So why couldn’t something similar be done with PEAs? If there is a claim that these ingredients are potentially unsafe (something that proponents vigorously dispute), why couldn’t a new regulation cover these as was done for the steroidal ingredients?
DEA listing paved way for steroids
The problems with this approach are many, experts say. Rick Collins, an attorney who has broad experience representing sports nutrition companies, said that while PEAs might represent a class of potentially troublesome compounds, the situation is considerably different than it was with steroids.
“Anabolic steroids were already controlled substances. The mechanism that was used in by the steroid control act was to expand the list of compounds already defined as anabolic steroids, as well as to reconfigure the definition of an anabolic steroid so as to allow other substances to be treated as controlled substances even though they were not specifically listed,” Collins told NutraIngredients-USA.
Having that prior controlled substances listing was a key element for the easy passage for the DASCA, Collins said. Scheduling a new substance through an administrative proceeding is a lengthy affair, though DEA can temporarily bypass that procedure via an emergency listing, as it attempted to do last year with kratom.
“In order to move an ingredient or compound into the Controlled Substances Act there needs to be regulatory action by the DEA providing notice and following the Administrative Procedures Act. Or Congress could take action on its own and draft a bill to put a particular compound or class of compounds into that classification,” he said.
Not a neat bundle
The problem with that approach, said Duffy MacKay, ND, executive vice president of scientific and regulatory affairs for the Council for Responsible Nutrition, is that PEAs don’t all fit into a neat mold as did the steroids, relatively speaking.
“The category doesn’t have as clearly defined limits as did the steroids. With steroids, they have similar chemical activity. But with stimulants, some are centrally acting, whereas some act peripherally. Some affect the central nervous system, others do not,” MacKay said.
“And then you overlay that with the fact that we have some legal stimulants like caffeine that is universally accepted,” he said.
MacKay said that definitional issue could make the process of putting all these ingredients into a single legislative basket too complicated.
“It was easy to get the DASCA passed, because there were no anabolic agents accepted for general use like caffeine is. So drafting legislation that would take care of PEAs in a clean way so that there are no unintended consequences would be tricky,” he said.
Solution: File NDIs
So MacKay said the situation is most likely to remain as it is. The solution would be for companies to file NDI notifications where appropriate. Many of the these formulators have tried to cloak their ingredients with Old Dietary Ingredient status, pointing to the purported botanical antecedents of these compounds. But MacKay said that clearly flies in the face of the letter and intent of DSHEA.
“If you remove it from the plant, if you concentrate it, it has been changed. Having a compound at 4 ppm in a plant is very different than if you have 50 mg of it in a capsule. If the industry would embrace that concept, and file notifications where appropriate, we could get some of these ingredients to market with confidence. The alternative is to play into the hands of our critics. Then we have people like Pieter Cohen who will pick at that scab and say there is not way the regulations are working like they are supposed to when there are all these products out there. It’s hard argument to win when these products are out there and they know there was no NDI filed,” he said.
Collins said there will be no shortage of new ingredients that could qualify for those listings. Thriving innovation is a durable feature of the sector.
“The history of the sports nutirition market generally has been a succession of compounds that build muscle or burn fat and when action is taken against one it’s only a matter of time before a replacement is identified,” he said.