UNPA moves to ban sale of BMPEA as uncertainty swirls around Acacia rigidula's status

The controversy surrounding the low-profile botanical Acacia rigidula and its purported amphetamine-like constituents seems to have caught regulators flat footed and has lead one trade association to ban the sale for its members of formulations featuring one of the chemicals said to be found in the plant: β-methylphenethylamine, or BMPEA.

BMPEA is a positional isomer of amphetamine.  This ingredient made headlines recently when a study headed by Dr Pieter Cohen of Harvard Medical School found BMPEA in varying quantities in 11 of 21 dietary supplements his team tested whose formulations were listed as being based on Acacia rigidula extracts (significantly, the rest had no detectable amounts of BMPEA.  More on that in a moment).  Cohen noted that while BMPEA has been known for a long time—it was first synthesized in the 1930s—there is no readily available credible safety data on its effects on humans.  The dosages Cohen found in his study ranged from a low of 3mg up to a high of 94 mg.  Cohen saw this as a clear potential safety concern, and urged FDA to take action to ban the ingredient

The potential safety concern has led the United Natural Products Alliance to announce its 'no-sale' policy as a condition of membership, effective immediately. UNPA said that the results of Cohen’s study and an earlier FDA-funded study on the products makes it clear that formulators are spiking BMPEA into the products for added physiological effect. UNPA noted that BMPEA is banned both by the World Anti Doping Agency and Europe’s Food Standards Agency.  The botanical has been linked with a brain hemorrhage case in Sweden.

The issue with BMPEA and its botanical or synthetic origin bears some similarities to the issue of DMAA. In the case of DMAA, whether the compound had a botanical origin (in that case, purported to be geranium) was ultimately determined to be moot, as even if that were true, the botanical source could never yield commercial quantities of the compound. Some online commentaries referenced by NutraIngredients-USA cite articles from the 90s that indicate some level of BMPEA as well as other stimulant compounds can be found in the plant. Boulder, CO-based botanist Trish Flaster said the species, which is a large bush or small tree species native to Texas and northern Mexico, is more properly referred to as Vachellia rigidula (Benth.) Seigler & Ebinger.

But UNPA noted that the earlier FDA-funded study, published in October 2013 in the Journal of Pharmaceutical and Biomedical Analysis, that found BMPEA at varying dosages in almost half of the 21 weigh loss labeled as containing Acacia rigidula, raised the issue that BMPEA is not present in commercially relevant quantities in the source plant. “It appears nearly impossible to achieve the amounts of (BM)PEA found in the dietary supplements by formulating them with plant material or extracts of A. rigidula,” UNPA says the FDA study concluded.

Cohen’s study, published April 7, 2015, in Drug Testing and Analysis, went further to claim that BMPEA had never been extracted from Acacia rigidula. “The dosages of BMPEA in supplements strongly suggest that the amphetamine isomer is synthetically produced and placed in the supplement to lead to physiologic effects,” Cohen’s team concluded.

Getting out ahead of issue

“Having become aware of these two studies identifying BMPEA in these products and understanding that the products do not contain the naturally occurring form of Acacia rigidula, prompt action was warranted,” said Loren Israelsen, UNPA president.

“As we have done before with no-sale policies for ephedra, DMAA and kratom (Mitragyna speciosa), we’re committed to moving quickly to define the boundaries of responsible practices within the industry. These studies prompted us to take this action, and UNPA will continue to do so as circumstances warrant,”  he added.

American Herbal Products Association president Michael McGuffin, who has had experience dealing with the intricacies of the DMAA question, said AHPA expects members to be able to prove the provenance of the ingredients they use.

AHPA has not studied this specific issue or researched the constituents of Acacia rigidula, but it is reasonable for any company that claims that an ingredient that it markets is a constituent of a botanical to be able to provide substantiation of this claim with scientific evidence that can withstand scrutiny by qualified experts. AHPA has a membership acceptance policy that requires applicants that make such claims to present such substantiation,” he said.

NDI, or not?

Also at issue is the regulatory status of the ingredient. As previously mentioned, A. rigidula (despite Flaster’s correction, all of the products in question refer to the plant this way) has not been a high profile botanical in trade. The recent spate of formulation activity on the fringes of the dietary supplement industry using this ingredient appears to be motivated by the search for a weight management alternative to ephedra, which was taken off the market over safety concerns in 2004.  

It seems an unlikely candidate for Old Dietary Status, but after a search of the records under both names for the plant, Siobhan DeLancey of FDA said that no NDI notification for the plant has been submitted.

“The FDA has not made a determination on whether Acacia rigidula requires an NDI or is grandfathered under DSHEA,” she said.

Having FDA perched on the fence in this way was met by bemusement on the part of some industry observers.

“That’s their prerogative to view it that way. But if they are not going to stand up the NDI clause, why have it?” said Daniel Fabricant, CEO of the Natural Products Association.

“This kind of statement is a disincentive for compliance and invitation to not comply with the NDI provision. What this statement from FDA is saying is that anyone is welcome to ignore the law as long as they don’t kill people,” said attorney Marc Ullman of the firm Ullman, Shapiro & Ullman.

Safe, or not?

DeLancey also said FDA does not at the moment share Cohen and Israelsen’s concern about the ingredient’s safety.

FDA prioritizes enforcement actions based on available resources and the level of safety concern. While our review of the available information on products containing BMPEA does not identify a specific safety concern at this time, if we determine that regulatory action is appropriate at a later time, the FDA will consider taking such action to protect consumers,” she said.

Cohen, who said he applauded UNPA's move, noted that an NDI notification on BMPEA or on A. rigidula extracts would at least provide for a safety review of the ingredient, something which does seem to have taken place thus far.

“These statements are completely impossible to square with the FDA’s own scientists’ conclusions back in 2013. Of course it requires an NDI. This response makes no sense.  It’s not just my opinion. We all agree on this one—it’s not controversial,” Cohen said.