DMAA Research and Realities

USP Labs has not given up its fight to show DMAA (1,3 -dimethylamylamine), a stimulant used in nutritional and sports supplements, is present in some field of geranium from somewhere in China. On the merits of investing in the fight to prove DMAA is naturally occurring in geranium, USP Labs has been dogged to prove its case.

Research from various sources has gone back and forth on the issue of DMAA's natural presence in geranium. Presumably to address questions raised by FDA and other on the legality of DMAA as a supplement relative to NDI notification requirements, USP Labs invested in a series of studies that have concluded DMAA exists naturally in geranium.

The latest such study from the University of Memphis sought to address the disparity of results and conclusions on this matter published in many different prior studies. The Memphis crew analyzed extracts from geranium plants acquired from specific fields in three distinct regions of ChinaKunming, Guiyang and Changzhoufrom three different harvests, including spring and summer. Their HPLC -MS (high performance liquid chromatography-mass spectrometry) analysis of extracts from these plants showed 1,3 and 1,4 DMAA were both present in this geranium. The samples were sent to another lab, which found similar results. "this is the first reported inter-laboratory analysis confirming the presence of 1,3-DMAA in a geranium plant (specifically Changzhou S11 sample)," the authors wrote.

Further, the researchers noted likely underestimation of the amounts of DMAA in geranium was due to matrix effects, which were countered by using a standard addition method that included comparing sample extracts to samples spiked with known quantities of both forms of DMAA. Researchers also addressed results published in July 2012 by University of Texas scientists who said analyzed commercial DMAA dietary supplements were synthetic in origin because their stereoisometric ratios of DMAA in were known indistinguishable from those identified in synthetic samples. The University of Memphis team found similar ratios in the plant samples from the three Chinese regions, indicating the use of these ratios to identify synthetic DMAA sources may not be accurate.

 In fact, researchers reported their results suggest "1,3-DMAA could be a natural product extract, fulfilling a requirement of the Dietary Supplement Health and Education Act (DSHEA)." However, they did also suggest a definitive approach to the question of DMAA's status as synthetic or natural may be via a multi-lab, blind analysis of identical samples known to contain DMAA (such as the Chinese samples they tested) and sample not expected to contain DMAA.

Unfortunately, such a study might not change the regulatory status of DMAA. In the United States, DMAA has come under scrutiny and action by FDA due to concerns over both legality and safety issues.

"Even if particular species of geranium from one region in China contains DMAA, [proponents] still haven't dealt with the NDI issue," assured Marc Ullman, of Ullman Shapiro & Ullman. He explained companies selling DMAA supplement are not selling geranium oil, which would be the ingredient qualifying for NDI notification exemption as marketed as a food before 1994.

FDA has been quite adamant on its strict interpretation of "chemically altered" versions of exempted foods marketed before 1994, reporting the agency considers such altered ingredients as NDIs. Ullman noted FDA has not updated its position on this exact matter, but his feeling is FDA will say DMAA isn't exempt, even if found in some fields of geranium in China. "The purpose of NDI notifications under DSHEA is for companies wishing to market NDIs to show the ingredients are reasonably expected to be safe," he reminded.

The question of safety is reportedly behind recent actions against the sale of DMAA as a supplement (or similar) by several governments around the world including the UK, New Zealand, Australia, Canada, Ireland, , as well as by the U.S. military.  See the recent Insider slideshow on the history of DMAA's recent legal and regulatory troubles, including FDA's string of warning letters sent to several marketers of DMAA-containing supplements.

Just this week, a survey published in the Archives of Internal Medicine reported all 16 DMAA products drawing FDA warning letters earlier this year can still be purchased online. The author, Creighton University associate professor Philip Gregory, PharmaD, said he thinks FDA is building a case to remove DMAA from the supplement market.

Despite a wide range of stakeholders calling for a ban of DMAA, some industry insiders and researchers have called existing and pending bans of DMAA short-sighted. Major retailer GNC has consistentlly supported its sale of DMAA supplements, saying the it accepts its vendor's assurances the products are safe and legal, and citing a lack of evidence showing safety concerns.

In a roundtable discussion on DMAA hosted by Australian sports supplement retail giant Serious Supplements, several participants argued an outright ban might not be the best option. Academic researcher Willem Koert said regulation and education might be better than banning DMAA, noting the few adverse events associated with the stimulant are no different than in the cases of caffeine and paracetamol, neither of which are banned despite widespread overuse and associated health problems.

The consensus among those agreeing with Koertincluding Patrick Arnold, the man who rejuvenated DMAA and was responsible for the infamous "clear" and "cream" at the heart of the steroids case against pro baseball player Barry Bondsis the current reformulation of formulas to replace DMAA with new alternatives, including higenamine and N-Methlytyramine.

"Yohimbine, beta-phenethylamine, hordenine, synephrine: where are the clinical studies demonstrating the safety for these ingredients?," Arnold asked, suggesting DMAA alternatives might be riskier than DMAA. "Yohimbine especially is an awful compound and I guarantee it put more people in the hospital than DMAA ever did."

Adel Moussa (aka Dr. Andro), German physicist and author of the supplement science blog SuppVersity, saidhis examination of data from the Texas Poison Center suggested other ingredientssuch as caffeine and yohimbinefound in the supplement connected to 45 of 56 health complaints could have been the cause of adverse events such as tachycardia and vomiting. However, Moussa ultimately said he still doesn't "shed a tear" for DMAA because there is still evidence the ingredient, which is 3.5-times more potent than ephedrine in terms of vessel-narrowing ability,  can do serious harm to the heart and brain. " And if you look around or ask people at the gym you will get tons of anecdotal evidence that even those who initially enjoyed the short-lived energy burst eventually realized that chronic use and the necessity to take more and more of an increasingly useless stimulant will overtax your central nervous system and eventually send you right down into the abyss of over training and chronic fatigue," he added.

(Note: See more about the roundtable here.)

For further evidence of the waning market for DMAA, the word from supplement liability insurers is coverage for DMAA supplements is increasingly difficult to secure. Greg Doherty, practice leader of the dietary supplement insurance division of Poms & Associates, said insurers were quick to create DMAA exclusions in their supplement policies after finding increasingly negative information on the ingredient. He noted ephedra's fall began when insurers excluded it, but were still left paying millions in ephedra claims after FDA banned the herb.