Final FDA warning letter delivers DMAA KO

In April 2013, FDA delivered the final blow: a public warning to consumers on the dangers of DMAA that included comments showing the agency is pushing to remove the ingredient from the market.

"The Food and Drug Administration (FDA) is using all available tools at its disposal to ensure that dietary supplements containing a stimulant called dimethylamylamine (DMAA) are no longer distributed and available for sale to consumers in the marketplace," the agency wrote.

The newest statement follows a series of warning letters the agency sent to DMAA marketers in April 2012 that called the ingredient synthetic and illegal for use in dietary supplements.

Since the original warning letters, most companies removed products containing DMAA from their shelves or reformulated them with DMAA alternatives. And now, USPlabs, maker of sports supplement Jack3d and the one company left fighting for DMAA, has thrown in the towel.

In an April 16 press release, USPlabs said it still believes DMAA is both legal and safe as a dietary supplement, but the company plans to phaseout products containing DMAA and replace them with new formulations for business reasons. "Despite being among the most studied ingredients ever with 11 published peer-reviewed clinical and analytical studies, the FDA has urged the industry to discontinue the use of 1,3-DMAA in dietary supplements," the company said, in the press release, emphasizing it disagrees with FDA's position. The company did not respond to a request for comment.

The No. 1 Issue

"While the letters sent to companies with products containing DMAA identified several issues with DMAA as a dietary ingredient, including that it doesnt meet any of the categories set forth in the definition for dietary supplements in the Federal Food, Drug and Cosmetic Act, the number one issue is safety," said Justin Prochnow, shareholder at Greenberg Traurig.

In FDA's most recent warning letter, the agency said it received 86 reports of illnesses and deaths associated with supplements containing DMAA. "While the composition of the ingredient has always been in existence, FDA did not really get involved until the number of adverse event reports (AER) became such that it felt it needed to take action," Prochnow said.

The move comes on the heels of several highly publicized deaths, including London marathoner Claire Squires, allegedly associated with the ingredient. Squires, who collapsed in the final stretches of the 2012 marathon, died of cardiac failure caused by the combination of exertion and DMAA toxicity, according to autopsy reports. The 30-year-old allegedly took Jack3d during the race.

In recent years, the United Kingdom ruled DMAA an unlicensed medicinal product, with New Zealand, Australia, Canada, Ireland and the U.S. military following suit.

USPlabs suffered another hit in February when the parents of a deceased soldier filed a wrongful death lawsuit in California state court against the company. USPlabs and GNC, where 22-year-old Michael Sparling purchased the supplement, have been accused of deceptively marketing Jack3d as safe and effective, failing to warn consumers about the potential health risks. In 2011, Sparling collapsed during a moderate workout with his unit, and died at a hospital several hours later of respiratory failure and cardiac arrest, according to the lawsuit. The soldier was said to have previously taken the recommended dose of Jack3d.

However, retailer GNC does not question the ingredient's safety, according to company spokesperson Laura Brophy. "Pending a recall order on the products from the FDA, GNC will continue selling what inventory we have left of the USPlabs product," she said.

While FDA's warning letter does not constitute agency action, Prochnow said it "indicates that the FDA is prepared to take further action to ensure that all DMAA is removed from dietary supplements."

In the letter, the agency noted among its enforcement tools, warning letters seek voluntary cooperation, which is the quickest way to remove an ingredient or product. However, the agency has also banned products such as ephedra, secured injunctions, conducted seizures, signed consent decrees and pressed criminal charges.

The next Ephedra?

"It's not the first time a comparison between ephedra and DMAA has come up," said Cara Welch, Ph.D., senior vice president of scientific and regulatory affairs, Natural Products Association (NPA). But as far as Welchand many other industry leadersare concerned, it should be the last time.

Originally used to treat asthma and bronchitis in Traditional Chinese Medicine (TCM), ephedra became a highly sought after dietary supplement ingredient in the 1990s for energy, weight loss and sports performance. However, FDA banned the ingredient in 2004 after countless reports of ephedra toxicity, including serious adverse events such as stroke, heart attack and death.

 "Ephedra was a legitimate dietary ingredient made from a botanical," Welch said, noting FDA's ban hinged on the ingredient's clear safety issue. "DMAA is on the flip side of thatwe're not sure of the safety, but it's clear it is not a dietary ingredient."

The $100,000 question

While ephedra was an established botanical ingredient, DMAA's origins aren't as obvious. In fact, USPlabs among other companies spent considerable time and resources trying to prove the stimulant is naturally occurring in geranium.

In the latest study commissioned by the company, University of Memphis researchers found 1,3 and 1,4 DMAA were present in geranium plants from three distinct Chinese regions using HPLC-MS (high-performance liquid chromatographymass spectrometry) analysis. The study authors concluded "1,3 DMAA could be a natural product extract;" however, DMAA supplements would still not quality for geranium oil's new dietary ingredient (NDI) exemption, explained Marc Ullman, partner, Ullman Shapiro & Ullman.

"Among the multitude of problems with DMAA is the significant question as to whether or not if even qualifies as a dietary ingredient in the first place," he said.

But at this point, Ullman explained, pursuing the issue would be an "insurmountable hurdle." Dietary supplement marketers would be putting themselvesand their customersat risk to still include the ingredient in their products.

"While there is no specific prohibition against using DMAA, with the FDAs position known to severely disfavor it, it has become a situation in which the potential risks, I would think, outweigh the potential benefits of selling  a product with DMAA," Prochnow said.

So is this the end of DMAA? It seems so.

"People aren't going to fight for DMAA anymore," Welch said. "As far as the industry and FDA is concerned, this is not a dietary ingredient, and it's not allowed in dietary supplements."

The next contender

When a publicized ingredient falls out of favor, companies often want to capitalize on the opening with the latest ingredient.   

Whatever that may be, Welch said the growing dietary supplement industry must keep safety at the forefront. "Resources and technology provide options, companies just need to make sure those options fit within the regulatory regime."

And "FDA is on red alert" for new versions of DMAA and spiked supplements, Ullman pointed out. His advice is simple: "Make sure what you're selling is legal."