Nutrex Responds to FDA DMAA Warning Letter

OVIDEO, Fla.Nutrex Research Inc. said it "vigorously disagrees with FDAs allegations" that its DMAA products are sold illegally in the United States, in an April 30, 2012, response to a warning letter sent by FDA. On May 11, Nutrex's sent a longer response to FDA, saying, "Nutrex firmly believes that dietary supplements containing DMAA as a dietary ingredient have always been and would continue to be, lawful products."

The warning letter sent to Nutrex was one of 10 FDA sent on April 24, 2012, to companies marketing products that contain DMAA.

Both responses to FDA were sent by Frederick A. Stearns, attorney at Keller and Heckman LLP, on behalf of Nutrex. In the first, shorter response, Stearns said Nutrexs dietary supplements are marketed lawfully, but the company reformulated and removed DMAA from its products. However, Stearns said this doesn't mean the company won't use DMAA in the future.

"Nutrex takes very seriously its ongoing responsibility to assure compliance with the FDA requirements that apply to its operations, and believes that it acted entirely properly and legally with respect to the products cited in the warning letter," Stearns wrote in the second letter.

 In the April 24, 2012, warning letter FDA said Nutrex Research Inc.'s products Hemo Rage Black, Lipo-6 Black Ultra Concentrate, Lipo-6 Black, Lipo-6 Black Hers Ultra Concentrate and Lipo-6 Black Hers were adulterated because they contained DMAA, listed as both  1,3- dimethylamylamine HCl and methylhexaneamine on the labels.

Food Supply

The agency said no information demonstrates that DMAA was marketed as a dietary ingredient in the United States before Oct. 15, 1994, nor is there information demonstrating that it is present in the food supply. Therefore, the agency said the company should have submitted a new dietary ingredient (NDI) notification, but it did not, so FDA considers the products adulterated.

Nutrex countered by saying DMAA is a component of geranium oil, which has been used in food for centuries. The company pointed to the 1996 Ping, et al., study  (Journal of Guizhou Institute of Technology. 1996 Feb;25(1):82-85.) that identified DMAA as a component of  geranium oil. Although the company noted the results of that analysis have been criticized recently, "those criticisms are unfounded, and a close examination of the Ping, et al., study shows that its original conclusions were correct." Nutrex also pointed to a Cantox Health Sciences International analysis (commissioned by DMAA marketer USPLabs) that demonstrated the occurrence of DMAA in the geranium plant. Nutrex said USPLabs is currently in the process of having these data prepared for and submitted to peer-reviewed journals for publication. Because DMAA has been a part of the food supply, Nutrex says no NDI notification is necessary to market it in the United States.

Safety

FDA said DMAA has no history of use or other evidence of safety, both of which are required when NDI notifications are submitted to provide reasonable assurance that an ingredient does not present a significant or unreasonable risk of illness or injury.

FDA said DMAA is in fact not safe because it narrows the blood vessels and arteries, which can lead to elevated blood pressure, shortness of breath, tightening of the chest and/or a possible myocardial infarction (heart attack). 

To this, Nutrex offered seven studies that it said support the view that DMAA is reasonably expected to be safe under its intended conditions of use. The seven studies are:

Further, Nutrex pointed to the millions of doses that consumers have used over the years to show when used as directed, dietary supplements containing DMAA have a record of safety.

Synthetic Botanical

Thirdly, FDA said Nutrex's DMAA products may be produced synthetically, which the agency says is illegal for sale in the United States. "Dietary ingredient," according to FDA, is defined as "a vitamin, mineral, amino acid, herb or other botanical or dietary substance for use by man to supplement the diet by increasing the total dietary intake, or a concentrate, metabolite, constituent, extract or combination of any dietary ingredient from the preceding categories." Synthetically produced DMAA does not fall into one of these categories, according to FDA, and is therefore, not a dietary ingredient and is not allowed for sale in the United States.

However, Nutrex said FDA is "demonstrably wrong" on two  points:(1) that a substance must have been commonly used as human food or drink" to be a dietary ingredient" and (2) that synthetic forms of naturally occurring substances cannot be dietary ingredients.

Nutrex said FDA's position that "dietary substance" means a substance that is commonly used as human food or drink is at odds with the legislative history of the Dietary Supplement Health and Education Act of 1994 (DSHEA). The company said Congress used the clause, dietary substance for use by man to supplement the diet by increasing the total dietary intake" to broaden, rather than limit, the scope of permitted dietary ingredients. This provision is a "catch-all," according to Nutrex, which FDA acknowledged in its preamble to regulation on nutrient content claims, health claims and statements of nutritional support for dietary supplements. In that, FDA included a list of items and foods that would fall under the other similar nutritional substances category, such as primrose oil, black currant seed oil, coldpressed flax seed oil  and coenzyme Q 10 (CoQ10). Nutrex said many of these ingredients were not commonly used in human food or drink.

Second, Nutrex said the definition of dietary ingredient" provides no basis for distinguishing between natural and nature-equivalent synthetic versions of the same substance. "When Congress wished to distinguish between dietary ingredients on the basis of how they were derived, it knew how to do so and used appropriate language (e.g., referring to foods that have not been chemically altered" in the new dietary ingredient definition of FDC Act § 413)," Stearns wrote in Nutrex's response to FDA.

Nutrex said FDA has explicitly acknowledged that it is permissible for dietary supplements to  contain synthetic dietary ingredients in the preamble to the final rule on nutrition labeling for dietary supplements. In that, FDA stated, dietary supplements can include natural and synthetic vitamins," and prohibited product labels that say a natural vitamin in a food is superior to an added or synthetic one." Further, Nutrex said FDA has acknowledged that folic acid, vitamin E and conjugated linoleic acid (CLA) may be synthetically derived and marketed as dietary ingredients.