Author Affiliations: Department of Medicine, Harvard Medical School, Cambridge Health Alliance, Somerville, Massachusetts.
The pharmaceutical amphetamine derivative 1,3-dimethylamylamine (DMAA) was introduced in 1948 as a nasal inhaler for rhinitis by Eli Lilly & Co. By the 1970s, it had been withdrawn as an approved pharmaceutical. Surprisingly, DMAA is currently used as an ingredient in roughly 200 sports supplements, many sold in major franchises throughout the United States, with sales topping $100 million in 2010 alone (Table).1- 4
For DMAA to be legally sold as a dietary supplement, it must be a naturally occurring substance with a documented history of use prior to 1994. Remarkably, the evidence to support the sale of DMAA-containing supplements hinges on a single study.5 In this 1 study, published in the now defunct Journal of the Guizhou Institute of Technology, geranium oil (extracted from the fresh leaves and stems of Pelargonium graveolens) was found to contain less than 0.7% DMAA based on a gas chromatography and mass spectrometry analysis. The researchers do not describe their methodology but presumably based their conclusions on matching an unknown peak spectrum of geranium oil with the library mass spectrum of DMAA. The appropriate confirmatory test, using a standardized preparation of DMAA to confirm its presence, was not described.
Since the publication of this study, more than a half-dozen peer-reviewed reports have been unable to confirm this finding.6 Health Canada, for one, has concluded that “there is no credible scientific evidence that DMAA is captured as an isolate of a plant.”6 This lack of evidence has not deterred multiple supplement companies from marketing DMAA as if it were isolated from geranium. For example, the popular Jack3d product (USPlabs) sold at GNC (General Nutrition Centers) is labeled as containing “1,3-dimethylamylamine (Geranium [Stem])” (label available from the author on request).
Given its wide availability, physicians should understand DMAA's potential health effects. Supplements containing DMAA have been implicated as potentially contributing agents in multiple serious adverse events, including panic attacks, seizures, stress-induced cardiomyopathy,7 and 2 deaths.2 In Europe and New Zealand, DMAA use as a party drug has been implicated in at least 1 hemorrhagic stroke.8 Causality has yet to be proven, but these adverse effects are consistent with DMAA's known pharmacologic actions. In The Dispensatory of the United States of America 1950 Edition,9 DMAA's systemic toxic effects in animals was described as “greater than that of ephedrine and less than that of amphetamine,”9(p2049) and the authors counseled that if DMAA's use as a nasal inhaler “produces side effects such as headache, nervousness, mental stimulation, or tremors, the drug should be discontinued.”9(p2049) Small trials have also demonstrated that DMAA-containing supplements increase blood pressure and heart rate.10
Last summer, Health Canada banned DMAA from all supplements,6 and last December, the US military removed DMAA-containing supplements from all military exchanges worldwide (Table).1 In late April 2012, 6 years after DMAA had been introduced as a dietary supplement, the US Food and Drug Administration (FDA) sent warning letters to 10 manufacturers requiring them to provide evidence to support their conclusion that DMAA is a safe supplement ingredient.11 Given that DMAA is a potentially dangerous ingredient and that manufacturers' claims that it is naturally derived are unsubstantiated, manufacturers and distributors should immediately recall all DMAA-containing supplements.
The extensive mainstream sales of DMAA combined with the FDA's delayed response expose the potentially serious public health risks entailed when consuming new supplement ingredients.
Correspondence: Dr Cohen, Harvard Medical School, Cambridge Health Alliance, 236 Highland Ave, Somerville, MA 02143 (firstname.lastname@example.org).
Published Online: May 7, 2012. doi:10.1001/archinternmed.2012.1677. Corrected May 14, 2012.
Financial Disclosure: None reported.
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