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The ECA stack is a drug combination used in weight loss and as a stimulant. ECA is an initialism for ephedrine, caffeine, and aspirin, with variants of it including the EC stack, which removes the aspirin for those who can not tolerate it. Dietary supplements based on or including elements of ECA were popular through the 1990s and early 2000s, but the marketing of ephedra- or ephedrine-containing stimulant combinations for weight loss and bodybuilding is now restricted or illegal in the United States, Canada and Netherlands due to reports of heart attack, stroke, and death associated with these supplements.
While it was available as a supplement, ECA was marketed with claims that it would aid weight loss, improve athletic performance and increase "energy".
Placebo-controlled studies have consistently found ephedrine in combination with caffeine to be effective in promoting moderate fat loss in the already-obese. Herbal supplements containing Ephedra aka Ma Huang - with or without caffeine - have similarly been demonstrated to be effective without significantly increased risk of adverse effects in studies ranging from 8 weeks to 6 months in length. A meta-analysis combining results from all available studies estimated average weight loss of 1 kg/month more than placebo.
There is insufficient evidence to support use of ephedra for athletic performance.
Natural supplements that contain ephedra (aka Ma Huang) as an ephedrine substitute have been linked to cases of heart attack, stroke, and death in healthy young adults even when taken at the labeled dosage. Evidence of serious harm is based only on self-reports of uncontrolled use by supplement users; when EC has been used as medically prescribed or in controlled studies, evidence of cardiovascular risk has not been proven.
A 2003 meta-analysis of all available studies and case reports concluded that:
ephedrine- and ephedra-containing dietary supplements [...] have harms in terms of a 2- to 3-fold increase in psychiatric symptoms, autonomic symptoms, upper gastrointestinal symptoms, and heart palpitations. More serious adverse effects from ephedra use cannot be excluded at a rate less than 1.0 per thousand, and case reports raise the possibility that a causal relationship with serious adverse events may exist.
A more recent (2008) case-crossover study that focused on the alleged cardiovascular risks concluded that:
prescription of an ephedrine/caffeine product was not associated with adverse cardiovascular outcomes. This was found across a wide range of patient subgroups, different cardiovascular outcomes, different assumptions about exposure, and different utilization patterns.
However, when an ephedra supplement company, Metabolife, in the USA was forced to release adverse event reports, cardiac and psychological reports were recorded in healthy young people at normal dosages.
Use in Denmark
An EC formulation called Letigen which combined 20 mg of synthetic ephedrine and 200 mg of caffeine (recommended dose: 1-3 pills per day depending on user tolerance) was approved for sale by prescription in Denmark in 1990. During the peak of its use (in 1999) roughly 2% of the Danish population was using it. That product's marketing was discontinued in 2002 upon the same sort of adverse reports seen in other countries but in 2008, a huge follow-up case-study failed to find any evidence of cardiovascular risk.
Due to deaths linked to ephedra-containing dietary supplements and the potential use of ephedrine as a precursor in illegal methamphetamine manufacture, many countries have taken steps to regulate these products.
Status in The United States
In the United States, it is illegal to market products containing ephedrine or ephedra alkaloids as a dietary supplement. In 2004, ephedra, a botanical source of ephedrine alkaloids, was banned by the U.S. Food and Drug Administration due to serious safety concerns, injuries, and deaths linked to ephedra-containing supplements. However, ephedrine itself has never been illegal in the United States and is currently available over-the-counter. Reporting requirements and quantity limitations vary by state.
Status in Canada
In January 2002, Health Canada issued a voluntary recall of all ephedrine products containing more than 8 mg per dose, all combinations of ephedrine with other stimulants such as caffeine, and all ephedrine products marketed for weight-loss or bodybuilding indications, citing a serious risk to health.
- "Dietary Supplements Containing Ephedrine Alkaloids". U.S. Food and Drug Administration. August 22, 2006. Retrieved July 7, 2009.
- "Health Canada requests recall of certain products containing Ephedra/ephedrine". Health Canada. January 9, 2002. Archived from the original on February 6, 2007. Retrieved July 7, 2009.
- Daly PA, Krieger DR, Dulloo AG, Young JB, Landsberg L (1993). "Ephedrine, caffeine and aspirin: safety and efficacy for treatment of human obesity". Int. J. Obes. Relat. Metab. Disord. 17 Suppl 1: S73–8. PMID 8384187.
- Boozer CN, Daly PA, Home P, Solomon JL, Blanchard D, Nasser JA, Strauss R, Meredith T (2002). "Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial". Int J Obes 26 (5): 593–604. doi:10.1038/sj/ijo/0802023.
In total, these suggest that herbal ephedra/caffeine herbal supplements, when used as directed by healthy overweight men and women in combination with healthy diet and exercise habits, may be beneficial for weight reduction without significantly increased risk of adverse events.
- Boozer CN, Nasser JA, Heymsfield SB, Wang V, Chen G, Solomon JL (2001). "An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial". Int. J. Obes. Relat. Metab. Disord. 25: 316–24. doi:10.1038/sj.ijo.0801539. PMID 11319627.
- Paul G. Shekelle, MD, PhD; Mary L. Hardy, MD; Sally C. Morton, PhD; Margaret Maglione, MPP; Walter A. Mojica, MD, MPH; Marika J. Suttorp, MS; Shannon Lt "prescription of an ephedrine/caffeine product was not associated with adverse cardiovascular outcomes. This was found across a wide range of patient subgroups, different cardiovascular outcomes, different assumptions about exposure, and different utilization pattern. Rhodes, MFA; Lara Jungvig, BA; James Gagné, MD "Efficacy and Safety of Ephedra and Ephedrine for Weight Loss and Athletic Performance: A Meta-analysis" JAMA. 2003;289:1537-1545
- "The use of dietary supplements that contain ephedra alkaloids may pose a health risk to some persons. These findings indicate the need for a better understanding of individual susceptibility to the adverse effects of such dietary supplements." Christine A. Haller, M.D., and Neal L. Benowitz, M.D. "Adverse Cardiovascular and Central Nervous System Events Associated with Dietary Supplements Containing Ephedra Alkaloids" New England Journal of Medicine, Volume 343:1833-1838 12/21/2000, Number 25
- Hallas Jesper; Bjerrum Lars; Støvring Henrik; Andersen Morten (2008). "Use of a Prescribed Ephedrine/Caffeine Combination and the Risk of Serious Cardiovascular Events: A Registry-based Case-Crossover Study". American Journal of Epidemiology 168 (8): 966–973. doi:10.1093/aje/kwn191.
Prescribed ephedrine/caffeine was not associated with a substantially increased risk of adverse cardiovascular outcomes in this study.
- Minority Staff Report, Special Investigations Division "Adverse Event Reports from Metabolife"