ECA stack

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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 and the Netherlands due to reports of heart attack, stroke, and death associated with these supplements. [1] [2]

Contents

Use as a supplement

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. [3] A meta-analysis combining results from all available studies estimated average weight loss of 1 kg/month more than placebo. [4] There is insufficient evidence to support use of ephedra for athletic performance. [4]

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. [5] 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." [4]

Dosage

Clinical trials indicate that the most effective dose is approximately 20mg of ephedrine and 200mg of caffeine, [6] while the most effective dose of aspirin has not been well-studied.[ citation needed ] However, this dosage has not been recommended by regulatory agencies such as the FDA and do not take into consideration mitigation of adverse side effects. [7]

Mechanism of action

The effects of the ECA stack on weight loss are primarily due to the ephedrine component. Ephedrine acts both as an α and β adrenergic agonist, stimulating the release of norepinephrine. [8] Increased circulating norepinephrine in the body then acts on brown adipose tissue and skeletal muscle [9] by increasing cyclic adenosine monophosphate (cAMP) levels. This causes a thermogenic effect, raising bodily heat production and increasing energy consumption in conjunction with the rest of the stack.

However, the body's negative feedback systems quickly activate to normalize metabolism. [10] [7] This takes the form of elevated phosphodiesterase enzyme activity within the cells, as well as prostaglandin release in the synaptic junctions; both of these degrade cAMP and mitigate the thermogenic effects. [10] Adenosine release in the brain additionally speeds the breakdown of cAMP. [10] Caffeine inhibits the production of phosphodiesterase inside the cell and therefore slows the degradation of cAMP. [7] It also binds with and competitively inhibits adenosine receptors in the brain, triggering the release of epinephrine and increasing cAMP levels further. [11] Aspirin inhibits prostaglandin production outside of the cells, which, in conjunction with caffeine, greatly prolongs the thermogenic effects and increased metabolism by sustaining elevated cAMP levels. [10]

Additionally, Ephedrine acts as an anorectic, or appetite-suppressing drug. However, the anorectic effect becomes less pronounced over time, as the body becomes tolerant of ephedrine to some degree. An estimated 75% of the efficacy of the ECA stack can be attributed to decreased appetite, while the remaining 25% is due to the thermogenic effects of the stack. [12]

The stimulating effects of caffeine and ephedrine are an additional contributing factor to weight loss. The stack's effect on the central nervous system results in increased aerobic exercise performance, measured as time until exhaustion relative to respiratory metrics. [13]

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. [1] 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. [14]

A Congressional report said that 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. [15]

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. [2]

As of June 28, 2024 all provinces and territories require single-ingredient ephedrine and pseudoephedrine products in retail settings to be sold behind the counter in pharmacies, and by pharmacists (or, in some cases, also by individuals working under the supervision of a pharmacist, such as pharmacy technicians), to prevent their misuse and diversion for unlawful purposes. https://www.canada.ca/en/health-canada/services/drugs-health-products/natural-non-prescription/regulation/interim-order-sale-certain-products-containing-ephedrine-pseudoephedrine/explanatory-note.html

Status 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. [16] That product's marketing was discontinued in 2002 upon the same sort of adverse reports seen in other countries. [16]

Related Research Articles

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Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class and is the most commonly consumed psychoactive substance globally. It is mainly used for its eugeroic, ergogenic, or nootropic properties. Caffeine acts by blocking binding of adenosine at a number of adenosine receptor types, inhibiting the centrally depressant effects of adenosine and enhancing the release of acetylcholine. Caffeine has a three-dimensional structure similar to that of adenosine, which allows it to bind and block its receptors. Caffeine also increases cyclic AMP levels through nonselective inhibition of phosphodiesterase, increases calcium release from intracellular stores, and antagonises GABA receptors, although these mechanisms typically occur at concentrations beyond usual human consumption.

<span class="mw-page-title-main">Herbal tea</span> Beverage made from infusing or decocting plant material in hot water

Herbal teas, technically known as herbal infusions, and less commonly called tisanes, are beverages made from the infusion or decoction of herbs, spices, or other plant material in hot water. Often herb tea, or the plain term tea, is used as a reference to all sorts of herbal teas. Many herbs used in teas/tisanes are also used in herbal medicine and in folk medicine.

<span class="mw-page-title-main">Pseudoephedrine</span> Pharmaceutical drug

Pseudoephedrine, sold under the brand name Sudafed among others, is a sympathomimetic medication which is used as a decongestant to treat nasal congestion. It has also been used off-label for certain other indications, like treatment of low blood pressure. At higher doses, it may produce various additional effects, including psychostimulant, appetite suppressant, and performance-enhancing effects. In relation to this, non-medical use of pseudoephedrine has been encountered. The medication is taken by mouth.

<span class="mw-page-title-main">Ephedrine</span> Medication and stimulant

Ephedrine is a central nervous system (CNS) stimulant and sympathomimetic agent that is often used to prevent low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred treatment. It is of unclear benefit in nasal congestion. It can be taken by mouth or by injection into a muscle, vein, or just under the skin. Onset with intravenous use is fast, while injection into a muscle can take 20 minutes, and by mouth can take an hour for effect. When given by injection, it lasts about an hour, and when taken by mouth, it can last up to four hours.

<span class="mw-page-title-main">Ephedra (medicine)</span> Medicinal preparation from the plant Ephedra sinica

Ephedra is a medicinal preparation from the plant Ephedra sinica. Several additional species belonging to the genus Ephedra have traditionally been used for a variety of medicinal purposes, and are a possible candidate for the soma plant of Indo-Iranian religion. It has been used in traditional Chinese medicine, in which it is referred to as Ma Huang, for more than 2,000 years. Native Americans and Mormon pioneers drank a tea brewed from other Ephedra species, called "Mormon tea" and "Indian tea".

An anorectic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss. These substances work by affecting the central nervous system or certain neurotransmitters to create a feeling of fullness or reduce the desire to eat. The understanding of anorexiant effects is crucial in the development of interventions for weight management, eating disorders, and related health concerns. The anorexiant effect can be induced through diverse mechanisms, ranging from hormonal regulation to neural signaling. Ghrelin, leptin, and peptide YY are among the hormones involved in appetite control. Additionally, neurotransmitters such as serotonin and dopamine in the central nervous system contribute significantly to the regulation of food intake.

<span class="mw-page-title-main">Anti-obesity medication</span> Class of pharmacological agents

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<span class="mw-page-title-main">Sibutramine</span> Appetite suppressant

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An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term complication is similar to adverse effect, but the latter is typically used in pharmacological contexts, or when the negative effect is expected or common. If the negative effect results from an unsuitable or incorrect dosage or procedure, this is called a medical error and not an adverse effect. Adverse effects are sometimes referred to as "iatrogenic" because they are generated by a physician/treatment. Some adverse effects occur only when starting, increasing or discontinuing a treatment. Using a drug or other medical intervention which is contraindicated may increase the risk of adverse effects. Adverse effects may cause complications of a disease or procedure and negatively affect its prognosis. They may also lead to non-compliance with a treatment regimen. Adverse effects of medical treatment resulted in 142,000 deaths in 2013 up from 94,000 deaths in 1990 globally.

Thermogenic means tending to produce heat, and the term is commonly applied to drugs which increase heat through metabolic stimulation, or to microorganisms which create heat within organic waste. Approximately all enzymatic reaction in the human body is thermogenic, which gives rise to the basal metabolic rate.

<span class="mw-page-title-main">Sports nutrition</span> Study and practice of nutrition to improve performance

Sports nutrition is the study and practice of nutrition and diet with regards to improving anyone's athletic performance. Nutrition is an important part of many sports training regimens, being popular in strength sports and endurance sports. Sports nutrition focuses its studies on the type, as well as the quantity of fluids and food taken by an athlete. In addition, it deals with the consumption of nutrients such as vitamins, minerals, supplements and organic substances that include carbohydrates, proteins and fats.

Hydroxycut is a brand of dietary supplements that is marketed as a weight loss aid. Hydroxycut was originally developed and manufactured by MuscleTech Research and Development; MuscleTech was sold to Iovate Health Sciences in 2003–2004 and declared bankruptcy in 2005; Iovate continues to use MuscleTech as a brand to market Hydroxycut.

Dexatrim is an over-the-counter (OTC) dietary supplement meant to assist with weight loss. Dexatrim claims it "gives you the power to lose weight, curb binges, and keep you in control of your diet." Current Dexatrim products available are in capsule form and include Dexatrim Max Complex 7, Dexatrim Max Daytime Appetite Control, Dexatrim Natural Green Tea, and Dexatrim Natural Extra Energy. The major active ingredients found in current Dexatrim products include caffeine, green tea extract, Asian (Panax) ginseng root extract, and dehydroepiandrosterone (DHEA).

Metabolife International, Inc. was a multi-level marketing company based in San Diego, California which manufactured dietary supplements. Metabolife's best-selling product, an ephedra supplement called Metabolife 356, once generated hundreds of millions of dollars in annual sales. However, Metabolife 356 and other ephedra-containing supplements were linked to thousands of serious adverse events, including deaths, which caused the U.S. Food and Drug Administration (FDA) to ban the sale of ephedra-containing dietary supplements in 2004.

<span class="mw-page-title-main">Methylhexanamine</span> Chemical compound

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<span class="mw-page-title-main">Weight management</span> Techniques for maintaining body weight

Weight management refers to behaviors, techniques, and physiological processes that contribute to a person's ability to attain and maintain a healthy weight. Most weight management techniques encompass long-term lifestyle strategies that promote healthy eating and daily physical activity. Moreover, weight management involves developing meaningful ways to track weight over time and to identify the ideal body weights for different individuals.

<span class="mw-page-title-main">Methylephedrine</span> Chemical compound

Methylephedrine, sold under the brand name Metheph among others, is a sympathomimetic medication described as an antiasthmatic agent and used to treat coughing and nasal congestion. It is reported to be used in various over-the-counter cough and cold preparations throughout the world, including Japan.

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Tedral, or theophylline/ephedrine/phenobarbital, is a medicine formerly used to treat respiratory diseases such as asthma, chronic obstructive lung disease (COPD), chronic bronchitis, and emphysema. It is a combination drug containing three active ingredients - theophylline, ephedrine, phenobarbital. This medication relaxes the smooth muscle of the airways, making breathing easier. The common side effects of Tedral include gastrointestinal disturbances, dizziness, headache and lightheadedness. However, at high dose, it may lead to cardiac arrhythmias, hypertension, seizures or other serious cardiovascular and/or central nervous system adverse effects. Tedral is contraindicated in individuals with hypersensitivity to theophylline, ephedrine and/or phenobarbital. It should be also used in caution in patients with cardiovascular complications, such as ischemic heart disease and heart failure and/or other disease conditions. It can cause a lot of drug–drug interactions. Therefore, before prescribing patient with Tedral, drug interactions profile should be carefully checked if the patient had other concurrent medication(s). Being used as a treatment option for respiratory diseases for decades, Tedral was withdrawn from the US market in 2006 due to safety concerns.

References

  1. 1 2 "Dietary Supplements Containing Ephedrine Alkaloids". U.S. Food and Drug Administration. August 22, 2006. Retrieved July 7, 2009.
  2. 1 2 "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.
  3. ↑ Daly, P. A.; Krieger, D. R.; Dulloo, A. G.; Young, J. B.; Landsberg, L. (1993). "Ephedrine, caffeine and aspirin: Safety and efficacy for treatment of human obesity". International Journal of Obesity and Related Metabolic Disorders. 17 (Suppl 1): S73–8. PMID   8384187.
  4. 1 2 3 Shekelle, Paul G.; Hardy, Mary L.; Morton, Sally C.; Maglione, Margaret; Mojica, Walter A.; Suttorp, Marika J.; Rhodes, Shannon L.; Jungvig, Lara; Gagné, James (2003). "Efficacy and Safety of Ephedra and Ephedrine for Weight Loss and Athletic Performance". JAMA. 289 (12): 1537–45. doi:10.1001/jama.289.12.1470. PMID   12672771.
  5. ↑ Haller, Christine A.; Benowitz, Neal L. (2000). "Adverse Cardiovascular and Central Nervous System Events Associated with Dietary Supplements Containing Ephedra Alkaloids". New England Journal of Medicine. 343 (25): 1833–1838. doi: 10.1056/NEJM200012213432502 . PMID   11117974. S2CID   76588785.
  6. ↑ Astrup, A.; Toubro, S. (1993). "Thermogenic, metabolic, and cardiovascular responses to ephedrine and caffeine in man". International Journal of Obesity and Related Metabolic Disorders. 17 (Suppl 1): S41-3. PMID   8384179.
  7. 1 2 3 Powers, M. E. (2001). "Ephedra and its application to sport performance: another concern for the athletic trainer?". Journal of Athletic Training . 36 (4): 420–424. PMC   155439 . PMID   16558668.
  8. ↑ Merck Manuals > EPHEDrine Archived 2011-03-24 at the Wayback Machine Last full review/revision January 2010
  9. ↑ Astrup, A.; Bülow, J.; Madsen, J.; Christensen, N. J. (1985). "Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man". American Journal of Physiology . 248 (5 Pt1): E507-515. doi:10.1152/ajpendo.1985.248.5.E507. PMID   3922230.
  10. 1 2 3 4 Dulloo, A. G. (1993). "Ephedrine, xanthines and prostaglandin-inhibitors: actions and interactions in the stimulation of thermogenesis". International Journal of Obesity and Related Metabolic Disorders. 17 (Suppl 1): S35-40. PMID   8384178.
  11. ↑ Chen, Jiang-Fan; Eltzschig, Holger K.; Fredholm, Bertil B. (2013). "Adenosine receptors as drug targets--what are the challenges?". Nature Reviews Drug Discovery . 12 (4): 265–286. doi:10.1038/nrd3955. PMC   3930074 . PMID   23535933.
  12. ↑ Astrup, Arne; Toubro, Søren; Christensen, Niels Juel; Quaade, Flemming (1992). "Pharmacology of thermogenic drugs". American Journal of Clinical Nutrition . 55 (1 Suppl): 246S–8S. doi: 10.1093/ajcn/55.1.246s . PMID   1345887.
  13. ↑ Bell, D. G.; Jacobs, I.; Zamecnik, J. (April 1998). "Effects of caffeine, ephedrine and their combination on time to exhaustion during high-intensity exercise". European Journal of Applied Physiology and Occupational Physiology. 77 (5): 427–433. doi:10.1007/s004210050355. PMID   9562293. S2CID   22465706.
  14. ↑ "Erowid Ephedrine Vault : Legal Status".
  15. ↑ Minority Staff Report, Special Investigations Division "Adverse Event Reports from Metabolife"
  16. 1 2 Hallas, J.; Bjerrum, L.; Stovring, H.; Andersen, M. (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. PMC   2565736 . PMID   18756018.
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