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The ECA stack is a drug combination used in weight loss and as a
stimulant Stimulants (also often referred to as psychostimulants or colloquially as uppers) is an overarching term that covers many drugs including those that increase activity of the central nervous system and the body, drugs that are pleasurable and inv ...
. ECA is an initialism for
ephedrine Ephedrine is a central nervous system (CNS) stimulant 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 ...
,
caffeine Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine t ...
, and
aspirin Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an antithrombotic. Specific inflammatory conditions which aspirin is used to treat inc ...
, 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 The United States of America (U.S.A. or USA), commonly known as the United States (U.S. or US) or America, is a country primarily located in North America. It consists of 50 states, a federal district, five major unincorporated territorie ...
,
Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tot ...
and Netherlands due to reports of heart attack, stroke, and death associated with these supplements.


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 Obesity is a medical condition, sometimes considered a disease, in which excess body fat has accumulated to such an extent that it may negatively affect health. People are classified as obese when their body mass index (BMI)—a person's we ...
. 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 ''Ephedra'' is a genus of gymnosperm shrubs. The various species of ''Ephedra'' are widespread in many arid regions of the world, ranging across southwestern North America, southern Europe, northern Africa, southwest and central Asia, norther ...
'') 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. 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."


Dosage

Clinical trials indicate that the most effective dose is approximately 20mg of ephedrine and 200mg of caffeine, while the most effective dose of aspirin has not been well-studied. However, this dosage has not been recommended by regulatory agencies such as the
FDA The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
and do not take into consideration mitigation of adverse side effects.


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 An adrenergic agonist is a drug that stimulates a response from the adrenergic receptors. The five main categories of adrenergic receptors are: α1, α2, β1, β2, and β3, although there are more subtypes, and agonists vary in specificity between ...
, stimulating the release of
norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...
.Merck Manuals > EPHEDrine
Last full review/revision January 2010
Increased circulating norepinephrine in the body then acts on brown adipose tissue and skeletal muscle by increasing
cyclic adenosine monophosphate Cyclic adenosine monophosphate (cAMP, cyclic AMP, or 3',5'-cyclic adenosine monophosphate) is a second messenger important in many biological processes. cAMP is a derivative of adenosine triphosphate (ATP) and used for intracellular signal transd ...
(cAMP) levels. This causes a
thermogenic 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 huma ...
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. This takes the form of elevated
phosphodiesterase A phosphodiesterase (PDE) is an enzyme that breaks a phosphodiester bond. Usually, ''phosphodiesterase'' refers to cyclic nucleotide phosphodiesterases, which have great clinical significance and are described below. However, there are many ot ...
enzyme activity within the cells, as well as
prostaglandin The prostaglandins (PG) are a group of physiologically active lipid compounds called eicosanoids having diverse hormone-like effects in animals. Prostaglandins have been found in almost every tissue in humans and other animals. They are derive ...
release in the synaptic junctions; both of these degrade cAMP and mitigate the thermogenic effects.
Adenosine Adenosine ( symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building ...
release in the brain additionally speeds the breakdown of cAMP. Caffeine inhibits the production of phosphodiesterase inside the cell and therefore slows the degradation of cAMP. It also binds with and competitively inhibits adenosine receptors in the brain, triggering the release of epinephrine and increasing cAMP levels further. 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. Additionally, Ephedrine acts as an
anorectic An anorectic or anorexic is a drug which reduces appetite, resulting in lower food consumption, leading to weight loss. By contrast, an appetite stimulant is referred to as orexigenic. The term is (from the Greek ''ἀν-'' (an-) = "without" a ...
, 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. 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.


Legal status

Due to deaths linked to ephedra-containing dietary supplements and the potential use of ephedrine as a precursor in illegal
methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamph ...
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 A dietary supplement is a manufactured product intended to supplement one's diet by taking a pill, capsule, tablet, powder, or liquid. A supplement can provide nutrients either extracted from food sources or that are synthetic in order ...
. In 2004,
ephedra Ephedra may refer to: * Ephedra (medicine), a medicinal preparation from the plant ''Ephedra sinica'' * ''Ephedra'' (plant), genus of gymnosperm shrubs See also * Ephedrine Ephedrine is a central nervous system (CNS) stimulant that is of ...
, a botanical source of ephedrine alkaloids, was banned by the
U.S. Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
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. A Congressional report said that when an ephedra supplement company,
Metabolife 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 o ...
, in the USA was forced to release adverse event reports, cardiac and psychological reports were recorded in healthy young people at normal dosages.Minority Staff Report, Special Investigations Division "Adverse Event Reports from Metabolife"
/ref>


Status in Canada

In January 2002,
Health Canada Health Canada (HC; french: Santé Canada, SC)Health Canada is the applied title under the Federal Identity Program; the legal title is Department of Health (). is the Structure of the Canadian federal government#Departments, with subsidiary unit ...
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.


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


References

{{DEFAULTSORT:Eca Stack Dietary supplements Bodybuilding supplements Stimulants