The ECA stack is a drug combination used in weight loss and as a
stimulant
Stimulants (also known as central nervous system stimulants, or psychostimulants, or colloquially as uppers) are a class of drugs that increase alertness. They are used for various purposes, such as enhancing attention, motivation, cognition, ...
. ECA is an initialism for
ephedrine
Ephedrine is a central nervous system (CNS) stimulant and sympathomimetic agent that is often used to prevent hypotension, low blood pressure during anesthesia. It has also been used for asthma, narcolepsy, and obesity but is not the preferred ...
,
caffeine
Caffeine is a central nervous system (CNS) stimulant of the methylxanthine chemical classification, class and is the most commonly consumed Psychoactive drug, psychoactive substance globally. It is mainly used for its eugeroic (wakefulness pr ...
, and
aspirin
Aspirin () is the genericized trademark for acetylsalicylic acid (ASA), a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and inflammation, and as an antithrombotic. Specific inflammatory conditions that aspirin is ...
, with variants of it including the EC stack, which removes the aspirin for those who can not tolerate it.
Dietary supplements
A dietary supplement is a manufactured product intended to supplement a person'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 ...
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 (USA), also known as the United States (U.S.) or America, is a country primarily located in North America. It is a federal republic of 50 U.S. state, states and a federal capital district, Washington, D.C. The 48 ...
and the
Netherlands
, Terminology of the Low Countries, informally Holland, is a country in Northwestern Europe, with Caribbean Netherlands, overseas territories in the Caribbean. It is the largest of the four constituent countries of the Kingdom of the Nether ...
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, considered by multiple organizations to be a disease, in which excess body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classified as obese when ...
. 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. 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, stimulating the release of
norepinephrine
Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...
.
[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, or cellular signal occurring within cells, that is important in many biological processes. cAMP is a derivative of adenosine tri ...
(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 human ...
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 oth ...
enzyme activity within the cells, as well as
prostaglandin
Prostaglandins (PG) are a group of physiology, physiologically active lipid compounds called eicosanoids that have diverse hormone-like effects in animals. Prostaglandins have been found in almost every Tissue (biology), tissue in humans and ot ...
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 build ...
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 is a drug that 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 desi ...
, 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 use, recreational or Performance-enhancing substance, performance-enhancing drug and less commonly as a secon ...
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 a person's diet by taking a pill (pharmacy), pill, capsule (pharmacy), capsule, tablet (pharmacy), tablet, powder, or liquid. A supplement can provide nutrients eithe ...
.
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.
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.
[Minority Staff Report, Special Investigations Division "Adverse Event Reports from Metabolife"](_blank)
/ref>
Status in Canada
In January 2002, Health Canada
Health Canada (HC; )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 units, department of the Gove ...
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.
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.
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