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The Ephedrine/Caffeine/Aspirin "stack" (ECA)



Aug 11, 2010
Let us warn you. This is not your typical, easy-reading, elementary science article. It contains some challenging stuff. We strongly recommend you read it, though, especially if the idea of pharmaceutically aided fat loss appeals to you on any level. Researchers Schmitz and Kneller have taken the now-famous ephedrine/caffeine/aspirin stack and put it under the microscope. Although the stack is undeniably effective, they have some strong reservations regarding its safety. Don't worry, though. They think they've found something far safer, far better, and quite legal. (Hey, we wouldn't ask you to read through complicated stuff if we weren't sure you were going to hit paydirt at the end of the article.)

The Ephedrine/Caffeine/Aspirin "stack" (ECA) has been utilized for over three years by various members of the bodybuilding and fitness community as a fairly effective tool to increase thermogenesis/lipolysis in order to reduce body adipose content. One of the components of ECA, ephedrine, is also found as the active ingredient in many over-the-counter (OTC) recreational drugs (e.g. Herbal Ecstasy®). Additionally, ephedrine has been directly implicated in the deaths of at least 13 people over the last 18 months as well as a substantial number of other Serious Adverse Events (SAE) requiring direct intervention by medical teams in hospital emergency departments across the country.

The sale of raw, bulk ephedrine powder to individuals has also been tightly controlled as this compound can be converted to amphetamine / methamphetamine by those with even a cursory knowledge of chemical synthesis. Recently, the Food and Drug Administration (FDA) has launched an exhaustive investigation regarding the safety of ephedrine and many states have elected to outright ban the OTC sale of it. Additionally, the World Health Organization (WHO) decided that it will recommend that countries change the status of ephedrine from OTC to prescription-only because of safety concerns. It is expected that the WHO will notify the US government of their intentions later this year, which will give the US enough time to take up a position before the United Nations Commission on Narcotic Drugs' annual meeting in 1999. It is the opinion of the authors that ephedrine will no longer be an OTC compound by the year 2000.

Through a review of contemporary literature we elected to ascertain if a suitable replacement for ephedrine or ECA could be found. In evaluating the data, we elected to pursue compounds that fell under certain parameters.

Compound(s) must be:

• legal to possess without a prescription from a health care provider
• fairly inexpensive
• readily obtainable in all US states and territories
• safer for humans than ephedrine
• naturally occurring and not prohibited by law from being sold as food supplements
• thermogenic and/or lipolytic in humans or acceptable mammalian models

Initially, we expected to find chemical entities with some thermogenic/lipolytic potential that approached—but did not equal/exceed—that of ephedrine or ECA. However, after a thorough review of studies in peer-reviewed medical journals, we have identified a common and oft overlooked compound that meets all of the criteria above and in fact, exceeds ephedrine's potential as a thermogenic and lipolytic slimming agent in humans. We have also concluded, based on our review of literature, that complete revision of ECA potentially yields a safer and more efficacious "stack". Before we enter into our discussion of our newly formulated "stack", we feel it necessary to discuss why we feel that ephedrine is an unsuitable compound based on it's relatively poor safety performance.


Ephedrine's {alpha-[1-(methylamino)ethyl]benzene-methanol} role as one of the key components of lipolytic agents sold OTC stems from it's mechanism of action and physiological effects. Ephedrine falls into a class of drugs called "sympathomimetic amines" which exhibit some of the stimulant properties of epinephrine and norepinephrine (Adrenalin and Noradrenaline). Ephedrine imparts a number of physiological effects after oral administration. It stimulates heart rate, contractility and cardiac output; increases blood pressure; increases the resistance to outflow of urine from the bladder; promotes dilation of the bronchioles; and is a potent central nervous system (CNS) stimulant.

These physiological effects account for both ephedrine's effectiveness as a "fat burner" and also for the unacceptably high number of SAEs recorded. A recent query of the Special Nutritionals Adverse Event Monitoring System at the FDA revealed that since 1996 there have been 13 deaths, one transient ischemic attack (stroke like event),three hypertensive crises, three episodes of syncope (passing out) and 5 life-threatening cardiac anomalies. An SAE can be defined as "any adverse drug experience occurring at any dose that results in any of the following outcomes: death or life threatening; persistent or significant disability/incapacity; requires or prolongs hospitalization; imparts a congenital anomaly; or other important events which may jeopardize the subject and may require medical or surgical intervention to prevent one of the above outcomes.

Although it is difficult to "prove" that a drug or medicinal product caused a particular symptom (this is a point the tobacco industry has relied on and abused for years),the close relationship between the known physiological effects and the adverse effects makes a convincing case for ephedrine as the cause in many or most cases of the described SAEs.

Ephedrine is rarely ingested as a pure drug. In the majority of the "stacks" and ephedrine products available in the fitness/weight loss market, a combination of ephedrine alkaloids is present.3 These alkaloids are also naturally-occurring chemical stimulants (e.g. methylephedrine). Although the proportions of these various alkaloids varies in commercial preparations, the most common alkaloid is indeed ephedrine. The source of the alkaloid can vary from a raw botanical; to powdered plant material; to concentrated extract (the majority of preparations).3

In addition to the unstandardized mix of ephedrine alkaloids in any given preparation, most of these supplements contain between 6 and 20 other bioactive ingredients. Some of these other ingredients have known or suspected physiological and pharmacological properties and have potential for interacting with ephedrine alkaloids to increase both the physiologal effects and significantly increase adverse reactions. One of these (caffeine) has been shown to increase the stimulant effect of ephedrine.4 It is well known that for both prescription and OTC medications, that the greater the number of substances, the greater the chance for known and unknown drug interactions.

Substances that have similar mechanisms of action such as ephedrine and caffeine (both CNS and cardiovascular stimulants),taken simultaneously , can have an additive (1 + 1 = 2) or synergistic (1 + 1 = 3) effect. The "buzz" or "rush" that recreational users sometimes get—which might be perceived by an increased heart rate or hyper-alertness—may actually be more of an adverse event. There is often a very narrow therapeutic range between a desired drug effect and an undesired adverse event. Factors known to increase the sensitivity of an individual to sympathomimetic amines (like ephedrine) are shown below.

Factors Influencing Sensitivity to Sympathomimetic Amines

Factor: Age
Example: Children, elderly

Factor: Genetics
Example: Altered metabolism

Factor: Physiologic states
Example: Exercise, underweight

Factor: Dieting practices
Example: Severe caloric or fluid restriction

Factor: Medications and food
Example: Certain antihypertensive medications, monoamine oxidase inhibitors, caffeine or other stimulants

Factor: Diseases
Example: Heart, thyroid or seizsure disorder, high blood pressure, depression, psychiatric conditions, prostate enlargement

The adverse effects associated with ephedrine alkaloids are troublesome for a number of reasons. First, they affect a variety of organ systems (cardiovascular, CNS, gastrointestinal) and have considerable toxicity (see list below). Secondly and perhaps most striking is that the SAEs associated with ephedrine occur in people who are usually quite healthy (see list below). The "typical" person (at least regarding other drugs) in whom adverse events occur are often elderly; infants or young children; male or female; who have known or yet unknown underlying medical problems and who take multiple prescription medications. The typical person experiencing an adverse event related to ephedrine is young, healthy, mostly female, takes no prescription medication and has no underlying medical condition.

It's not too surprising when a 65-year-old man with a known history of severe cardiovascular disease has a heart attack while shoveling the snow from his driveway, but when a 30-year-old woman experiences a massive heart attack, it's noteworthy because we don't expect a healthy 30-year-old to have any of the known risk factors for a heart attack, let alone actually experience a heart attack.

Since 1993, The FDA has received more than 800 reports of illness and injuries associated with the use of more than 100 different dietary supplements that contained—or were thought to contain—ephedrine alkaloids. As previously mentioned, at least 13 deaths associated with ephedrine use have been reported since 1996, mostly in young, otherwise-healthy individuals. Because of concern about the popularity and easy availability of ephedrine alkaloids, and because of the perceived public safety issue, the FDA has called for significant changes in dose, labeling, information to consumers, and duration of use with regards to ephedrine alkaloids. These changes include:

A) Limiting to an 8 mg dose per serving of ephedrine alkaloids.
B) Clearly indicating the potential health hazards on an easily seen label.
C) Limiting the duration of use to seven consecutive days.

An expert panel of physicians, scientists and public health specialists at the FDA, after careful considerations, believe that the above steps are necessary to alert the public and protect the public from potential SAEs associated with regular and chronic ephedrine use.

Serious Adverse Events Associated With Ephedrine Alkaloids

Organ System: Cardiovascular
Signs / Symptoms: Cardiac arrest and DEATH, severe hypertension, heart rhythm disturbances, myocardial infarction, stroke

Organ System: Nervous
Signs / Symptoms: Seizures, psychosis, SUICIDE or suicidal ideation, altered or loss of consciousness

Organ System: Gastrointestinal
Signs / Symptoms: Hepatitis (increased liver enzymes such as transaminases)

Characteristics of SAE's Associated With Ephedrine5

• Cardiovascular and nervous system most commonly affected
• Patterns of symptoms consistent across different populations
• Occurred both in healthy individuals and those with underlying disease
• Majority of events (>75%) occurred in females
• Many signs and symptoms occurred in young adults who are normally at low risk for the described events (e.g. heart attack and stroke)
• 84% of cases reported in people <49 years of age
• 59% of SAEs occurred within 4 weeks of starting; 14% on the first day
• 92% of SAEs occurred in people trying to lose weight or increase energy; 5% for athletic enhancement; 2% for recreational euphoria


Aspirin {salicyclic acid acetate} and it's naturally occurring methyl ester (methyl salicylate)—found in the leaves of Gaultheria procumbrens and on the bark of Betula lenta—have long been used as analgesics, anti-inflammatories, antipyretics and recently as anti-coagulants. The "A" portion of ECA, aspirin has been thought of potentiating the thermogenic and lipolytic properties of both ephedrine and caffeine. Recent research seems to contradict this however. At a study at The University of London's Department of Nutrition and Dietetics, 40 women (20 non-obese and 20 obese) were given either ephedrine and caffeine (30 mg and 100 mg) or ephedrine, caffeine and aspirin (30 mg, 100 mg, and 300 mg) post prandially (1050 kJ liquid meal). Using indirect calorimetry, observations were made in all groups every 30 minutes for 160 minutes. There was no significant differences between the groups that received aspirin and the groups that did not. We conclude that aspirin does not potentiate the acute thermic effect of ephedrine and caffeine.6

In another study conducted at King's College in London, it was demonstrated that aspirin does not potentiate the thermogenic response to ephedrine in lean women and only slightly so in obese women.7 The increase seen in this study represented a 1.2 kcal per hour increase in metabolism for lean women and a 2.4 kcal per hour increase in metabolism in obese women over use of ephedrine alone, which over an entire week, would represent less than one ounce of bodyweight. We feel that this is insignificant.7

Based on these two studies, we feel that aspirin and its analogs do not play a substantial role in inducing or increasing thermogenesis and/or lipolysis but they do have the potential to induce SAEs when consumed over long periods of time (e.g. ulceration of the stomach and increases in bleeding times). Therefore, we feel that aspirin and it's analogs should not be used in any thermogenic/lipolytic stack.

By Stephen Schmitz, MD, MPH
and Bruce Kneller, BSN-RN


Staff Member
Aug 11, 2010
10 years ago I couldn't do a workout without this stack. I do miss ephedrine...