ECA stack

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]

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.