Obesity

Obesity is "the" health problem in developed countries. In the USA and western Europe more then 45 percent of the population suffers from moderate or severe overweight [I]

The market for weight loss supplements

Market Agencies estimate that the U.S. market for weight loss supplements covers sixty percent of the world market for those products. Most data about the market for slimming products are collected in the U.S.A. .

The journal Nutrition Business Journal estimated the size of the weight loss supplement market for the U.S. at about 1.7 billion U.S. dollars. [iii] This estimate is lower than in previous years. The market is still recovering from the terrible blow that the U.S. government handed out in 2004. In that year the U.S. government - and other governments followed the U.S. example - prohibited the most popular dietary supplement in the world: the ECA combination.

 
The ephedrine-caffeine combination

The combination of ephedrine and caffeine is the brainchild of a Danish doctor from the town of Elsinore. In 1972 he gave these pills to his obese patients. Media coverage and word-of-mouth advertising soon lead to thousands of Danes using those pills.

 The 'Elsinore pills', as newspapers called it, contained caffeine and ephedrine (in short CE) in a ratio of 10:1. Usually they contained 200 mg caffeine and 20 mg of ephedrine. Users took the pills 2-3 times a day. The ingredients stimulate the burning of energy by the body, and in theory the ingredients work in synergy with each other. Ephedrine mimics the effects of metabolic hormones such as adrenaline and noradrenaline; The stack forces fat cells to release fatty acids to the bloodstream so that muscles can burn them. This also happens when adrenaline or nor-adrenaline interacts with receptors on the outside of the cell. The sensitivity of the cell to these signals depend to a large extent on the messenger molecule cAMP. Caffeine increases the concentration of the cAMP molecule in the cell by sabotaging PDE enzyme that breaks down cAMP. Caffeine will therefore increase cAMP levels in the cell, and thus make the cells more sensitive to adrenaline and nor-adrenaline. Together with Ephedrine you have a very powerfull stack. The CE combination is not only active in fat cells. In other tissues this stack increases the consumption of energy by increasing the metabolism of cells.
Studies on the effectiveness of the combination of both drugs tell varying results. Some studies show that people on a diet lose an extra few pounds if they take the ECA pills. [Iv] Other studies report better results. In a Hungarian study persons on a diet taking weight-loss supplement with CE pills lose four times more weight than those given a placebo, [v] and according to a Danish study, the CE-mix is at least as effective as amphetamine and dexfenfluramine. [Vi]

The ephedrine-caffeine-aspirin combination (ECA)

In the nineties people find information about weight-loss supplements with the help of internet easy and fast.  The combination of caffeine and ephedrine spreads like wild fire under internet users. Internet Companies try to make the combination more effective by adding aspirin or salicylic acid to the CE stack. Salicylic acid inhibits the enzyme COX-1, which plays a key role in the production of inflammatory factors such as prostaglandins PGE1 and PGE2. [Vii] These inflammatory factors inhibit the release of noradrenaline. Because aspirin paralyzes the production of inflammatory factors, in theory aspirin switches of a feedback mechanism by which the body weakens the stimulating effect of caffeine and ephedrine. Users who make their ECA combination, add a 350 mg aspirin (A) daily dose to their CE stack. Some only take an aspirin child dose: 80 mg. Not everyone is convinced of the usefulness of the aspirin addition to this combination. Critics point out that the same prostaglandins also increase production of cAMP in cells.
 

ECA supplements

The first ECA products that appear on the market contain pure ephedrine, pure caffeine and pure aspirin. They sell very well for a very limited time - that is until the authorities intervene. Pharmacological substances do not belong in a food supplement. Businesses are clever and thus find legal replacements in plant extracts like guarana or kola nut (containing caffeine), Ephedra-sinica (containing ephedrine) and white willow bark (containing an analogue of aspirin). From 2000 and on these supplements get an increasingly bad publicity when medical journals begin to publish cases in which users of these supplements develop cardiac or vascular diseases and even die. [Viii] The main cause of these incidents are the ephedrines in the supplements. The adrenaline-imitating substances constrict capillaries, and therefore increase blood pressure and increase the risk of a myocardial infarction or a stroke. Cardiologists detect cardiac arrhythmia in all subjects within a few hours after they took an ECA supplement. [Ix] Although surveys among users, paid by manufacturers of weight loss resources, did not show significant risks, [x] more incidents in 2004 eventually leads to a ban on Ephedra supplements with plant extracts containing ephedra. [xi] Shortly after the U.S. government enact the ban in the EU countries follow the U.S. example.
 

Alternatives to the ECA stack

Even before the ephedra-ban took effect, the supplement industry began to develop alternative products. Usually this meant that the companies sought alternatives to the banned Ephedra extracts. Most manufacturers used (still use) (even) higher doses of caffeine, extracts of green tea and citrus Citrus aurantium. The most active substances in these extracts are respectively the epigallocatechin gallate polyphenol (EGCG) and the to ephedrine related synephrine.
 

EGCG

The full effect of EGCG is still not completely clear. An important mechanism of EGCG is that it slows down the enzyme catechol-O-methyltransferase. This enzyme deactivates the metabolism boosting hormones adrenaline and nor-adrenaline. A recent insight is that EGCG directly stimulates the body's energy consumption, and EGCG increases the activity of the energy-generating mitochondria in cells. Studies demonstrated the effect of  green tea extract on weight loss and body composition. According to a recent study green tea (three times a day a supplement with 250 mg of green tea extract) raises energy consumption by a modest 90 kcal / day. [Xii] The quality of the green tea extract used, was a low quality extract; every day the subjects consumed less than 100 mg EGCG.

Caffeine enhances the effects of EGCG. In a Canadian study green tea and EGCG (three times daily 200 mg of caffeine (in the form of guarana extract) plus 270-1200 mg EGCG) increased energy consumption of the body with 158-197 kcal / day. [Xiii] Weight Loss Supplements with suchlike high doses EGCG are not yet on the market.

One problem with EGCG is that EGCG supplements are active in several places of the body, and besides that EGCG has effects that reduce fat stores, EGCG may as well have effects that counteract the reduction of fat stores. For example EGCG increases the uptake of glucose by cells by enhancing the sensitivity to insulin. [Xiv] This effect is less desirable while following a slimming diet. Cells that take in more glucose are less likely to burn fat. Therefore researchers stress that green tea supplements work much better when following a diet which is low in carbohydrates. [Xv]

Citrus aurantium

Extracts of Citrus aurantium citrus contain multiple ephedrine-like substances. Besides synephrine the extracts also contain tyramine, octopamine, tyramine and N-methyl-hordenine. The combination used is 400 mg caffeine (in the form of extracts) and 40 mg of synephrine (also in the form of extracts) per pill. Users would then have to take 1 to 3 pills per day to lose weight.

Supplements makers base their weight loss claims on test tube studies that suggest that compounds in Citrus aurantium have similar effects as ephedrine. But researchers highly doubt  whether the extracts actually work. The reasons is because the effect in cell studies of the Citrus aurantium compounds do not come close to the effects of ephedrine.

In the most promising study in terms of results, heavy dose preparations were used. Daily and for 6 weeks long users took a pill containing 975 mg Citrus aurantium, 528 mg caffeine and 900 mg St. John's wort; the users lost about 7 pounds more than non-users. [Xvi] To what extent ephedrine-like substances caused this weight loss is not clear. Summary studies could never conclude that Citrus aurantium works. [Xvii]

Another cause of concern is that weight loss supplements with Citrus aurantium would, according to case studies in the medical literature, not be without risks - and thus can lead to heart disease. [Xviii] A case report about a young man who got a heart attack after use of a synephrine based stacker.

Verdict on ephedra (ECA) replacements

Green tea and citrus aurantium stacks are NOT substitutes for the banned ephedra based stacks. We can not blame this to the supplement industry. To this day even pharmacologists did not find or developed effective weight loss medication. According to a recent survey study done by the University of Alberta the most successful medicine against weight loss currently on the market is rimonabant. Rimonabant allows users to shed about (only) 10 pounds on average yearly.[Xix] The human body is primarily set on storage of body fat, and not to lose that fat. We are built to survive periods of famine and scarcity, not to survive periods of blessing and abundance.