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  1. #1
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    Ephedra/Ephedrine Information

    There has been much talk on ephedra and ephedrine lately on the boards so I figured I would put some information up about them...

    Ephedra/ephedrine: cardiovascular and CNS effects

    Reason for posting: Health Canada warns that some over-the-counter supplements used to increase energy and promote weight loss and bodybuilding pose a serious risk to health.1 The warning applies to supplements containing the herb ephedra or its alkaloid derivative, ephedrine; in Canada, ephedrine is authorized for use only as a nasal decongestant.

    More than 60 adverse events — suicide, psychotic episodes, seizure, stroke and cardiovascular events ranging from hypertension to myocardial infarction — have been reported in Canada.2 Other recognized adverse effects include anxiety, tremors, headaches, insomnia and flushing.3 An independent analysis of 140 adverse events reported to the US Food and Drug Administration (FDA) between June 1997 and March 1999 found that 47% involved the cardiovascular system and 18% the central nervous system (CNS).4 Health Canada has recalled unapproved herbal preparations containing more than the recommended dose of ephedrine.1,2,3,5 In addition, the manufacturers of approved commercial higher-dose preparations are being asked to submit data demonstrating their safety and efficacy.2

    The drugs: Ephedra sinica, also known as ma huang, is the source of the alkaloid ephedrine. Other related ephedra alkaloids not encompassed by the current advisory include pseudoephedrine, norpseudoephedrine, methylephedrine and norephedrine (also known as phenylpropanolamine, a nasal decongestant taken off the market in 2001 because of its association with hemorrhagic stroke6). In traditional Asian medicines, ephedra-based products are sometimes used as bronchodilators.

    Ephedrine is a sympathomimetic drug prescribed as a nasal decongestant, with properties similar to epinephrine; its effects on both a- and b-adrenergic receptors and its central effects resemble those of amphetamines (see figure).7 The adverse effects of ephedrine are hypothesized to be related to coronary artery constriction, vasospasm, shortening of cardiac refractory periods allowing re-entrant cardiac arrhythmias, hypertension -induced subarachnoid hemorrhage, cerebral artery vasoconstriction and sympathomimetic -induced platelet activation.4

    Products containing ephedrine are not to be used by people with heart disease, hypertension, diabetes, thyroid disease, enlarged prostate, anxiety and restlessness or glaucoma, people taking monoamine oxidase inhibitors or women who are pregnant or lactating.

    Ephedrine often exists in unapproved herbal preparations that also contain caffeine (sometimes called "herbal ecstasy") and ASA. These combination products may augment ephedrine's cardiac and CNS effects8 and should not be used.3

    Hundreds of unapproved products containing ephedra or ephedrine exist, including ma huang, E. sinica, Sida cordifolia and epitonin.3 Approved preparations, mostly nasal decongestants, range in dose from 0.13 to 25 mg per tablet. Health Canada recommends that the dose be restricted to 8 mg of ephedrine per dose and 32 mg per day, for a period no longer than 7 days.1

    What to do: Physicians should ask about the use of over-the-counter herbal and dietary supplements, particularly if patients want to lose weight, improve their exercise tolerance, seek extended periods of wakefulness (such as long-distance truck drivers) or use traditional remedies. Products containing ephedra or ephedrine are currently marketed only as nasal decongestants, and health claims pertaining to appetite suppression and other supposed benefits are not allowed. Enquiries about concurrent sources of caffeine (e.g., green tea, cola nut, yerba mate and yohimbe3) may also be warranted. Patients using products containing ephedra or ephedrine, especially in doses above the recommended limits, should be warned of the potential serious adverse events. Health Canada also recommends that patients use only approved products — those with a drug identification number (DIN).

    Eric Wooltorton Editorial Fellow, CMAJ Barbara Sibbald Associate Editor (News), CMAJ

    References

    Health Canada requests recall of certain products containing Ephedra/ephedrine. Ottawa: Health Canada; 2002 Jan 9. Available: http://www.hc-sc.gc.ca/english/prote...2/2002_01e.htm (accessed 2002 Feb 5).
    Ephedra/ephedrine — frequently asked questions. Ottawa: Health Canada; Jan 2002. Available: www .hc-sc.gc.ca/english/protection/warnings /2002 /2002 _01 ebk2.htm (accessed 2002 Feb 5).
    Advisory not to use products containing Ephedra or ephedrine. Ottawa: Health Canada; 2001 Jun 14. Available: http://www.hc-sc.gc.ca/english/prote...1/2001_67e.htm (accessed 2002 Feb 5).
    Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:833-8.
    Sibbald B. Voluntary recall of ephedra products not enough, MD says. CMAJ 2002;166(2):225. Available: www.cma.ca/cmaj/vol-166/issue-2/0225.asp[Free Full Text]
    Health Canada withdraws drug products containing phenylpropanolamine (PPA) from the market. Ottawa: Health Canada; 2001 May 30. Available: www .hc -sc.gc.ca/english/protection/warnings /2001 /2001 _61 e .htm (accessed 2002 Feb 5).
    Ephedrine HCl. In: Compendium of pharmaceuticals and specialties. 36th ed. Ottawa: Canadian Pharmacists Association, 2001.
    Smith M. Ma huang. In: Herbs: everyday reference for health professionals. Ottawa: Canadian Pharmacists Association and CMA; 2000. p. 153-5.
    Matt Weik, BS, CSCS, CPT, CSN
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    This article was too long to post so here is the link...

    http://jama.ama-assn.org/cgi/content/full/289.12.1537v1
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    CYCLING PERFORMANCE TIPS
    Ephedra and Ephedrine for Athletic Performance Enhancement
    Clinical Efficacy and Side Effects
    Source Under its Evidence-based Practice Program, the Agency for Healthcare Research and Quality (AHRQ) developes scientific information for other agencies and organizations on which to base clinical guidelines, performance measures, and other quality improvement tools.
    Overview AHRQ addressed research questions regarding the efficacy of herbal ephedra and ephedrine for athletic performance through a comprehensive literature review and synthesis of evidence. They assessed the safety of these products through review of clinical trials. Meta-analysis was performed where appropriate. In addition, they reviewed herbal ephedra- and ephedrine-related adverse events reports on file with the U.S. Food and Drug Administration (FDA), published case reports, and reports to a manufacturer of ephedra-containing products.

    After searching published reports, journal articles, conference presentations, and various sources of unpublished studies, AHRQ identified 52 controlled clinical trials of ephedrine or herbal ephedra for weight loss or athletic performance in humans. The FDA provided copies of over 1,000 adverse event reports (AERs) related to herbal ephedra and 125 AERs related to ephedrine.

    Efficacy for Physical Performance Enhancement: The effect of ephedrine on athletic performance was assessed in seven studies. No studies have assessed the effect of herbal ephedra-containing dietary supplements on athletic performance. The few studies that assessed the effect of ephedrine on athletic performance have, in general, included only small samples of fit individuals (young male military recruits) and have assessed the effects only on very short-term immediate performance. Thus, these studies did not assess ephedrine as it is used in the general population. The data support a modest effect of ephedrine plus caffeine on very short-term athletic performance. No studies have assessed the sustained use of ephedrine on performance over time. The only study that assessed the additive effects of these agents reported that ephedrine must be supplemented with caffeine to affect athletic performance.

    Safety Issues: The data on adverse events were drawn from clinical trials and case reports published in the literature, submitted to the FDA, and reported to Metabolife, a manufacturer of ephedra-containing supplement products. The strongest evidence for causality should come from clinical trials; however, in most circumstances, such trials do not enroll sufficient numbers of patients to adequately assess the possibility of rare outcomes. Such was the case with our review of ephedrine and ephedra-containing dietary supplements. Even in aggregate, the clinical trials enrolled only enough patients to detect a serious adverse event rate of at least 1.0 per 1,000.

    For rare outcomes, we reviewed case reports, but a causal relationship between ephedra or ephedrine use and these events cannot be assumed or proven. Evidence from controlled trials was sufficient to conclude that the use of ephedrine and/or the use of ephedra-containing dietary supplements or ephedrine plus caffeine is associated with two to three times the risk of nausea, vomiting, psychiatric symptoms such as anxiety and change in mood, autonomic hyperactivity, and palpitations. The majority of case reports are insufficiently documented to make an informed judgment about a relationship between the use of ephedrine or ephedra-containing dietary supplements and the adverse event in question. For prior consumption of ephedra-containing products, AHRQ identified two deaths, three myocardial infarctions, nine cerebrovascular accidents, three seizures, and five psychiatric cases as sentinel events; for prior consumption of ephedrine, AHRQ identified three deaths, two myocardial infarctions, two cerebrovascular accidents, one seizure, and three psychiatric cases as sentinel events. AHRQ identified 43 additional cases as possible sentinel events with prior ephedra consumption and seven additional cases as possible sentinel events for prior ephedrine consumption. About half the sentinel events occurred in persons aged 30 years or younger. Classification as a sentinel event does not imply a proven cause and effect relationship.

    AHRQ did not assess the plethora of additional symptoms that have been reported in the published literature and the FDA Medwatch file for ephedra-containing dietary supplements and ephedrine products. Availability of Full Report: Printed copies may be obtained free of charge from the AHRQ Publications Clearinghouse by calling 800-358-9295. Requesters should ask for Evidence Report/Technology Assessment No. 76, Ephedra and Ephedrine for Weight Loss and Athletic Performance Enhancement: Clinical Efficacy and Side Effects. The Evidence Report can also be downloaded as a zipped Word® or PDF file online at: http://www.ahrq.gov/clinic/evrptfiles.htm#ephedra.
    Matt Weik, BS, CSCS, CPT, CSN
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    Ephedra (Ephedrine Sulfate)
    Also known as: Ephedra, Ephedra Sinica, Ma-huang, Desert Herb, Joint Fir, Popotillo, Sea Grape, Teamster’s Tea, Yellow horse, Epitonin, Ephedrine, PPA

    Historical Perspective: Ephedra Sinica is an herb which has been used in traditional Chinese medicine for over 5,000 years and is considered the world’s oldest medicine. Healers have used this herb to treat asthma, coughs, colds, and induce sweating. Most naturally growing ephedra is found in
    temperate climates, in China, Mongolia, Southern Siberia and Japan, usually on sandy seashores. On Dec.30, 2003, the Food and Drug Administration (FDA) issued a consumer alert on the safety of dietary
    supplements containing ephedra. The alert advised consumers to immediately stop buying and using ephedra products. On April 12, 2004, FDA announced that the fi nal rule went into effect prohibiting the sale of dietary supplements containing ephedra alkaloids (ephedra) because these supplements present an unreasonable risk of illness or injury. Copies of the consumer alert, notice letter to ephedra manufacturers, and press releases, and other documents about FDA’s Actions on ephedra can be found at http://www.fda.gov/oc/initiatives/ephedra/.

    Common Uses: Aid in weight loss, increase energy, sexual enhancement and produce euphoria.
    Ephedrine is used medicinally for the relief of asthma, allergies, colds, and hay fever (available in overthe-
    counter cold remedies).

    Form(s) Used: The primary form of ephedra is in tablet or capsule form. Ephedra is not commonly available in its pure form, but in combination with several other ingredients -- other ingredients include
    caffeine in the following forms: guarana, guara concentrate extract, kola and kola nut. Stevia and garcinia cambogia can also be found in ephedra containing supplements.

    Potential Side Effects: Ephedra may cause addiction, headache, insomnia, nervousness, agitation, dizziness, vomiting, diffi cult urination, manic episodes, kidney stones, hepatitis, high blood pressure,
    heart palpitations, tachycardia, heart attack, stroke and death. Side effects of ephedra use are often intensifi ed by the other ingredients commonly available as an additive to the product, such as caffeine.

    Food-Drug-Supplement Interactions: MAO inhibitors, digoxin, caffeine, over-the-counter cold remedies, and stimulants.

    Contraindication to Use: Pregnancy, breast feeding, Graves’ disease, high blood pressure, heart disease and obesity.

    Research Data on Safety and Effi cacy: Case studies on hundreds of individuals indicate that ephedra and ephedra-containing products are not safe for use. The FDA lists ephedra as a potentially dangerous supplement on its warnings and safety information page, and has proposed safety
    measures for manufacturers of ephedra-containing products. Many sport associations, including the International Olympic Committee, have banned ephedra use.

    Bottom Line: Ephedra is not recommended for use due to it’s serious, life-threatening side effects. It is illegal for manufacturers to sell and distribute dietary supplements containing ephedra.

    Bottom Line: Ephedra is not recommended for use due to it’s serious, life-threatening side effects. It is illegal for manufacturers to sell an distribute dietary supplements containing ephedra.

    http://chppm-www.apgea.army.mil/dhpw/Wellness.aspx
    USACHPPM Directorate of Health Promotion and Wellness
    DIETARY SUPPLEMENT FACT SHEET

    References:
    1. American Journal of Addictions, Fall 1998, 7 (4): 256-61.
    2. American Journal of Kidney Diseases, Jul 1998, 32 (1):153-9.
    3. British Medical Journal, 21 SEP 1996, 313 (7059), p. 756.
    4. Journal of Emergency Medicine, 17 (2):289-91, 1999 Mar-Apr.
    5. The American Journal of Psychiatry, NOV 1998, 155 (11), p 1627.
    6. The New England Journal of Medicine, 5 APR 2001, 344 (14), pp 1095-1097.
    Matt Weik, BS, CSCS, CPT, CSN
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    This is a very good read...

    http://www.rand.org/publications/RB/RB4556/
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    IMPORTANT:

    FYI: Herbal Ephedra and Ephedrine HCL both stimulate CNS and SNS to some degree. Pure Ephedrine HCL, due to the lack of the 5 other alkaloids, has a MILDER CNS effect (less side effects / jitters) but still has SOME CNS effect while maintaining a powerful SNS effect.

    Ephedrine Alkaloids (in herbal Ephedra):

    (-) ephedrine
    (+) pseudoephedrine
    (-) methylephedrine
    (-) norephedrine
    (+) norpseudoephedrine
    (+) methylpseudoephedrine

    <img src="http://faculty.washington.edu/chudler/nsdivide.gif">

    another good read:

    http://forum.bodybuilding.com/showthread.php?t=316758

    <img src="http://technologyorgasm.com/upload/ECA.jpg">
    Last edited by pu12en12g; 08-14-2005 at 09:21 AM.
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    Matt Weik, BS, CSCS, CPT, CSN
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    Thanks Pu12...
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    Here is a link talking about Ephedra & Caffeine & Asprin for Maximum Weight Loss...

    http://www.undergroundsports.com/eph...da_article.htm
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    Another ephedra study...

    http://www.swedish.org/17680.cfm
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    Here is an old article from BodyBuilding.com

    http://www.bodybuilding.com/fun/md4.htm
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    1.0 Introduction
    Herbal thermogenic weight loss products usually contain quite a few ingredients, however, the scientific research shows that only two ingredients are necessary: ephedrine and caffeine. Some of the extra ingredients may increase thermogenesis a little bit, but make no mistake about it, ephedrine and caffeine are the only NECESSARY ingredients. If you do not understand why a thermogenic formula MUST contain both ephedrine and caffeine, then take a moment to look at my illustrations in "How ECA Works."

    The purpose of this post is (I) to answer some common stacking questions (II) to cut through the hype and evaluate the ephedrine and caffeine content of herbal versions of the ECA stack (III) to categorize the supplements according to the number of capsules one must take to get a single dose containing 20 mg of ephedrine and 200 mg of caffeine and (IV) to list the price of the largest size bottle and calculate the price per dose based on the 20/200 dosage. Obviously, I could not calculate the price per dose for products that are not standardized to the 20/200 amount.

    Note: Although yohimbe is a legitimate thermogenic, the focus of this post is ephedrine-based formulas. I plan to write about standardized yohimbe supplements in the near future. However, it is NOT a good idea to combine ephedrine and yohimbe.
    2.0 Calculating The Ephedrine/Caffeine Content
    The only herbal thermogenic products worth considering are standardized extracts containing approximately 20 mg of ephedrine and 200 mg of caffeine. It usually takes two or three capsules to reach the full 20/200 dose. In properly formulated supplements, 2 or 3 capsules usually contain about 334 mg of ma huang extract (6% ephedrine) and 910 mg guarana extract (22% caffeine). In order to qualify as a properly formulated supplement, the math has to add up (334 mg times 6% (.06) = 20 mg of ephedrine).

    Sometimes you will see a label that reads "ma huang extract" -- this is no good because it does not state the amount of extract (mg) in the capsule or the potency (%) of the extract. Sometimes herbs are listed as a "4:1 concentrate" -- this is no good because you do not know the original potency of the herb that was concentrated. Thus, in both of these examples, there is no way to calculate the exact amount of ephedrine in the supplement. In cases like these, where there is insufficient data to do the math, I would not buy the product.

    2.1 Where Does The 20/200 Amount Come From?
    Arne Astrup et al. (1, 2) tested several ephedrine/caffeine combinations (10 mg/200 mg, 20 mg/100 mg, and 20 mg/200 mg) and compared them to the combined thermogenic effect of ephedrine and caffeine given separately. Unlike the other dosages, the 20 mg/200 mg combination exceeded the predicted additive effect, so the researchers said that the 20/200 combination has a "supra-additive thermogenic synergism" (1). In other words, the 20/200 dosage/ratio causes a synergistic effect where 1+1=3.

    However, one thing that is rarely mentioned is that these tests were performed on only "Six healthy, normal weight subjects of both sexes" (1). Since it is well known that obese people respond differently to thermogenic stimuli, I find it odd that they used "normal weight" individuals for these tests. Anecdotally, however, 20-25 mg ephedrine and 200 mg of caffeine seems to work quite well for most obese people. Also, a number of studies, including a 50-week clinical trial (3), reported good results with the 20/200 combination. So, the 20/200 combination three times per day seems to be the best way to go, but it's not written in stone.

    3.0 What About Willow Bark/Aspirin?
    The use of willow bark as a substitute for aspirin has been questioned. According to Mowrey's book (4-BK), willow bark (salicin) acts more like sodium salicylate than aspirin (acetylsalicylic acid). If Mowrey is correct, then willow bark would not be an effective substitute for aspirin in the ECA stack because sodium salicylate does not irreversibly inhibit prostaglandin formation by acetylating the cyclooxygenase enzyme. For more information on this, check out the illustrations in my post, "How ECA Works." However, Mowrey also states that "We must note that the possible lack of activity of salicin on thermogenesis is currently just a theory."

    Clearly, the best way to inhibit peripheral prostaglandin synthesis is to take real aspirin. Therefore, whether one takes an herbal stack or a "mini-thin" stack, it is arguably a good idea to take one 81 mg enteric-coated aspirin per day. I would classify aspirin as optional -- ephedrine and caffeine works quite well without aspirin. I would not take more than one 81 mg enteric-coated aspirin per day because higher doses of aspirin greatly increase the risk of getting an ulcer. Thus, I prefer herbal stacks that do NOT contain willow bark.
    3.1 What About Synephrine, St. John's Wort, Carnitine, HCA, etc., etc., etc?
    There are quite a few supplements that may have a small fat burning effect; however, none of these supplements come close to matching the thermogenic effect of ephedrine and caffeine. Lets put this in perspective: almost without exception, reduced sympathetic activity and blunted thermogenic responses have been found to be a MAJOR factor in EVERY type of obesity that scientists have studied. We are talking about approximately 100 years of scientific research here. Then, in the 1980s, scientists screened all sorts of drugs and found that the ephedrine/caffeine combination was the best way to correct this thermogenic defect (5, 6, 7). ECA is the state-of-the-art obesity drug. Any company that says they have something better than ECA is lying.

    OK. Now that we have put this in perspective, lets take a brief look at some of this stuff:

    Ma huang Free Formulas: Obviously these are a rip-off because they contain no ephedrine.

    Herbal Phen/Fen: Generally, these contain ma huang (ephedrine) and St. John's Wort. Ephedrine is not very effective unless it is taken with caffeine. Indeed, the Astrup/Toubro team of researchers from Denmark found that "the ephedrine/caffeine combination is effective, while caffeine and ephedrine separately are ineffective for the treatment of human obesity" (13). St. John's Wort might be a helpful addition to the ECA stack, but it cannot replace caffeine in a thermogenic formula. If you do not understand this, you should read "How ECA Works."

    Synephrine and HCA: If there was 1% as much research as hype, this stuff would rule.

    Nutrients: (chromium, carnitine, potassium, magnesium, choline, etc.) Many herbal thermogenic products contain small token amounts of these nutrients. I take large doses of a variety of nutrients for their health-promoting effect. Unfortunately, at best, they have only a modest effect on your waistline. Read The Magnesium Lottery to learn about my favorite addition to the ECA stack.

    Tyrosine/Phenylalanine: These amino acids are a good addition to the ECA stack -- especially if you are dieting and not getting enough protein. (Both of these amino acids are precursors to catecholamines.) Thus, many obese people find that they feel better when they take these amino acids -- especially if they are taken on an empty stomach to avoid competitive transport across the blood-brain barrier (BBB). This helps to ensure that there is adequate noradrenaline production. This phenomena should not be confused with the dubious and unfortunately-named "adrenal exhaustion syndrome."

    Green Tea: Dulloo et al. (12) recently found that green tea has more thermogenic effect than can be explained by its caffeine content. For more information see Green Tea and Thermogenesis.
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    From the UC Davis Nutrition Department...

    http://nutrition.ucdavis.edu/InfoSheets/ephedra.htm
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    3.2 What About Cycling And Adrenal Exhaustion?
    You can read every single medical study on ECA and you won't find anything about cycling or adrenal exhaustion. Not a word. In a way, this situation is really rather funny and absurd. Although there is a ton of scientific research on ECA, bodybuilders and herbalists tend to put their own spin on the data, and most doctors are amazingly ignorant about anything that is not approved by the FDA. So, unless you read the medical research, it's almost impossible to separate the facts from the spin, hype, and political BS.

    Lets start with cycling. Once upon a time, bodybuilders found some fascinating information about a drug called clenbuterol in animal science journals. They learned that high doses of clenbuterol can build muscle and, since it directly stimulates the beta 2 adrenergic receptors, it even increases thermogenesis. Cycling clenbuterol was found to be more effective for bulking up farm animals so, of course, bodybuilders started cycling clenbuterol.

    What does this have to do with ECA? Not much, but since the drugs are similar in some respects, bodybuilders started cycling ECA. And, of course, a number of companies that try to maintain the appearance of being on the cutting edge also started to recommend that people "cycle" their thermogenic supplements. So, amazingly, obese people are being told to cycle ECA because of some studies with a different drug that bulked up farm animals. As you will see in "The Beta 3 Scandal" section of this post, techniques that are effective with clenbuterol are not such a good idea for obese people who use ECA.

    Meanwhile, some herbalists came up with a theory that thermogenic supplements stress the adrenal glands. Why? Well, thermogenic supplements cause the adrenal glands to release adrenaline. Of course, the exact same thing happens in response to the normal stress of daily living, and when you exercise, and when you eat a meal, and when you go outside in cold weather, etc., etc., etc. The adrenal glands certainly don't sound like wimps to me, but why ruin a good theory with facts? Still, it's a shame they came up with such a horrible name that generates an image of the adrenal glands getting worked to death. Poor ephedrine -- it doesn't even get a fair shake from people who advocate its use.

    But when it comes to not being able to get a fair shake, obese people win the prize. Unfortunately the "adrenal exhaustion" theory also perpetuates prejudice against obese people because it ignores the fact that, in addition to subnormal noradrenaline release by the nerve endings of the sympathetic nervous system, obese people also release insufficient adrenaline from the adrenal medulla: "Another abnormality being noted with increasing frequency in human obesity is reduced adrenaline (Ad) levels in plasma, both at rest or in response to a stimulus such as physical activity" (17). By the way, this adrenaline deficiency persists even if you lose weight (18, 19-NA), setting the stage for the inevitable regain.

    Thus, although ECA causes the adrenal medulla to release more adrenaline, this is actually just bringing us up to a more normal level. Although some herb sellers talk about "stressing" the adrenals, the reality is that ECA merely normalizes this biochemical imbalance. At any rate, undaunted by the fact that obesity researchers have never found a single incidence of "adrenal exhaustion" in all their studies on ECA, the herbalists started selling a variety of herbs to "protect" your adrenals. By the way, the herbalists agree with the bodybuilders that you should cycle ECA. However, their "reasoning" is quite different -- the herbalists believe that you should cycle thermogenic supplements in order to "rest" your adrenals. Ugh!
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    Pu12, hopefully with both of us doing this it will settle a lot of the questions people have and ask on here... or not since no one searches, lol. Oh well...
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    3.3 The Beta-3 Scandal: The Discovery
    OK, enough of this foolishness, why is cycling ECA not recommended (or even mentioned) by research scientists? Simple, because the mode of action of ECA is different. Clenbuterol is a highly selective drug that becomes less effective after a short period of time because it selectively stimulates the beta 2 receptors, which downregulate. ECA, on the other hand, non-selectively stimulates all the beta receptors.

    Remember how we learned that, in the 1980s, scientists screened drugs for their thermogenic potential? Well, when they tested non-selective adrenergic drugs like ephedrine, the scientists were surprised to find that the thermogenic effect was maintained and even increased with chronic use (26). Dulloo found that "agonists for the classical post-synaptic adrenoceptors [selective drugs] were found to be much less effective in chronically enhancing thermogenesis and fat losses than sympathetic stimulants [non-selective drugs] capable of increasing the synaptic levels of NA [noradrenaline] e.g. ephedrine, yohimbine, tranylcypromine" (8) [emphasis added].

    Anecdotally, this persistent thermogenic effect has been experienced by people who have taken ECA non-stop for many years. Personally, I have taken ECA for over a decade and it still works for me. Furthermore, Toubro et al. found that ECA kept working throughout a 50-week clinical trial: "The major finding of this drug study indicates that a combination of ephedrine (20 mg) and caffeine (200 mg) taken orally three times a day as an adjuvant to a low calorie diet improves weight loss for 24 weeks. Furthermore, the combination can maintain or slightly improve weight loss during treatment from weeks 26-50" (10). When taken chronically, ECA lowers your set point by normalizing an important part of your biochemistry.

    Here is how it works: Ephedrine works by stimulating the release of the bodies own noradrenaline, which stimulates ALL the adrenergic receptors. The stimulant side effects subside because they are primarily mediated by the beta-1 and beta-2 receptors, which downregulate during chronic use. Thus, the scientists were startled when they found that the thermogenic effect actually INCREASED with chronic use.

    This phenomena led scientists to believe that there must be an undiscovered receptor involved in noradrenaline-induced thermogenesis. Then the scientists found that -- even after blocking all the known adrenergic receptors -- non-selective drugs like ephedrine still caused a significant thermogenic effect. The evidence supporting the existence of an undiscovered receptor that is stimulated by noradrenaline continued to increase.

    Eventually, this led to the discovery of the beta 3 receptor, which is more resistant to desensitization (20, 21, 22, 23) than the other beta receptors -- and that is why the thermogenic effect of ECA is maintained so well during chronic use. Now you know why it is not necessary to "cycle" ECA. Indeed, why would you want to maintain the side effects when you can enjoy increased fat burning without ANY stimulation?

    Cycling clenbuterol to try to prevent desensitization of the beta 2 receptors makes sense, but ECA is an entirely different story. ECA involves noradrenaline and the beta-3 receptors. The two drugs are similar in some ways, but in this extremely important way, it is like comparing apples and oranges.

    OK, but why does the thermogenic effect INCREASE when you take ECA regularly? Because a thermogenic tissue called brown fat has a lot of beta-3 receptors that are stimulated by noradrenaline, which is released when you take non-selective sympathomimetic drugs like ephedrine. This stimulation of beta-3 receptors actually causes the brown fat to grow -- and more brown fat equals more thermogenesis. Fascinating stuff, this ephedrine. Like I said, apples and oranges.

    Liu et al. (9) investigated this thermogenic mechanism:

    "Ephedrine is believed to have some direct effect on both alpha adrenoceptors and beta adrenoceptors, but AT THERAPEUTIC DOSES, ephedrine exerts its thermogenic effect almost entirely via stimulating noradrenaline release from the sympathetic nerve terminals [endings] . . . at least 40% of the [thermogenic] response is mediated by an atypical receptor, which is presumed to be the beta 3-adrenoceptor." [emphasis added]
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    From George Mason University...

    http://www.stats.org/record.jsp?type=news&ID=434
    Matt Weik, BS, CSCS, CPT, CSN
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    3.4 The Beta 3 Scandal: The Truth Withheld
    The pharmaceutical companies know all about the beta-3 receptor and thermogenesis. In fact, they have spent many years and lots of money developing drugs that stimulate this fat burning mechanism. The last thing in the world they want to see is people taking inexpensive thermogenic supplements instead of paying $3.00 a pill for their upcoming prescription drugs. As you can see, this massive investment of time and money is threatened by herbal thermogenic supplements that use your body's own noradrenaline to stimulate the beta-3 receptors. Needless to say, the pharmaceutical companies are not too happy with mother nature!

    By 1986, after decades of animal research, Dulloo and Miller had clearly established that obese humans suffered from a noradrenaline deficiency that could be corrected by the ephedrine/caffeine combination:

    "It would seem that a deficiency of NA [noradrenaline] due to reduced SNS [sympathetic nervous system] activity, rather than an insensitivity to NA, is primarily responsible for the apparently higher efficiency of energy utilization in the obese or post-obese. The present study shows that this situation may be relieved by sympathomimetic drugs like the ephedrine methylxanthines [caffeine] preparation which normalizes their subnormal thermogenic response to food . . . Such ephedrine/methylxanthine preparations could be useful as aids in the treatment of obesity" (24).

    Dulloo and Miller repeatedly tried to get the medical industry to use this combination to help obese people but the medical/pharmaceutical industry turned a deaf ear and kept their eyes focused on the bottom line ($$$) as they continued developing beta 3 drugs. I know this sounds like the Twilight Zone, but obese people eventually found out about this life saving information because bodybuilders dug up the research and started using ephedrine/caffeine to burn fat while preparing for bodybuilding contests! Eventually the information spread outside the bodybuilding world and -- finally -- obese people found out about it. Is that mind-blowing or what??? Think about it. Hundreds of thousands of obese people dying year after year after year -- and this is how we found out about a life saving medication!

    I've been researching thermogenesis for over a decade and I still find it hard to believe that muscleheads have done more to help obese people than the medical establishment. At any rate, since 1986 roughly 4 million people have died of obesity-related deaths. There is no way to calculate what percentage of these victims could have been helped if the truth about ECA had not been withheld, however, this is clearly a tragedy of historic proportions.

    By 1992 obesity scientists were so frustrated with this tragic situation that they organized an international symposium in an attempt to get the medical/pharmaceutical industry to use ECA. In the editorial they explained why scientists from around the globe felt they had to do this:

    "something had to be done to help the existing obese population, and what better way than to use a drug that was already available, and had stood the test of time. We hope that this symposium will help convince a much larger number of people that this is still a viable approach, and that large clinical trials with ephedrine, or combinations of ephedrine with other common, established drugs are both necessary and ethically justified" (11-NA).

    Unfortunately, even this was not enough to pull greedy eyes off the bottom line. In the face of overwhelming evidence from obesity scientists and clinicians from all over the world, the medical/pharmaceutical industry once again proved that it is only interested in making us pay through the nose for prescription drugs that are VERY similar to ECA (chronic use). Dulloo and Stock were so candid about this scandalous situation that even I was shocked. They really let the cat out of the bag: "most, if not all of the undesirable side-effects of ephedrine exhibit tachyphylaxis [desensitization], whereas the thermogenic effects are preserved or even enhanced by chronic treatment. This later phenomenon suggests that it may not be necessary to develop selective drugs (eg. B3-agonists)" [beta-3 drugs] (11-NA). The side effects go away but the fat burning continues or even increases!

    We have a tragic situation where an estimated 300,000 people die each year of obesity-related conditions, and for well over a decade, the medical/pharmaceutical industry has stubbornly refused to use these life-saving thermogenic supplements. Apparently, they are willing to pretend that there is no way to help obese people until they can price-gouge us with prescription beta-3 drugs. Meanwhile, obesity scientists are saying that ECA is so safe and effective that it "may not be necessary to develop selective drugs (eg. B3-agonists)" [beta-3 drugs] (11-NA).

    This is most remarkable since scientists almost always use careful, measured language. But how much avoidable death can one watch before speaking out? Thus, numerous researchers have been candid about this situation: "the ephedrine/caffeine mixture can promote not only fat loss but also preservation of free fatty mass [muscle] during weight reduction in obese individuals. These properties make these compounds very similar to the ideal pharmacological treatment" (25-NA) [emphasis added]. And now, 8 years after the international symposium the medical industry is still not using -- or even telling obese people the truth about -- the ephedrine/caffeine combination. If obesity was not such a stigmatized condition there would be a criminal investigation of this callous disregard for human life.

    Furthermore, as if that's not bad enough, the FDA is acting like a hired gun protecting the investments of the pharmaceutical industry by flooding the media with dubious MedWatch reports designed to scare people away from thermogenic supplements and set the stage for an outright ban of ephedrine. If their evil plan is successful, by the time the prescription beta-3 drugs finally become available, ephedrine and ma huang will be taken off the market. This, of course, would ensure windfall profits for the drug companies and (eventually) FDA officials, who enjoy revolving-door employment with the pharmaceutical industry.

    The big losers, of course, will be the obese people who can't afford the "new" prescription drugs (and people who find that they responded better to ECA). Well, I guess you got to break a few eggs to maintain a monopoly. I hope enough people read the medical literature and speak out about this scandalous situation before it's too late.
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    4.0 Do Not Start With The Full Dose
    Warning: This information is based on research, common practices, and my own ideas. These dosage ideas may not be appropriate for you -- I present this information so you can discuss it with your doctor. For more information, read the Terms of Service.


    The main advantage of herbal stacks is that it takes 2-4 capsules to get the full dose. This makes it easy to start the ECA stack at a low dose and avoid any unpleasant stimulant side effects. The rule of thumb is if it is unpleasant take less. The stimulant effect subsides with regular use but the thermogenic effect continues. Anecdotally, many people take a half dose (10/100) for the first couple of weeks and report a mild increase in energy, some appetite suppression, and no unpleasant side effects. However, as you will see, the research suggests that the low dose period should, in some cases, be much longer. This must be individualized since people adapt at different rates. Lets look at the research:

    Toubro et al. (3) started moderately overweight people out at the full dose (20 mg ephedrine & 200 mg caffeine) and found that the stimulant side effects were not harmful, but can last for quite some time: "The side-effects are minor and transient and no clinically relevant withdrawal symptoms have been observed . . . Eighty percent of symptoms lasted less than 4 weeks, 13% lasted 4-8 weeks, 5% lasted 8-12 weeks and the remaining 2% lasted 12-16 weeks." Many people have found that you can avoid these side effects by starting with a half dose.

    Based on the research, this is a logical way to start the ECA stack:
    Week 1-4 (half dose): 10 mg ephedrine and 100 mg caffeine taken 30 minutes before each meal.
    Week 5 (full dose): 20 mg ephedrine and 200 mg caffeine taken 30 minutes before each meal.

    Some people skip the dinner dose during the first month if they have trouble sleeping. If the herbal stack upsets your stomach, try taking it WITH each meal. If that does not help, stop taking the herbal stack and try half of an ephedrine tablet and a 100 mg caffeine capsule (no aspirin) WITH each meal. In addition, people who are unusually sensitive to stimulants may find it best to start at 1/3 or even 1/4 the full dose. This is easily accomplished with herbal stacks that require 3 or 4 capsules to get the full dose. These products are listed in the Price Comparison.


    4.1 Is ECA Safe?
    Contrary to the sensationalized media stories about people that took 20 times the proper dose (and people with preexisting conditions who should not have taken ECA), all the research and extensive clinical data from Denmark shows that -- for healthy obese people -- ECA is quite safe. Indeed, there is so much data documenting the safety of ECA that it is amazing that the mainstream media has managed to avoid it. For example, how come they never tell the American people about the large, "double-blind multi-centre trial in general practice" in Denmark (14). That's right, when the media (and the FDA) portray thermogenic supplements as untested and dangerous, it is an outright lie. In fact, in Denmark, ephedrine and caffeine (EC) is "licensed as a prescription drug" (1) and doctors prescribed 9.6 million daily doses over a two year period (14). Ironically, its safety record is one of the reasons why it is such a popular obesity medication.

    As we have discussed, if you start the stack at the full dose, some people experience transitory stimulation-related side effects (hand tremor, insomnia, etc.) And even this can be largely avoided if you start with a very low dose. The safety data from Denmark -- after 9.6 million doses -- shows nothing worse than these minor side effects!

    Of course, nothing on the planet earth is totally safe for everyone, but if you compare the Denmark safety data with all the major problems caused by acetaminophen, countless OTC medications, or virtually anything in the PDR (Physicians Desk Reference), it is indisputably clear that thermogenic supplements do not deserve the scorn that is being heaped upon them.

    Breum et al. wrote about the large "double-blind multi-centre trial in general practice" (14) in the "International Journal of Obesity and Related Metabolic Disorders." Here is what they had to say about ephedrine and caffeine (EC):

    "During the last two years defined doses daily more than 9.6 million of the EC combination have been used in Denmark, but only 86 adverse drug reactions have been reported to the health authorities, of which none were cases of gastrointestinal bleeding or other kinds of haemorrhagic episodes . . . Both diastolic and systolic BP declined during treatment with both drugs" (14).

    Good grief, did you catch that last sentence? Their blood pressure declined!!! How did that happen? It's simple, ECA causes weight loss and the reduction in weight lowers your blood pressure! That means that people who take ECA and lose weight are far less likely to have a heart attack or stroke. In the U.S. there are an estimated 300,000 obesity-related deaths each year. How many lives could be saved if obese people took thermogenic supplements and lost weight and lowered their blood pressure?

    When obese people worry about the safety of ECA, it's like a guy in a pool of quicksand worrying about getting a rope burn while he's being rescued. The only thing more dangerous than untreated obesity is listening to the mainstream media and the FDA.

    Another thing that the 'altruists' in government and the media conveniently neglect to mention is the fact that a recent meta-analysis of adverse drug reactions in hospitalized patients found that prescription drugs are "between the fourth and sixth leading cause of death" in the United States (15). We are talking about an estimated 2.2 million serious adverse drug reactions and 106,000 deaths each year from prescription drugs! By the way, they define "serious adverse drug reactions" as "those that required hospitalization, were permanently disabling, or resulted in death" (15). How dare they portray supplements as dangerous?

    On the surface, all this hysteria about supplements seems crazy, but there is a method to their madness: the pharmaceutical companies want the government to implement insanely expensive regulations to crush the relatively small supplement companies that couldn't possibly afford the onerous regulatory burden. Then, when the dust settles, the pharmaceutical industry enjoys monopoly profits as they pick the most profitable pieces out of the rubble. Of course, the consumers also end up paying for all the absurd regulations. (This has already happened in many countries -- see my post on "use patents" for more info.) Sadly, you will even see this agenda promoted in medical journals: one anonymous editorial went so far as to say regulations for supplements should be "at least as stringent as those for conventional therapy" (16-NA).

    Of course, this is sold to the public as altruistic consumer protection. But anyone who looks at the safety data can easily see that this is total bull. Thus, might I suggest that before they even think about messing with the supplement industry, they should concentrate their efforts on figuring out why all their regulations do not stop prescription drugs from killing hundreds of thousands of Americans.

    This deceitful, hypocritical, power-grabbing propaganda needs to be publically challenged. Nobel Prize-winning economist, Milton Friedman, said it best: "Any increase in the FDA's authority over anything is a clear and present danger to the nations health." Truer words have never been spoken. The facts about ECA inescapably lead one to the same conclusion: any increase in the FDA's authority over thermogenic supplements is a clear and present danger to the health of obese people.
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    From the US Department of Health and Human Services...

    http://www.ahrq.gov/clinic/epcsums/ephedsum.pdf
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    4.2 Massive Obesity
    Massively obese people often have a very low levels of sympathetic activity. This causes their adrenergic receptors to upregulate. In other words, sensitivity to catecholamines is increased (via more receptors) in an attempt to compensate for the low levels of noradrenaline (NA) and adrenaline (ADR). Thus, when a massively obese person starts taking thermogenic supplements they may find that they are extremely sensitive to the stimulant effect. Although this condition is only temporary, some massively obese people may have to start with a very low dose of ECA. It would be tragic if someone, whose life could be saved by thermogenic supplements, gave up because of temporary side effects that can be avoided if one starts out at a low enough dose.

    Indeed, initial sensitivity to thermogenic supplements may actually be an indication that your obesity is largely caused by subnormal sympathetic tone. Dulloo and Miller (6) noticed a big difference between lean and massively obese animals when they were screening thermogenic drugs:

    "They were much less effective in lean animals. These findings lend support to the concept that obesity is due to a diminished activity of the sympathetic nervous system . . . Thus drugs that would correct the defect in the obese would effectively increase thermogenesis in these animals, whereas they would be of relatively little value in normal lean animals that have no such defective mechanism."

    Are you beginning to see why some people do not respond to ECA? Thermogenic supplements correct a specific biochemical defect, and if your sympathetic activity is relatively normal, you may very well end up scratching your head and asking "what's the big deal with that ECA stuff?" Meanwhile, the guy down the street is burning fat like crazy and telling you that it's the best thing since sliced bread!

    You see, after a short while, both the stimulation and the appetite suppression go away and -- in the long run -- the effectiveness of ECA depends on the normalization of noradrenaline and adrenaline release. Thus, if you are a massively obese person with extremely low sympathetic tone, you are probably going to be amazed at how effective ECA is. However, if you have a relatively small amount of weight to lose and/or relatively normal sympathetic tone, you might lose weight until the appetite suppression stops, but then the party might be pretty much over for you. Likewise, if your main biochemical imbalance is serotonin deficiency, then ECA can't do much for you. It all makes perfect sense when you read enough science to cleanse your head of all the prejudice and false assumptions about obesity.

    Lets clear up another false assumption. Obviously, the beta-3 drugs that are being developed cannot completely normalize someone who has a serious noradrenaline/adrenaline (NA/ADR) deficiency because these drugs only act upon one specific type of adrenergic receptor. You see, although the beta-1 and beta-2 receptors are largely responsible for the temporary undesirable side effects of ECA, under-stimulation of these receptors (due to NA/ADR deficiency) will cripple your fat burning ability. This is especially important for massively obese people with extremely low sympathetic tone.

    Up-regulation of the beta 1 and beta 2 receptor cannot completely compensate for a serious NA/ADR deficiency. Unlike ECA, the beta 3 drugs do not correct this deficiency. The beta-3 receptor has been estimated to be responsible for about 40% of noradrenaline-based fat burning (9). Do you see what I'm saying? ALL the adrenergic receptors contribute to normal fat burning. Thus, NO selective drug can completely make up for a serious NA/ADR deficiency. Understanding this important fact may be the difference between life and death for some massively obese people.

    You see, obesity is a REAL disease and ECA helps to normalize our fat burning ability by correcting a specific biochemical imbalance. How could it possibly work for everyone? But the people who are most likely to benefit from it are the people who NEED it the most -- the massively obese. When people refer to thermogenic supplements as "appetite suppressants," they are ignoring the very heart of our disease and perpetuating prejudiced attitudes and ignorant treatment methods that don't have a snowballs chance of working in the long run. Let your speech reflect the science of liberation rather than old, offensive, "sloth and gluttony" nonsense. Obesity is a REAL disease. Think about it.

    Furthermore, juvenile-onset morbid obesity is a chronic condition that requires life-long treatment. If you stop taking thermogenics, you will revert back to your old abnormal biochemistry and -- like a mirror image -- your set point will return to your previous level of obesity. Why can some people eat whatever they want and not get fat? Biochemistry! Your weight is a mirror image of your biochemistry. This is especially true in cases where a massively obese individual has a normal appetite. The downside to this reality is that, if you have several biochemical imbalances, ECA probably will not lower your set point as much as you would like. If you find yourself in this position, a couple of likely culprits are serotonin and insulin. Conventional weight loss methods have a near 100% long-term failure rate because they do not address the fact that obesity is a REAL disease. Such thinking reflects prejudice, not science.

    OK, lets look at the science and see what we can come up with for a massively obese person who has a high initial sensitivity to sympathetic stimulants. Toubro et al. (3) started moderately overweight people out at the full dose (20 mg ephedrine & 200 mg caffeine) and found that the stimulant side effects can last for quite some time:

    "The side-effects are minor and transient and no clinically relevant withdrawal symptoms have been observed . . . Eighty percent of symptoms lasted less than 4 weeks, 13% lasted 4-8 weeks, 5% lasted 8-12 weeks and the remaining 2% lasted 12-16 weeks."

    There is no direct data to tell us if a person who starts at less than the full dose will adapt at the same rate, however, the Toubro et al. study should serve as a rough guide. Notice how very few people felt any stimulation by the third month? Using a model where the dosage is increased by one capsule per month until the full dose is achieved, an herbal formula where three capsules equaled the full dose would reach the full dose at the beginning of the third month (week 9). A four capsule formula would reach the full dose at the beginning of the fourth month (week 13). Here is an example for a three capsule formula:

    Week 1-4: One capsule (1/3 dose) three times daily.
    Week 5-8: Two capsules (2/3 dose) three times daily.
    Week 9: Three capsules (full dose) three times daily.

    5.0 Selecting a Good Thermogenic Formula

    Despite the hype, herbal stacks are not better than home-brew stacks (mini thins and caffeine capsules). The "extra" ingredients in the herbal stacks add little to the fat burning effect. In addition, if you review the price data, you will see that the stacks with lots of "extra" ingredients cost twice as much. These "extra" ingredients are simply not worth the "extra" expense. On the other hand, due to the political situation, the home brew stack is becoming more expensive than some of the better herbal stacks.

    At any rate, the important thing is the ephedrine/caffeine content. The ephedrine/caffeine combination corrects a specific biochemical imbalance that is extremely common among the obese -- and there are decades of scientific research on this. Ignore the hype. Real science gets real results! If you have not done so, check out the illustrations in my post, "How ECA Works." As they say, "a picture is worth a thousand words."

    As discussed earlier in this FAQ, I prefer formulas that do not contain willow bark. I also do not recommend formulas that contain synephrine -- based on its mode of action, it is unlikely to increase fat burning. And these formulas are almost always more expensive. Although yohimbe is a legitimate thermogenic, I do not recommend formulas that combine ephedrine (or related alkaloids) and yohimbe. I have experimented with these combinations and after a short period of time the body temperature returns to the same level as with plain ephedrine/caffeine formulas. So what's the point of taking additional stimulants?

    When Dulloo and Miller screened drugs to determine their thermogenic potential, they were looking for a way to normalize the sympathetic tone and adrenergic biochemistry of obese people -- without the problems associated with most stimulants. The synergistic effect of caffeine made it possible to normalize our biochemistry with a low dose of ephedrine. The result was ECA -- the safest and most effective obesity drug in existence. Obesity is a real disease and we would be well advised to ignore the endless marketing hype and follow the path blazed by scientists like Dulloo, Miller, Stock, Rothwell, Arch, and others.
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    Other References:

    1.) Astrup A and Toubro S "Thermogenic, metabolic, and cardiovascular responses to ephedrine and caffeine in man" Int J Obes Relat Metab Disord 1993, Vol 17 Suppl 1 Pg S41-3, PMID: 0008384179.

    2.) Astrup A, Toubro S, Cannon S, Hein P, Madsen J "Thermogenic synergism between ephedrine and caffeine in healthy volunteers: a double-blind, placebo-controlled study" Metabolism 1991, Vol 40 (3), Pg 323-9, PMID: 0002000046.

    3.) Toubro S, Astrup A, Breum L, Quaade F "The acute and chronic effects of ephedrine/caffeine mixtures on energy expenditure and glucose metabolism in humans" Int J Obes Relat Metab Disord 1993, Vol 17 Suppl 3 Pg S73-7; discussion S82. PMID: 0008124407.

    4-BK.) Mowrey, Daniel B. Ph.D. "Fat Management : The Thermogenic Factor" Victory Publications, 1994. ISBN: 0-936261-07-2.

    5.) Dulloo AG and Miller DS "Screening of drugs for thermogenic anti-obesity properties: antidepressants" Ann Nutr Metab 1987, Vol 31 (2), Pg 69-80, PMID: 0003592617.

    6.) Dulloo AG and Miller DS "Thermogenic drugs for the treatment of obesity: sympathetic stimulants in animal models" Br J Nutr 1984, Vol 52 (2), Pg 179-96, PMID: 0006477859.

    7.) Massoudi M, Evans E, Miller DS "Thermogenic drugs for the treatment of obesity: screening using obese rats and mice" Ann Nutr Metab 1983, Vol 27 (1), Pg 26-37, PMID: 0006830140.

    8.) Dulloo, AG "Ephedrine, xanthines and prostaglandin-inhibitors: actions and interactions in the stimulation of thermogenesis." Int J Obes 1993 Feb, Vol 17 (Suppl 1), Pg S35-40, PMID: 0008384178.

    9.) Liu YL, Toubro S, Astrup A, Stock MJ "Contribution of beta 3-adrenoceptor activation to ephedrine-induced thermogenesis in humans" Int J Obes Relat Metab Disord 1995 Sep, Vol 19 (9), Pg 678-85, PMID: 0008574280.

    10.) Toubro S, Astrup A, Breum L, Quaade F "The acute and chronic effects of ephedrine/caffeine mixtures on energy expenditure and glucose metabolism in humans." Int J Obes Relat Metab Disord 1993 Dec, Vol 17 (Suppl 3), Pg S73-7; discussion S82, PMID: 0008124407.

    11-NA.) Dulloo AG and Stock MJ "Ephedrine in the treatment of obesity" Int J Obes Relat Metab Disord 1993, Vol 17 Suppl 1 Pg S1-2, PMID: 0008384172.

    12.) Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, Chantre P, Vandermander J "Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans" Am J Clin Nutr 1999, Vol 70 (6), Pg 1040-5. PMID: 0010584049.

    13.) Astrup A, Breum L, Toubro S, Hein P, Quaade F "The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet. A double blind trial" Int J Obes Relat Metab Disord 1992, Vol 16 (4), Pg 269-77. PMID: 0001318281.

    14.) Breum L, Pedersen JK, Ahlstrom F, and Frimodt-Moller J. "Comparison of an ephedrine/caffeine combination and dexfenfluramine in the treatment of obesity. A double-blind multi-centre trial in general practice." Int J Obes Relat Metab Disord. 1994 Feb, 18(2):99-103, PMID: 0008148931.

    15.) Lazarou J, Pomeranz BH, and Corey PN. "Incidence of adverse drug reactions in hospitalized patients: a meta- analysis of prospective studies." JAMA. 1998 Apr 15; 279(15):1200-5, PMID: 0009555760.

    16-NA.) "Alternative medicine--how safe is it? [editorial]" Adverse Drug React Toxicol Rev 1998 Nov, Vol 17 (4), Pg 205-7, PMID: 10196625.

    17.) Young JB and Macdonald IA. "Sympathoadrenal activity in human obesity: heterogeneity of findings since 1980." Int J Obes Relat Metab Disord. 1992 Dec; 16(12):959-67, PMID: 0001335975.

    18.) Bryde Andersen H, Raben A, Astrup A, Christensen NJ "Plasma adrenaline concentration is lower in post-obese than in never- obese women in the basal state, in response to sham-feeding and after food intake" Clin Sci (Colch) 1994, Vol 87 (1), Pg 69-74. PMID: 0008062522.

    19-NA.) Andersen HB, Raben A, Astrup A, Christensen NJ "Plasma adrenaline increases during sham-feeding in normal subjects but not in post-obese women" Int J Obes Relat Metab Disord 1993, Vol 17 Suppl 3 Pg S96; discussion S97. PMID: 0008124413.

    20.) Curran PK and Fishman PH "Endogenous beta 3- but not beta 1-adrenergic receptors are resistant to agonist-mediated regulation in human SK-N-MC neurotumor cells" Cell Signal 1996, Vol 8 (5), Pg 355-64, PMID: 0008911684.

    21.) Langin D, Tavernier G, Lafontan M "Regulation of beta 3-adrenoceptor expression in white fat cells" Fundam Clin Pharmacol 1995, Vol 9 (2), Pg 97-106, PMID: 0007628838.

    22.) Lipworth BJ "Clinical pharmacology of beta 3-adrenoceptors" Br J Clin Pharmacol 1996, Vol 42 (3), Pg 291-300, PMID: 0008877018.

    23.) Nantel F, Bouvier M, Strosberg AD, Marullo S "Functional effects of long-term activation on human beta 2- and beta 3- adrenoceptor signalling" Br J Pharmacol 1995, Vol 114 (5), Pg 1045-51, PMID: 0007780639.

    24.) Dulloo AG and Miller DS "The thermogenic properties of ephedrine/methylxanthine mixtures: human studies" Int J Obes 1986, Vol 10 (6), Pg 467-81, PMID: 0003804564.

    25-NA.) Pasquali R and Casimirri F "Clinical aspects of ephedrine in the treatment of obesity" Int J Obes Relat Metab Disord 1993, Vol 17 Suppl 1 Pg S65-8, PMID: 0008384185.

    26.) Astrup A, Lundsgaard C, Madsen J, Christensen NJ "Enhanced thermogenic responsiveness during chronic ephedrine treatment in man" Am J Clin Nutr 1985, Vol 42 (1), Pg 83-94, PMID: 0004014068
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    Old post from teenbodybuilding.com...

    http://www.teenbodybuilding.com/brent14.htm
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