by Thomas Incledon, PhD(c), RD, LD/LN, RPT, NSCA-CPT, CSCS
Losing weight, slimming down and toning up are goals that many of us have. After countless hours of aerobics, days in the weight room, and living on enough food that would leave even Tweety Bird feeling hungry, there’s always some stubborn fat that stays behind. One strategy that is becoming increasingly popular is the use of fat burning compounds to elevate metabolism and increase fat loss while restricting calories. In this article, the natural and synthetic forms of the fat burning agent ephedrine will be compared. In addition, the effects of both types of products on weight loss will be examined and the side effects and concerns of both will be discussed.
Ephedrine: What is it?
Ephedrine has been available in both prescription and over-the-counter (OTC) forms as a bronchodilator since the 1950s. It is a drug that can mimic the effects of norepinephrine on other tissues and organs in the body. For this reason it is referred to as a sympathomimetic agent. It accomplishes these actions by either increasing the release of the neurotransmitter norepinephrine, or by binding to receptor sites for norepinephrine [1]. Norepinephrine is the same as noradrenaline, the structural cousin of the “fight or flight” hormone adrenaline. So, by stimulating a low level fight or flight response, ephedrine was thought to be a potentially useful compound for enhancing weight loss in obese subjects. Many studies have been done on weight loss and the effects of ephedrine alone and in combination with other agents [2-12].
Natural Ephedrine Containing Products
While ephedrine was being shown to be useful for weight-loss, unethical drug-chemists were also finding it could be converted into the street drug known as methamphetamine. In response, the FDA proposed stricter guidelines on the sale and distribution of ephedrine-containing over-the-counter (OTC) agents. This led to supplement companies, anxious to sell a product with a high-income potential, to seek out naturally occurring herbs that contained ephedrine. The most commonly used herb is Ma-Huang. This herb contains the dried stems of plants from the Ephedra species. This practice is believed to have been used by the Chinese for over 500 years [13, 14]. However, it was not until 1885 that ephedrine was first isolated from plants [15].
Today, we know that there are more then 40 species of Ephedra plants. These plants contain a variety of ephedrine-like compounds that can be referred to simply as alkaloids. The most abundant Ephedra alkaloid is ephedrine, but norephedrine, pseudoephedrine, methylephedrine, and norpseudoephedrine have also been reported [15]. Initially when herbal ephedrine preparations became available OTC, the amount or concentration of ephedrine was not standardized. That meant from one capsule to the next, different amounts of ephedrine could be present. In addition, the OTC herbal preparations could contain anywhere from 6-20 different alkaloids [16-19]. Now most companies list a standardized extract on the Supplement Facts label on the back of a product. It shows the serving size, such as 1 or 2 capsules, the amount of the extract, say 336 mg, and the standardized concentration of the extract, say 6%. To calculate how much ephedrine is in each serving, multiply the amount of the extract by the standardized concentration of the extract. In this example, 336 mg x 0.06 (6%) = 20.16, or about 20 mg. Unfortunately, what you don’t see is how much of the other alkaloids are in the product. These agents can also exert sympathetic-like actions on various tissues in the body. By not knowing exactly what you are getting, it is more difficult to avoid side effects. Since the Supplement Facts label does not list the other alkaloids and the content of the alkaloids can vary from product to product, it probably safest to assume that they are all present. The best that you can do is to check all of the possible contraindications for ingredients that could be in the herbal product and thereby avoid any potential side effects (these will be covered in part three of the series).
Ephedrine or Natural Version: Which is better?
Ephedrine is usually available OTC in a variety of products. The natural products are also readily available OTC, but along with the ephedrine you get other alkaloids.. A comparison of commercial supplements containing Ephedra and ephedrine tablets was done using five men and five women, all in the age range from 22 to 40 years of age [18]. The absorption rates of ephedrine from the Ephedra supplements and the changes in plasma ephedrine concentrations were very similar to ephedrine administration. From this data alone, one might assume that as long as the herbal products contain ephedrine, the biological effects and actions should be similar. However, we know that on a gram by gram basis, commercial supplements can provide anywhere from 0.3 to 56 mg/g of alkaloids [16]. Some products did not contain any ephedrine, while others contained ephedrine and other alkaloids. It may be possible that there is a synergistic effect of the alkaloids. If this is the case, then sympathetic stimulation may be greater. Could this result in greater weight loss? Or could you lose more fat and less muscle than dieting alone? Science hasn’t answered these questions yet. While the absorption and plasma changes of ephedrine may be similar for herbal products and ephedrine, what has yet to be studied are the combined absorption and plasma changes of all the alkaloids in herbal supplements.
Anecdotally, many people claim that they feel more energetic and lose weight faster after using a variety of the herbal supplements. While this may or may not be true (we have to allow that there may be a possible placebo effect), it should be pointed out that it isn’t known if the effects are due to the actions of the ephedrine, another alkaloid, or some combination. So if you want greater control over what you are taking, then stick with ephedrine products. If you want the potential to burn additional fat, due to the presence of more alkaloids, then go with an herbal preparation. In the next part of this series, the dosages used in research for weight loss will be covered.
For many people, dieting alone to lose weight is not easy. Exercise with calorie counting or fat counting is the most effective method for losing weight and should always remain the first choice for weight loss. But today everyone wants a quick and easy way to lose weight. Part 1 of this series examined the differences between ephedrine and natural herbal products containing ephedrine. This article presents the effects of both products on weight loss. The side effects and concerns of ephedrine containing products will be presented in part three, so read all three parts prior to making a decision on the use of ephedrine-containing products as part of your weight loss strategy.
Getting Started
From a mathematical model, weight gain or weight loss simply occurs as the result of calories going into the body exceeding calories going out of the body. In more simple words this means that you eat more than you burn off. There are many factors that influence how much food we eat and what our activity levels are. In terms of a weight loss strategy, it makes more sense to begin an exercise program first, restrict calories next, and later on utilize other methods to assist with the weight loss if necessary. In future articles we will cover a variety of weight loss strategies.
Ephedrine, Metabolism and Weight Loss
Ephedrine is a stimulant. After a single dose, ephedrine can elevate metabolism at rest [20] and increase the metabolic response to a meal [21]. Since ephedrine can elevate metabolism, it was speculated that perhaps it would be effective as a weight loss agent in the treatment of obesity. Putting things into perspective, by elevating your metabolism, more kilocalories are burned per minute then you would normally burn. If you don’t eat more food to compensate for the additional kilocalories that you burn off from the ephedrine, it would seem logical to expect to lose some weight.
When 50 milligrams (mg) was given three times per day to some obese men and women, it did not cause any additional weight loss, but it did partially slow down the resting metabolism decline that occurs with weight loss [9]. The study was designed so that ephedrine was administered for only 2 weeks during a 6-week diet. The treatment was short (only 2 weeks) and body composition was not measured, so while this study hints at some potential of ephedrine, it’s effectiveness for weight loss was not demonstrated.
Ephedrine and Caffeine
The combination of 20 mg ephedrine + 200 mg caffeine was found to work better then either agent alone in stimulating fasting, resting metabolism [22]. In addition, the combination of 22 mg ephedrine, 30 mg caffeine, and 50 mg theophylline was also found to be more effective then ephedrine alone in increasing resting metabolic rate during fasted and fed conditions [23].
Since ephedrine and caffeine combinations appear more effective in elevating metabolism, it makes sense that their effectiveness as weight loss agents would be investigated. In a comparative study of dexfenfluramine vs 20 mg ephedrine + 200 mg caffeine, both treatments were found to be equally effective [3]. However, by week 15, the ephedrine + caffeine group appeared to still be losing weight, while the dexfenfluramine group appeared to reach a plateau [3]. While the final analysis did not show any statistical difference between the groups for all the subjects, it did show a significant effect of ephedrine + caffeine on weight loss in the more obese subjects. Perhaps a longer treatment period (greater then 15 weeks) would have shown significant effects for all subjects.
The effect of ephedrine on body composition was not analyzed very carefully in earlier studies. Previous evidence indicated that ephedrine may exert a nitrogen sparing effect [9]. If this is true, then one would expect more fat loss and less muscle loss while using ephedrine to lose weight. Since caffeine increases ephedrine’s metabolic effects, perhaps it would also enhance the protein sparing effects. Well, research from another lab indicated that ephedrine + caffeine may promote more fat loss while preserving lean body mass [24]. Additionally, in the same study, the researchers concluded that ephedrine and caffeine are not valid for weight loss independently, but when combined are effective in the treatment of obesity.
Ephedrine and Other Agents
In one study, 30 mg of ephedrine and 300 mg of aspirin increased the thermic effects of a meal in obese but not lean women [25]. However, the metabolic rates were only measured up to 160 minutes, which is less then 3 hours. The measurements of metabolic rate beyond 160 minutes, possibly up to 240 minutes, would have been more practical. In a later study, the same group found that 30 mg aspirin did not increase the thermic effect of 30 mg ephedrine + 100 mg caffeine [26]. However, metabolic rates were elevated in some women but not others, and metabolism was still elevated at 160 minutes [26]. So, the short-term evidence regarding the use of aspirin increasing the metabolic effects of ephedrine and caffeine in women is still unclear. Long term studies on the impact of aspirin on weight loss have yet to be published.
In rat studies, the amino acid L-tyrosine has been shown to increase the appetite suppressing effects of ephedrine [27] and a constituent of hot red pepper capsaicin has been shown to increase brown adipose tissue thermogenesis (conversion of stored fat energy into heat energy) [28]. At present there is no published research in humans on the effects of products containing ephedrine, caffeine, and/or aspirin, and/or tyrosine, and/or capsaicin on weight loss. Future research on these combinations is needed to determine if they are effective and safe.
Things to Consider
Now you may be wondering where the weight loss research is on natural herbal products containing ephedrine and caffeine. Unfortunately, after a thorough Medline search, no research studies were found on Ephedra products and weight loss. So can the scientific evidence from ephedrine and caffeine studies apply to herbal preparations containing the same agents? If the herbal agents contain only ephedrine and caffeine then you would expect the same results that were found in the studies, as long as the same dosages are used. However, as pointed out in the last article, most herbal products contain more then just ephedrine or caffeine. There are several studies in the works right now on the effects of herbal products on weight loss. In the near future we should be able to have more definitive information regarding herbal products. For now, consider these points:
The most effective dosages for elevating metabolism and inducing weight loss were either 20 mg ephedrine and 200 mg caffeine or 22 mg ephedrine, 30 mg caffeine, and 50 mg theophylline. The two dosages were never compared on the same subjects, so we can’t say which of the two is more effective. Most companies currently sell herbal products that offer about 20 mg ephedrine and 200 mg caffeine as part of a standardized extract. These dosages were given three times per day in the previous studies. Taking more may not be safe since there is limited data on higher dosages.
No studies compared the effects of ephedrine and caffeine against exercise, or the effects of ephedrine and caffeine on the results from exercise-induced weight loss. In my private practice, many people anecdotally report that the herbal products help them lose weight. I find that later they regain the lost weight. Taking weight loss agents without making the necessary lifestyle changes (reducing excessive food intake and increasing physical activity) may be a plan for failure. Exercise first, diet second, and then try the weight loss agents if you are stuck at a plateau. This will minimize your dependency on them and any potential side effects.
Complaints to the FDA
From 1993 to 1997, the FDA received more than 800 reports of problems associated with the use of over 100 ephedrine alkaloid-containing dietary supplements [29]. The complaints included “nervous system and cardiovascular system effects such as increased blood pressure, tremor, abnormal heart rhythm, seizure, psychosis, stroke, heart attack, and death. Most of these events occurred in otherwise healthy young to middle-aged adults using the products for weight control or increased energy” [29].
Information such as the complaints against ephedrine containing products is important and should not be taken lightly. Ephedrine and related alkaloids, while occurring naturally, can be powerful stimulants. Ephedrine has been implicated in cases of cardiomyopathy [30-32] psychosis [14, 33-35], and fatalities [13, 36, 37]. It would seem logical that any product containing ephedrine, such as an Ephedra extract, may also have the potential for such side effects. Sure enough, there are reports that Ephedra products were implicated in psychosis [38, 39], mania [40-43], and fatalities [15, 44, 45].
Sitting on the fence
When reviewing reports of adverse events, you could probably find enough facts to support both sides of the fence. On one side, you could find information that shows ephedrine-containing products are safe and on the other side, you could defend the position that ephedrine-containing products are dangerous. Over 800 complaints for a type of product seems like a large number until one considers the number of people using ephedrine-containing products. At the time of writing this article, an accurate estimate of ephedrine users is not available. Rather than scrutinizing each report or trying to accurately estimate what the incidence of adverse consequences is, a different approach may be more successful. Armed with information, you can make the best choices to minimize your chances of developing any adverse effects.
Taking products safely
If your goal is weight loss, an improved lifestyle is your first objective. Part of this improvement should be to incorporate regular physical activity into your life. The next part should be to tune-up your eating habits. After these strategies have been implemented and you still want to lose weight, only then would you consider the use of ephedrine-containing products. Many people find the side effects like elevated heart rate and raised blood pressure of these products to be tolerable. While a variety of studies have found ephedrine, alone and in conjunction with other agents, to be safe [2, 3, 5, 10, 11, 46, 47], you need to understand the parameters of this research. The total amount of ephedrine ingested per day ranged between 60-75 mg and was usually divided over three dosages (20-25 mg per dose). The subjects were pre-screened by a physician familiar with the side effects of ephedrine and its combinations. So if you want to take ephedrine-containing products, make sure that you read the label and find out what you are taking. Most importantly, find a physician who understands what your goals are and knows the potential problems associated with the use of ephedrine-containing products and who can pre-screen you to make sure there are no unforeseen complications. Remember to keep these products out of the reach of children. Avoid using ephedrine-containing products (or make sure that you have a doctor’s consent) if you are pregnant or nursing, have high blood pressure, heart or thyroid disease, diabetes, difficulty in urination due to prostate enlargement, or if taking monoamine oxidase (MOA) inhibitors or any other prescription drug. Reduce or discontinue use if nervousness, tremor, irritability, rapid heartbeat, sleeplessness, loss of appetite, or nausea occur.
Information, Education, and Resources
Many people enjoy the “energy boost” they get from these ephedrine-containing products and should keep in mind that situations of abuse can occur. Remember that taking too much of a stimulant can have dire consequences. To avoid excess consumption and/or an inadvertent dependence, consumers need to educate themselves on the potential dangers and safe ingestion limits of ephedrine-containing products. Access to medical databases like Medline (http://igm.nlm.nih.gov/index.html) or the International Bibliographic Information on Dietary Supplements (IBIDS) (http://odp.od.nih.gov/ods/databases/ibids.html) can help you to stay on top of the latest research on these and other products. In addition, checking the FDA website at (http://ww.fda.gov/) can give you safety information on ephedrine and other products.
So now that you know how to educate yourself what other concerns are there? Some supplements simply do not contain what their labels claim, and/or the labels encourage greater intake of these products than would be considered safe by most healthcare professionals. The problem in this case is not ephedrine, rather it is the fact that the label information is misleading. There are resources for you to use if you feel that an ephedrine –containing product has misleading information. If you have a physical problem from ingesting an ephedrine-containing product, the first thing is to seek medical attention. If you have an ethical concern, you can report a complaint at the FDA’s MEDWATCH website: http://www.fda.gov/medwatch. If you feel that you have been victimized, you can seek out legal help at http://www.civilrights.com/ephedra.html or http://ephedrainjury.com/index.html.
As consumers we expect that information associated with products is accurate and not misleading, but even more importantly, we expect that products be accurately labeled. One way this can be accomplished is by the random testing of supplements to verify that they meet label claims.
References:
1. Astrup, A., et al., Pharmacology of thermogenic drugs. Am J Clin Nutr, 1992. 55(1 Suppl): p. 246S-248S.
2. Astrup, A., et al., 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. 16(4): p. 269-77.
3. Breum, L., et al., 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. 18(2): p. 99-103.
4. Buemann, B., et al., The effect of ephedrine plus caffeine on plasma lipids and lipoproteins during a 4.2 MJ/day diet. Int J Obes Relat Metab Disord, 1994. 18(5): p. 329-32.
5. Daly, P.A., et al., Ephedrine, caffeine and aspirin: safety and efficacy for treatment of human obesity. Int J Obes Relat Metab Disord, 1993. 17 Suppl 1: p. S73-8.
6. Geissler, C.A., Effects of weight loss, ephedrine and aspirin on energy expenditure in obese women. Int J Obes Relat Metab Disord, 1993. 17 Suppl 1: p. S45-8.
7. Krieger, D.R., et al., Ephedrine, caffeine and aspirin promote weight loss in obese subjects. Trans Assoc Am Physicians, 1990. 103: p. 307-12.
8. Malecka-Tendera, E., Effect of ephedrine and theophylline on weight loss, resting energy expenditure and lipoprotein lipase activity in obese over-fed rats. Int J Obes Relat Metab Disord, 1993. 17(6): p. 343-7.
9. Pasquali, R., et al., Effects of chronic administration of ephedrine during very-low-calorie diets on energy expenditure, protein metabolism and hormone levels in obese subjects. Clin Sci (Colch), 1992. 82(1): p. 85-92.
10. Toubro, S., et al., The acute and chronic effects of ephedrine/caffeine mixtures on energy expenditure and glucose metabolism in humans. Int J Obes Relat Metab Disord, 1993. 17 Suppl 3: p. S73-7; discussion S82.
11. Toubro, S., et al., Safety and efficacy of long-term treatment with ephedrine, caffeine and an ephedrine/caffeine mixture. Int J Obes Relat Metab Disord, 1993. 17 Suppl 1: p. S69-72.
12. Toubro, S. and A. Astrup, Randomised comparison of diets for maintaining obese subjects’ weight after major weight loss: ad lib, low fat, high carbohydrate diet v fixed energy intake. Bmj, 1997. 314(7073): p. 29-34.
13. Backer, R., et al., Fatal ephedrine intoxication. J Forensic Sci, 1997. 42(1): p. 157-9.
14. Roxanas, M.G. and J. Spalding, Ephedrine abuse psychosis. Med J Aust, 1977. 2(19): p. 639-40.
15. Mack, R.B., “All but death, can be adjusted”. Ma Huang (ephedrine) adversities. N C Med J, 1997. 58(1): p. 68-70.
16. Betz, J.M., et al., Chiral gas chromatographic determination of ephedrine-type alkaloids in dietary supplements containing Ma Huang. J AOAC Int, 1997. 80(2): p. 303-15.
17. Flurer, C.L., et al., Determination of ephedrine compounds in nutritional supplements by cyclodextrin-modified capillary electrophoresis. J Chromatogr B Biomed Appl, 1995. 669(1): p. 133-9.
18. Gurley, B.J., et al., Ephedrine pharmacokinetics after the ingestion of nutritional supplements containing Ephedra sinica (ma huang). Ther Drug Monit, 1998. 20(4): p. 439-45.
19. Hanna, G.M., Determination of ephedrine, pseudoephedrine, and norephedrine in mixtures (bulk and dosage forms) by proton nuclear magnetic resonance spectroscopy. J AOAC Int, 1995. 78(4): p. 946-54.
20. Astrup, A., et al., Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man. Am J Physiol, 1985. 248(5 Pt 1): p. E507-15.
21. Evans, E. and D.S. Miller, The effect of ephedrine on the oxygen consumption of fed and fasted subjects. Proc Nutr Soc, 1977. 36(3): p. 136A.
22. Astrup, A., et al., Thermogenic synergism between ephedrine and caffeine in healthy volunteers: a double-blind, placebo-controlled study. Metabolism, 1991. 40(3): p. 323-9.
23. Dulloo, A.G. and D.S. Miller, The thermogenic properties of ephedrine/methylxanthine mixtures: human studies. Int J Obes, 1986. 10(6): p. 467-81.
24. Astrup, A., et al., The effect of ephedrine/caffeine mixture on energy expenditure and body composition in obese women. Metabolism, 1992. 41(7): p. 686-8.
25. Horton, T.J. and C.A. Geissler, Aspirin potentiates the effect of ephedrine on the thermogenic response to a meal in obese but not lean women. Int J Obes, 1991. 15(5): p. 359-66.
26. Horton, T.J. and C.A. Geissler, Post-prandial thermogenesis with ephedrine, caffeine and aspirin in lean, pre-disposed obese and obese women. Int J Obes Relat Metab Disord, 1996. 20(2): p. 91-7.
27. Hull, K.M. and T.J. Maher, L-tyrosine potentiates the anorexia induced by mixed-acting sympathomimetic drugs in hyperphagic rats. J Pharmacol Exp Ther, 1990. 255(2): p. 403-9.
28. Yoshida, T., et al., Effects of capsaicin and isothiocyanate on thermogenesis of interscapular brown adipose tissue in rats. J Nutr Sci Vitaminol (Tokyo), 1988. 34(6): p. 587-94.
29. Nightingale, S.L., From the Food and Drug Administration. JAMA, 1997. 278(1): p. 15.
30. Heyman, S.N., D. Mevorach, and J. Ghanem, Hypertensive crisis from chronic intoxication with nasal decongestant and cough medications. Dicp, 1991. 25(10): p. 1068-70.
31. To, L.B., et al., Ephedrine-induced cardiomyopathy. Med J Aust, 1980. 2(1): p. 35-6.
32. Van Mieghem, W., E. Stevens, and J. Cosemans, Ephedrine-induced cardiopathy. Br Med J, 1978. 1(6116): p. 816.
33. Herridge, C.F. and M.F. a’Brook, Ephedrine psychosis. Br Med J, 1968. 2(598): p. 160.
34. Lambert, M.T., Paranoid psychoses after abuse of proprietary cold remedies. Br J Psychiatry, 1987. 151: p. 548-50.
35. Whitehouse, A.M. and J.M. Duncan, Ephedrine psychosis rediscovered. Br J Psychiatry, 1987. 150: p. 258-61.
36. Garriott, J.C., et al., Five cases of fatal overdose from caffeine-containing “look-alike” drugs. J Anal Toxicol, 1985. 9(3): p. 141-3.
37. Bruno, A., K.B. Nolte, and J. Chapin, Stroke associated with ephedrine use. Neurology, 1993. 43(7): p. 1313-6.
38. Doyle, H. and M. Kargin, Herbal stimulant containing ephedrine has also caused psychosis [letter; comment]. Bmj, 1996. 313(7059): p. 756.
39. Kalix, P., The pharmacology of psychoactive alkaloids from ephedra and catha. J Ethnopharmacol, 1991. 32(1-3): p. 201-8.
40. Capwell, R.R., Ephedrine-induced mania from an herbal diet supplement [letter]. Am J Psychiatry, 1995. 152(4): p. 647.
41. Clovis, W.L., Mania and cough syrup [letter; comment]. J Clin Psychiatry, 1993. 54(5): p. 200.
42. Hoaken, P.C., Secondary mania: aggravation of a sub-clinical condition. Psychiatr J Univ Ott, 1987. 12(1): p. 47-8.
43. Lake, C.R., et al., Psychomotor stimulant-induced mania in a genetically predisposed patient: a review of the literature and report of a case. J Clin Psychopharmacol, 1983. 3(2): p. 97-100.
44. Josefson, D., Herbal stimulant causes US deaths [news]. Bmj, 1996. 312(7043): p. 1378-9.
45. Adverse events associated with ephedrine-containing products—Texas, December 1993-September 1995. MMWR Morb Mortal Wkly Rep, 1996. 45(32): p. 689-93.
46. Astrup, A., L. Breum, and S. Toubro, Pharmacological and clinical studies of ephedrine and other thermogenic agonists. Obes Res, 1995. 3 Suppl 4: p. 537S-540S.
47. Atkinson, R.L., et al., Combined drug treatment of obesity. Obes Res, 1995. 3 Suppl 4: p. 497S-500S.
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