Natural Foods Merchandiser

Wondering About Weight Loss

Ephedra (Ephedra sinica) is also known as Ma Huang and grows in Asia, Europe and the United States. The herb contains ephedrine and other similar alkaloids—including pseudoephedrine, norephedrine, norpseudo-ephedrine and methylephedrine—and acts as a stimulant. Ephedra in dietary weight loss supplements is typically standardized to contain 6 percent to 8 percent of the active ephedrine alkaloids.

Since the 1980s, more than 150 scientific papers have been published on synthetic ephedrine, and there has been an increasing number of studies on ephedra. Almost 90 percent of the studies examining ephedrine-containing products of synthetic or herbal origin report a positive effect on body weight with modest side effects, whereas a few papers and individual reports contain minor to major side effects. For most, the benefits of weight reduction override the potential risks associated with weight loss products.

Caffeine, also a stimulant, is used with ephedra to enhance its thermogenic effects. Thermogenesis is the process of increasing an individual's metabolic or calorie-burning rate. Burned calories are sometimes fat cells, but not always.

Ephedra-caffeine Product Efficacy
To date, only a few published herbal ephedra/caffeine studies have systematically examined product safety and efficacy for prolonged periods. And only one published full-length study has used pure ephedra and a botanical caffeine source. C.N. Boozer and colleagues published results of this six-month herbal ephedra-caffeine study.1 In this study, 167 subjects were randomized to receive either the herbal ephedra-caffeine combo (90 mg ephedra and 192 mg caffeine daily) or a placebo. All subjects were asked to eat normally, but restrict their fat intake (consistent with the guidelines of the American Heart Association) and to walk three times a week for exercise (30 minutes per session). Subjects were initially monitored weekly and thereafter monthly for the duration of the study. Researchers monitored blood pressure, heart rate and weight and also administered electrocardiograms, blood work and symptom questionnaires. This allowed for monitoring perceived and actual side effects.

Ephedra's health risks have prompted lawsuits, bans and the removal of products from shelves. For more on the controversial herb, see "Governments Continue Crackdown on Ephedra" and "Ban Threats Speed Ephedra Decisions," NFM January 2003.
The results indicated the herbal ephedra-caffeine combo caused twice the weight loss of placebo (approximately 5.3 kg versus 2.6 kg) and 1.6 times greater reduction in body fat (4.3 percent versus 2.7 percent). Researchers also found the herbal treatment caused small changes in blood pressure and heart rate, but no cardiac arrhythmias (by Holter monitor and EKG evaluations, respectively). The small changes in blood pressure caused three people in the placebo group and two people in the treatment group to drop out of the study. When data were examined for before and after changes, there were no significant differences in blood pressure measurements between the groups. Self-reported adverse events included dry mouth, heartburn and insomnia (higher in treatment versus placebo); however, all other adverse events were similar between groups. The authors concluded: "Herbal ephedra/caffeine, when used as directed by healthy overweight men and women in combination with healthy diet and exercise habits, may be beneficial for weight reduction without significantly increased risk of adverse effects." The authors caution that study results may not apply for those with medical conditions. Also, the ratio of ephedrine to caffeine in the product used is different from products currently available, which could explain the severity of side effects.

These same researchers examined the weight loss product Metabolife-356.2 San Diego, Calif.-based Metabolife Inc. sponsored the eight-week study in which overweight men and women who were otherwise relatively healthy took either a placebo or 72 mg of ephedrine alkaloids and 240 mg of caffeine daily. When diet and exercise were similar, there was a significant difference in weight loss and fat loss between those taking the ephedra-caffeine product and placebo. Subjects taking ephedra-caffeine lost four times as much weight and 10 times as much body fat as those on placebo. The most frequent adverse events in the ephedra-caffeine group were anxiety, headaches and insomnia. More than 20 percent of those in the ephedra-caffeine group dropped out or were removed by a research physician because of adverse events potentially linked to the product—palpitations, elevated blood pressure, irritability—whereas none of those on placebo had any adverse events. The authors concluded the tested product caused a significant reduction in body weight, but because of the adverse events observed, longer-term studies were necessary.

Another study showed a branded product containing herbal ephedrine and caffeine was effective for weight loss.3 Researchers tested Xenadrine RFA-1 produced by Cytodyne Technologies of Manasquan, N.J. In the eight-week study, 30 overweight healthy adults were randomized to either the experimental or placebo group. All subjects were asked to mildly restrict their food intake (approximately 1,800 kcals per day) and participate in guided exercise three times a week. Researchers found those taking the ephedra-caffeine product lost a significantly greater amount of body weight and body fat percentage than those on placebo, but absolute body fat lost (in pounds) was not greater. There were no untoward effects on blood pressure, heart rate, serial EKGs or on blood tests measuring blood sugar, liver or kidney function. The authors concluded that within the confines tested, the supplement was safe and effective for weight reduction.

Researchers presented findings of a 12-week study comparing Xenadrine RFA-1 with the prescription medicine orlistat (Roche Pharmaceuticals' Xenical) for weight loss at the 2002 National Strength and Conditioning Association's annual meeting.4 The study involved healthy overweight women who were asked to follow a mildly restrictive diet (25 kcals per kg body weight), exercise three times a week and take a multivitamin/mineral daily. Those in the ephedra-caffeine group lost 4.58 kg while participants taking orlistat lost 1.63 kg, a statistically significant difference. Side effects were not noted in the study abstract presentation. This research deserves a full-length article and repetition by a second laboratory.

In 1999, researchers evaluated the effects of Mississauga, Ontario, Canada-based MuscleTech Research and Development's Hydroxycut.5 This eight-week study involved 24 overweight healthy adult subjects. The researchers wanted to see if the herbal ephedra-caffeine product promoted weight loss without exercise, so they split the group into three. One group received the ephedra-caffeine supplement and exercised, the second group took ephedra-caffeine and did not exercise and the third group took placebo and exercised. Subjects who exercised did so for 30 minutes three times a week. At the end of the study, subjects taking ephedra-caffeine and exercising lost 3.8 kg, but the two other groups did not lose significant weight. The nonexercising ephedra-caffeine group had significantly suppressed appetites. Ephedra-caffeine did not cause significant adverse events or changes in blood pressure, heart rate or serial EKGs, nor in hydration status or blood work. The authors concluded the appetite suppressing effects of herbal ephedra-caffeine deserved more attention, and that different forms of exercise in conjunction with ephedra-caffeine for weight loss should be evaluated.

The Hydroxycut ephedra-caffeine formula used in the published studies is no longer available, so prior safety and efficacy data may not be applicable to the current product. The two main ingredients (herbal ephedra and caffeine) remain unchanged in the current formulation, however.

Synthetic Ephedra-caffeine And Athletic Performance
Scientists have investigated the effects of ephedrine or ephedrine plus caffeine on exercise performance in healthy people. The combination has more of an effect on exercise than ephedrine alone. In one study, the participants given 81 mg ephedrine and 405 mg caffeine experienced increased heart rate during exercise (compared with placebo), increased ability to exercise longer and the perception that exercise was easier.6 In a follow-up study, researchers tested ephedra-caffeine in the Canadian military and reported that 75 mg of ephedrine and 275 mg of caffeine allowed healthy male subjects to run faster and feel like they exerted themselves less than those taking placebo.7 Although these studies demonstrate ephedra-caffeine has a positive impact on certain aspects of exercise, the degree to which the combination enhances performance has not been established. Also, to date, there is no published research evaluating the performance effects of herbal ephedra-caffeine.

Cautions, Caveats And Dose
Herbal ephedra-caffeine, its synthetic relative ephedrine and the combination of ephedrine and caffeine all can have side effects.8 For this reason, anyone interested in using such products should have a health care provider's approval first. Side effects associated with ephedra-caffeine include dizziness, headache, tremor, depressed mood, euphoria, insomnia, dry mouth, postural low-blood pressure (hypotension), increased blood pressure (hypertension), palpitations, racing heart (tachycardia) and constipation. Researchers also have noted nervousness, transient increased blood sugar values and increased sweating. Because ephedrine and ephedra-caffeine are stimulants, stroke and heart attack are also possible side effects. In the largest published report on ephedrine, CANTOX Health Services International, based in Mississauga, Ontario, Canada, determined that a 90 mg daily dose, separated into three 30 mg doses, results in no adverse events.9 CANTOX researchers also found that side effects are typically observed with a 150 mg daily dose. In most of the clinical studies, side effects associated with ephedra-caffeine subside after three to four weeks. The CANTOX report indicates that to avoid side effects, ephedrine doses should not exceed 90 mg per day. Anyone with blood pressure problems, especially high blood pressure, thyroid disease, depression, diabetes, prostate enlargement or peptic ulcers should avoid ephedrine. Further, anyone taking MAO inhibitors should not take ephedrine.

The most common dose of ephedrine is 20 mg three times daily. Often this is combined with caffeine in a 1:10 ratio—every 20 mg ephedra is typically paired with approximately 200 mg caffeine. However, herbal ephedra-caffeine, which includes various other ephedrine alkaloids and constituents, has not been directly compared with synthetic ephedra-caffeine for effectiveness or safety.

Label Accuracy
The University of Arkansas pharmacology department analyzed 20 commonly available herbal ephedrine products to see if label content matched product content.10 All but one product tested contained herbal ephedrine. However, the amount varied greatly from 1.09 mg to 15.33 mg per capsule. Many product labels did not specify whether the label claim for ephedrine was for ephedra alkaloids or the chemical ephedrine. Thus, the analysis showed that products may not contain what the labels state, and that it is wholly possible ingredient doses will vary from batch to batch. The analysis also showed 55 percent of the supplements either failed to make an ephedra alkaloid claim or exceeded the amount on the label by 20 percent. Product variability ranged from 0 percent to 154 percent of the label claims.

The Future Of Ephedra-caffeine Supplements
Although research so far indicates ephedra-caffeine products, when combined with a healthy diet and exercise, can help people lose weight, there is still much to learn. Certainly more research is needed to ascertain the mechanism of action, safety and efficacy of ephedra-caffeine products, to provide data for products prior to marketing, to strengthen patent applications and to build a better reputation with retailers, consumers and the medical community. In the meantime, urge customers to work with a health care provider if they want to include ephedra-caffeine formulas in their weight loss programs.

Douglas S. Kalman M.S., R.D., F.A.C.N., is a director at Miami Research Associates (, an independent research company that conducts pharmaceutical and dietary supplements clinical studies. He is a spokesperson for the American College of Sports Medicine and a fellow of the American College of Nutrition. He can be reached at [email protected].

Disclosure: Kalman's corporate employees have received research grants from several ephedra-caffeine marketers, including Cytodyne Technologies and MuscleTech R&D. Kalman has also served as an expert witness for Cytodyne.


1. Boozer CN, et al. Herbal ephedra/caffeine for weight loss: a six-month randomized safety and efficacy trial. Int J Obesity 2002;26:593-604.

2. Boozer CN, et al. An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial. Int J Obesity 2001;25:316-24.

3. Kalman DS, et al. Effects of a weight loss aid in healthy overweight adults: double-blind, placebo controlled clinical trial. Curr Ther Res Clin Exp 2000;61:199-205.

4. Colker CM, Swain MA. A randomized comparative study evaluating a non-prescription ephedrine-based dietary supplement versus a prescription fat blocking medication for weight loss in healthy overweight women. Poster sessions—2002 NSCA National Conference, Las Vegas.

5. Colker CM, et al. Double-blind placebo-controlled evaluation of the safety and efficacy of ephedra, caffeine and salicin for short-term weight reduction in overweight subjects. J Exer Physiol-online 1999;2(4). Available:

6. Bell DG, et al. Effects of caffeine, ephedrine and their combination on time to exhaustion during high-intensity exercise. Eur J Appl Physiol Occup Physiol 1998;77(5):427-33.

7. Bell DG, Jacob I. Combined caffeine and ephedrine ingestion improves run times of Canadian Forces warrior test. Aviat Space Environ Med 1999;70(4):325-9.

8. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000;343:1833-88.

9. Council for Responsible Nutrition. Safety assessment and determination of a tolerable upper limit for ephedra. Prepared by CANTOX Health Services International. Dec. 19, 2000. Available:

10. Gurley BJ, et al. Content versus label claims in ephedra-containing dietary supplements. Am J Health-Syst Pharm 2000;57.

Natural Foods Merchandiser volume XXIV/number 2/p. 54, 56

Myths and Misrepresentations

Probably the biggest myth regarding thermogenics was recently published by the New England Journal of Medicine.1 In an analysis of the cardiovascular and central nervous system effects associated with the use of ephedra-containing dietary sup-plements, doctors Haller and Benowitz state, "...our findings arouse concern about the risks of these products, given that they have no scientifically established benefits." Because there are more than 150 scientific studies published since the mid-1980s, I believe Haller and Benowitz, along with the publication's reviewers, ignored a large body of evidence demonstrating that ephedrine and caffeine are effective weight loss aids.

At least 20 studies show ephedra-caffeine therapy is beneficial for weight loss at doses of 50­150 mg per day of ephedrine (in divided doses throughout the day).2 Many clinical studies support ephedra's use for other conditions, but its greatest benefit may be to the obese. For the overweight and obese, ephedra-caffeine has both safety and efficacy data to support its use in healthy people. Wise use includes involving a health care provider.


1. Haller CA, Benowitz NL. Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000; 343:1833-88.

2. Council for Responsible Nutrition. Safety assessment and determination of a tolerable upper limit for ephedra. Prepared by CANTOX Health Services International. 2000 Dec 19. Available:

Natural Foods Merchandiser volume XXIV/number 2/p. 56

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