Although published studies support ephedra?s utility as a weight-control agent, political heat is forcing manufacturers and suppliers to look beyond ma huang. Leading researcher Richard B. Kreider, PhD, surveys the potential of various ephedra alternatives in fighting the battle of the bulge.
Supplements containing synthetic and herbal sources of ephedrine and caffeine (EC) have been reported to safely and effectively promote weight loss in a number of clinical trials.1-5 Despite this impressive efficacy and safety record, the US Food and Drug Administration (FDA) and the medical community continue to warn against the use of EC-containing supplements. Their rationale is based on medical case reports submitted to the FDA's Adverse Event Monitoring System that suggest a link between people who have taken ephedrine-containing supplements and resulting medical complications, such as high blood pressure, elevated heart rate, arrhythmias and stroke.6
Although attempts to ban the sale of over-the-counter supplements containing ephedrine alkaloids have been unsuccessful in the US, considerable political pressure continues to limit the sale of ephedrine-containing supplements. For example, several speakers at the recent conference on performance-enhancement products hosted by the National Institutes of Health/Office of Dietary Supplements (NIH/ODS) and Council for Responsible Nutrition (CRN) said that athletes seeking to enhance performance were taking "dangerous" ephedra (Ephedra sinica) supplements that caused "serious side effects." One speaker indicated that the American Medical Association (AMA) plans to pressure Congress to ban all over-the-counter supplements containing ephedrine alkaloids and require companies to list possible side effects and drug interactions on supplement labels and to report adverse events.
Given this political climate, it would seem prudent for the supplements industry to take several courses of action.
Demonstrated safety and efficacy would make it difficult for the FDA to champion legislation limiting the sale of ephedrine-containing supplements. However, this would require that each supplement formulation that contains ephedrine alkaloids be tested in order to rule out any possible adverse synergistic activity with various other ingredients that may be found in a particular formulation—clearly a challenge, given the hundreds of products in different combinations on the market.
Weight-loss supplements typically can be classified in one of six categories as described in the table above. Ideally, an effective nonephedra-containing weight-loss supplement would help increase basal metabolic rate (BMR) and/or suppress appetite without stimulating the sympathetic nervous system or providing controversial thyroid-stimulating hormones. Moreover, it should be an inexpensive supplement/dietary strategy that can be used safely in a variety of populations without adverse side effects. The following strategies and nutrients may possess some of these characteristics.
- Diet foods, meal replacement powders (MRP) and ready-to-drink (RTD) supplements are probably the best alternative to using ephedrine-containing thermogenic supplements. These low-carbohydrate, low-fat, high-protein foods help maintain a low-calorie diet (LCD, typically 5001,500 calories/day) and research indicates that they are a safe and efficacious way of achieving significant weight loss.
- For example, researchers in Norway reported that 127 overweight volunteers who maintained a low-calorie diet for eight weeks experienced 12.7kg (12.6 per cent) loss in total body mass, 9.5kg loss in body fat (23.8 per cent), and 3.2kg (5.2 per cent) loss in lean body mass. Researchers at West Virginia University reported that the addition of a resistance-training programme whilst maintaining a VLCD (800 kcal/day for 12 weeks) resulted in a better preservation of lean body mass and resting metabolic rate (RMR) compared with subjects maintaining a low-calorie diet whilst engaged in an endurance training regimen.8
In a study conducted at Cedars-Sinai Medical Center in Los Angeles, researchers reported that a medically supervised weight-loss programme involving behavioral modification and a low-calorie diet resulted in 23kg weight loss and that 61 per cent of the participants maintained at least 50 per cent weight loss at 12 and 18 month follow-ups.9 Finally, Arizona State University researchers recently reported that postprandial thermogenesis increased 100 per cent on a high-protein, low-fat diet vs. a high-carbohydrate, low-fat diet in healthy young women.10
These and other findings indicate that maintaining a hypocaloric diet (typically using high-protein MRPs and/or RTDs) can promote weight loss, particularly when combined with a comprehensive exercise and behavioral modification programme. This segment of the nutrition industry offers an effective alternative for individuals wishing to lose weight without using ephedra-containing supplements.
- Sympathetic nervous system (SNS) mitigators address one of the common complaints about EC-containing supplements—that they overstimulate the SNS, leading to nervousness, increased heart rate, elevated blood pressure and increased susceptibility to cardiac arrhythmias in some individuals.6 An area of emerging research is to identify nutrients that may mitigate some of these potential sympathmimetic side effects while promoting the positive effects on weight loss.
Although studies in this area are limited, one group of researchers recently presented their findings on the use of saw palmetto (Serenoa repens) extract with an EC supplement.11 In this study, five healthy, overweight adults took 15mg ephedrine and related alkaloids, 150mg caffeine, and 720mg saw palmetto extract twice daily for 14 days. Subjects were given a series of tests prior to supplementation and at 3, 7 and 14 days of supplementation. Results revealed that EC with saw palmetto had no effects on heart rate variability, blood pressure, blood glucose, serial EKGs, sleep quality/habits or perception of stress. In addition, there was a significant trend toward weight and body-fat reduction as well as increased vigor. The researchers suggested that although more studies are needed, the addition of saw palmetto to EC supplements may blunt the sympathomimetic response to EC supplements whilst promoting weight and fat loss. This may allow more people to tolerate EC-containing supplements for weight loss.
- Green tea contains high amounts of caffeine and catechin polyphenols, which possess antioxidant properties. Consequently, green tea has primarily been marketed as an antioxidant supplement.12 However, researchers theorise that green tea increases energy expenditure by stimulating brown adipose tissue (BAT) thermogenesis.
In one study, researchers at the University of Fribourg, Switzerland, concluded that green tea supplementation (90mg epigallocatechin gallate) in combination with 50mg caffeine significantly increased 24-hour energy expenditure and fat utilisation in humans.13,14 The thermogenic effects of green tea supplementation were much greater than when an equivalent amount of caffeine was evaluated, thereby suggesting a synergistic effect. (There was little to no effect with caffeine alone, but adding caffeine promoted a greater effect than when green tea was used alone. This response is similar to the synergistic activity of ephedrine, caffeine and aspirin.)
Theoretically, increases in energy expenditure may help individuals lose weight and/or manage body composition. For this reason, some supplements manufacturers are adding green tea to thermogenic supplements and are marketing green tea as a weight-loss supplement. Although these reports about green tea hold promise, additional research is necessary to determine whether green tea supplementation actually does promote weight loss before conclusions can be drawn.
- Phosphates, specifically the role of sodium and calcium phosphate on energy metabolism and exercise performance, have been studied for decades.15 These studies reveal that sodium phosphate supplementation appears to possess ergogenic (performance-enhancing) properties, particularly in endurance exercise events.
More recently, researchers have suggested that phosphate supplementation may affect energy expenditure. For example, in such a study, researchers in Poland reported that phosphate supplementation during a four-week weight-loss programme increased RMR and respiratory exchange ratio among 36 obese women. This suggests greater carbohydrate utilisation and caloric expenditure during submaximal cycling exercise.16 In addition, these same researchers reported that phosphate supplementation during an eight-week weight-loss program increased RMR by 12 to 19 per cent and prevented a normal decline in thyroid hormones.17 Although the rate of weight loss was similar in this trial, results suggest that phosphate supplementation may influence the metabolic rate, possibly by affecting thyroid hormones. Consequently, phosphate could serve as a potential thermogenic nutrient in nonephedrine-based supplements.
- 7-Keto DHEA is marketed as a more effective form of dehydroepiandrosterone (DHEA), levels of which have been reported to decline with age in humans.18 This decline has been associated with increased fat accumulation and risk of heart disease.19 Since DHEA is a naturally occurring compound, it has been suggested that dietary supplementation of DHEA may help maintain DHEA availability, maintain and/or increase testosterone levels, reduce body fat accumulation, and/or reduce risk of heart disease as one ages.19-21
Although animal studies have generally supported this theory, the effects of DHEA supplementation on body composition in human trials have been mixed.20,21 Enter 7-Keto DHEA, a metabolite of DHEA that is believed to have DHEA-like properties. However, unlike DHEA, it is not converted into the sex steroids testosterone and estrogens in vivo, which may cause some unwanted side effects.
Although data are limited, one group of researchers reported that 200mg/day 7-Keto DHEA supplementation during eight weeks of training promoted a greater loss in body mass and fat mass while increasing the thyroid hormone triiodothyronine (T3).22 No significant effects were observed on thyroid stimulating hormone (TSH), thyroxine (T4) or other hormones. Although more research is needed, these findings help support 7-Keto DHEA's role as an effective weight-loss supplement. There is limited safety and efficacy data on 7-Keto DHEA. Although this study indicated it is well-tolerated, long-term effects of increasing T3 need to be examined further.
Ephedrine-containing supplements will continue to be controversial, moreso because of politics than from hard science.
- Forskolin (Coleus forskohlii) is a plant native to India that has been used for centuries in traditional Ayurvedic medicine, primarily to treat skin disorders and respiratory problems.23 It has been reported to reduce blood pressure, increase the heart's ability to contract, help inhibit platelet aggregation, improve lung function and aid in the treatment of glaucoma.23,24 With regard to weight loss, forskolin has been reported to increase cyclic adenosine monophosphate (AMP) and thereby stimulate fat metabolism.25,26 Theoretically, forskolin may therefore serve as an effective weight-loss supplement.
In support of this theory, researchers at Sabinsa Corporation (the principal source for forskolin standardised extracts in the US) reported that when six overweight female volunteers took 250mg of a 10 per cent forskolin extract twice daily for eight weeks, they lost 7.25 pounds of body weight and showed a 7.7 per cent loss of bioelectrical impedance (BIA)-determined body fat.27
These preliminary findings on a possible alternative to ephedrine-containing supplements provided some industry excitement. However, a recent study conducted in our lab reported that 250mg of a 10 per cent forskolin extract taken twice daily for 12 weeks did not significantly decrease body mass or dual energy X-ray absorptiometer (DEXA)-determined fat mass in a group of inactive obese women asked to maintain their normal diet and activity level.28 But the women who took the placebo gained weight, suggesting that forskolin may help mitigate weight gain in this population. Although these are not dramatic findings, it is possible that forskolin is beneficial to weight loss while maintaining a controlled diet and/or during a supervised exercise programme.
- Hydroxycitric acid (HCA), contained in Garcinia cambogia, is a nutrient that some researchers believe may increase fat oxidation by inhibiting citrate lyase and lipogenesis as well as by suppressing appetite. Theoretically, this may promote fat loss over time. Although most studies indicate that HCA supplementation (1.53g/day) does not affect energy expenditure or body composition in humans,29-31 a recent study presented at the 2002 Experimental Biology meeting in New Orleans may revitalise interest.32
In this randomised study, 48 participants took either 2,800mg HCA or a placebo 30 minutes prior to meals (i.e., 8.4g/day) for eight weeks. Both groups were placed on a 2,000 calories/day diet and engaged in a supervised walking program. Results revealed that subjects ingesting HCA lost 4.8 per cent of body weight and 6.8 per cent of body mass index over the eight-week period, whereas subjects in the placebo group lost 1.8 per cent and 2 per cent, respectively. In addition, there was some evidence that HCA improved blood lipid profiles and serum leptin levels. Although body composition was not measured in this study, these findings help support evidence that high-dose HCA supplementation may serve as an effective weight-loss supplement.
Science Vs. Politics
Well-controlled clinical research trials indicate that use of nutritional supplements containing ephedrine alkaloids promote weight loss with no significant adverse side effects in apparently healthy individuals. However, the sale and use of ephedrine-containing nutritional supplements will continue to be controversial since various groups exert political pressure to limit their availability.
Members of the nutrition industry should continue to conduct safety and efficacy studies on supplements containing ephedrine alkaloids, as well as explore various nonephedrine-containing nutritional alternatives to promote weight loss. Preliminary research suggests several nutrients may hold promise. An even greater number, some with limited effects, others of the 'too early to tell' variety, also wait in the wings . However, additional research is needed to examine safety and efficacy before conclusions can be drawn.
Richard B. Kreider, PhD, EPC, FACSM, FASEP, has published more than 150 research articles and abstracts in scientific journals. This month he takes a position as professor and chair of the department of health, human performance and recreation at Baylor University, Waco, Texas.
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