New Weight-control Options

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.

Types of weight-loss supplements
  • Diet foods, meal replacement powders (MRP) and ready-to-drink (RTD) supplements
  • Appetite suppressants and fat blockers
  • Thermogenic products
  • Lipolytic nutrients
  • Psychotropic nutrients/herbs
  • Herbal diuretics
Fund clinical trials to document the safety and efficacy of ephedra- and caffeine-containing nutritional supplements.

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.

  • Coordinate a campaign to educate the public and medical community regarding the safety and efficacy of nutritional supplements containing ephedra so that people can make informed decisions regarding whether to use them or not.
  • Explore possible nutritional alternatives to ephedrine-containing weight-loss supplements. The following discussion describes some nutrients that recent research suggests may offer promise in promoting weight loss and therefore may serve as alternatives to ephedra-based supplements.

    Possible Alternatives
    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.

      Ephedrine-containing supplements will continue to be controversial, moreso because of politics than from hard science.
      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.
    • 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.


    1. Dulloo AG. Herbal simulation of ephedrine and caffeine treatment of obesity. Int J Obes 2002;26:590-2.

    2. Boozer CN, et al. An herbal supplement containing ma huang-guarana for weight loss: a randomized, double-blind trial. Int J Obes Relat Metab Disord 2001;25(3):316-24.

    3. Molnar D, et al. Safety and efficacy of treatment with an ephedrine/caffeine mixture. The first double-blind placebo-controlled pilot study in adolescents. Int J Obes Relat Metab Disord 2000;24(12):1573-8.

    4. Greenway FL, et al. Pharmaceutical cost savings of treating obesity with weight loss medications. Obes Res 1999;7(6):523-31.

    5. Boozer CN, et al. Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial. Int J Obes 2002;26:593-604.

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

    7. Hoie LH, et al. Reduction of body mass and change in body composition on a very low calorie diet. Int J Obes Relat Metab Disord 1993;17(1):17-20.

    8. Bryner RW, et al. Effects of resistance vs. aerobic training combined with an 800 calorie liquid diet on lean body mass and resting metabolic rate. Am Coll Nutr 1999;18(2):115-21.

    9. Kern PA, et al. Combined use of behavior modification and very low-calorie diet in weight loss and weight maintenance. Am J Med Sci 1994;307(5):325-8.

    10. Johnston CS, et al. Postprandial thermogenesis is increased 100% on a high-protein, low-fat diet versus a high-carbohydrate, low-fat diet in healthy, young women. J Am Coll Nutr 2002;21:55-61.

    11.Kalman D, et al. A pilot trial examining the influence of Serenoa repens upon sympathomimetic response to ephedra alkaloids and caffeine in healthy, overweight adults. Am J Clin Nutr 2002;75(2):S369.

    12. Nakagawa K, et al. Tea catechin supplementation increases antioxidant capacity and prevents phospholipid hydroperoxidation in plasma of humans. J Agric Food Chem 1999;47(10):3967-73.

    13. Dulloo AG, et al. Green tea and thermogenesis: interactions between catechin-polyphenols, caffeine and sympathetic activity. Int J Obes Relat Metab Disord 2000;24(2):252-8.

    14. Dulloo AG, et al. 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 2000;70(6):1040-5.

    15. Kreider RB. Phosphorus supplementation in exercise and sport. In: Driskell J, Wolinsky I, editors. Macroelements, water, and electrolytes in sports nutrition.Boca Raton (FL): CRC Press LLC;. 1999. p 29-46.

    16. Kaciuba-Uscilko H, et al. Effect of phosphate supplementation on metabolic and neuroendocrine responses to exercise and oral glucose load in obese women during weight reduction. J Physiol Pharmacol 1993;44:425-40.

    17. Nazar K, et al. Phosphate supplementation prevents a decrease of triiodothyronine and increases resting metabolic rate during low energy diet. J Physiol Pharmacol 1996;47:373-83.

    18. Denti L, et al. Effects of aging on dehydroepiandrosterone sulfate in relation to fasting insulin levels and body composition assessed by bioimpedance analysis. Metabolism 1997;46:826-32.

    19. De Pergola G, et al. Body fat accumulation is possibly responsible for lower dehydroepiandrosterone circulating levels in premenopausal women. Int J Obes 1996;20:1105-10.

    20. Nestler JE, et al. Dehydroepiandrosterone reduces serum low density lipoprotein levels and body fat but does not alter insulin sensitivity in normal men. J Clin Endocrinol Metab 1988;66:57-61.

    21. Vogiatzi MG, et al. Dehydroepiandrosterone in morbidly obese adolescents: effects on weight, body composition, lipids, and insulin resistance. Metabolism 1996;45:1011-5.

    22. Kalman DS, et al. A randomized double-blind, placebo-controlled study of 3-acetyl-7-oxo-dehydroepiandrosterone in healthy overweight adults. Curr Thera 2000;61:435-42.

    23. Ammon HPT, Müller AB. Forskolin: from an Ayurvedic remedy to a modern agent. Planta Medica 1985 Dec;473-7.

    24. de Souza NJ, et al. Forskolin: a labdane diterpenoid with antihypertensive, positive inotropic, platelet aggregation inhibitory, and adenylate cyclase activating properties. Med Res Rev 1983;3(2):201-19.

    25. Seamon KB, et al. Forskolin: unique diterpene activator of adenylate cyclase in membranes and in intact cells. Proc Nat Acad Sci USA 1981;78:3363-7.

    26. Litosch I, et al. Forskolin as an activator of cyclic AMP accumulation and lipolysis in rat adipocytes. Mol Pharmacol 1982;22:109-15.

    27. Badmaev V, et al. Diterpene forskolin (Coleus forskohlii, Benth.): A possible new compound for reduction of body weight by increasing lean body mass. Technical Report. Sabinsa Corporation, Piscataway, NJ. Available:

    28. Kreider RB, et al. Effects of Coleus forskohlii supplementation on body composition and markers of health in sedentary overweight females. Experimental Biology 2002 Late Breaking Abstracts. LB305: 2002.

    29. Kriketos AD, et al. (-)-Hydroxycitric acid does not affect energy expenditure and substrate oxidation in adult males in a post-absorptive state. Int J Obes Relat Metab Disord 1999;23(8):867-73.

    30. Heymsfield SB, et al. Garcinia cambogia (hydroxycitric acid) as a potential antiobesity agent: a randomized controlled trial. J Am Med Assn 1998;11;280(18):1596-600.

    31. Mattes RD, Bormann L. Effects of (*)-hydroxycitric acid on appetitive variables. Physiol Behav 2000;71(1-2):87-94.

    32. Preuss HG, et al. Effect of hydroxycitric acid on weight loss, body mass index and plasma leptin levels in human subjects. FASEB J 2002;16:(5):A1020

    Disagreement Brews Between Colleges And Professional Ranks

    Amidst the controversy over the safety and efficacy of ephedra and caffeine in weight-loss products, several highly influential US organisations are at odds over the use of these substances.

    In what is now considered a benchmark study, investigators at Harvard, Columbia and other prominent US academic institutions published, in the May issue of the International Journal of Obesity, the results of an independent study that supports the safety and efficacy of the herb mixed with caffeine for weight loss.

    Meanwhile, effective this month, the US National Football League (NFL) has banned the use of ephedrine among players seeking to enhance their athletic performance. The NFL has initiated year-round random drug testing over health concerns associated with the use of stimulants among its professional athletes.

    —Sue Blanchard

    Additional Opportunities In Weight Control

    The following nutraceuticals have varying degrees of data to back their potential utility as weight-control agents. These have been broken down into three separate categories.

    Unheralded Ingredients
    Calcium has been reported to suppress 1,25-dihydroxyvitamin D and fat metabolism. Recent research suggests dietary calcium intake is negatively correlated with weight1 and that dietary supplementation of calcium (800­1,300 mg/day) promotes weight and fat loss.2

    Medium-chain triglycerides (MCT) promote a greater energy expenditure than ingesting fat-containing long-chain triglycerides (LCT) in animal studies. Theoretically, the increased energy expenditure may help manage body weight. To support this theory, researchers at McGill University in Montreal, Quebec, reported that a diet containing 50 per cent dietary fat as MCT promoted a slightly greater weight loss (-1.45kg) than when ingesting fat as LCT (-1.06kg), apparently due to a greater resting energy expenditure measured on days 2 and 28 of the diet.3

    Glucagon-like peptide-1 (GLP-1) derivative NN2211 has been shown to suppress appetite and promote weight loss in rats and pigs.4,5 Hansen and colleagues recently evaluated the effects of subcutaneous administration of different levels of NN2211 in obese rhesus monkeys to determine whether NN2211 affects appetite and/or weight loss.6 Results revealed that NN2211 suppressed appetite and promoted a modest loss in body weight. The researchers concluded that NN2211 may have strong potential in the treatment of obesity in humans but that additional research is needed.

    Oxidative uncouplers (UCP), such as 2,4-dinitrophenol (DNP), promote 'oxidative uncoupling' in the electron transport system, thereby increasing thermogenesis.7,8 However, DNP was not found to be well-tolerated in humans.9 More recently, there has been interest in determining whether uncoupling proteins and/or the lichen usnic acid can affect thermogenesis and/or weight loss. It is unclear whether UCP or usnic acid can safely promote weight loss in humans.

    Limited Effects
    Chromium supplementation, despite some promising data in diabetic populations,10 by and large does not affect body composition in healthy individuals.11,12Chitosan feedings in several animal studies result in decreased fat absorption, increased fecal fat content and/or lower cholesterol.13,14 However, chitosan supplementation does not appear to alter body composition when administered to people following their normal diet.15,16

    Conjugated linoleic acids (CLA) added to dietary feed: Animal studies have indicated that it decreases body fat and increases muscle mass. However, research on humans has been unconvincing because most studies report that CLA supplementation (1.7 to 12g/day for four weeks to six months) has limited or no effects on weight or fat loss.17-23

    L-carnitine has been thought to promote fat metabolism leading to weight loss. However, most studies indicate that L-carnitine has limited to no effects on body composition.24,25

    Pyruvate taken in large quantities (6-16g/day) in the form calcium pyruvate mildly promotes fat loss in obese populations.26-31 However, there is no evidence that supplementation with more reasonable doses of pyruvate (0.5-2g/day) promotes fat loss.

    Effects Unknown
    Betaine, a digestive enzyme, is specifically involved in the metabolism of choline and homocysteine. A number of studies have evaluated the effects of betaine feedings on liver metabolism, fat metabolism and fat deposition in animals.32,33 Although the potential theoretical rationale of betaine supplementation is interesting, it is unclear whether betaine supplementation could effectively affect weight loss.

    Gymnema sylvestre is purported to affect glucose and fat metabolism as well as inhibit sugar cravings. Some recent published data indicate that short- and long-term oral supplementation of Gymnema sylvestre in rats fed normal and high-fat diets may have some positive effects on fat metabolism, blood lipid levels and/or weight gain/fat deposition.34,35 Whether Gymnema sylvestre supplementation affects lipid metabolism or body composition in humans is unclear.


    1. Davies KM, et al. Calcium intake and body weight. J Clin Endocrinol Metab 2000;85:4635-8.

    2. Zemel MB, et al. Dietary calcium and dairy products accelerate weight and fat-loss during energy restriction in obese adults. Clin Nutri 2002;75(2):S342-3.

    3. St-Onge MP, Jones P. Medium chain triglyceride consumption increases energy expenditure relative to long chain triglyceride in overweight men. Clin Nutr 2002;75(2):S340.

    4. Turton MD, et al. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature 1996;379:69-72.

    5. Larsen PJ, et al. Systemic administration of the long-acting GLP-1 derivative NN2211 induces lasting and reversible weight loss in both normal and obese rats. Diabetes 2001;50:2530-9.

    6. Hansen BC, et al. Obese rhesus monkeys show reduced food intake and weight loss during treatment with NN2211, a long-acting GLP-1 derivative. Clin Nutr 2002;75(2):S393.

    7. Parascandola J. Dinitrophenol and bioenergetics: an historical perspective. Mol Cell Biochem 1974;5:69-77.

    8. Abo-Khatwa AN, et al. Lichen acids as uncouplers of oxidative phosphorylation of mouse-liver mitochondria. Nat Toxins 1996;4:96-102.

    9. Kurt TL, et al. Dinitrophenol in weight loss: the poison center and public health safety. Vet Hum Toxicol 1986;28:574-5.

    10. Crawford V, et al. Effects of niacin-bound chromium supplementation on body composition in overweight African-American women. Diabetes Obes Metab 1999;1(6):331-711.

    11. Walker LS, et al. Chromium picolinate effects on body composition and muscular performance in wrestlers. Med Sci Sports Exerc 1998;30(12):1730-7.

    12. Lukaski HC, et al. Chromium supplementation and resistance training: effects on body composition, strength, and trace element status of men. Am J Clin Nutr 1996;63(6):954-65.

    13. Gallaher CM, et al. Cholesterol reduction by glucomannan and chitosan is mediated by changes in cholesterol absorption and bile acid and fat excretion in rats. J Nutr 2000;130(11):2753-9.

    14. Chiang MT, et al. Effect of dietary chitosans with different viscosity on plasma lipids and lipid peroxidation in rats fed on a diet enriched with cholesterol. Biosci Biotechnol Biochem 2000;64(5):965-71.

    15. Pittler MH, et al. Randomized, double-blind trial of chitosan for body weight reduction. Eur J Clin Nutr 1999;53(5):379-81.

    16. Ho SC, et al. In the absence of dietary surveillance, chitosan does not reduce plasma lipids or obesity in hypercholesterolaemic obese Asian subjects. Singapore Med J 2001;42(1):006-10.

    17. Riserus U, et al. Conjugated linoleic acid (CLA) reduced abdominal adipose tissue in obese middle-aged men with signs of the metabolic syndrome: a randomised controlled trial. Int J Obes Relat Metab Disord 2001;25(8):1129-35.

    18. Blankson H, et al. Conjugated linoleic acid (CLA) reduces body fat mass in overweight or obese humans. J Nutr 2000;130:2943-8.

    19. Beuker F, et al. CLA and body styling. Symposium: Vitamine und Zusatzstoffe. Jena (Th*r.) 1999;7:229-37.

    20. Von Loeffelholz C, et al. Influence of conjugated linoleic acid (CLA) supplementation on body composition and strength in bodybuilders. Symposium: Vitamine und Zusatzstoffe. Jena (Th*r.) 1999;238-43.

    21. Zambell KL, et al. Conjugated linoleic acid supplementation in humans: effects on body composition and energy expenditure. Lipids 2000;35:777-82.

    22. Medina EA, et al. Conjugated linoleic acid supplementation in humans: effects on circulating leptin concentrations and appetite. Lipids 2000;35:783-8.

    23. Kreider R, et al. Effects of conjugated linoleic acid (CLA) supplementation during resistance-training on body composition, bone density, strength, and selected hematological markers. J Strength Cond Res 2002;16(3): In press.

    24. Brass EP. Supplemental carnitine and exercise. Am J Clin Nutr 2000;72(2 Suppl):618S-23S.

    25. Villani RG, et al. L-Carnitine supplementation combined with aerobic training does not promote weight loss in moderately obese women. Int J Sport Nutr Exerc Metab 2000;10(2):199-207.

    26. Stanko RT, et al. Body composition, energy utilization, and nitrogen metabolism with a 4.25-MJ/d low-energy diet supplemented with pyruvate. Am J Clin Nutr 1992;56(4):630-5.

    27. Stanko RT, et al. Pyruvate supplementation of a low-cholesterol, low-fat diet: effects on plasma lipid concentrations and body composition in hyperlipidemic patients. Am J Clin Nutr 1994;59(2):423-7.

    28. Stanko RT, Arch JE. Inhibition of regain in body weight and fat with addition of 3-carbon compounds to the diet with hyperenergetic refeeding after weight reduction. Int J Obes Relat Metab Disord 1996;20(10):925-30.

    29. Kalman D, et al. The effects of pyruvate supplementation on body composition in overweight individuals. Nutrition 1999;15(5):337-40.

    30. Stone MH, et al. Effects of in-season (5 weeks) creatine and pyruvate supplementation on anaerobic performance and body composition in American football players. Int J Sport Nutr 1999;9(2):146-65.

    31. Kreider R., et al. Effects of pyruvate supplementation during training on body composition and metabolic responses to exercise. Med Sci Sport Exer 1998;30:S62.

    32. Garcia Neto M, et al. Influence of dietary protein level on the broiler chicken's response to methionine and betaine supplements. Poult Sci 2000;79(10):1478-84.

    33. Overland M, et al. Effect of trimethylamine oxide and betaine in swine diets on growth performance, carcass characteristics, nutrient digestibility, and sensory quality of pork. J Anim Sci 1999;77(8):2143-53.

    34. Shigematsu N, et al. Effect of administration with the extract of Gymnema sylvestre R. Br leaves on lipid metabolism in rats. Biol Pharm Bull 2001;24(6):713-7.

    35. Shigematsu N, et al. Effect of long term-administration with Gymnema sylvestre R. BR on plasma and liver lipid in rats. Biol Pharm Bull 2001;24(6):643-9.

    Marketing Applications For Ephedra Alternatives

    When evaluating ingredients for obesity and fat-loss products and technologies, marketers and product developers must consider the fine balance between optimisation of the consumer experience, technological possibility and cost.

    Take hydroxycitric acid (HCA). As pointed out in the main story, subjects in a new efficacy study consumed a large amount of extract—8.4 grams. Consuming that much presents an obvious consumer compliance barrier to the marketer—not to mention the cost to buy that much of any substance.

    Of interest is the fact that this study, yet to survive peer-review, is the first study to show mild, market-relevant weight-loss in humans with Garcinia cambogia/HCA supplementation. But will it make it to store shelves? It's debatable. A consumer purchasing a single-ingredient HCA product might pay $20 for 56 grams of extract (60 per cent HCA). To use the product as indicated in this study, the same bottle would translate into a four-day supply. To maintain a programme like this for one month would cost $150, more than many consumers would be keen to consider.

    Clearly, if marketers and product developers want positive consumer experiences, attention to detail is required in areas critics cite as the Achilles' heel of the functional foods and dietary supplements industries. Marketers need to be diligent in researching and developing ingredients that are economically feasible at practical dosages. Get it right and the payoff in the weight-loss market could be very fat indeed.

    —Tim Avila/IMAGINutrition

    Intellectual Property And Technology Assessment

    The U.S. champion of intellectual property as it relates to weight-loss supplements may be Nutrition 21's chromium picolinate, whose composition-of-matter patent (US patent 4315927) long ago expired. This type of patent, equivalent to an innovator preparation drug (a new drug), prevents any party from making, using, selling or even importing the compound. Although expiration of the patent did allow other companies to begin making and selling this ingredient in the U.S., Nutrition 21 filed and was issued numerous other patents seeking a market exclusive on combinations including this form of chromium.

    However, the original chromium picolinate patent was issued only in the US, allowing unfettered international practice of the patent. Thus, monitoring the geographic patent filing strategy of companies may provide 'open windows' through which the patents may be practiced legally in certain countries without the economic burden of litigation (due to infringement) or licensing and royalty fees associated with a license.

    Unfortunately, chromium picolinate has yet to emerge as a GRAS food ingredient, limiting its use to only dietary supplements.

    Interestingly, the majority of the published research on chromium picolinate has shown this chromium complex to be without effect upon body weight or fat mass in humans. This underscores an important observation: A patent does not mean potent or effective. Indeed, many weight-loss patents are filed and issued with no proof of principle data, in either animals or humans.

    Although a well-drafted patent accompanied by an effective enforcement strategy can mean a market monopoly, consumer satisfaction associated with use of the invention (read: weight/fat loss) will ultimately and sometimes rapidly define sales velocity, market share and the invention's life cycle. A patent can exist, but its real-world market value may be negligible, extending no farther than the 'Patented' statement on a label.

    Once patents are filed, vigilant and intelligent enforcement in the marketplace is required—else why patent it in the first place? For instance, Arkopharma patented green tea for obesity (WO0041708; filed January 2000), yet there's no question of an abundance of infringement and data piracy of green tea.

    Cocktail patents—those where a multitude of different ingredients and extracts are combined—abound but are typically narrow in their allowed claims. One example is from a recently issued two-page US patent (6383482) calling out a weight-loss composition containing green tea extract, hydroxycitric acid, 5-hydroxytryptophan, glucomannan, chromium picolinate and Lactobacillus. Obviously, a patent of this brevity lacks any confirmatory data regarding the composition's efficacy. A simple circumvention tactic is to drop one or more of the ingredients and sell the cocktail as such.

    Another example (US patent 5914326) unites a pyruvate source, chromium picolinate, L-carnitine and a source of hydroxycitric acid as a composition for weight loss. An apparently easy circumvention tactic would be to use a different chromium ligand, such as chromium nicotinate or citrate.

    Why file a patent then, if circumvention can be so easy? The better question to ask: How can one draft a patent that is difficult to circumvent and has much market value?

    —Anthony Almada/IMAGINutrition

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