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Multinutrient supplement containing ephedra and caffeine causes weight loss and improves metabolic risk factors in obese women: a randomized controlled trial

International Journal of Obesity volume 30, pages 1545–1556 (2006)Cite this article

Abstract

Objective:

To determine the safety and efficacy of a dietary supplement with a low dose of ephedra and caffeine in overweight/obese premenopausal female subjects.

Design:

A 9-month, double-blind, randomized control study compared the efficacy and safety of a dietary supplement with ephedra and caffeine to a control supplement.

Subjects:

Sixty-one healthy, premenopausal women with body mass index (BMI) from 27 to 39 kg/m2 were randomly assigned and received a dietary supplement (40 mg/day ephedra alkaloids, 100 mg/day caffeine, high potency mixture of vitamins, minerals, omega-3 fatty acids) or a control supplement for 9 months.

Measurements:

Efficacy: changes in body weight, body composition, lipids, insulin, leptin, adiponectin, ghrelin, and self-reports of physical activity, diet and quality of life indices. Safety: blood pressure, heart rate, electrocardiograms, urinalysis, blood histology, serum chemistry measures and self-reported symptoms.

Results:

Forty-one women completed the study. The treatment group lost significantly more body weight (−7.18 kg) and body fat (−5.33 kg) than the control group (−2.25 and −0.99 kg, respectively), and showed significant declines in heart rate, serum cholesterol, triglycerides, cholesterol to high-density lipoprotein ratio, glucose, fasting insulin, and leptin. Blood pressure, electrocardiograms, other clinical chemistry measures, blood histology, urinalysis, and self-reported physical activity were similar in the groups. Minor symptoms included dry mouth, insomnia, nervousness and palpitations. The treatment group reported more energy and decreased appetite compared to controls and scored higher on a quality of life domain assessing vitality.

Conclusion:

A dietary supplement containing a low potency ephedra/caffeine mixture appeared safe and effective in causing loss of weight and body fat, and improving several metabolic parameters, including insulin sensitivity and lipid profiles when tested under physician supervision. Such supplements could be a useful tool to assist with weight loss.

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References

  1. Flegal KM, Carroll MD, Ogden CL, Johnson CL . Prevalence and trends in obesity among US adults, 1999–2000. JAMA 2002; 288: 1723–1727.

    Article  PubMed  Google Scholar 

  2. Flegal KM, Carroll MD, Kuczmarski RJ, Johnson CL . Overweight and obesity in the United States: prevalence and trends, 1960–1994. Int J Obes Relat Metab Disord 1998; 22: 39–47.

    CAS  PubMed  Google Scholar 

  3. Finkelstein EA, Fiebelkorn IC, Wang G . State-level estimates of annual medical expenditures attributable to obesity. Obes Res 2004; 12: 18–24.

    Article  PubMed  Google Scholar 

  4. Stafford RS, Farhat JH, Misra B, Schoenfeld DA . National patterns of physician activities related to obesity management. Arch Fam Med 2000; 9: 631–638.

    Article  CAS  PubMed  Google Scholar 

  5. Wadden TA, Anderson DA, Foster GD, Bennett A, Steinberg C, Sarwer DB . Obese women's perceptions of their physicians' weight management attitudes and practices. Arch Fam Med 2000; 9: 854–860.

    Article  CAS  PubMed  Google Scholar 

  6. Astrup A, Breum L, Toubro S, Hein P, Quaade F . The effect and safety of an ephedrine/caffeine compound compared to ephedrine, caffeine and placebo in obese subjects on an energy restricted diet. A double blind trial. Int J Obes Relat Metab Disord 1992; 16: 269–277.

    CAS  PubMed  Google Scholar 

  7. Boozer CN, Nasser JA, Heymsfield SB, Wang V, Chen G, Solomon JL . An herbal supplement containing Ma Huang-Guarana for weight loss: a randomized, double-blind trial. Int J Obes Relat Metab Disord 2001; 25: 316–324.

    Article  CAS  PubMed  Google Scholar 

  8. Boozer CN, Daly PA, Homel P, Solomon JL, Blanchard D, Nasser JA et al. Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial. Int J Obes Relat Metab Disord 2002; 26: 593–604.

    Article  CAS  PubMed  Google Scholar 

  9. Department of Health and Human Services, Food and Drug Administration. Final rule declaring dietary supplements containing ephedrine alkaloids adulterated because they present an unreasonable risk. Available at: http://www.fda.gov/OHRMS/DOCKETS/98fr/1995n-0304-nfr0001.pdf. Accessed April 12, 2004.

  10. Dallal G . Randomization. http://www.randomization.com/ [website]. July 27, 2003. Available at http://www.randomization.com/. Accessed November 18, 2002.

  11. Van Loan MD WP, Matthie J, Mayclin PL . Use of bio-impedance spectroscopy (BIS) to determine extracellular fluid (ECF), intracellular fluid (ICF), total body water (TBW), and fat free mass (FFM). In: Ellis KJ, Eastman JD (eds). Human Body Composition. Plenum Press: New York, 1993. pp 67–70.

    Chapter  Google Scholar 

  12. Perloff D, Grim C, Flack J, Frolich ED, Hill M, McDonald M, Morgenstern BZ . Human blood pressure determination by sphygmomanometry. Circulation 1993; 88: 2460–2470.

    Article  CAS  PubMed  Google Scholar 

  13. Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997; 157: 2413–2446.

  14. Lee HC, Curry DL, Stern JS . Tonic sympathetic nervous system inhibition of insulin secretion is diminished in obese Zucker rats. Obesity Res 1993; 1: 371–376.

    Article  CAS  Google Scholar 

  15. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    Article  CAS  PubMed  Google Scholar 

  16. United Stated Department of Health and Human Services. Coding Symbol and Thesaurus for Adverse Event Terminology (COSTART). US Department of Health and Human Services: Rockville, MD, 1990.

  17. Block G, Woods M, Potosky A, Clifford C . Validation of a self-administered diet history questionnaire using multiple diet records. J Clin Epidemiol 1990; 43: 1327–1335.

    Article  CAS  PubMed  Google Scholar 

  18. Blair SN, Haskell WL, Ho P, Paffenbarger RS, Vranizan KM, Farquhar JW et al. Assessment of habitual physical activity by a seven-day recall in a community survey and controlled experiments. Am J Epidemiol 1985; 122: 794–804.

    Article  CAS  PubMed  Google Scholar 

  19. Ware Jr JE, Sherbourne CD . The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care 1992; 30: 473–483.

    Article  PubMed  Google Scholar 

  20. Neter J, Kutner MH, Nachstheim CJ, Wasserman W . Applied Linear Statistical Models 4th edn. Chicago: Irwin, 1995.

    Google Scholar 

  21. Unnebrink K, Windeler J . Intention-to-treat: methods for dealing with missing values in clinical trials of progressively deteriorating diseases. Stat Med 2001; 20: 3931–3946.

    Article  CAS  PubMed  Google Scholar 

  22. Gadbury GL, Coffey CS, Allison DB . Modern statistical methods for handling missing repeated measurements in obesity trial data: beyond LOCF. Obes Rev 2003; 4: 175–184.

    Article  CAS  PubMed  Google Scholar 

  23. SAS Institute I. The SAS System for Windows, Version 9.1. SAS Institute: Cary, NC, 2003.

  24. Bland JM, Altman DG . Transformations, means and confidence intervals. BMJ 1996; 312: 1079.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Haller CA, Benowitz NL . Adverse cardiovascular and central nervous system events associated with dietary supplements containing ephedra alkaloids. N Engl J Med 2000; 343: 1833–1838.

    Article  CAS  PubMed  Google Scholar 

  26. Shekelle PG, Hardy ML, Morton SC, Maglione M, Mojica WA, Suttorp MJ et al. Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis. JAMA 2003; 289: 1537–1545.

    CAS  PubMed  Google Scholar 

  27. McBride BF, Karapanos AK, Krudysz A, Kluger J, Coleman CI, White CM . Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine: a randomized controlled trial. JAMA 2004; 291: 216–221.

    Article  CAS  PubMed  Google Scholar 

  28. Haller CA, Jacob P, Benowitz NL . Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use. Clin Pharmacol Ther 2002; 71: 421–432.

    Article  CAS  PubMed  Google Scholar 

  29. Greenway FL, de Jonge L, Blanchard D, Frisard M, Smith SR . Effect of a dietary herbal supplement containing caffeine and ephedra on weight, metabolic rate, and body composition. Obes Res 2004; 12: 1152–1157.

    Article  PubMed  Google Scholar 

  30. Coffey CS, Steiner D, Baker BA, Allison DB . A randomized double-blind placebo-controlled clinical trial of a product containing ephedrine, caffeine, and other ingredients from herbal sources for treatment of overweight and obesity in the absence of lifestyle treatment. Int J Obes Relat Metab Disord 2004; 28: 1411–1419.

    Article  CAS  PubMed  Google Scholar 

  31. Fairfield KM, Fletcher RH . Vitamins for chronic disease prevention in adults: scientific review. JAMA 2002; 287: 3116–3126.

    Article  CAS  PubMed  Google Scholar 

  32. Singh RB, Beegom R, Rastogi SS, Gaoli Z, Shoumin Z . Association of low plasma concentrations of antioxidant vitamins, magnesium and zinc with high body fat per cent measured by bioelectrical impedance analysis in Indian men. Magnesium Res 1998; 11: 3–10.

    CAS  Google Scholar 

  33. Chen MD, Song YM, Lin PY . Zinc may be a mediator of leptin production in humans. Life Sci. 2000; 66: 2143–2149.

    Article  CAS  PubMed  Google Scholar 

  34. Westerterp-Plantenga MS, Kovacs EM . The effect of (−)-hydroxycitrate on energy intake and satiety in overweight humans. Int J Obes Relat Metab Disord 2002; 26: 870–872.

    Article  CAS  PubMed  Google Scholar 

  35. Shara M, Ohia SE, Yasmin T, Zardetto-Smith A, Kincaid A, Bagchi M et al. Dose- and time-dependent effects of a novel (−)-hydroxycitric acid extract on body weight, hepatic and testicular lipid peroxidation, DNA fragmentation and histopathological data over a period of 90 days. Mol Cell Biochem 2003; 254: 339–346.

    Article  CAS  PubMed  Google Scholar 

  36. Dubuc GR, Phinney SD, Stern JS, Havel PJ . Changes of serum leptin and endocrine and metabolic parameters after 7 days of energy restriction in men and women. Metabolism 1998; 47: 429–434.

    Article  CAS  PubMed  Google Scholar 

  37. Keim NL, Stern JS, Havel PJ . Relation between circulating leptin concentrations and appetite during a prolonged, moderate energy deficit in women. Am J Clin Nutr 1998; 68: 794–801.

    Article  CAS  PubMed  Google Scholar 

  38. Rosenbaum M, Murphy EM, Heymsfield SB, Matthews DE, Leibel RL . Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones. J Clin Endocrinol Metab 2002; 87: 2391–2394.

    Article  CAS  PubMed  Google Scholar 

  39. Havel PJ . Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes 2004; 53: S143–S151.

    Article  CAS  PubMed  Google Scholar 

  40. Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002; 346: 1623–1630.

    Article  PubMed  Google Scholar 

  41. Faraj M, Havel PJ, Phelis S, Blank D, Sniderman AD, Cianflone K . Plasma acylation-stimulating protein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab 2003; 88: 1594–1602.

    Article  CAS  PubMed  Google Scholar 

  42. Fine JT, Colditz GA, Coakley EH, Moseley G, Manson JE, Willett WC et al. A prospective study of weight change and health-related quality of life in women. JAMA 1999; 282: 2136–2142.

    Article  CAS  PubMed  Google Scholar 

  43. Daly PA, Krieger DR, Dulloo AG, Young JB, Landsberg L . Ephedrine, caffeine and aspirin: safety and efficacy for treatment of human obesity. Int J Obes Relat Metab Disord 1993; 17 (Suppl 1): S73–S78.

    PubMed  Google Scholar 

  44. Dulloo AG . Ephedrine, xanthines and prostaglandin-inhibitors: actions and interactions in the stimulation of thermogenesis. Int J Obes Relat Metab Disord 1993; 17 (Suppl 1): S35–S40.

    CAS  PubMed  Google Scholar 

  45. Haller CA, Jacob P, Benowitz NL . Short-term metabolic and hemodynamic effects of ephedra and guarana combinations. Clin Pharmacol Ther 2005; 77: 560–571.

    Article  CAS  PubMed  Google Scholar 

  46. Ray S, Phadke S, Patel C, Hackman RM, Stohs S . Short-term and long-term in vivo exposure to an ephedra- and caffeine-containing metabolic nutrition system does not induce cardiotoxicity in B6C3F1 mice. Arch Toxicol 2005; 79: 330–340.

    Article  CAS  PubMed  Google Scholar 

  47. Hutton B, Fergusson D . Changes in body weight and serum lipid profile in obese patients treated with orlistat in addition to a hypocaloric diet: a systematic review of randomized clinical trials. Am J Clin Nutr 2004; 80: 1461–1468.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Kimberley Hansen BS for her clinical skills and Kimber Stanhope and James Graham for their technical assistance with the endocrine assays. The study was supported in part by an unrestricted gift from AdvoCare International, LP, Carrollton, TX.

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Authors and Affiliations

  1. Department of Nutrition, University of California, Davis, CA, USA

    R M Hackman, P J Havel, E M Noceti, J S Stern & C L Keen

  2. Department of Internal Medicine, University of California, Davis, CA, USA

    H J Schwartz, J C Rutledge, J S Stern & C L Keen

  3. Department of Statistics, California State University, East Bay, CA, USA

    M R Watnik

  4. Department of Pharmacy Science, Creighton University, Omaha, USA

    S J Stohs

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  1. R M Hackman
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Correspondence to R M Hackman.

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Hackman, R., Havel, P., Schwartz, H. et al. Multinutrient supplement containing ephedra and caffeine causes weight loss and improves metabolic risk factors in obese women: a randomized controlled trial. Int J Obes 30, 1545–1556 (2006). https://doi.org/10.1038/sj.ijo.0803283

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