Dietary supplements containing plant-derived ephedrine (ma huang) and caffeine (guarana) are widely promoted and used for weight loss, body building and exercise enhancement. Amidst reports of numerous adverse events, regulatory changes regarding ephedrine/caffeine-containing dietary supplements are being considered including changes in warning statements, dose limits and product claims. Few scientific studies have addressed the pharmacologic effects of plant-derived ephedrine and caffeine during rest or exercise. Drs Haller and Benowitz propose clinical research studies aimed at generating pharmacokinetic and pharmacodynamic data on ma huang/guarana-containing supplements to guide regulatory policy regarding the safety of marketing these products. Specific studies will examine the following: Hypothesis 1. These products are not subject to the same pre-market testing requirements as drugs and may contain more or less quantities of active constituents than declared on the product label.
We aim to meausre levels of ephedrine alkaloids and methylxanthines in 4 lots of 6 commercial brands and perform a broad screen for drugs and contaminants. Hypothesis 2: Plant-derived ephedrine and caffeine may have different pharmacological properties than pure rug onus. Other herbal ingredients in commercial products may augment the stimulant effects of ephedrine and caffeine.
We aim to characterize the pharmacokinetics of plant-derived ephedrine and caffeine taken in combination with other herbs as marketed compared to pure ephedrine and caffeine, alone and in combination, and measure clinical effects under resting conditions. Hypothesis 3: Increases in heart rate and blood pressure that occur during exercise may be augmented by sympathomirruetic effects of ephedrine and caffeine taken together. Other herbal ingredients in thermogenic supplements may aggravate these stimulant effects.
We aim to compare the clinical effects of plant-derived ephedrine and caffeine dietary supplements compared to pure ephedrine and caffeine alone and together when taken prior to strenuous exercise. Additional studies will address the effects of individual risk factors such as gender, hypertension and diabetes and dose response and multiple dose regimens. The long-term objective for the proposed studies is to develop Dr. Haller into an independent career clinical researcher in this field of study.

National Institute of Health (NIH)
National Center for Complementary & Alternative Medicine (NCCAM)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZAT1-B (03))
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Hopp, Craig
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University of California San Francisco
Internal Medicine/Medicine
Schools of Medicine
San Francisco
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Haller, Christine A; Duan, Minjing; Jacob 3rd, Peyton et al. (2008) Human pharmacology of a performance-enhancing dietary supplement under resting and exercise conditions. Br J Clin Pharmacol 65:833-40
Haller, Christine A (2006) Clinical approach to adverse events and interactions related to herbal and dietary supplements. Clin Toxicol (Phila) 44:605-10
Csajka, C; Haller, C A; Benowitz, N L et al. (2005) Mechanistic pharmacokinetic modelling of ephedrine, norephedrine and caffeine in healthy subjects. Br J Clin Pharmacol 59:335-45
Haller, Christine A; Jacob, Peyton; Benowitz, Neal L (2005) Short-term metabolic and hemodynamic effects of ephedra and guarana combinations. Clin Pharmacol Ther 77:560-71
Haller, Christine A; Meier, Kathryn H; Olson, Kent R (2005) Seizures reported in association with use of dietary supplements. Clin Toxicol (Phila) 43:23-30
Haller, Christine A; Benowitz, Neal L; Jacob 3rd, Peyton (2005) Hemodynamic effects of ephedra-free weight-loss supplements in humans. Am J Med 118:998-1003
Jacob 3rd, Peyton; Haller, Christine A; Duan, Minjiang et al. (2004) Determination of ephedra alkaloid and caffeine concentrations in dietary supplements and biological fluids. J Anal Toxicol 28:152-9
Haller, Christine A; Jacob 3rd, Peyton; Benowitz, Neal L (2004) Enhanced stimulant and metabolic effects of combined ephedrine and caffeine. Clin Pharmacol Ther 75:259-73
Haller, Christine A; Duan, Minjing; Benowitz, Neal L et al. (2004) Concentrations of ephedra alkaloids and caffeine in commercial dietary supplements. J Anal Toxicol 28:145-51
Haller, Christine A; Anderson, Ilene B; Kim, Susan Y et al. (2002) An evaluation of selected herbal reference texts and comparison to published reports of adverse herbal events. Adverse Drug React Toxicol Rev 21:143-50

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