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Br J Clin Pharmacol. 2008 Jun;65(6):833-40. doi: 10.1111/j.1365-2125.2008.03144.x. Epub 2008 Mar 13.

Human pharmacology of a performance-enhancing dietary supplement under resting and exercise conditions.

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  • 1Department of Medicine, Division of Clinical Pharmacology, University of California, San Francisco, San Francisco General Hospital, San Francisco, CA, USA. challer@amgen.com



Performance-enhancing dietary supplements have not been clinically tested for safety or efficacy. In clinical trials performed under resting conditions, performance-enhancing supplements raise blood pressure and affect glucose homeostasis. The effect of exercise on the pharmacokinetics and pharmacodynamics of stimulant herbals is unknown.


Supplement-induced effects on blood pressure and glucose levels are not ameliorated by exercise. Exercise does not affect the kinetics of stimulant ingredients, caffeine and synephrine. Performance-enhancing supplement use modestly improves exercise tolerance. AIMS Dietary supplements (DS) promoted to enhance athletic performance often contain herbal sympathomimetics such as Citrus aurantium (synephrine) and caffeine. We aimed to characterize the pharmacology of a performance-enhancing DS in the setting of exercise.


Ten healthy adults (three women) aged 20-31 years participated in a three-arm, double-blind, placebo-controlled, crossover study. Subjects ingested one dose of DS (Ripped Fuel Extreme Cut(R) with 21 mg synephrine and 304 mg caffeine by analysis) under resting conditions and 1 h prior to moderately intense exercise (30 min on cycle ergometer at 75-80% HR(max)), with a placebo (PLC)/exercise control. Plasma synephrine and caffeine concentrations were measured over 12 h, and vital signs, serum electrolytes, oxygen consumption and perceived exercise exertion were monitored.


No significant adverse events occurred. Synephrine and caffeine pharmacokinetics were unaffected by exercise. Post-exercise diastolic blood pressure was higher after DS (peak mean 71.7 +/- 8.7 mmHg) than PLC (63.0 +/- 4.9 mmHg) (p = 0.007). There were no substantial treatment-related differences in post-exercise HR, systolic blood pressure, or temperature. Postprandial plasma glucose increased to 121.0 +/- 31.6 mg dl(-1) with DS and exercise vs. 103.7 +/- 25.5 mg dl(-1) with PLC and exercise (P = 0.004). No treatment differences in exercise-related oxygen consumption, serum lactate, or insulin were observed. Exercise was rated less difficult with DS than PLC (P = 0.001).


Blood pressure and plasma glucose increased post-exercise with DS use, which could be detrimental in some people. Exercise was perceived as less strenuous after DS, presumably due to the stimulant effects of caffeine.

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