Haller · Clinical pharmacology and therapeutics 2002 · uncontrolled single-arm trial · n=8

Pharmacology of ephedra alkaloids and caffeine after single-dose dietary supplement use.

Cited 120 times in the scientific literature.

Level 4 - case-series / case-control

Uncontrolled single-arm pharmacokinetic and pharmacodynamic study (case series / single-arm trial)

PubMed 12087345 · doi:10.1067/mcp.2002.124523 · record verified 2026-08-27

What was done

Eight healthy adults ingested a single oral dose of a thermogenic dietary supplement containing 20 mg ephedrine alkaloids and 200 mg caffeine after an overnight fast. Researchers collected serial plasma and urine samples over 14 hours to analyze ephedrine alkaloid and caffeine concentrations using liquid chromatography-tandem mass spectrometry, while monitoring blood pressure and heart rate.

What was found

Plasma clearance and elimination half-lives for ephedrine, pseudoephedrine, and caffeine were comparable to published pharmaceutical values. Mean systolic blood pressure increased significantly to a maximum of 14 mm Hg above baseline at 90 minutes post-ingestion (P < .001), while diastolic blood pressure changes were not significant. Mean heart rate reached a peak increase of 15 beats/min above baseline at 6 hours post-ingestion (P < .001). In two subjects taking oral contraceptives, caffeine half-life was longer (15.5 +/- 0.3 hours vs 5.6 +/- 1.7 hours) and oral clearance was lower (0.34 +/- 0.01 mL/min. kg vs 0.99 +/- 0.41 mL/min. kg) compared to non-users.

Why it matters

The study demonstrates that botanical ephedra and caffeine supplements exhibit pharmacokinetics similar to synthetic formulations and cause significant acute increases in blood pressure and heart rate.

Limits

The sample size was very small (n = 8) and lacked a placebo or control comparator. The study evaluated only a single acute dose over 14 hours in healthy volunteers, without assessing repeated dosing or high-risk populations.

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