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Effects of caffeine with repeated dosing.
C P Denaro1, C R Brown, P Jacob
1Department of Medicine, University of California, San Francisco.
European Journal of Clinical Pharmacology
|January 1, 1991
Summary
Regular high-dose caffeine intake may lead to persistent pharmacodynamic effects, even with tolerance development. This suggests that the body
Area of Science:
- Pharmacology
- Human Physiology
- Metabolism Studies
Background:
- Caffeine's dose-dependent metabolism has been established.
- Understanding persistent pharmacodynamic effects of caffeine is crucial.
Purpose of the Study:
- To investigate persistent pharmacodynamic actions of caffeine despite tolerance development.
- To assess the impact of regular, high-dose caffeine consumption on physiological parameters.
Main Methods:
- Nine healthy subjects participated in a randomized, placebo-controlled study.
- Subjects received placebo, low-dose (4.2 mg.kg-1.day-1), or high-dose (12 mg.kg-1.day-1) caffeine for 5 days.
- Measurements included blood pressure, heart rate, plasma glucose, norepinephrine, and free fatty acids (FFA).
Main Results:
- Complete tolerance to caffeine's effects on blood pressure, heart rate, and glucose was observed after 5 days.
- A trend for increased plasma norepinephrine and FFA was noted with high-dose caffeine.
- Significant differences in norepinephrine levels were observed within 12-hour periods with high-dose caffeine.
Conclusions:
- Regular high-dose caffeine intake (12 mg.kg-1.day-1) may induce pharmacodynamic effects not fully counteracted by tolerance.
- Tolerance mechanisms might be overwhelmed by nonlinear caffeine accumulation when metabolism saturates.