Caffeine Use in Sports, Pharmacokinetics in Man, and Cellular Mechanisms of Action

Abstract

Caffeine is the most widely consumed psychoactive 'drug' in the world and probably one of the most commonly used stimulants in sports. This is not surprising, since it is one of the few ergogenic aids with documented efficiency and minimal side effects. Caffeine is rapidly and completely absorbed by the gastrointestinal tract and is readily distributed throughout all tissues of the body. Peak plasma concentrations after normal consumption are usually around 50 microM, and half-lives for elimination range between 2.5-10 h. The parent compound is extensively metabolized in the liver microsomes to more than 25 derivatives, while considerably less than 5% of the ingested dose is excreted unchanged in the urine. There is, however, considerable inter-individual variability in the handling of caffeine by the body, due to both environmental and genetic factors. Evidence from in vitro studies provides a wealth of different cellular actions that could potentially contribute to the observed effects of caffeine in humans in vivo. These include potentiation of muscle contractility via induction of sarcoplasmic reticulum calcium release, inhibition of phosphodiesterase isoenzymes and concomitant cyclic monophosphate accumulation, inhibition of glycogen phosphorylase enzymes in liver and muscle, non-selective adenosine receptor antagonism, stimulation of the cellular membrane sodium/potassium pump, impairment of phosphoinositide metabolism, as well as other, less thoroughly characterized actions. Not all, however, seem to account for the observed effects in vivo, although a variable degree of contribution cannot be readily discounted on the basis of experimental data. The most physiologically relevant mechanism of action is probably the blockade of adenosine receptors, but evidence suggests that, at least under certain conditions, other biochemical mechanisms may also be operational.

The effect of caffeine, green tea and tyrosine on thermogenesis and energy intake

“…Lopez- et al (2006) have found an association between weight regain and habitual coffee consumption, whereas other studies have not confirmed this finding (Astrup et al, 1992;Pasman et al, 1997). This may be influenced by the fact that natural sources of caffeine also contain widely varying mixtures of other xanthines and of other substances, such as tannins, which could affect energy balance (Magkos and Kavouras, 2005). The rather high thermogenic response to 50 mg caffeine in the present study may partly be explained by the subjects' relatively low habitual intake of coffee.…”

Rapamycin and mTOR kinase inhibitors

“…Plasma levels above 200 μM are toxic in humans. Caffeine is used medically to treat apnea of prematurity and is a component of various headache and pain remedies [71]. Theophylline causes bronchodilator and antiinflammatory responses and has long been used clinically for the treatment of asthma and other respiratory diseases.…”

The effect of caffeine on working memory load-related brain activation in middle-aged males

“…Females were not included due to gender differences in caffeine consumption and metabolism (Carrillo and Benitez, 1996;Magkos and Kavouras, 2005). The study was approved by the medical ethical committee at Maastricht University academic hospital.…”