Influence de l'exercice physique sur l'élimination de la caféine et de ses métabolites monodéméthylés

Abstract

L'excrétion urinaire de la caféine et de ses métabolites xanthiques monodéméthylés, chez deux populations de cyclotouristes (hommes et femmes), a été mesurée par chromatographie gazeuse/spectrométrie de masse et fragmentométrie, au repos et à l'effort, après administration orale de 350 mg de caféine pure en solution aqueuse. Dans le cadre des contrôles antidopages, quatre constatations peuvent être faites: la seule expression de l'élimination urinaire utilisable est la concentration instantanée en μg/ml; les différences d'élimination, en fonction du sport (plus ou moins énergétique), semblent remettre en cause l'utilisation d'un seul taux limite réglementaire; enfin, la réglementation du CIO, en autorisant la présence de caféine (pour des taux inférieurs à 12 μg/ml) et en interdisant ses métabolites en tant que substances apparentées, est contradictoire. Caffeine (1,3,7-trimethylxanthine), and its major monodemethylated xanthic metabolites (MXM), especially theobromine and theophylline, are among the most widely and frequently consumed alcaloïds throughout the world. Methylxanthines are present in coffee, tea, chocolate, various cola-flavored “soft drinks”. Caffeine (CA), possesses several pharmacological actions such as stimulation of the central nervous system and cardiac muscle, diuretic effect and various metabolic actions ( Leblanc et al , 1985 ; Arogyasami et al , 1989). By its stimulant properties, caffeine is also used as a doping agent in sport. Caffeine is the only doping substance for which an upper limit of urinary excretion (12 μg/ml) has been established. Urinary excretion of caffeine and its monodemethylated xanthic metabolites by two populations of cyclotourists (men and women) at rest and during exercise, after oral administration of 350 mg caffeine in aqueous solution, was measured by capillary gas chromatography/mass spectrometry using selected ion monitoring according to the procedure of Duthel et al , 1990. The protocol chosen for this study (table I) allowed us to establish the role of physical exercise upon elimination of caffeine and its MXM. The mean concentration (μg/ml) of urinary excretion of caffeine and its MXM at rest (R 1 ), during exercise (E 1 ) and after exercise (E 2 ), (table II), shows that values are always higher in the female population; levels of caffeine for R 1 , E 1 and E 2 are respectively: 5.40, 3.27 and 4.44 μg/ml in men; 8.23, 4.40 and 6.54 μg/ml in women. Comparison of values at rest and during exercise (R 1 / E 1 ), shows a significant difference (Student's paired t -test), for caffeine in both populations, for MXM in the male population and no significant difference for MXM in the female population. The elimination ratio, ER: eliminated quantity by hour upon administred quantity for each kilogram of body weight (table III), cancels the weight's differences between the two genders and increases the significance of female results. The ANOVA test, applied to ER results, shows that both populations have similar urinary excretions (table III). Table IV shows that the percentages' mean of each metabolite upon the sum of metabolites is approximately the same at rest and exercise for both populations; percentages'means at R 1 , E 1 and E 2 for theobromine (TB), paraxanthine (PX) and theophylline (TP), are respectively, for men and women: TB: 40.04 and 40.69; PX: 55.23 and 54.93; TP: 4.73 and 4.29. Finally this study demonstrates the interest of the concentrations' ratio (table V) between the sum of metabolites and caffeine (ΣMetab/CA). Within the framework of doping controls, three observations can be established: the most appropriate expression of urinary elimination is instantaneous urinary concentration in μg/ml; differences in caffeine elimination according to various sporting events (more or less energetic sports), seem inconsistent with the use of a single authorized limit level; moreover, the regulation of the IOC appears contradictory in authorizing the presence of caffeine (with levels lower than 12 μg/ml) and prohibiting its metabolites, the so-called related substances.