The Pharmacology and Toxicology of Caffeine

Abstract

The widespread use of caffeine is most commonly linked to the stimulatory action it has on the central nervous system. Generally, adverse effects include gastrorrhea, insomnia, and diuresis. Tolerance and withdrawal symptoms have been observed and excessive consumption can lead to an anxiety neurosis condition (caffeinism). The actions of caffeine may involve its effects on neurotransmitter turnover and metabolism; its promotion of the cellular messenger, cAMP; its sensitization of the calcium releasing mechanisms of cellular reticulum; or its antagonism of the autacoid, adenosine. Caffeine lethality is rare in man but caffeine poisoning with its gastrointestinal, CNS, and cardiovascular stimulation could especially be hazardous to children. Most of the mutagenicity work has been performed in organisms whose cellular DNA synthesis and repair mechanism vary significantly from those found in man. The work in human cell lines suggests that caffeine‐induced chromosomal breakage, with its lack of chromatid exchange would promote cell lethality, not muta‐genticity. Nothing but circumstantial evidence implicates caffeine as a human carcinogen or teratogen. Involvement of caffeine as a cocarcinogen or a coteratogen (which includes effects on gamete production or fetal development) appears far more likely, but neither has even begun to be truly evaluated. Basic metabolism of caffeine involves the processes of N‐demethylation, hydration, and oxidation; and most likely requires the cytochrome P1‐450 system. Though various metabolites of caffeine are pharmacologically active, the extent of involvement of individual metabolites in the pharmacological or toxicological responses of caffeine in man is still unknown.

General and Genetic Toxicology of Guayusa Concentrate (Ilex guayusa)

“…Effects of caffeine and other phosphodiesterase inhibitors on salivary glands are well known. [89][90][91][92][93][94][95][96][97][98][99] In a 1-year study in Wistar rats, hyperemia was observed at doses above 181 mg/ kg. 100 In the NTP study on caffeine in Fischer rats, a dosedependent effect on cellular enlargement in salivary glands was noted and considered to be adaptive.…”

AUTORADIOGRAPHIC DISPOSITION OF 14C‐CAFFEINE IN MALE, FEMALE, AND PREGNANT MICE

“…Caffeine and its metabolites, theobromine, theophylline, and paraxanthine, have all been identified in human amniotic fluid but it is not known whether they are from a maternal or fetal source (Sommer et ah 1975). No distinction of metabolites was possible in the autoradiographs, but previous work (Lachance 1982) and the labelling of this isotope would suggest that the purine structure was responsible for the radioactivity noted.…”

“…The issue of the teratogenic potential of caffeine in humans and laboratory animals has been debated for some time (Mulvihill 1973;Lachance 1982). After a single caffeine injection of 250 mgkg ip to pregnant mice, the incidences of embryonic death and malformations (consisting of limb-reducing deformities and cleft palate) were significant-'All correspondence sent to Dr. Michael P. Lachance at the above address.…”

Pharmacological potential of methylxanthines: Retrospective analysis and future expectations

“…Through time, conflicting reports were published suggesting mutagenic potential for caffeine (Dambrosio 1994;Lachance 1982;Rosenkranz and Ennever 1987), although today it is assumed that the regular and normal consumption (< 300 mg caffeine per day) would not result in mutagenic effects in humans (Dambrosio 1994;Nawrot et al 2003). In fact, caffeine has been related with cancer-protective outcomes, since it was shown to inhibit tumor proliferation (0.044% caffeine in water for 22 weeks (Lu et al 2006b) or 0.3% for 3 days, both in mice (Ryzhov et al 2007)) and vascularization (exposition of cancer cell lines to caffeine 10 mM for 1 h) (Merighi et al 2007).…”