RECENT ADVANCES IN CAFFEINE AND THEOBROMINE TOXICITIES - A REVIEW

Caffeine and theobromine are purine alkaloids widely consumed as stimu lants and snacks in coffee and cocoa based foods and most often as par t of ingredients in drugs. Man has enjoyed a long history of consumpti on of caffeine and theobromine. Recent interest in these two alkoloids , however, is centered on their potential reproductive toxicities. Caf feine and theobromine are now known to cross the placental and blood b rain barrier thus potentially inducing fetal malformation by affecting the expression of genes vital in development. The developing fetus ma y not have developed enzymes for detoxification of these methylxanthin e allcaloids via demethylation. There is a need, therefore, to protect the conceptus against 'insults' from teratogens of this nature. Apart from its reproductive toxicity, the presence of caffeine and theobrom ine in cocoa could limit its potentials as a nourishing food. This is an issue that needs to be addressed by nutritionists and the food indu stry at large. This paper discusses the natural sources, consumption a nd uses, toxicity and the major advances in the reproductive toxicolog y of caffeine and theobromine. The biosynthesis of these compounds in plants, metabolism in mammalian systems and the involvement of cytochr ome P450 are reviewed and summarized. Evidence in favor of the toxicit y of these compounds in experimental animals is presented with emphasi s on the implications of these findings in humans. The paper concludes with a call for caution in the use of caffeine and theobromine pendin g further and more elaborate investigations.