Evaluation of the genotoxicity data on caffeine.

The potential health effects of caffeine have been investigated for over two decades in a variety of model systems including limited human populations. Thus, it is probably one of the most extensively studied natural occurring dietary chemicals. One area which has received a great deal of attention is the potential genotoxic property of caffeine. To better understand whether caffeine itself or in combination with other agents exhibits genotoxic effects, hundreds of research studies published over the past 5 years have been reviewed. These studies have utilized a number of animal, prokaryotic, eukaryotic, and mammalian cell culture model systems. They have investigated the effects of caffeine alone or in combination with other physical and chemical agents on many aspects of cell division, chromosome stability, toxicity, and mutagenicity. A number of effects have been observed. However, they usually appear after very high doses (> 1 mM) of caffeine in combination with genotoxins, and are usually specific to certain cell types and/or cellular parameters. Humans, on the other hand, consume much less caffeine in the diet, with peak serum levels in the micromolar range 10- and 1000-fold higher compared to levels in animal and cell culture models. Thus, it is difficult to implicate caffeine, even at the highest levels of dietary consumption, as a genotoxin to humans.