Gastrointestinal and metabolic effects of methylxanthines.

This chapter has covered a wide range of different actions of methylxanthines. They are able to slightly reduce the tone of the lower esophageal sphincter. This is of little concern in the normal individual, but in patients with a reduced initial tone it might lead to heartburn. Coffee intake has been associated with gastritis, but the role of methylxanthines in this effect is obscure. High doses of methylxanthines are also known to be emetic. Practically every function in the intestine can be influenced by high doses of methylxanthines, but the mechanisms involved and the biological significance remain largely obscure. Although in vitro studies with high doses of methylxanthines have demonstrated effects on secretion from salivary glands and exocrine pancreas, there is little evidence that this is clinically important in man. There is also small effects on insulin, glucagon, and TSH secretion. There is a consistent effect on fatty acid mobilization from adipose tissue, which may be of importance, eg, by improving physical performance and by increasing the overall metabolic rate. There is also some evidence for long-term effects on fat depots. By contrast, the effects on carbohydrate metabolism are much less prominent and reproducible, and may to some extent be secondary to altered lipid metabolism. Despite more than a century of effort to elucidate the actions of methylxanthines in man, one of the major conclusions to be drawn is that there is a need for further studies. In view of the newer ideas about the mechanism of action of caffeine and other methylxanthines, careful studies, especially of long-term effects of methylxanthines on several aspects of gastrointestinal function, on calcium homeostasis, on body composition, and on physical performance, would be desirable.