Nutrition and chemical biotransformations in man

Nutritional factors are important in the regulation of drug metabolism in animals and in man. The average plasma half-life of antipyrine decreased 41 % and the plasma half-life of theophylline decreased 36% when the diets of normal volunteers were changed from their customary home diets to diets that contained high protein and low carbohydrate. When the subjects were shifted from this high protein-low carbohydrate diet to a high carbohydrate-low protein diet, the average antipyrine and theophylline half-lives increased 63% and 46%, respectively. Feeding a charcoal-broiled beef-containing diet to human volunteers for 4 days significantly decreased the plasma half-life of antipyrine. This diet also decreased the plasma levels of orally administered phenacetin without influencing the plasma concentrations of phenacetin's principal metabolite, N-acetyl-p-aminophenol, or the plasma half-life of phenacetin, which suggests that feeding charcoal-broiled beef enhances the metabolism of phenacetin in the gastrointestinal tract and/or during its first pass through the liver. This effect of charcoal-broiled beef was not caused by a change in dietary protein but was probably caused by polycyclic hydrocarbon enzyme inducers in the charcoal-broiled beef. Some subjects had large changes in drug metabolism when their diets were changed, whereas other subjects had little or no response to altered dietary regimens, which indicates marked individuality in the responsiveness of different people to changes in the diet. The intestinal metabolism of phenacetin was stimulated in rats fed a diet that contained charcoal-broiled beef, Brussels sprouts, or cabbage. Feeding Brussels sprouts or cabbage to rats also enhanced the intestinal metabolism of 7-ethoxycoumarin, benzo[a] pyrene, and hexobarbital. Pretreatment of rats with several indoles that are present in cabbage and Brussels sprouts stimulated the intestinal metabolism of phenacetin, 7-ethoxycoumarin, benzo[a] pyrene, and hexobarbital. Additional studies are needed to more fully explore the effects of dietary factors on the action of drugs, environmental pollutants, and normal body constituents in humans.