Nutrition and drug‐metabolizing enzymes

The role played by nutrition and nutritional status in drug metabolism, as distinct from the effects of diet plus nonnutrient components on these reactions, is discussed. The cytochrome P‐450‐dependent mixed‐function oxidation (MFO) activity, primarily located in the liver, and such other reactions involving the transferases and hydrases which, on theoretic grounds, may become rate limiting during nutritional alteration determine the degree of the biologic response. This is exemplified by the relationship between dietary protein deficiency which decreases MFO activity and increases the duration of action of barbiturates by decreasing their rates of metabolism and tissue clearance. Male Sprague‐Dawley weanling rats were fed on a deficient diet of 5% protein and compared with controls on 20% protein. In the protein‐deficient animals, the liver cells were larger, there were fewer per liver weight as demonstrated by DNA content, the cells were higher in lipid content, and the liver contained less protein per unit weight than that of control animals. Preliminary experiments to examine a possible relationship between protein intake and certain types of cancer were undertaken. The effect of protein deficiency on the proportion of a 3H‐AFB1 dose which binds critical macromolecules in liver nuclei was studied. An important finding was that protein‐deficient diets depressed the binding to DNA by 70%. If, indeed, as recently postulated, 80 to 90% of human cancers are due to environmental chemicals and chemical carcinogens require metabolic activation, the question is posed whether nutritional manipUlation, particularly of the amount of dietary protein, may modify carcinogenic susceptibility. Similarly, nutritional status could also significantly affect pharmacologic response and environmental chemical insult.