Effects of dietary fat on drug metabolism

The fact that nutriture affects drug metabolism and drug action in laboratory animals is undisputable. Activation or detoxification of drugs and potential carcinogens can also be modified by diet. The quantity and quality of dietary fat affects lipid composition and physical characteristics of biological membranes and enzymatic activity of several components of the drug metabolizing enzyme system. These changes have been associated with alterations in the physiological response to drugs and to the resulting mutagenicity and carcinogenicity of procarcinogens. It is suggested by these data that dietary fat, by altering fatty acid composition of biological membranes, alters the physical and biochemical characteristics of these membranes, thereby directly affecting drug entrance into the membrane; the stability of the membrane; the potential for lipid peroxidation; and the activity of the phospholipid dependent enzymes associated with these membranes. The fact that these membrane associated changes can occur rapidly and that brief periods of fatty acid deprivation can profoundly affect the inducibility of these enzymes by xenobiotics suggests that the potential for drug-nutrient interactions exists in the absence of frank nutrient deficiency states.