Nutritional parameters that alter hepatic drug metabolism, conjugation, and toxicity

A major concern of contemporary medicine is the adverse effects resulting from the use of prescribed and over-the-counter pharmacologic agents. In many cases more than one drug is taken at the same time, which increases the risk of overloading the detoxification mechanisms. If the individual has poor nutritional status, the system becomes even more inefficient. The liver contains the most important of these detoxification systems: the cytochrome P-450-dependent mixed function oxidase (MFO) and several conjugation enzymes, e.g., sulfotransferase, glucuronyl transferase, and glutathione transferase, which convert lipophilic compounds to more water-soluble products to enhance their excretion. The balance of these reactions determines the rate of metabolism and clearance of xenobiotic agents, and regulates in part the degree of intracellular damage. Nutritional factors, including proteins, carbohydrates, fats, vitamins, and minerals, affect the efficiency of these reactions. Changes in intracellular metabolism can alter not only the enzyme levels but also the availability of their cofactors, e.g., NADPH, UDPGA (uridine diphosphate glucuronic acid), PAPS (3'-phosphoadenosine-5'-phosphosulfate), and GSH. Diets restricted in calories, protein, or essential fatty acids, as well as those having low quality protein or high sugar content, can affect the component enzymes, cytochrome P-450 and the cytochrome P-450 reductase, and the MFO activity toward a variety of drugs. In addition, deficiencies of specific vitamins (riboflavin, ascorbic acid, and vitamins A and E) and minerals (iron, copper, zinc, and magnesium) affect the components and activities of the system in unique ways. Insight into the regulation of the hepatic detoxification mechanism can be gained by using nutrient variables to perturb the system.