Current concepts in nutrition最新文献

Ther are several main mechanisms that allow us to understand a number of the hepatic and metabolic effects of ethanol. Ethanol is oxidized in the liver to two products (hydrogen and acetaldehyde), to which many of the effects of ethanol can be attributed. The hydrogen generated alters the redox state, and though this effect is attenuated after chronic ethanol consumption, it may still be sufficient to explain alterations in lipid metabolism, possibly increased collagen deposition, and, under special circumstances, depression of protein synthesis. Acetaldehyde impairs microtubules, decreases protein secretion, and causes protein retention and ballooning of the hepatocyte. Acetaldehyde exerts toxicity also with regard to other key cellular functions, particularly in the mitochondria, and it may promote peroxidation of the cellular membranes. It is noteworthy that after chronic consumption of ethanol, there is increased acetaldehyde, in part because of decreased disposition in the mitochondria and partly because of induction of an alternative pathway of ethanol metabolism, namely the microsomal ethanol-oxidizing system. Indeed, this MEOS increases in activity after chronic ethanol consumption, with cross induction and acceleration of the metabolism of other drugs and increased lipoprotein production with hyperlipemia. There is also increased microsomal activation of hepatotoxic compounds (including drugs and possibly vitamin A). Fibrosis and cirrhosis can develop despite an associated adequate diet and even in the absence of alcoholic hepatitis. They are preceded by myofibroblasts and fibroblast proliferation. What eventually causes the increased number of myofibroblasts and promotes fibrosis is unclear, nor do we know the relative role of hepatocytes or mesenchymal cells in the process of fibroplasis. Possibly selective roles in this process of specific nutritional factors remain to be elucidated.

In conclusion, there are several drug types that can interfere with vitamin B6 metabolism. In most cases, the interaction involves a complex formation between the drug (or a derivative) and the reactive coenzyme PLP, resulting in a Schiff base. Such an interaction leads to an inactivation of PLP (and also of the drug). Other types of interaction involve (a) stimulation of vitamin B6-dependent pathways and (b) competition with PLP for the binding site on the enzyme. Examples of the above are the steroid hormones (oral contraceptives). In most instances, overt symptoms of vitamin B6 deficiency due to chronic ingestion of these drugs are observed, and neurological problems seem to be rather frequent. Because of the reactive nature of the coenzyme PLP and the ease with which it can interact with drugs, sub-clinical (marginal) vitamin B6 deficiency should be suspected in the absence of overt clinical signs. Once the vitamin B6 problem has been identified, the condition can usually be treated by judicious use of large doses of vitamin B6 without compromising the clinical efficacy of the drug.

From our present state of knowledge of drug effects on nutrient absorption, we are able to conclude that drugs may promote, retard, or inhibit nutrient uptake. Drug-nutrient interactions can be intraluminal and direct, or extraluminal with indirect influence of the drug on nutrient absorption. We have learned that drug-induced malabsorption becomes symptomatic and causes nutritional deficiencies with chronic use of drugs that have the potential to cause malabsorption, or with abuse of such drugs. Finally, we are impressed by predisposing factors, which include the disease for which the drug is administered, the time at which the drug is taken, alcohol intake, and preexistent malnutrition, and which can contribute to the etiology of the malabsorption state.