Ethanol has a profound effect on the absorption of many nutrients, which may be mediated in part by various factors or may have an effect directly on the absorption of actively transported substances. There is some evidence that chronic ethanol feeding may interfere with the passive transport, perhaps by reducing the absorptive area. Recent evidence has brought into question the criteria previously accepted for active or passive transport, and the effects of the multiple variables which may influence absorption at physiological levels need to be controlled and separately evaluated. The effects of ethanol will vary depending on the dose, the route and duration of administration, the animal species investigated, the experimental methods employed and the substance and its concentrations tested. If you add to this the clear demonstration in man that malnutrition per se may reduce absorption, the complexity of the situation will become apparent. The fundamental question is whether the malabsorption of specific substances in the malnourished alcoholic will adversely affect morbidity, intellectual potential and rehabilitation, and increase mortality. The answer to these questions will depend upon longitudinal studies with agreed significant parameters that will be directly altered as a result of nutrient deficit. The absorption of a limited number of substances has been discussed in this chapter but it is apparent that there are many more substances whose absorption has never been studied. Since all substances are not equally affected, and the absorption of certain nutrients may be enhanced, ethanol and malnutrition will likely present the body with an imbalance where nutrient requirements are fulfilled to varying degrees. It thus becomes apparent that the effects of ethanol and nutrient deficiency are inseparable, both contributing to altered intermediary metabolism and tissue damage in alcoholism. There is gathering evidence that brain damage may be directly related to nutrient deficit and the rate of tissue repair would be severely impaired. What then is the contribution of malabsorption, which will sometimes be intermittent and at other times prolonged when it occurs over an extended period? Although more evidence is required in a greater number of patients with varying degrees of liver damage, defined nutritional intake and established blood ethanol levels, it is already apparent that within the wide individual variation, the absorption of certain substances may be severely impaired. The attractive suggestion of adding nutrients to beverages and thereby supplementing intake as the ethanol consumption increases requires more work to show that malabsorption would not be a limiting factor and to determine which nutrients should be added. More attention should be paid to the possibility of altering the molecular structure and thereby changing the mode of transport as shown for thiamine. It will be essential to establish that the different molecular forms will be palatable and stable, that they can be absorbed, that they can be stored to the same extent and that they are biologically active. There has been a tendency to define toxic levels of ethanol in terms of its effect on the liver. However, recent evidence indicates that liver damage does not parallel the effects on the brain, which are probably of far greater importance. Although no figures are available, chronic ethanol-related brain damage is a major cause of long-term hospitalization, with lesser degrees of brain injury frequently undocumented and often disregarded. There is a well-established relationship between vitamin deficiency and altered brain function, although our knowledge concerning the mechanisms of various forms of brain damage is very limited. Detailed studies of Wernicke’s encephalopathy and its relationship to thiamine deficiency have been carried out, but there is evidence that brain damage which precedes the classical picture is often missed and much remains to be learnt about the natural history of other forms of brain injury. Preliminary studies suggest that some may be reversible and related to abnormalities in thiamine or vitamin B6 metabolism. Ethanol probably affects intestinal transport by altering the physical properties of the intestinal membrane and/or by inhibiting the activity of such membrane-bound enzymes as Na+ -K+-ATPase which are involved in active transport. Since similar mechanisms are involved in the transport of nutrients into other tissues, much work remains to be done to determine how this may be influenced by ethanol and malnutrition under varying conditions. However, our understanding of its effect on the mechanisms of transport remains to be clarified. There is gathering evidence that malnutrition will potentiate tissue injury and sometimes may be a causal factor. Until the significant chain of events in tissue necrosis has been established, the contribution of malnutrition will remain uncertain but most would agree that nutrition plays a key role in limiting and repairing the induced damage.