Alcohol: Its metabolism and interaction with nutrients

Tn the past, alcoholic liver disease was attributed exclusively to dietary deficiencies, but experimental and judicious clinical studies have now esta blished alcohol's hepatotoxicity. Despite an adequate diet, it can contribu te to the entire spectrum of liver diseases, mainly by generating oxidative stress through its microsomal metabolism via cytochrome P4502E1 (CYP2E1). It also interferes with nutrient activation, resulting in changes in nutrit ional requirements. This is exemplified by methionine, one of the essential amino acids for humans, which needs to be activated to S-adenosylmethionin e (SAMe), a process impaired by liver disease. Thus, SAMe rather than methi onine is the compound that must be supplemented in the presence of signific ant liver disease. In baboons, SAMe attenuated mitochondrial lesions and re plenished glutathione; it also significantly reduced mortality in patients with Child A or B cirrhosis. Similarly, decreased phosphatidylethanolamine methyltransferase activity is associated with alcoholic liver disease, resu lting in phosphatidylcholine depletion and serious consequences for the int egrity of membranes. This can be offset by polyenylphosphatidylcholine (PPC ), a mixture of polyunsaturated phosphatidylcholines comprising dilinoleoyl phosphatidylcholine (DLPC), which has high bioavailability. PPC (and DLPC) opposes major toxic effects of alcohol, with down-regulation of CYP2E1 and reduction of oxidative stress, deactivation of hepatic stellate cells, and increased collagenase activity, which in baboons, results in prevention of ethanol-induced septal fibrosis and cirrhosis. Corresponding clinical trial s are ongoing.