Nutritional Management of Alcoholic Liver Disease : Part 2

by National Institute of Health

(Page 7 of 7)

Another important antioxidant is vitamin E. Alcoholics with cirrhosis often have low vitamin E levels in the liver, whereas alcoholics without cirrhosis generally have vitamin E levels within the normal range. Therefore, administration of vitamin E supplements may be useful only for some alcoholics. Moreover, studies in baboons have found that animals with normal vitamin E levels in the liver still developed fibrosis or even cirrhosis. Vitamin E also showed no positive effect in a trial of patients with alcoholic cirrhosis who received supplements of the compound. These observations suggest that although vitamin E deficiency increases the liver's vulnerability to alcohol, normal vitamin E levels may not be able to prevent the developmenst of alcoholic liver disease, particularly fibrosis.

Emerging Therapies

S-adenosylmethionine (SAMe). Because nutritional supplementation of the antioxidant GSH or its component cysteine is not an effective way to ensure adequate GSH levels in the livers of alcoholics, investigators have looked for other compounds that can promote GSH production. The ultimate precursor of cysteine is the amino acid methionine. Before cysteine is generated, methionine is converted in the cell to SAMe; however, the enzyme that mediates this reaction is much less active in patients with liver disease. Consequently, administration of methionine itself is not useful in these patients; in fact, excess methionine can have some adverse effects on liver function.

Because patients with alcoholic liver disease can produce little SAMe, and the existing SAMe is used up rapidly to generate new GSH, SAMe deficiency typically develops in the cells of these patients. This deficiency can be corrected, however, by administering supplemental SAMe. The effectiveness of this approach has been shown in both animals and humans. In baboons, SAMe administration resulted in a corresponding improvement in alcohol-induced liver injury, as shown by less GSH depletion as well as by changes in the activities of certain enzymes that serve as indicators of liver function, and by the production of fewer abnormal mitochondria.

In humans, a clinical trial in which SAMe was given to patients with alcoholic cirrhosis according to strict scientific standards also achieved significant therapeutic success. When patients with the most severe liver disease were excluded, those who received SAMe were significantly less likely to die or require a liver transplant within the next 2 years than were patients who had received an inactive substance. Moreover, the study detected virtually no harmful side effects of SAMe treatment. Therefore, this approach appears to hold promise for the treatment of patients with alcoholic liver disease and should be investigated further.

PPC. One of the harmful consequences of alcohol breakdown by the MEOS is the formation of ROS, which among other effects can cause lipid peroxidation. Not all fat molecules, however, are equally sensitive to peroxidation. For example, polyunsaturated fats are more susceptible than monounsaturated or saturated fats. With fat molecules containing additional phosphate groups (phospholipids), however, the opposite may occur - polyunsaturated phospholipids may be particularly resistant to peroxidation. This hypothesis is supported by studies evaluating the effects of the compound polyenylphosphatidylcholine (PPC) in animal models. In these studies, PPC, which is a mixture of molecules known as phosphatidylcholines (extracted from soybeans), prevented lipid peroxidation and attenuated the associated liver injury in rats that had been treated with hepatic toxins. Furthermore, PPC decreased oxidative stress and prevented the development of alcohol-induced cirrhosis in baboons. Clinical trials currently are being conducted to test the effectiveness of PPC in the treatment of alcoholic liver disease.

Silymarin. Another antioxidant that has shown positive results in experimental animals is a molecule called silymarin, the active constituent of milk thistle. Some clinical trials have shown that this compound has beneficial effects such as improved survival in patients with alcoholic liver disease. Other controlled studies, however, have not verified such an action. Additional clinical trials to determine the usefulness of this compound for treating alcoholics with liver disease now are under way.

Summary

Chronic drinkers, particularly those who consume a substantial portion of their daily calories in the form of alcohol, often show evidence of malnutrition such as deficits in amino acids, proteins, and certain vitamins. These deficits can derive from an inadequate diet as well as from alcohol's effects on these nutrients and their metabolism. Particularly common is a deficit in vitamin A, which is required for proper eye function and bone growth. Moreover, both vitamin A deficits and excessive vitamin A levels can lead to liver damage, including fibrosis. Therefore, administering vitamin A to correct a deficiency is difficult and should be controlled carefully, particularly in the presence of alcohol abuse, which exacerbates vitamin A's toxicity.

Potentially harmful compounds, which, in combination with other nutritional factors, can lead to liver damage and other alcohol-related disorders, are generated not only by alcohol itself but also by its metabolism via ADH or the MEOS. Particularly important is the MEOS, which, among other functions, influences fat metabolism. Chronic alcohol consumption activates the MEOS and may thereby contribute to the development of a fatty liver. Other byproducts of MEOS-mediated alcohol degradation, such as ROS, also alter fat metabolism and damage the liver by promoting lipid peroxidation.

Because alcoholics frequently have poor nutritional status, which is further exacerbated by alcohol's effects on the body's metabolism, nutritional approaches may be useful in the treatment of alcoholic patients, including those with alcoholic liver disease. Possible approaches include nutritional supplementation to compensate for deficits in nutrients, as well as administration of antioxidants to counteract the alcohol-induced increase in oxidative stress and the resulting liver damage. Because of the potential usefulness of such an approach, several new compounds currently are being studied in clinical trials. If they prove effective, these nutritional management approaches could be important tools in the prevention or amelioration of alcoholic liver disease.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.