beta-carotene and Liver-Cirrhosis--Alcoholic

Isozymes of alcohol and other dehydrogenases convert ethanol and retinol to their corresponding aldehydes in vitro. In addition, new pathways of retinol metabolism have been described in hepatic microsomes that involve, in part, cytochrome P450s, which can also metabolize various drugs. In view of these overlapping metabolic pathways, it is not surprising that multiple interactions between retinol, ethanol, and other drugs occur. Accordingly, prolonged use of alcohol, drugs, or both, results not only in decreased dietary intake of retinoids and carotenoids, but also accelerates the breakdown of retinol through cross-induction of degradative enzymes. There is also competition between ethanol and retinoic acid precursors. Depletion ensues, with associated hepatic and extrahepatic pathology, including carcinogenesis and contribution to fetal defects. Correction of deficiency through vitamin A supplementation has been advocated. It is, however, complicated by the intrinsic hepatotoxicity of retinol, which is potentiated by concomitant alcohol consumption. By contrast, beta-carotene, a precursor of vitamin A, was considered innocuous until recently, when it was found to also interact with ethanol, which interferes with its conversion to retinol. Furthermore, the combination of beta-carotene with ethanol results in hepatotoxicity. Moreover, in smokers who also consume alcohol, beta-carotene supplementation promotes pulmonary cancer and, possibly, cardiovascular complications. Experimentally, beta-carotene toxicity was exacerbated when administered as part of beadlets. Thus ethanol, while promoting a deficiency of vitamin A also enhances its toxicity as well as that of beta-carotene. This narrowing of the therapeutic window for retinol and beta-carotene must be taken into account when formulating treatments aimed at correcting vitamin A deficiency, especially in drinking populations.

Topics: Animals; Antioxidants; beta Carotene; Carcinogens; Central Nervous System Depressants; Drug Synergism; Ethanol; Humans; Liver; Liver Cirrhosis, Alcoholic; Lung Neoplasms; Microsomes, Liver; Vitamin A; Vitamin A Deficiency

We found lower plasma beta-carotene concentrations in alcoholics than in control subjects, but heavy drinkers (> or = 200 g/d) had about twice the beta-carotene of those drinking less (P < 0.01), with a significant correlation between plasma beta-carotene and alcohol intake (r = 0.6, P < 0.001). When beta-carotene beadlets (30-60 mg/d) were administered to hospitalized alcoholics given controlled diets, those with cirrhosis had a much lower plasma beta-carotene response than those without; the latter in turn responded with lower beta-carotene concentrations than did control subjects. Plasma retinol, alpha-tocopherol, and other carotenoids, such as lycopene, did not differ significantly. We concluded that plasma beta-carotene is relatively increased by heavy alcohol consumption, whereas in patients with liver damage, especially cirrhosis, it is lowered. In these patients, beta-carotene supplementation may be justified, but this should be coupled with control of drinking because of possible hepatotoxic alcohol-beta-carotene interactions.

Topics: Adult; Alcoholism; Analysis of Variance; beta Carotene; Carotenoids; Cholesterol; Chromatography, High Pressure Liquid; Ethanol; Humans; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Vitamin A; Vitamin E

Carotenoids and tocopherols are major natural protective agents against free radical-mediated liver damage, but their levels in diseased liver are largely uncharted. Therefore we carried out measurements with high-pressure liquid chromatography of alpha- and beta-carotene, lycopene, cryptoxanthin, lutein and zeaxanthin, total retinoids and alpha- and gamma-tocopherol. Liver tissue was obtained from percutaneous needle biopsies, livers of transplant recipients or a donor bank. Compared with controls (transplant donors; n = 13), levels of all carotenoids and retinoids were extremely low at all stages of liver disease. Patients with alcoholic cirrhosis (n = 11) had 20- and 25-fold decreases of levels of lycopene (p < 0.001) and alpha- and beta-carotene (p < 0.005), respectively. Even in subjects with less severe alcoholic liver disease (steatosis, perivenular fibrosis, portal fibrosis; n = 14) and in patients with nonalcoholic liver disease (n = 13), levels were four to six times lower than those in normal subjects. By contrast, levels of alpha-tocopherol were decreased significantly only in patients with cirrhosis, who displayed a threefold reduction. In the serum of most patients, lycopene and tocopherol concentrations were not depressed, whereas one third of alpha- and beta-carotene levels were low, probably reflecting poor dietary intake. A significant correlation was observed between serum and liver alpha- and beta-carotene levels (p < 0.0001; r = 0.715). However, of the patients with extremely low liver alpha- and beta-carotene concentrations, more than half had blood levels in the normal range, suggesting that liver disease interferes with the uptake, excretion or, perhaps, metabolism of alpha- and beta-carotene. In the cirrhotic livers of eight candidates for liver transplantation, the ratios of alpha- and beta-carotene to total retinoids and of beta-carotene to retinoids were much higher than those in normal livers, suggesting some impairment in the conversion of alpha- and beta-carotene to retinoids. In most cases, even with high ratios, absolute levels of hepatic alpha- and beta-carotene and retinoids were severely depressed. We concluded that, even in the presence of normal serum levels alpha- and beta-carotene, tocopherol and lycopene, patients with cirrhosis have extremely low hepatic levels.

Topics: Adult; beta Carotene; Biopsy, Needle; Carotenoids; Chromatography, High Pressure Liquid; Cryptoxanthins; Humans; Liver; Liver Cirrhosis, Alcoholic; Liver Diseases; Lutein; Lycopene; Male; Middle Aged; Reference Values; Retinoids; Vitamin E; Xanthophylls; Zeaxanthins

The antioxidant status of alcoholic patients was assessed by direct measurement of the plasma antioxidants alpha-tocopherol and beta-carotene and of selenium as a marker of glutathione peroxidase. Overall, the alcoholic group showed significant decreases in the mean plasma values of beta-carotene, zinc and selenium when compared to the control subjects. When the patients were subdivided according to their liver histology, beta-carotene showed a progressive decrease in plasma concentration with increasing liver damage, whereas alpha-tocopherol levels were only depleted in the patients with cirrhosis. There were significant decreases in the plasma concentrations of both alpha-tocopherol and selenium in all patients with alcoholic skeletal muscle myopathy, whereas patients with normal muscle biopsies showed adequate antioxidant status. Such results support a role for free radical-mediated damage in end organ injury, particularly myopathy, in alcohol misusers.

Topics: Adult; Alcoholism; Antioxidants; beta Carotene; Biopsy; Carotenoids; Fatty Liver, Alcoholic; Female; Humans; Liver; Liver Cirrhosis, Alcoholic; Liver Diseases, Alcoholic; Liver Function Tests; Male; Middle Aged; Muscles; Muscular Diseases; Selenium; Vitamin A; Vitamin E