Differential depletion of carotenoids and tocopherol in liver disease

Authors

  • Maria A. Leo,

    1. Section of Liver Disease and Nutrition Bronx Veterans Affairs Medical Center and Mt. Sinai School of Medicine, New York, New York 10468
    2. Alcohol Research and Treatment Center Bronx Veterans Affairs Medical Center and Mt. Sinai School of Medicine, New York, New York 10468
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  • Alan S. Rosman,

    1. Section of Liver Disease and Nutrition Bronx Veterans Affairs Medical Center and Mt. Sinai School of Medicine, New York, New York 10468
    2. Alcohol Research and Treatment Center Bronx Veterans Affairs Medical Center and Mt. Sinai School of Medicine, New York, New York 10468
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  • Charles S. Lieber M.D.

    Corresponding author
    1. Section of Liver Disease and Nutrition Bronx Veterans Affairs Medical Center and Mt. Sinai School of Medicine, New York, New York 10468
    2. Alcohol Research and Treatment Center Bronx Veterans Affairs Medical Center and Mt. Sinai School of Medicine, New York, New York 10468
    • Alcohol Research and Treatment Center (151/G), Veterans Affairs Medical Center, 130 West Kingsbridge Road, Bronx, NY 10468
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Abstract

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 α- and β-carotene, lycopene, cryptoxanthin, lutein and zeaxanthin, total retinoids and α- and γ-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 α- and β-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 α-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 α- and β-carotene levels were low, probably reflecting poor dietary intake. A significant correlation was observed between serum and liver α- and β-carotene levels (p <0.0001; r = 0.715). However, of the patients with extremely low liver α- and β-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 α- and β-carotene. In the cirrhotic livers of eight candidates for liver transplantation, the ratios of α- and β-carotene to total retinoids and of β-carotene to retinoids were much higher than those in normal livers, suggesting some impairment in the conversion of α- and β-carotene to retinoids. In most cases, even with high ratios, absolute levels of heptic α- and β-carotene and retionids were severely depressed. We concluded that, even in the presence of normal serum levels α- and β-carotene, tocopherol and lycopene, patients with cirrhosis have extremely low hepatic levels. (HEPATOLOGY 1993;17:977–986.)

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