Differential depletion of carotenoids and tocopherol in liver disease

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 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.