Interaction of Ethanol With β–Carotene: Delayed Blood Clearance and Enhanced Hepatotoxicity

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Abstract
ABSTRPlCT: Because we had found that ethanol interacts with retinol, we investigated whether it also affects its precursor, β–carotene. In 14 baboons fed ethanol (50% of total energy) for 2 to 5 yr with a standard amount of β–carotene (one 200–gm carrot/day), levels of β–carotene were much higher than in controls fed isocaloric carbohydrate, both in plasma (122.5 ± 30.9 nmol/dl vs. 6.3 ± 1.4 nmol/dl; p < 0.005) and in liver (7.9 ± 1.1 nmol/gm vs. 1.8 ± 0.5 nmol/gm; p < 0.001). Even 20 days after withdrawal of the carrots, plasma β–carotene levels remained higher in alcohol–fed baboons than in controls (10.1 ± 3.8 nmol/dl vs. < 0.1 nmol/dl). Next, the diet was supplemented with β–carotene beadlets: in four pairs of baboons given a low dose of β–carotene (3 mg/1,000 kcal), plasma levels were significantly higher in alcohol–fed animals than in controls, even when expressed per cholesterol (although the latter increased with alcohol intake). Seven pairs of animals were given a higher dose (30 mg/1,000 kcal) of β–carotene for 1 mo, followed, in four pairs, by 45 mg for another month. On cessation of β–carotene treatment, plasma levels decreased more slowly in the alcohol–fed baboons than in the controls. Percutaneous liver biopsy specimens revealed that liver concentrations of β–carotene correlated with plasma levels but were higher in the alcohol–fed baboons than in the control baboons, whereas the β–carotene–induced increase in liver retinoids was lower (p < 0.02). Furthermore, the ethanol–induced liver depletion of total retinoids (432 ± 103 nmol/gm vs. 1,711 ± 103 in controls; p < 0.001) was not corrected (637 ± 149 vs. 2,404 ± 74; p < 0.001), despite the massive supplementation with β–carotene. Moreover, in the animals fed alcohol with β–carotene, multiple ultrastructural lesions appeared, with autophagic vacuoles, abundant myelin figures, degenerated mitochondria and increased blood levels of the mitochondrial enzyme glutamic dehydrogenase. The histological changes were either absent or much less prominent in the baboons given β–carotene with the control diet or in animals fed the ethanol or control diets without β–carotene. Thus the combination of an increase in plasma and liver β–carotene after ethanol and a relative lack of a corresponding rise in retinol suggests interference with the conversion of β–carotene to vitamin A. Because of an associated exacerbation of the liver toxicity, we conclude that β–carotene must be administered cautiously in the presence of heavy alcohol consumption because the optimal human therapeutic dose remains to be defined. (Hepatology 1992;15:883-891).