Alcohol, vitamin A, and β-carotene: adverse interactions, including hepatotoxicity and carcinogenicity

Abstract

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.

Nutritional deficiencies in German middle-class male alcohol consumers: relation to dietary intake and severity of liver disease

“…These changes were more pronounced as the severity of the liver disease increased and were also observed in patients with advanced non-alcoholic cirrhosis (Naveau et al, 1997). The normal energy and protein intakes in the subgroup with alcoholic cirrhosis in the present study might be explained by the exclusion of patients with advanced stages of cirrhosis (Child C) and also by the fact that most alcohol consumers in Germany remain in the economic range of what is called 'middle-class' in many industrialized countries (Italian Multicentre, 1994;Leo & Lieber, 1999;Naveau et al, 1997;Sarin et al, 1997).…”

“…In this population alcohol is added to the diet rather than replacing nutrients derived from food sources. These results differ from those reported in most studies performed in the USA and in some other countries, in which malnutrition seems to be frequent and the leading cause of a deficient nutritional state (Hurt et al, 1981, Italian Multicentre, 1994Leevy et al, 1965, Leo & Lieber, 1999McClain & Su, 1983;Mezey, 1991;Naveau et al, 1997;Patek et al, 1975;Sarin et al, 1997). However, the plasma content of several vitamins (vitamin C, E, carotenoids) and trace elements (zinc, selenium) was significantly reduced in the alcohol consumers, the depression being independent of the stage of ALD.…”

“…Reduced circulating concentrations of retinol and carotenoids in patients with alcoholic liver disease have been reported by other groups (Ahmed et al, 1994;Italian Multicentre, 1994;Landig et al, 1998;Leo et al, 1993;Leo & Lieber, 1999). The markedly decreased blood concentration of carotenoids may, at least partially, be caused by malabsorption which is frequently observed in imbibing alcoholics and in subjects with more advanced alcoholic liver disease.…”

“…Both the nutrient intake and the nutritional status of alcohol consumers are markedly influenced by many factors such as severity and duration of alcohol abuse, the presence, type and severity of somatic complications caused by excessive drinking and by economic and social circumstances. Since most earlier studies on the association of alcohol abuse and nutritional deficiencies have focused either on 'skid row' alcoholics or on alcoholics with severe somatic diseases (Leevy et al, 1965;McClain & Su, 1983;Patek et al, 1975), it was assumed that the overall nutritional disturbances in alcohol consumers had been overestimated (Italian Multicentre, 1994;Leo & Lieber, 1999;Mills et al, 1983;Morgan, 1988;Salaspuro, 1993). In fact, the nutritional intake and status of alcohol consumers without major medical complications was not found to be markedly inferior to that of non-alcohol abusers particularly among those with similar economic and social backgrounds (Gruchow et al, 1985;Hillers & Massey, 1985;Hurt et al, 1981;Mezey, 1991;Rissanen et al, 1987).…”

“…In addition, this may be caused by maldigestion because of changes in the biliary secretion of bile acids (Bode & Bode, 1992). The reduced content of carotenoids in alcohol consumers might be of special importance with respect to their role in the antioxidative defense system against reactive oxygen species (Leo & Lieber, 1999).…”