title: Alcohol, vitamin A, and beta-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.
authors.affiliation: Section of Liver Disease and Nutrition, the Alcohol Research and Treatment Center, Bronx VA Medical Center and Mount Sinai School of Medicine, NY 10468, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Leo
authors.forename: C S
authors.initials: CS
authors.lastname: Lieber
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000009:adverse effects* / Q000378:metabolism; D002273:Carcinogens / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000009:adverse effects* / Q000378:metabolism; D004357:Drug Synergism; D000431:Ethanol / Q000009:adverse effects* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism; D008175:Lung Neoplasms / Q000139:chemically induced; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D014801:Vitamin A / Q000009:adverse effects* / Q000378:metabolism; D014802:Vitamin A Deficiency / Q000378:metabolism; D019207:beta Carotene / Q000009:adverse effects* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D002273:Carcinogens; D002492:Central Nervous System Depressants; D019207:beta Carotene; D014801:Vitamin A; D000431:Ethanol