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

Isozymes of alcohol and other dehydrogenases convert ethanol and retinol to their corresponding aldehydes in vitro. In addition, new pathways of retin ol metabolism have been described in hepatic microsomes that involve, in pa rt, cytochrome P450s, which can also metabolize various drugs. In view of t hese overlapping metabolic pathways, it is not surprising that multiple int eractions between retinol, ethanol, and other drugs occur. Accordingly prol onged 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 comp etition between ethanol and retinoic acid precursors. Depletion ensues, wit h associated hepatic and extrahepatic pathology, including carcinogenesis a nd contribution to fetal defects. Correction of deficiency through vitamin A supplementation has been advocated. It is, however, complicated by the in trinsic hepatotoxicity of retinol, which is potentiated by concomitant alco hol consumption. By contrast, beta-carotene, a precursor of vitamin A, was considered innocuous until recently, when it was found to also interact wit h ethanol, which interferes with its conversion to retinol. Furthermore, th e combination of beta-carotene with ethanol results in hepatotoxicity. More over, in smokers who also consume: alcohol, beta-carotene supplementation p romotes pulmonary cancer and, possibly, cardiovascular complications. Exper imentally, beta-carotene toxicity was exacerbated when administered Its par t 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 acc ount when formulating treatments aimed at correcting vitamin A deficiency, especially in drinking populations.