Toxicological and Epigenetic Studies of Two Types of Ale Beer, Tyrosol and Iso-Alpha Humulone

Abstract

Although many benefits drawn from beer consumption are claimed, the epidemiological records are contradictory with respect to cancer prevention. The purpose of this study was to investigate the possible health-related activities involving genome safety and the ageing processes of two types of lyophilised ale beers (blond and stout), as well as two of their bioactive compounds (tyrosol and iso-alpha humulone). A multipurpose trial set of in vivo toxicity, antitoxicity, mutagenicity, antimutagenicity, lifespan and healthspan assays using Drosophila melanogaster were used. In parallel, several in vitro assays were designed using the cancer cell line HL-60 in order to establish the possible chemopreventive activity of the selected substances, where epigenetic modulation of DNA methylation changes, clastogenic activity and tumour cell inhibition growth were evaluated. The safety of the four substances was confirmed: lyophilised blond ale beer (LBAB), lyophilised stout ale beer (LSAB), tyrosol and iso-alpha humulone were neither toxic nor genotoxic. Moreover, all substances, except tyrosol, revealed the ability to protect individual genomes against oxidative radicals and to exert antimutagenic activity against the genotoxin hydrogen peroxide. With respect to the degenerative process indicators of lifespan and healthspan, tyrosol was the only compound that did not exert any influence on the life extension of Drosophila; LBAB induced a significant lifespan extension in D. melanogaster; LSAB and its distinctive compound iso-alpha humulone induced a reduction in longevity. The in vitro assays showed the cytotoxic activity of LBAB, LSAB and tyrosol against HL-60 cells. Moreover, proapoptotic DNA fragmentation or DNA strand breakage was observed for both types of beers and iso-alpha humulone at different concentrations. Furthermore, the lyophilised ale beers and tyrosol exhibited an increasing genome-wide methylation status, while iso-alpha humulone exhibited a demethylation status in repetitive cancer cell sequences. Although the biological activities assigned to beer consumption cannot be linked to any specific molecule/element due to the complexity of the phenolic profile, as well as the multifactor brewing process, the results obtained let us propose lyophilised ale beers as safe potential nutraceutical beverages when consumed in moderate amounts. The prevention of toxicity and genetic oxidative damage, as well as the induction of tumor cell death and modulation of the methylation status, are the key activities of beer that were shown in the present research.