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A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties.
Authors:M Harwood  B Danielewska-Nikiel  J F Borzelleca  G W Flamm  G M Williams  T C Lines
Affiliation:CANTOX Health Sciences International, 2233 Argentia Road, Suite 308, Mississauga, Ontario, Canada L5N 2X7. mharwood@cantox.com
Abstract:Quercetin is a naturally-occurring flavonol (a member of the flavonoid family of compounds) that has a long history of consumption as part of the normal human diet. Because a number of biological properties of quercetin may be beneficial to human health, interest in the addition of this flavonol to various traditional food products has been increasing. Prior to the use of quercetin in food applications that would increase intake beyond that from naturally-occurring levels of the flavonol in the typical Western diet, its safety needs to be established or confirmed. This review provides a critical examination of the scientific literature associated with the safety of quercetin. Results of numerous genotoxicity and mutagenicity, short- and long-term animal, and human studies are reviewed in the context of quercetin exposure in vivo. To reconcile results of in vitro studies, which consistently demonstrated quercetin-related mutagenicity to the absence of carcinogenicity in vivo, the mechanisms that lead to the apparent in vitro mutagenicity, and those that ensure absence of quercetin toxicity in vivo are discussed. The weight of the available evidence supports the safety of quercetin for addition to food.
Keywords:ADI, acceptable daily intake   AOM, azoxymethane   BBN, N-nitroso-n-butyl-(4-hydroxybutyl)amine   BF, bracken fern   CO2, carbon dioxide   COMT, catechol-O-methyltransferase   DMBA, 7,12-dimethylbenz[a]anthracene   ENNG, N-ethyl-N′-nitro-N-nitrosoguanidine   GPx, glutathione peroxidase   GR, glutathione reductase   GS, reactive thiyl radicals   GSH, glutathione (reduced)   GST, glutathione-S-transferase   H2O2, hydrogen peroxide   LC50, 50% lethal concentration   LEC, Long-Evans Cinnamon   MAM, methylazoxymethanol acetate   MDA, malondialdehyde   NADH, β-nicotinaide adenine dinucleotide   NF-κB, nuclear factor κB   NIDDK, National Institute of Diabetes and Digestive and Kidney Diseases   NIH, National Institutes of Health   NMU, N-nitrosomethylurea   NOx, nitrates plus nitrites   NTP, National Toxicology Program   ROS, reactive oxygen species   SOD, superoxide dismutase   SD, sulfer transferase   t.i.d, three times daily   TBARS, thiobarbituric acid   TBHQ, tert- butylhydroquinone   UDP-GT, UDP-glucuronsyl transferase
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