Do flavan-3-ols from green tea reach the human brain? ANDREA ZINI 1,† , DANIELE DEL RIO 2,† , AMANDA J. STEWART 3 , JESSICA MANDRIOLI 1 , ELISA MERELLI 1 , PATRIZIA SOLA 1 , PAOLO NICHELLI 1 , MAURO SERAFINI 4 , FURIO BRIGHENTI 2 , CHRISTINE A. EDWARDS 5 , & ALAN CROZIER 3 1 Department of Neuroscience, University of Modena and Reggio Emilia, Modena, Italy, 2 Human Nutrition Unit, Department of Public Health, University of Parma, Parma, Italy, 3 Plant Products and Human Nutrition Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, UK, 4 Unit of Human Nutrition, Antioxidant Research Laboratory, National Institute for Food and Nutrition Research, Rome, Italy, and 5 Division of Developmental Medicine, Human Nutrition Section, Yorkhill Hospitals, University of Glasgow, Glasgow, UK (Received 31 October 2005; revised 6 February 2006; accepted 15 February 2006) Abstract Following acute ingestion of green tea by six human subjects, HPLC-MS 2 analysis revealed that flavan-3-ol methyl, glucuronide and sulfate metabolites appeared in the bloodstream but did not pass through the blood – cerebrospinal fluid barrier. These observations emphasize the discrepancies between in vitro and in vivo evidence on the neuroprotective role of these compounds. If, as has been proposed, green tea exerts neuroprotective effects, this finding indicates that the active components are not flavan-3-ols or their metabolites. Alternatively, a systemic action may be hypothesised whereby dietary flavan-3-ols up-regulate antioxidant defences and/or reduce inflammation, the benefit of which may be effective throughout the body. Keywords: Antioxidant, catechins, cerebrospinal fluid, flavan-3-ols, green tea Introduction Oxidative stress and consequent damage to biomole- cules in specific brain regions are associated with neurodegenerative diseases (Andersen 2004; Buhmann et al. 2004). Flavonoids have been recently described as neuroprotectants operating through several different mechanisms. Principally, they prevent or reduce oxidation, chelate iron and exert anti-inflammatory action in vitro and in vivo (Gilgun- Sherki et al. 2004). Moreover, they are reported to activate survival genes and cell signalling pathways, and to regulate mitochondrial function (Mandel and Youdim 2004). Among the flavonoids, catechins and their gallate derivatives, which are flavan-3-ols, are of interest, as they are strong antioxidants and are especially abundant in green tea (Stewart et al. 2005). Recent epidemiological studies have shown a reduced risk of Alzheimer’s and Parkinson’s diseases associated with intake of green tea (Weinreb et al. 2004). Additionally, animal studies have shown suppression of age related brain atrophy and cognitive dysfunction and reduced ischemia-induced brain damage associ- ated with green tea consumption (Unno et al. 2004). It has been reported that methyl and glucuronide flavan-3-ol metabolites reach the brain of rats, albeit it in minute amounts, after the ingestion of (2 )-epicatechin (Abd El Mohsen et al. 2002), however, the amounts administered orally were somewhat in excess of what could be ingested as part of a typical meal. There is no information with human subjects on the ability of catechin metabolites to cross the blood– brain barrier (BBB) making it difficult to draw firm ISSN 1028-415X print/ISSN 1476-8305 online q 2006 Informa UK Ltd. DOI: 10.1080/10284150600637739 Correspondence: A. Crozier, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Graham Kerr Building, Glasgow G12 8QQ, UK. Tel: 44 141 330 4613. Fax: 44 141 330 5394. E-mail: a.crozier@bio.gla.ac.uk † These authors contributed equally to the paper. Nutritional Neuroscience, February/April 2006; 9(1/2): 57–61