@article{c1f3c23bca7340e49403cd441315b200,
title = "Identification and quantification of (poly)phenol and methylxanthine metabolites in human cerebrospinal fluid: evidence of their ability to cross the BBB",
abstract = "Increasing evidence suggests that dietary (poly)phenols and methylxanthines have neuroprotective effects; however, little is known about whether they can cross the blood-brain barrier (BBB) and exert direct effects on the brain. We investigated the presence of (poly)phenol and methylxanthine metabolites in plasma and cerebrospinal fluid (CSF) from 90 individuals at risk of dementia using liquid chromatography-mass spectrometry and predicted their mechanism of transport across the BBB using in silico modelling techniques. A total of 123 and 127 metabolites were detected in CSF and plasma, respectively. In silico analysis suggests that 5 of the 20 metabolites quantified in CSF can cross the BBB by passive diffusion, while at least 9 metabolites require the aid of cell transporters to cross the BBB. Our results showed that (poly)phenols and methylxanthines are bioavailable, can cross the BBB via passive diffusion or transport carriers, and can reach brain tissues to exert neuroprotective effects.",
author = "{Le Sayec}, Melanie and Diogo Carregosa and Khadija Khalifa and {de Lucia}, Chiara and Dag Aarsland and Santos, {Cl{\'a}udia N.} and Ana Rodriguez-Mateos",
note = "Funding Information: The authors thank Anthony Sullivan, Chris Titman, and Neil Loftus from Shimadzu UK Ltd for their support on the LC-MS/MS instrument. The authors also want to acknowledge and thank the participants for their kind effort during the study and all the research staff members at the three sites for their assistance and contribution to the conduction of the trial. Sources of support for the work : This work was funded by a grant from Nasjonalforeningen and Evonik Operations GmbH to D. A. and A. R. M. iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is cofunded by Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia (FCT)/Minist{\'e}rio da Ci{\^e}ncia e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement and European Research Council (ERC) under the European Union's Horizon 2020 research and innovation programme under grant agreement no. 804229, is acknowledged. Publisher Copyright: {\textcopyright} 2023 The Royal Society of Chemistry.",
year = "2023",
month = sep,
day = "5",
doi = "10.1039/d3fo01913f",
language = "English",
volume = "14",
pages = "8893 -- 8902",
journal = "Food and Function",
issn = "2042-6496",
publisher = "RSC - Royal Society of Chemistry",
number = "19",
}