Dokument: Effects of flavanol monomers and procyanidins on vascular function

Titel:Effects of flavanol monomers and procyanidins on vascular function
Weiterer Titel:Die Auswirkungen von Flavanol-Monomeren und Procyaniden auf die Gefäßfunktion
URL für Lesezeichen:https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=61166
URN (NBN):urn:nbn:de:hbz:061-20221114-105955-6
Kollektion:Dissertationen
Sprache:Englisch
Dokumententyp:Wissenschaftliche Abschlussarbeiten » Dissertation
Medientyp:Text
Autor: Weber, Timon [Autor]
Dateien:
[Dateien anzeigen]Adobe PDF
[Details]3,02 MB in einer Datei
[ZIP-Datei erzeugen]
Dateien vom 10.11.2022 / geändert 10.11.2022
Beitragende: Heiß, Christian [Gutachter]
Prof. Dr. Haendeler, Judith [Gutachter]
[im Online-Personal- und -Vorlesungsverzeichnis LSF anzeigen]
Stichwörter:Flavanole / Kakao / Endotheliale Dysfunktion / Procyanidine
Dewey Dezimal-Klassifikation:600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit
Beschreibungen:Flavanole sind sekundäre Pflanzenstoffe und Bestandteile unserer Nahrungszufuhr, vornehmlich im Rahmen der Ingestion von Kakaobohnen, aber auch von roten Trauben, Rotwein, grünem Tee, Äpfeln und Beeren. Vorangegangene Studien zeigen einen Zusammenhang zwischen der Einnahme von Kakaoflavanolen (CF) und der Verbesserung der Gefäßfunktion, selbst bei gesunden, jungen Probanden. Abhängig vom Grad der Polymerisation (DP) besteht die Zusammensetzung der CF größtenteils aus dem Monomer (−)-Epicatechin (∼20%, DP1) und den oligomerischen Procyaniden (∼80%, DP2–10).
Ziel dieser Studie ist es, den relativen Beitrag der Flavanol-Monomere und Procyanide zur Verbesserung der Gefäßfunktion im Zusammenhang mit der Aufnahme von Kakaoflavanolen bei jungen und gesunden Probanden zu bestimmen.
Demzufolge wurde eine randomisierte, doppelblinde, kontrollierte, dreiarmige Interventionsstudie im Parallelgruppendesign durchgeführt. Es wurden 45 junge, gesunde männliche Probanden rekrutiert. Der primäre Endpunkt der Studie war das Ergebnis der Fluss-vermittelten Vasodilatation (FMD). Als sekundäre Endpunkte wurden die Konzentrationen der strukturverwandten Epicatechin-Metaboliten (SREMs) in Blut und Urin festgelegt. Tertiäre Endpunkte waren die weiteren Gradmesser der Gefäßfunktion, wie Pulswellengeschwindigkeit (PWV), Blutdruck (BP), Cholesterinwerte und Blutzuckerwerte.
Nach Messung der Ausgangswerte erfolgte die Einnahme von Kapseln, die entweder einen DP1-10 Kakaoextrakt, einen DP2-10 Kakaoextrakt oder keinerlei CF beinhalteten. Die Kapseln ohne CF (Kontrolle) bestanden im Übrigen aus den gleichen Makro- und Mikronährstoffen wie die übrigen Testsubstanzen. Nach 2 Stunden wurden die Messungen wiederholt. Nach täglicher Einnahme der jeweiligen Kapseln über 30 Tage erfolgte eine Wiederholung der Messreihen zur Bestimmung von chronischen und akut auf chronischen Effekten.
Die Einnahme von DP1-10 führte zu einem signifikanten Anstieg der FMD-Werte, erhöhten Konzentrationen von SREMs im Blut sowie Abnahme der PWV und der BP-Werte. Diese Veränderungen konnten sowohl nach der Einnahme von DP2-10 als auch der Kontrolle nicht verzeichnet werden. Eine signifikante Reduzierung der Cholesterinwerte war nach der Einnahme von DP1-10 und DP 2-10 ersichtlich, verglichen mit der Kontrollgruppe.
Die Verbesserung der Gefäßfunktion nach der Einnahme von CF ist vornehmlich mit der Einnahme des Flavanolmonomers in Verbindung zu bringen und dem daraus resultierenden Anstieg der zirkulierenden Metaboliten im Blutplasma junger und gesunder Männer. Der vorrangige Anteil der CF, die Procyanide, als auch derer vom Mikrobiom abgeleiteten Kataboliten zeigen keinen signifikanten Effekt hinsichtlich der Gefäßfunktion. Die Reduzierung der Cholesterinwerte kann mit der Einnahme von Procyaniden in Verbindung gebracht werden, ist allerdings nicht sicher einem Effekt der Monomere zuzuordnen. Hinsichtlich dessen, als auch der Wirkung auf andere Kohorten, ist weitere Forschung notwendig.

Flavanols are plant secondary metabolites particularly abundant in cocoa, red grapes, red wine, green tea, apples, and berries. Earlier studies strongly suggest that consumption of cocoa flavanols (CF) can improve endothelial function both acutely and after short-term daily consumption. Such improvements have not only been observed in subjects with endothelial dysfunction but also in healthy and young subjects. CFs comprise different compounds, which are classified according to their degree of polymerisation (DP) in monomers, of which the most abundant are (−)-epicatechin (∼20%, DP1) and the oligomeric procyanidins (∼80%, DP2–10). Despite efforts to elucidate mechanisms of action, currently, it is unknown whether the monomers, the oligomers, or both are the bioactive compounds in cocoa exerting beneficial effects on vascular function.
This study aims to determine the relative contribution of flavanol monomers and procyanidins to the improvement of vascular function associated with CF intake in young and healthy subjects.
Accordingly, a randomised, double-blind, controlled, three-arm intervention study was conducted in a parallel-group design. Forty-five young, healthy male subjects were recruited. The primary endpoint of the study was the outcome of flow-mediated vasodilation (FMD). Secondary endpoints were the concentrations of structurally related epicatechin metabolites (SREMs) in blood and urine. Tertiary endpoints were the other grade measures of vascular function, such as pulse wave velocity (PWV), blood pressure (BP), cholesterol levels and blood glucose levels.
After baseline measurements were taken, capsules containing either DP1-10 cocoa extract, DP2-10 cocoa extract, or no CF were taken. The capsules without CF (control) consisted of the same macro- and micronutrients as the other test substances. The measurements were repeated after 2 hours. After daily intake of the respective capsules for 30 days, the series of measurements was repeated to determine chronic and acute on chronic effects.
Consumption of DP1-10 led to a significant increase in FMD values (at 2 h and 1 month post-consumption), raised concentration of SREMs in blood plasma, and decreases in PWV, BP, and total cholesterol levels. Meanwhile, the consumption of DP2-10 had no significant effects in any parameter, except for a significant decrease in total cholesterol levels compared to the control.
The current findings indicate that the improvements in vascular function after CF consumption are linked to the flavanol monomers and consecutively the increase of SREMs in the blood plasma of young and healthy humans. The cocoa procyanidins did not seem to affect vascular function. However, the reduction of total cholesterol can be linked to their consumption. Further work is, therefore, necessary to understand the mechanisms of action and generalisability of our findings to the general population.
Quelle:Actis-Goretta, L., Lévèques, A., Giuffrida, F., Romanov-Michailidis, F., Viton, F., Barron, D., Duenas-Paton, M., Gonzalez-Manzano, S., Santos-Buelga, C., Williamson, G., Dionisi, F., 2012. Elucidation of (−)-epicatechin metabolites after ingestion of chocolate by healthy humans. Free Radical Biology and Medicine 53, 787–795. https://doi.org/10.1016/j.freeradbiomed.2012.05.023
Adamson, G.E., Lazarus, S.A., Mitchell, A.E., Prior, R.L., Cao, G., Jacobs, P.H., Kremers, B.G., Hammerstone, J.F., Rucker, R.B., Ritter, K.A., Schmitz, H.H., 1999. HPLC Method for the Quantification of Procyanidins in Cocoa and Chocolate Samples and Correlation to Total Antioxidant Capacity. J. Agric. Food Chem. 47, 4184–4188. https://doi.org/10.1021/jf990317m
Agewall, S., 2000. Does a glass of red wine improve endothelial function? European Heart Journal 21, 74–78. https://doi.org/10.1053/euhj.1999.1759
Anderson, T.J., Uehata, A., Gerhard, M.D., Meredith, I.T., Knab, S., Delagrange, D., Lieberman, E.H., Ganz, P., Creager, M.A., Yeung, A.C., Selwyn, A.P., 1995. Close relation of endothelial function in the human coronary and peripheral circulations. Journal of the American College of Cardiology 26, 1235–1241. https://doi.org/10.1016/0735-1097(95)00327-4
Aune, D., 2019. Plant Foods, Antioxidant Biomarkers, and the Risk of Cardiovascular Disease, Cancer, and Mortality: A Review of the Evidence. Advances in Nutrition 10, S404–S421. https://doi.org/10.1093/advances/nmz042
Aune, D., Giovannucci, E., Boffetta, P., Fadnes, L.T., Keum, N., Norat, T., Greenwood, D.C., Riboli, E., Vatten, L.J., Tonstad, S., 2017. Fruit and vegetable intake and the risk of cardiovascular disease, total cancer and all-cause mortality-a systematic review and dose-response meta-analysis of prospective studies. Int J Epidemiol 46, 1029–1056. https://doi.org/10.1093/ije/dyw319
Baba, S., Osakabe, N., Yasuda, A., Natsume, M., Takizawa, T., Nakamura, T., Terao, J., 2000. Bioavailability of (-)-epicatechin upon intake of chocolate and cocoa in human volunteers. Free Radical Research 33, 635–641. https://doi.org/10.1080/10715760000301151
Babcock, M.C., DuBose, L.E., Witten, T.L., Brubaker, A., Stauffer, B.L., Hildreth, K.L., Moreau, K.L., 2021. Assessment of macrovascular and microvascular function in aging males. Journal of Applied Physiology 130, 96–103. https://doi.org/10.1152/japplphysiol.00616.2020
Balzer, J., Rassaf, T., Heiss, C., Kleinbongard, P., Lauer, T., Merx, M., Heussen, N., Gross, H.B., Keen, C.L., Schroeter, H., Kelm, M., 2008. Sustained Benefits in Vascular Function Through Flavanol-Containing Cocoa in Medicated Diabetic Patients. Journal of the American College of Cardiology 51, 2141–2149. https://doi.org/10.1016/j.jacc.2008.01.059
Beecher, G.R., 2003. Overview of Dietary Flavonoids: Nomenclature, Occurrence and Intake. The Journal of Nutrition 133, 3248S-3254S. https://doi.org/10.1093/jn/133.10.3248S
Benjamin, E.J., Blaha, M.J., Chiuve, S.E., Cushman, M., Das, S.R., Deo, R., de Ferranti, S.D., Floyd, J., Fornage, M., Gillespie, C., Isasi, C.R., Jiménez, M.C., Jordan, L.C., Judd, S.E., Lackland, D., Lichtman, J.H., Lisabeth, L., Liu, S., Longenecker, C.T., Mackey, R.H., Matsushita, K., Mozaffarian, D., Mussolino, M.E., Nasir, K., Neumar, R.W., Palaniappan, L., Pandey, D.K., Thiagarajan, R.R., Reeves, M.J., Ritchey, M., Rodriguez, C.J., Roth, G.A., Rosamond, W.D., Sasson, C., Towfighi, A., Tsao, C.W., Turner, M.B., Virani, S.S., Voeks, J.H., Willey, J.Z., Wilkins, J.T., Wu, J.HY., Alger, H.M., Wong, S.S., Muntner, P., 2017. Heart Disease and Stroke Statistics—2017 Update: A Report From the American Heart Association. Circulation 135. https://doi.org/10.1161/CIR.0000000000000485
Black, M.A., Cable, N.T., Thijssen, D.H.J., Green, D.J., 2008. Importance of Measuring the Time Course of Flow-Mediated Dilatation in Humans. Hypertension 51, 203–210. https://doi.org/10.1161/HYPERTENSIONAHA.107.101014
Bordoni, A., Amaretti, A., Leonardi, A., Boschetti, E., Danesi, F., Matteuzzi, D., Roncaglia, L., Raimondi, S., Rossi, M., 2013. Cholesterol-lowering probiotics: in vitro selection and in vivo testing of bifidobacteria. Appl Microbiol Biotechnol 97, 8273–8281. https://doi.org/10.1007/s00253-013-5088-2
Borges, G., Ottaviani, J.I., van der Hooft, J.J.J., Schroeter, H., Crozier, A., 2018. Absorption, metabolism, distribution and excretion of (−)-epicatechin: A review of recent findings. Molecular Aspects of Medicine 61, 18–30. https://doi.org/10.1016/j.mam.2017.11.002
Brunt, V.E., Casso, A.G., Gioscia-Ryan, R.A., Sapinsley, Z.J., Ziemba, B.P., Clayton, Z.S., Bazzoni, A.E., VanDongen, N.S., Richey, J.J., Hutton, D.A., Zigler, M.C., Neilson, A.P., Davy, K.P., Seals, D.R., 2021. Gut Microbiome-Derived Metabolite Trimethylamine N-Oxide Induces Aortic Stiffening and Increases Systolic Blood Pressure With Aging in Mice and Humans. Hypertension 78, 499–511. https://doi.org/10.1161/HYPERTENSIONAHA.120.16895
Buijsse, B., Feskens, E.J.M., Kok, F.J., Kromhout, D., 2006. Cocoa Intake, Blood Pressure, and Cardiovascular Mortality: The Zutphen Elderly Study. Arch Intern Med 166, 411. https://doi.org/10.1001/archinte.166.4.411
Cardona, F., Andrés-Lacueva, C., Tulipani, S., Tinahones, F.J., Queipo-Ortuño, M.I., 2013. Benefits of polyphenols on gut microbiota and implications in human health. The Journal of Nutritional Biochemistry 24, 1415–1422. https://doi.org/10.1016/j.jnutbio.2013.05.001
Carrizales-Sánchez, A.K., García-Cayuela, T., Hernández-Brenes, C., Senés-Guerrero, C., 2021. Gut microbiota associations with metabolic syndrome and relevance of its study in pediatric subjects. Gut Microbes 13, 1960135. https://doi.org/10.1080/19490976.2021.1960135
Castle, S.M., 2017. Pure (-)-epicatechin and high-flavanol milk chocolate improves flow-mediated dilatation in healthy men: a clinical trial-based investigation (PhD thesis). University of Reading.
Cecarini, V., Cuccioloni, M., Zheng, Y., Bonfili, L., Gong, C., Angeletti, M., Mena, P., Del Rio, D., Eleuteri, A.M., 2021. Flavan‐3‐ol Microbial Metabolites Modulate Proteolysis in Neuronal Cells Reducing Amyloid‐beta (1‐42) Levels. Mol. Nutr. Food Res. 65, 2100380. https://doi.org/10.1002/mnfr.202100380
Celermajer, D.S., Sorensen, K.E., Gooch, V.M., Spiegelhalter, D.J., Miller, O.I., Sullivan, I.D., Lloyd, J.K., Deanfield, J.E., 1992. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. The Lancet 340, 1111–1115. https://doi.org/10.1016/0140-6736(92)93147-F
Chiva-Blanch, G., Arranz, S., Lamuela-Raventos, R.M., Estruch, R., 2013. Effects of Wine, Alcohol and Polyphenols on Cardiovascular Disease Risk Factors: Evidences from Human Studies. Alcohol and Alcoholism 48, 270–277. https://doi.org/10.1093/alcalc/agt007
Cook, C., Cole, G., Asaria, P., Jabbour, R., Francis, D.P., 2014. The annual global economic burden of heart failure. International Journal of Cardiology 171, 368–376. https://doi.org/10.1016/j.ijcard.2013.12.028
Croci, S., D’Apolito, L.I., Gasperi, V., Catani, M.V., Savini, I., 2021. Dietary Strategies for Management of Metabolic Syndrome: Role of Gut Microbiota Metabolites. Nutrients 13, 1389. https://doi.org/10.3390/nu13051389
Crozier, A., 2013. Absorption, metabolism, and excretion of (–)-epicatechin in humans: an evaluation of recent findings. The American Journal of Clinical Nutrition 98, 861–862. https://doi.org/10.3945/ajcn.113.072009
D’Agostino, R.B., Pencina, M.J., Massaro, J.M., Coady, S., 2013. Cardiovascular Disease Risk Assessment: Insights from Framingham. Glob Heart 8, 11–23. https://doi.org/10.1016/j.gheart.2013.01.001
Dahlöf, B., 2010. Cardiovascular Disease Risk Factors: Epidemiology and Risk Assessment. The American Journal of Cardiology 105, 3A-9A. https://doi.org/10.1016/j.amjcard.2009.10.007
Davis, N., Katz, S., Wylie-Rosett, J., 2007. The Effect of Diet on Endothelial Function. Cardiology in Review 15, 62–66. https://doi.org/10.1097/01.crd.0000218824.79018.cd
Davison, K., Berry, N.M., Misan, G., Coates, A.M., Buckley, J.D., Howe, P.R.C., 2010. Dose-related effects of flavanol-rich cocoa on blood pressure. J Hum Hypertens 24, 568–576. https://doi.org/10.1038/jhh.2009.105
Davison, K., Coates, A.M., Buckley, J.D., Howe, P.R.C., 2008. Effect of cocoa flavanols and exercise on cardiometabolic risk factors in overweight and obese subjects. Int J Obes 32, 1289–1296. https://doi.org/10.1038/ijo.2008.66
Day, A.J., Cañada, F.J., Dı́az, J.C., Kroon, P.A., Mclauchlan, R., Faulds, C.B., Plumb, G.W., Morgan, M.R.A., Williamson, G., 2000. Dietary flavonoid and isoflavone glycosides are hydrolysed by the lactase site of lactase phlorizin hydrolase. FEBS Letters 468, 166–170. https://doi.org/10.1016/S0014-5793(00)01211-4
De Bruyne, T., Steenput, B., Roth, L., De Meyer, G., Santos, C., Valentová, K., Dambrova, M., Hermans, N., 2019. Dietary Polyphenols Targeting Arterial Stiffness: Interplay of Contributing Mechanisms and Gut Microbiome-Related Metabolism. Nutrients 11, 578. https://doi.org/10.3390/nu11030578
De Caterina, R., Zampolli, A., Del Turco, S., Madonna, R., Massaro, M., 2006. Nutritional mechanisms that influence cardiovascular disease. The American Journal of Clinical Nutrition 83, 421S-426S. https://doi.org/10.1093/ajcn/83.2.421S
Del Rio, D., Rodriguez-Mateos, A., Spencer, J.P.E., Tognolini, M., Borges, G., Crozier, A., 2013. Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid Redox Signal 18, 1818–1892. https://doi.org/10.1089/ars.2012.4581
Di Lorenzo, C., Colombo, F., Biella, S., Stockley, C., Restani, P., 2021. Polyphenols and Human Health: The Role of Bioavailability. Nutrients 13, 273. https://doi.org/10.3390/nu13010273
Doshi, S.N., Naka, K.K., Payne, N., Jones, C.J., Ashton, M., Lewis, M.J., Goodfellow, J., 2001. Flow-mediated dilatation following wrist and upper arm occlusion in humans: the contribution of nitric oxide. Clin Sci (Lond) 101, 629–635.
Dower, J.I., Geleijnse, J.M., Gijsbers, L., Zock, P.L., Kromhout, D., Hollman, P.C., 2015. Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: a randomized, double-blind, placebo-controlled, crossover trial. The American Journal of Clinical Nutrition 101, 914–921. https://doi.org/10.3945/ajcn.114.098590
Duffy, S.J., Keaney Jr, J.F., Holbrook, M., Gokce, N., Swerdloff, P.L., Frei, B., Vita, J.A., 2001. Short- and Long-Term Black Tea Consumption Reverses Endothelial Dysfunction in Patients With Coronary Artery Disease. Circulation 104, 151–156. https://doi.org/10.1161/01.CIR.104.2.151
Dupont, W.D., Plummer, W.D., 1990. Power and sample size calculations. Controlled Clinical Trials 11, 116–128. https://doi.org/10.1016/0197-2456(90)90005-M
Durazzo, A., Lucarini, M., Souto, E.B., Cicala, C., Caiazzo, E., Izzo, A.A., Novellino, E., Santini, A., 2019. Polyphenols: A concise overview on the chemistry, occurrence, and human health. Phytotherapy Research 33, 2221–2243. https://doi.org/10.1002/ptr.6419
Dzau, V.J., Antman, E.M., Black, H.R., Hayes, D.L., Manson, J.E., Plutzky, J., Popma, J.J., Stevenson, W., 2006. The Cardiovascular Disease Continuum Validated: Clinical Evidence of Improved Patient Outcomes: Part I: Pathophysiology and Clinical Trial Evidence (Risk Factors Through Stable Coronary Artery Disease). Circulation 114, 2850–2870. https://doi.org/10.1161/CIRCULATIONAHA.106.655688
Endemann, D.H., 2004. Endothelial Dysfunction. Journal of the American Society of Nephrology 15, 1983–1992. https://doi.org/10.1097/01.ASN.0000132474.50966.DA
Engler, M.B., Engler, M.M., Chen, C.Y., Malloy, M.J., Browne, A., Chiu, E.Y., Kwak, H.-K., Milbury, P., Paul, S.M., Blumberg, J., Mietus-Snyder, M.L., 2004. Flavonoid-Rich Dark Chocolate Improves Endothelial Function and Increases Plasma Epicatechin Concentrations in Healthy Adults. Journal of the American College of Nutrition 23, 197–204. https://doi.org/10.1080/07315724.2004.10719361
Esser, D., Mars, M., Oosterink, E., Stalmach, A., Müller, M., Afinan, L.A., 2014. Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men. FASEB j. 28, 1464–1473. https://doi.org/10.1096/fj.13-239384
Estruch, R., Ros, E., Salas-Salvadó, J., Covas, M.-I., Corella, D., Arós, F., Gómez-Gracia, E., Ruiz-Gutiérrez, V., Fiol, M., Lapetra, J., Lamuela-Raventos, R.M., Serra-Majem, L., Pintó, X., Basora, J., Muñoz, M.A., Sorlí, J.V., Martínez, J.A., Fitó, M., Gea, A., Hernán, M.A., Martínez-González, M.A., 2018. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J Med 378, e34. https://doi.org/10.1056/NEJMoa1800389
Faridi, Z., Njike, V.Y., Dutta, S., Ali, A., Katz, D.L., 2008. Acute dark chocolate and cocoa ingestion and endothelial function: a randomized controlled crossover trial. The American Journal of Clinical Nutrition 88, 58–63. https://doi.org/10.1093/ajcn/88.1.58
Flammer, A.J., Sudano, I., Wolfrum, M., Thomas, R., Enseleit, F., Periat, D., Kaiser, P., Hirt, A., Hermann, M., Serafini, M., Leveques, A., Luscher, T.F., Ruschitzka, F., Noll, G., Corti, R., 2012. Cardiovascular effects of flavanol-rich chocolate in patients with heart failure. European Heart Journal 33, 2172–2180. https://doi.org/10.1093/eurheartj/ehr448
Franco, R., Oñatibia-Astibia, A., Martínez-Pinilla, E., 2013. Health Benefits of Methylxanthines in Cacao and Chocolate. Nutrients 5, 4159–4173. https://doi.org/10.3390/nu5104159
Gayer, B.A., Avendano, E.E., Edelson, E., Nirmala, N., Johnson, E.J., Raman, G., 2019. Effects of Intake of Apples, Pears, or Their Products on Cardiometabolic Risk Factors and Clinical Outcomes: A Systematic Review and Meta-Analysis. Current Developments in Nutrition 3, nzz109. https://doi.org/10.1093/cdn/nzz109
GBD 2017 Diet Collaborators, 2019. Health effects of dietary risks in 195 countries, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 393, 1958–1972. https://doi.org/10.1016/S0140-6736(19)30041-8
Gheorghe, A., Griffiths, U., Murphy, A., Legido-Quigley, H., Lamptey, P., Perel, P., 2018. The economic burden of cardiovascular disease and hypertension in low- and middle-income countries: a systematic review. BMC Public Health 18, 975. https://doi.org/10.1186/s12889-018-5806-x
Gonthier, M.-P., Donovan, J.L., Texier, O., Felgines, C., Remesy, C., Scalbert, A., 2003. Metabolism of dietary procyanidins in rats. Free Radical Biology and Medicine 35, 837–844. https://doi.org/10.1016/S0891-5849(03)00394-0
GraphPad Software, Inc., 2021. . How Prism generates random numbers. URL https://www.graphpad.com/guides/prism/latest/statistics/stat_how_prism_generates_random_num.htm. (accessed 6.11.21).
Grassi, D., Desideri, G., Necozione, S., Lippi, C., Casale, R., Properzi, G., Blumberg, J.B., Ferri, C., 2008. Blood Pressure Is Reduced and Insulin Sensitivity Increased in Glucose-Intolerant, Hypertensive Subjects after 15 Days of Consuming High-Polyphenol Dark Chocolate. The Journal of Nutrition 138, 1671–1676. https://doi.org/10.1093/jn/138.9.1671
Grassi, D., Necozione, S., Lippi, C., Croce, G., Valeri, L., Pasqualetti, P., Desideri, G., Blumberg, J.B., Ferri, C., 2005. Cocoa Reduces Blood Pressure and Insulin Resistance and Improves Endothelium-Dependent Vasodilation in Hypertensives. Hypertension 46, 398–405. https://doi.org/10.1161/01.HYP.0000174990.46027.70
Greyling, A., van Mil, A.C.C.M., Zock, P.L., Green, D.J., Ghiadoni, L., Thijssen, D.H., 2016. Adherence to guidelines strongly improves reproducibility of brachial artery flow-mediated dilation. Atherosclerosis 248, 196–202. https://doi.org/10.1016/j.atherosclerosis.2016.03.011
Hadi, H.A.R., Carr, C.S., Al Suwaidi, J., 2005. Endothelial dysfunction: cardiovascular risk factors, therapy, and outcome. Vasc Health Risk Manag 1, 183–198.
Harris, R.A., Nishiyama, S.K., Wray, D.W., Richardson, R.S., 2010. Ultrasound Assessment of Flow-Mediated Dilation. Hypertension 55, 1075–1085. https://doi.org/10.1161/HYPERTENSIONAHA.110.150821
Hartley, L., Igbinedion, E., Holmes, J., Flowers, N., Thorogood, M., Clarke, A., Stranges, S., Hooper, L., Rees, K., 2013. Increased consumption of fruit and vegetables for the primary prevention of cardiovascular diseases. Cochrane Database of Systematic Reviews 2021. https://doi.org/10.1002/14651858.CD009874.pub2
Heidemann, C., Schulze, M.B., Franco, O.H., van Dam, R.M., Mantzoros, C.S., Hu, F.B., 2008. Dietary Patterns and Risk of Mortality From Cardiovascular Disease, Cancer, and All Causes in a Prospective Cohort of Women. Circulation 118, 230–237. https://doi.org/10.1161/CIRCULATIONAHA.108.771881
Heiss, C., Finis, D., Kleinbongard, P., Hoffmann, A., Rassaf, T., Kelm, M., Sies, H., 2007. Sustained Increase in Flow-Mediated Dilation After Daily Intake of High-Flavanol Cocoa Drink Over 1 Week. Journal of Cardiovascular Pharmacology 49, 74–80. https://doi.org/10.1097/FJC.0b013e31802d0001
Heiss, C., Jahn, S., Taylor, M., Real, W.M., Angeli, F.S., Wong, M.L., Amabile, N., Prasad, M., Rassaf, T., Ottaviani, J.I., Mihardja, S., Keen, C.L., Springer, M.L., Boyle, A., Grossman, W., Glantz, S.A., Schroeter, H., Yeghiazarians, Y., 2010. Improvement of Endothelial Function With Dietary Flavanols Is Associated With Mobilization of Circulating Angiogenic Cells in Patients With Coronary Artery Disease. Journal of the American College of Cardiology 56, 218–224. https://doi.org/10.1016/j.jacc.2010.03.039
Heiss, C., Kleinbongard, P., Dejam, A., Perré, S., Schroeter, H., Sies, H., Kelm, M., 2005. Acute Consumption of Flavanol-Rich Cocoa and the Reversal of Endothelial Dysfunction in Smokers. Journal of the American College of Cardiology 46, 1276–1283. https://doi.org/10.1016/j.jacc.2005.06.055
Heiss, C., Rodriguez-Mateos, A., Kelm, M., 2015a. Central Role of eNOS in the Maintenance of Endothelial Homeostasis. Antioxidants & Redox Signaling 22, 1230–1242. https://doi.org/10.1089/ars.2014.6158
Heiss, C., Sansone, R., Karimi, H., Krabbe, M., Schuler, D., Rodriguez-Mateos, A., Kraemer, T., Cortese-Krott, M.M., Kuhnle, G.G.C., Spencer, J.P.E., Schroeter, H., Merx, M.W., Kelm, M., 2015b. Impact of cocoa flavanol intake on age-dependent vascular stiffness in healthy men: a randomized, controlled, double-masked trial. AGE 37, 56. https://doi.org/10.1007/s11357-015-9794-9
Henning, S.M., Wang, P., Abgaryan, N., Vicinanza, R., de Oliveira, D.M., Zhang, Y., Lee, R.-P., Carpenter, C.L., Aronson, W.J., Heber, D., 2013. Phenolic acid concentrations in plasma and urine from men consuming green or black tea and potential chemopreventive properties for colon cancer. Mol. Nutr. Food Res. 57, 483–493. https://doi.org/10.1002/mnfr.201200646
Hollands, W.J., Philo, M., Perez‐Moral, N., Needs, P.W., Savva, G.M., Kroon, P.A., 2020. Monomeric Flavanols Are More Efficient Substrates for Gut Microbiota Conversion to Hydroxyphenyl‐γ‐Valerolactone Metabolites Than Oligomeric Procyanidins: A Randomized, Placebo‐Controlled Human Intervention Trial. Mol. Nutr. Food Res. 64, 1901135. https://doi.org/10.1002/mnfr.201901135
Hollands, W.J., Tapp, H., Defernez, M., Perez Moral, N., Winterbone, M.S., Philo, M., Lucey, A.J., Kiely, M.E., Kroon, P.A., 2018. Lack of acute or chronic effects of epicatechin-rich and procyanidin-rich apple extracts on blood pressure and cardiometabolic biomarkers in adults with moderately elevated blood pressure: a randomized, placebo-controlled crossover trial. The American Journal of Clinical Nutrition 108, 1006–1014. https://doi.org/10.1093/ajcn/nqy139
Hollman, P.C., Arts, I.C., 2000. Flavonols, Flavones and Flavanols: Nature, Occurrence and Dietary Burden. Journal of the Science of Food and Agriculture 80, 1081–1093. https://doi.org/10.1002/(SICI)1097-0010(20000515)80:7<1081::AID-JSFA566>3.0.CO;2-G
Hooper, L., Kay, C., Abdelhamid, A., Kroon, P.A., Cohn, J.S., Rimm, E.B., Cassidy, A., 2012. Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. The American Journal of Clinical Nutrition 95, 740–751. https://doi.org/10.3945/ajcn.111.023457
Horn, P., Amabile, N., Angeli, F.S., Sansone, R., Stegemann, B., Kelm, M., Springer, M.L., Yeghiazarians, Y., Schroeter, H., Heiss, C., 2014. Dietary flavanol intervention lowers the levels of endothelial microparticles in coronary artery disease patients. Br J Nutr 111, 1245–1252. https://doi.org/10.1017/S0007114513003693
Inaba, Y., Chen, J.A., Bergmann, S.R., 2010. Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis. Int J Cardiovasc Imaging 26, 631–640. https://doi.org/10.1007/s10554-010-9616-1
Jo, S., Kim, S., Shin, D.H., Kim, M.-S., 2020. Inhibition of SARS-CoV 3CL protease by flavonoids. Journal of Enzyme Inhibition and Medicinal Chemistry 35, 145–151. https://doi.org/10.1080/14756366.2019.1690480
Joannides, R., Haefeli, W.E., Linder, L., Richard, V., Bakkali, E.H., Thuillez, C., Lüscher, T.F., 1995. Nitric Oxide Is Responsible for Flow-Dependent Dilatation of Human Peripheral Conduit Arteries In Vivo. Circulation 91, 1314–1319. https://doi.org/10.1161/01.CIR.91.5.1314
Jokinen, E., 2015. Obesity and cardiovascular disease. Minerva Pediatr 67, 25–32.
Karatzis, E., Papaioannou, T.G., Aznaouridis, K., Karatzi, K., Stamatelopoulos, K., Zampelas, A., Papamichael, C., Lekakis, J., Mavrikakis, M., 2005. Acute effects of caffeine on blood pressure and wave reflections in healthy subjects: should we consider monitoring central blood pressure? International Journal of Cardiology 98, 425–430. https://doi.org/10.1016/j.ijcard.2003.11.013
Kasprzak, J.D., Kłosińska, M., Drozdz, J., 2006. Clinical aspects of assessment of endothelial function. Pharmacol Rep 58 Suppl, 33–40.
Kim, Y., Je, Y., 2017. Flavonoid intake and mortality from cardiovascular disease and all causes: A meta-analysis of prospective cohort studies. Clinical Nutrition ESPEN 20, 68–77. https://doi.org/10.1016/j.clnesp.2017.03.004
Kirch, N., Berk, L., Liegl, Y., Adelsbach, M., Zimmermann, B.F., Stehle, P., Stoffel-Wagner, B., Ludwig, N., Schieber, A., Helfrich, H.-P., Ellinger, S., 2018. A nutritive dose of pure (–)-epicatechin does not beneficially affect increased cardiometabolic risk factors in overweight-to-obese adults—a randomized, placebo-controlled, double-blind crossover study. The American Journal of Clinical Nutrition 107, 948–956. https://doi.org/10.1093/ajcn/nqy066
Kozłowska, A., Szostak-Wegierek, D., 2014. Flavonoids--food sources and health benefits. Rocz Panstw Zakl Hig 65, 79–85.
Kuhnle, G.G., 2012. Nutritional biomarkers for objective dietary assessment. J. Sci. Food Agric. 92, 1145–1149. https://doi.org/10.1002/jsfa.5631
Kusano Bucalen Ferrari, C., Percário, S., Carlos Costa Baptista Silva, J., Aparecida Ferraz da Silva Torres, E., 2015. An Apple Plus a Brazil Nut a Day Keeps the Doctors Away: Antioxidant Capacity of Foods and their Health Benefits. CPD 22, 189–195. https://doi.org/10.2174/1381612822666151117122715
K�hnau, J., 1976. The Flavonoids. A Class of Semi-Essential Food Components: Their Role in Human Nutrition, in: Bourne, G.H. (Ed.), World Review of Nutrition and Dietetics. S. Karger AG, pp. 117–191. https://doi.org/10.1159/000399407
LeBlanc, J.G., Milani, C., de Giori, G.S., Sesma, F., van Sinderen, D., Ventura, M., 2013. Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Current Opinion in Biotechnology 24, 160–168. https://doi.org/10.1016/j.copbio.2012.08.005
Leeson, P., Thorne, S., Donald, A., Mullen, M., Clarkson, P., Deanfield, J., 1997. Non-invasive measurement of endothelial function: effect on brachial artery dilatation of graded endothelial dependent and independent stimuli. Heart 78, 22–27. https://doi.org/10.1136/hrt.78.1.22
Leslie, J.L., Annex, B.H., 2018. The Microbiome and Endothelial Function: An Investigative Fountain or Analytical Morass. Circ Res 123, 1015–1016. https://doi.org/10.1161/CIRCRESAHA.118.313813
Libby, P., Buring, J.E., Badimon, L., Hansson, G.K., Deanfield, J., Bittencourt, M.S., Tokgözoğlu, L., Lewis, E.F., 2019. Atherosclerosis. Nat Rev Dis Primers 5, 56. https://doi.org/10.1038/s41572-019-0106-z
Manach, C., Milenkovic, D., Van de Wiele, T., Rodriguez-Mateos, A., de Roos, B., Garcia-Conesa, M.T., Landberg, R., Gibney, E.R., Heinonen, M., Tomás-Barberán, F., Morand, C., 2017. Addressing the inter-individual variation in response to consumption of plant food bioactives: Towards a better understanding of their role in healthy aging and cardiometabolic risk reduction. Mol. Nutr. Food Res. 61, 1600557. https://doi.org/10.1002/mnfr.201600557
Manach, C., Scalbert, A., Morand, C., Rémésy, C., Jiménez, L., 2004. Polyphenols: food sources and bioavailability. The American Journal of Clinical Nutrition 79, 727–747. https://doi.org/10.1093/ajcn/79.5.727
Mancini, G.B.J., Yeoh, E., Abbott, D., Chan, S., 2002. Validation of an automated method for assessing brachial artery endothelial dysfunction. Can J Cardiol 18, 259–262.
Mars, Inc., 2021. Mars Edge. Mars Edge. URL https://www.mars.com/made-by-mars/edge (accessed 6.19.21).
Martín, M.Á., Ramos, S., 2021. Impact of Dietary Flavanols on Microbiota, Immunity and Inflammation in Metabolic Diseases. Nutrients 13, 850. https://doi.org/10.3390/nu13030850
Matsuzawa, Y., Kwon, T., Lennon, R.J., Lerman, L.O., Lerman, A., 2015. Prognostic Value of Flow‐Mediated Vasodilation in Brachial Artery and Fingertip Artery for Cardiovascular Events: A Systematic Review and Meta‐Analysis. JAHA 4. https://doi.org/10.1161/JAHA.115.002270
Medical Imaging Applications, 2021. Vascular Tools 5, Retrieved from http://www.mia-llc.com/flyer/MIA-FLYER-VT5.pdf.
Mele, L., Carobbio, S., Brindani, N., Curti, C., Rodriguez-Cuenca, S., Bidault, G., Mena, P., Zanotti, I., Vacca, M., Vidal-Puig, A., Del Rio, D., 2017. Phenyl-γ-valerolactones, flavan-3-ol colonic metabolites, protect brown adipocytes from oxidative stress without affecting their differentiation or function. Mol. Nutr. Food Res. 61, 1700074. https://doi.org/10.1002/mnfr.201700074
Milenkovic, D., Rodriguez‐Mateos, A., Lucosz, M., Istas, G., Declerck, K., Sansone, R., Deenen, R., Köhrer, K., Corral‐Jara, K.F., Altschmied, J., Haendeler, J., Kelm, M., Berghe, W.V., Heiss, C., 2022. Flavanol Consumption in Healthy Men Preserves Integrity of Immunological‐Endothelial Barrier Cell Functions: Nutri(epi)genomic Analysis. Molecular Nutrition Food Res 2100991. https://doi.org/10.1002/mnfr.202100991
Mogollon, J.A., Bujold, E., Lemieux, S., Bourdages, M., Blanchet, C., Bazinet, L., Couillard, C., Noël, M., Dodin, S., 2013. Blood pressure and endothelial function in healthy, pregnant women after acute and daily consumption of flavanol-rich chocolate: a pilot, randomized controlled trial. Nutr J 12, 41. https://doi.org/10.1186/1475-2891-12-41
Naylor, L.H., Weisbrod, C.J., O’Driscoll, G., Green, D.J., 2005. Measuring peripheral resistance and conduit arterial structure in humans using Doppler ultrasound. Journal of Applied Physiology 98, 2311–2315. https://doi.org/10.1152/japplphysiol.01047.2004
Njike, V.Y., Faridi, Z., Shuval, K., Dutta, S., Kay, C.D., West, S.G., Kris-Etherton, P.M., Katz, D.L., 2011. Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults. International Journal of Cardiology 149, 83–88. https://doi.org/10.1016/j.ijcard.2009.12.010
on behalf of the EuroFIR consortium, Kiely, M., Black, L.J., Plumb, J., Kroon, P.A., Hollman, P.C., Larsen, J.C., Speijers, G.J., Kapsokefalou, M., Sheehan, D., Gry, J., Finglas, P., 2010. EuroFIR eBASIS: application for health claims submissions and evaluations. Eur J Clin Nutr 64, S101–S107. https://doi.org/10.1038/ejcn.2010.219
Oteiza, P.I., Fraga, C.G., Galleano, M., 2021. Linking biomarkers of oxidative stress and disease with flavonoid consumption: From experimental models to humans. Redox Biology 42, 101914. https://doi.org/10.1016/j.redox.2021.101914
Ottaviani, J.I., Borges, G., Momma, T.Y., Spencer, J.P.E., Keen, C.L., Crozier, A., Schroeter, H., 2016. The metabolome of [2-14C](−)-epicatechin in humans: implications for the assessment of efficacy, safety and mechanisms of action of polyphenolic bioactives. Sci Rep 6, 29034. https://doi.org/10.1038/srep29034
Ottaviani, J.I., Fong, R., Kimball, J., Ensunsa, J.L., Britten, A., Lucarelli, D., Luben, R., Grace, P.B., Mawson, D.H., Tym, A., Wierzbicki, A., Khaw, K.-T., Schroeter, H., Kuhnle, G.G.C., 2018a. Evaluation at scale of microbiome-derived metabolites as biomarker of flavan-3-ol intake in epidemiological studies. Sci Rep 8, 9859. https://doi.org/10.1038/s41598-018-28333-w
Ottaviani, J.I., Heiss, C., Spencer, J.P.E., Kelm, M., Schroeter, H., 2018b. Recommending flavanols and procyanidins for cardiovascular health: Revisited. Molecular Aspects of Medicine 61, 63–75. https://doi.org/10.1016/j.mam.2018.02.001
Ottaviani, Javier I, Kwik-Uribe, C., Keen, C.L., Schroeter, H., 2012. Intake of dietary procyanidins does not contribute to the pool of circulating flavanols in humans. The American Journal of Clinical Nutrition 95, 851–858. https://doi.org/10.3945/ajcn.111.028340
Ottaviani, Javier I., Momma, T.Y., Kuhnle, G.K., Keen, C.L., Schroeter, H., 2012. Structurally related (−)-epicatechin metabolites in humans: Assessment using de novo chemically synthesized authentic standards. Free Radical Biology and Medicine 52, 1403–1412. https://doi.org/10.1016/j.freeradbiomed.2011.12.010
Palmnäs, M., Brunius, C., Shi, L., Rostgaard-Hansen, A., Torres, N.E., González-Domínguez, R., Zamora-Ros, R., Ye, Y.L., Halkjær, J., Tjønneland, A., Riccardi, G., Giacco, R., Costabile, G., Vetrani, C., Nielsen, J., Andres-Lacueva, C., Landberg, R., 2020. Perspective: Metabotyping—A Potential Personalized Nutrition Strategy for Precision Prevention of Cardiometabolic Disease. Advances in Nutrition 11, 524–532. https://doi.org/10.1093/advances/nmz121
Panche, A.N., Diwan, A.D., Chandra, S.R., 2016. Flavonoids: an overview. J Nutr Sci 5, e47. https://doi.org/10.1017/jns.2016.41
Pang, J., Zhang, Z., Zheng, T., Bassig, B.A., Mao, C., Liu, X., Zhu, Y., Shi, K., Ge, J., Yang, Y., Dejia-Huang, null, Bai, M., Peng, Y., 2016. Green tea consumption and risk of cardiovascular and ischemic related diseases: A meta-analysis. Int J Cardiol 202, 967–974. https://doi.org/10.1016/j.ijcard.2014.12.176
Papaioannou, T., Karatzi, K., Karatzis, E., Papamichael, C., Lekakis, J., 2005. Acute effects of caffeine on arterial stiffness, wave reflections, and central aortic pressures. American Journal of Hypertension 18, 129–136. https://doi.org/10.1016/j.amjhyper.2004.08.017
Pedersen, H.K., Gudmundsdottir, V., Nielsen, H.B., Hyotylainen, T., Nielsen, T., Jensen, B.A.H., Forslund, K., Hildebrand, F., Prifti, E., Falony, G., Le Chatelier, E., Levenez, F., Doré, J., Mattila, I., Plichta, D.R., Pöhö, P., Hellgren, L.I., Arumugam, M., Sunagawa, S., Vieira-Silva, S., Jørgensen, T., Holm, J.B., Trošt, K., Consortium, M., Kristiansen, K., Brix, S., Raes, J., Wang, J., Hansen, T., Bork, P., Brunak, S., Oresic, M., Ehrlich, S.D., Pedersen, O., 2016. Human gut microbes impact host serum metabolome and insulin sensitivity. Nature 535, 376–381. https://doi.org/10.1038/nature18646
Pollastri, S., Tattini, M., 2011. Flavonols: old compounds for old roles. Annals of Botany 108, 1225–1233. https://doi.org/10.1093/aob/mcr234
Preik, M., Lauer, T., Heiß, C., Tabery, S., Strauer, B.E., Kelm, M., 2003. Automated Ultrasonic Measurement of Human Arteries for the Determination of Endothelial Function. Ultraschall in Med 21, 195–198. https://doi.org/10.1055/s-2000-7989
Raman, G., Avendano, E.E., Chen, S., Wang, J., Matson, J., Gayer, B., Novotny, J.A., Cassidy, A., 2019. Dietary intakes of flavan-3-ols and cardiometabolic health: systematic review and meta-analysis of randomized trials and prospective cohort studies. The American Journal of Clinical Nutrition 110, 1067–1078. https://doi.org/10.1093/ajcn/nqz178
Rassaf, T., Rammos, C., Hendgen-Cotta, U.B., Heiss, C., Kleophas, W., Dellanna, F., Floege, J., Hetzel, G.R., Kelm, M., 2016. Vasculoprotective Effects of Dietary Cocoa Flavanols in Patients on Hemodialysis: A Double–Blind, Randomized, Placebo–Controlled Trial. CJASN 11, 108–118. https://doi.org/10.2215/CJN.05560515
Rees, A., Dodd, G., Spencer, J., 2018. The Effects of Flavonoids on Cardiovascular Health: A Review of Human Intervention Trials and Implications for Cerebrovascular Function. Nutrients 10, 1852. https://doi.org/10.3390/nu10121852
Ren, Y., Liu, Y., Sun, X.-Z., Wang, B.-Y., Zhao, Y., Liu, D.-C., Zhang, D.-D., Liu, X.-J., Zhang, R.-Y., Sun, H.-H., Liu, F.-Y., Chen, X., Cheng, C., Liu, L.-L., Zhou, Q.-G., Zhang, M., Hu, D.-S., 2019. Chocolate consumption and risk of cardiovascular diseases: a meta-analysis of prospective studies. Heart 105, 49–55. https://doi.org/10.1136/heartjnl-2018-313131
Richelle, M., Tavazzi, I., Enslen, M., Offord, E., 1999. rich. Eur J Clin Nutr 53, 22–26. https://doi.org/10.1038/sj.ejcn.1600673
Ried, K., Fakler, P., Stocks, N.P., 2017. Effect of cocoa on blood pressure. Cochrane Database of Systematic Reviews 2017. https://doi.org/10.1002/14651858.CD008893.pub3
Riedl, A., Gieger, C., Hauner, H., Daniel, H., Linseisen, J., 2017. Metabotyping and its application in targeted nutrition: an overview. Br J Nutr 117, 1631–1644. https://doi.org/10.1017/S0007114517001611
Rios, L.Y., Bennett, R.N., Lazarus, S.A., Rémésy, C., Scalbert, A., Williamson, G., 2002. Cocoa procyanidins are stable during gastric transit in humans. The American Journal of Clinical Nutrition 76, 1106–1110. https://doi.org/10.1093/ajcn/76.5.1106
Robbins, R.J., Leonczak, J., Li, Julia, Johnson, J Christopher, Collins, T., Kwik-Uribe, C., Schmitz, H.H., Collaborators:, Austad, J., Bhandari, S., Cifuentes, T., Derck, V., Ellem, S., Ellingson, D., Gallegos, T., Groves, M., Grypa, R., Gu, L., Hongyu, W., Huang, D., Johnson, J C, Jones, M., Kremers, B., Kuhnle, G., Li, J, Mateos, A.R., Ottavian, J., Schaneberg, B., Spencer, J., Sullivan, D., Vidts, K., Wang, W., Williamson, G., Zapf, M., 2012. Determination of Flavanol and Procyanidin (by Degree of Polymerization 1–10) Content of Chocolate, Cocoa Liquors, Powder(s), and Cocoa Flavanol Extracts by Normal Phase High-Performance Liquid Chromatography: Collaborative Study. Journal of AOAC INTERNATIONAL 95, 1153–1160. https://doi.org/10.5740/jaoacint.12-162
Rodriguez-Mateos, A., Cifuentes-Gomez, T., Gonzalez-Salvador, I., Ottaviani, J.I., Schroeter, H., Kelm, M., Heiss, C., Spencer, J.P.E., 2015. Influence of age on the absorption, metabolism, and excretion of cocoa flavanols in healthy subjects. Mol. Nutr. Food Res. 59, 1504–1512. https://doi.org/10.1002/mnfr.201500091
Rodriguez-Mateos, A., Jose Oruna-Concha, M., Kwik-Uribe, C., Vidal, A., Spencer, J.P.E., 2012. Influence of sugar type on the bioavailability of cocoa flavanols. Br J Nutr 108, 2243–2250. https://doi.org/10.1017/S0007114512000475
Rodriguez-Mateos, A., Rendeiro, C., Bergillos-Meca, T., Tabatabaee, S., George, T.W., Heiss, C., Spencer, J.P., 2013. Intake and time dependence of blueberry flavonoid–induced improvements in vascular function: a randomized, controlled, double-blind, crossover intervention study with mechanistic insights into biological activity. The American Journal of Clinical Nutrition 98, 1179–1191. https://doi.org/10.3945/ajcn.113.066639
Rodriguez-Mateos, A., Weber, T., Skene, S.S., Ottaviani, J.I., Crozier, A., Kelm, M., Schroeter, H., Heiss, C., 2018. Assessing the respective contributions of dietary flavanol monomers and procyanidins in mediating cardiovascular effects in humans: randomized, controlled, double-masked intervention trial. Am J Clin Nutr 108, 1229–1237. https://doi.org/10.1093/ajcn/nqy229
Rue, E.A., Rush, M.D., van Breemen, R.B., 2018. Procyanidins: a comprehensive review encompassing structure elucidation via mass spectrometry. Phytochem Rev 17, 1–16. https://doi.org/10.1007/s11101-017-9507-3
Sánchez-Patán, F., Chioua, M., Garrido, I., Cueva, C., Samadi, A., Marco-Contelles, J., Moreno-Arribas, M.V., Bartolomé, B., Monagas, M., 2011. Synthesis, Analytical Features, and Biological Relevance of 5-(3′,4′-Dihydroxyphenyl)-γ-valerolactone, a Microbial Metabolite Derived from the Catabolism of Dietary Flavan-3-ols. J. Agric. Food Chem. 59, 7083–7091. https://doi.org/10.1021/jf2020182
Sansone, R., Ottaviani, J.I., Rodriguez-Mateos, A., Heinen, Y., Noske, D., Spencer, J.P., Crozier, A., Merx, M.W., Kelm, M., Schroeter, H., Heiss, C., 2017. Methylxanthines enhance the effects of cocoa flavanols on cardiovascular function: randomized, double-masked controlled studies. Am J Clin Nutr 105, 352–360. https://doi.org/10.3945/ajcn.116.140046
Sansone, R., Rodriguez-Mateos, A., Heuel, J., Falk, D., Schuler, D., Wagstaff, R., Kuhnle, G.G.C., Spencer, J.P.E., Schroeter, H., Merx, M.W., Kelm, M., Heiss, C., for the Flaviola Consortium, European Union 7th Framework Program, 2015. Cocoa flavanol intake improves endothelial function and Framingham Risk Score in healthy men and women: a randomised, controlled, double-masked trial: the Flaviola Health Study. Br J Nutr 114, 1246–1255. https://doi.org/10.1017/S0007114515002822
Scalbert, A., Williamson, G., 2000. Dietary Intake and Bioavailability of Polyphenols. The Journal of Nutrition 130, 2073S-2085S. https://doi.org/10.1093/jn/130.8.2073S
Scholz, Williamson, 2007. Interactions Affecting the Bioavailability of Dietary Polyphenols in Vivo. International Journal for Vitamin and Nutrition Research 77, 224–235. https://doi.org/10.1024/0300-9831.77.3.224
Schroeter, H., Heiss, C., Balzer, J., Kleinbongard, P., Keen, C.L., Hollenberg, N.K., Sies, H., Kwik-Uribe, C., Schmitz, H.H., Kelm, M., 2006. (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proceedings of the National Academy of Sciences 103, 1024–1029. https://doi.org/10.1073/pnas.0510168103
Schroeter, H., Keen, C.L., Sesso, H.D., Manson, J.E., Lupton, J.R., 2015. Is this the end of (−)-epicatechin, or not? New study highlights the complex challenges associated with research into the cardiovascular health benefits of bioactive food constituents. The American Journal of Clinical Nutrition 102, 975–976. https://doi.org/10.3945/ajcn.115.117283
Sesso, H.D., Manson, J.E., Aragaki, A.K., Rist, P.M., Johnson, L.G., Friedenberg, G., Copeland, T., Clar, A., Mora, S., Moorthy, M.V., Sarkissian, A., Carrick, W.R., Anderson, G.L., for the COSMOS Research Group, Manson, J.E., Sesso, H.D., Rist, P.M., Lagerstrom, S.R., Bassuk, S.S., Wang, L., Hazra, A., Gibson, H., LeBoff, M.S., Mora, S., Okereke, O.I., Tobias, Deirdre K, Cook, N.R., Chandler, P.D., Christen, W., Friedenberg, G., Copeland, T., Hanna, J., Clar, A., D’Agostino, D., Vinayagamoorthy, M., Gibson, H., Kim, E., Van Denburgh, M., Kotler, G., Li, C., Bubes, V., Sarkissian, A., Smith, D., Pereira, E.C., Okeke, M., Roche, E., Bates, D., Ridge, C., Phillips, A., Salvo, B., Wilson, A., Hall, L., Baez, J., Sim, Y.-H., Cardoso, H., Senor, G., Rudnicki, C., Huynh, H., Nguyen, V., Terrell, N., Holman, B.A., Walter, J., Johnson, L.F., Casarella, A., O’Connell, J., Christen, W., Lagerstrom, S.R., Djoussé, L., Chandler, P.D., Hazra, A., Tobias, Deidre K, Farukhi, Z.M., Wang, L., Zhang, X., Breen, K., Menjin, G.V., Rodriguez, R., Curry, S., Mora, S., Arsenault, L., Solano, O., Weinberg, A., Coates, J., Kilroe, M., Zernicke, L., Hasson, K., Matthew, K., Mora, S., Pfeffer, C., Duszlak, J., Bates, D., Guzman, V., Falcon, J., Romero, A., Kupets, H., Cortez, F., LeSuer, J.C., Hrbek, A., Bowes, E., Quinn, P., Mele, M., Anderson, G.L., Johnson, L., Tinker, L.F., Aragaki, A.K., Herndon, M., Mann, S.L., Pettinger, M., Hunt, R.P., Carrick, B., Szyperski, K., Proulx-Burns, L., Burrows, E., Limacher, M., Hsia, J., Asaithambi, G., Khan, M., Nagaraja, N., Ocava, L.C., Wold, J., Silver, B., Connelly, S., Van Lom, G., Garvida, C., Hightower, K., Spaulding, P., Lin, W., Schoenberg, J., Olee, P., Cohen, L.S., Colton, T., Henderson, I.C., Hulley, S., Lichtenstein, A.H., Passamani, E.R., Silliman, R.A., Wenger, N., Ludlam, S.E., Schroeter, H., Fare, M., Ottawani, J., Kwik-Uribe, C., Arnaiz, C., Costanza, A., Greene, J., Hennessey, P., Vadlamani, S., Karmsetty, M., Martini, P., van Klinken, J.-W., Shah, A., Stern, L., 2022. Effect of cocoa flavanol supplementation for prevention of cardiovascular disease events: The COSMOS randomized clinical trial. The American Journal of Clinical Nutrition nqac055. https://doi.org/10.1093/ajcn/nqac055
Sitia, S., Tomasoni, L., Atzeni, F., Ambrosio, G., Cordiano, C., Catapano, A., Tramontana, S., Perticone, F., Naccarato, P., Camici, P., Picano, E., Cortigiani, L., Bevilacqua, M., Milazzo, L., Cusi, D., Barlassina, C., Sarzi-Puttini, P., Turiel, M., 2010. From endothelial dysfunction to atherosclerosis. Autoimmunity Reviews 9, 830–834. https://doi.org/10.1016/j.autrev.2010.07.016
Sorrenti, V., Ali, S., Mancin, L., Davinelli, S., Paoli, A., Scapagnini, G., 2020. Cocoa Polyphenols and Gut Microbiota Interplay: Bioavailability, Prebiotic Effect, and Impact on Human Health. Nutrients 12, 1908. https://doi.org/10.3390/nu12071908
Spencer, J.P.E., 2003. Metabolism of Tea Flavonoids in the Gastrointestinal Tract. The Journal of Nutrition 133, 3255S-3261S. https://doi.org/10.1093/jn/133.10.3255S
Su, J.B., 2015. Vascular endothelial dysfunction and pharmacological treatment. WJC 7, 719. https://doi.org/10.4330/wjc.v7.i11.719
Sui, Y., Shi, J., Cai, S., Xiong, T., Xie, B., Sun, Z., Mei, X., 2021. Metabolites of Procyanidins From Litchi Chinensis Pericarp With Xanthine Oxidase Inhibitory Effect and Antioxidant Activity. Front. Nutr. 8, 676346. https://doi.org/10.3389/fnut.2021.676346
Sun, J., Buys, N., Shen, S., 2013. Dietary Patterns and Cardiovascular Disease-Related Risks in Chinese Older Adults. Front. Public Health 1. https://doi.org/10.3389/fpubh.2013.00048
Sun, Y., Zimmermann, D., De Castro, C.A., Actis-Goretta, L., 2019. Dose–response relationship between cocoa flavanols and human endothelial function: a systematic review and meta-analysis of randomized trials. Food Funct. 10, 6322–6330. https://doi.org/10.1039/C9FO01747J
Tajima, E., Sakuma, M., Tokoi, S., Matsumoto, H., Saito, F., Watanabe, R., Toyoda, S., Abe, S., Inoue, T., 2020. The comparison of endothelial function between conduit artery and microvasculature in patients with coronary artery disease. Cardiol J 27, 38–46. https://doi.org/10.5603/CJ.a2018.0077
Takase, B., Uehata, A., Akima, T., Nagai, T., Nishioka, T., Hamabe, A., Satomura, K., Ohsuzu, F., Kurita, A., 1998. Endothelium-dependent flow-mediated vasodilation in coronary and brachial arteries in suspected coronary artery disease. The American Journal of Cardiology 82, 1535–1539. https://doi.org/10.1016/S0002-9149(98)00702-4
Tao, W., Zhang, Y., Shen, X., Cao, Y., Shi, J., Ye, X., Chen, S., 2019. Rethinking the Mechanism of the Health Benefits of Proanthocyanidins: Absorption, Metabolism, and Interaction with Gut Microbiota. Comprehensive Reviews in Food Science and Food Safety 18, 971–985. https://doi.org/10.1111/1541-4337.12444
Taubert, D., Roesen, R., Lehmann, C., Jung, N., Schömig, E., 2007. Effects of Low Habitual Cocoa Intake on Blood Pressure and Bioactive Nitric Oxide: A Randomized Controlled Trial. JAMA 298, 49. https://doi.org/10.1001/jama.298.1.49
ter AVEST, E., Holewijn, S., Stalenhoef, A.F.H., de GRAAF, J., 2005. Variation in non-invasive measurements of vascular function in healthy volunteers during daytime. Clinical Science 108, 425–431. https://doi.org/10.1042/CS20040300
Thijssen, D.H.J., Bruno, R.M., van Mil, A.C.C.M., Holder, S.M., Faita, F., Greyling, A., Zock, P.L., Taddei, S., Deanfield, J.E., Luscher, T., Green, D.J., Ghiadoni, L., 2019. Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans. European Heart Journal 40, 2534–2547. https://doi.org/10.1093/eurheartj/ehz350
Tritto, I., Ambrosio, G., 2004. The multi-faceted behavior of nitric oxide in vascular “inflammation”: catchy terminology or true phenomenon? Cardiovascular Research 63, 1–4. https://doi.org/10.1016/j.cardiores.2004.04.028
Tzounis, X., Rodriguez-Mateos, A., Vulevic, J., Gibson, G.R., Kwik-Uribe, C., Spencer, J.P., 2011. Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study. The American Journal of Clinical Nutrition 93, 62–72. https://doi.org/10.3945/ajcn.110.000075
Vallance, P., Leone, A., Moncada, S., Calver, A., Collier, J., 1992. Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure. The Lancet 339, 572–575. https://doi.org/10.1016/0140-6736(92)90865-Z
Van Bortel, L.M., Laurent, S., Boutouyrie, P., Chowienczyk, P., Cruickshank, J.K., De Backer, T., Filipovsky, J., Huybrechts, S., Mattace-Raso, F.U.S., Protogerou, A.D., Schillaci, G., Segers, P., Vermeersch, S., Weber, T., 2012. Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. Journal of Hypertension 30, 445–448. https://doi.org/10.1097/HJH.0b013e32834fa8b0
van Bussel, B.C., Henry, R.M., Ferreira, I., van Greevenbroek, M.M., van der Kallen, C.J., Twisk, J.W., Feskens, E.J., Schalkwijk, C.G., Stehouwer, C.D., 2015. A Healthy Diet Is Associated with Less Endothelial Dysfunction and Less Low-Grade Inflammation over a 7-Year Period in Adults at Risk of Cardiovascular Disease. The Journal of Nutrition 145, 532–540. https://doi.org/10.3945/jn.114.201236
Van Camp, G., 2014. Cardiovascular disease prevention. Acta Clinica Belgica 69, 407–411. https://doi.org/10.1179/2295333714Y.0000000069
van Mil, A.C.C.M., Greyling, A., Zock, P.L., Geleijnse, J.M., Hopman, M.T., Mensink, R.P., Reesink, K.D., Green, D.J., Ghiadoni, L., Thijssen, D.H., 2016. Impact of volunteer-related and methodology-related factors on the reproducibility of brachial artery flow-mediated vasodilation: analysis of 672 individual repeated measurements. Journal of Hypertension 34, 1738–1745. https://doi.org/10.1097/HJH.0000000000001012
Vandvik, P.O., Lincoff, A.M., Gore, J.M., Gutterman, D.D., Sonnenberg, F.A., Alonso-Coello, P., Akl, E.A., Lansberg, M.G., Guyatt, G.H., Spencer, F.A., 2012. Primary and Secondary Prevention of Cardiovascular Disease. Chest 141, e637S-e668S. https://doi.org/10.1378/chest.11-2306
Vlachojannis, J., Erne, P., Zimmermann, B., Chrubasik-Hausmann, S., 2016. The Impact of Cocoa Flavanols on Cardiovascular Health: Cocoa Flavanols and Cardiovascular Health. Phytother. Res. 30, 1641–1657. https://doi.org/10.1002/ptr.5665
Wang-Polagruto, J.F., Villablanca, A.C., Polagruto, J.A., Lee, L., Holt, R.R., Schrader, H.R., Ensunsa, J.L., Steinberg, F.M., Schmitz, H.H., Keen, C.L., 2006. Chronic Consumption of Flavanol-rich Cocoa Improves Endothelial Function and Decreases Vascular Cell Adhesion Molecule in Hypercholesterolemic Postmenopausal Women: Journal of Cardiovascular Pharmacology 47, S177–S186. https://doi.org/10.1097/00005344-200606001-00013
Weiss, N., Keller, C., Hoffmann, U., Loscalzo, J., 2002. Endothelial dysfunction and atherothrombosis in mild hyperhomocysteinemia. Vasc Med 7, 227–239. https://doi.org/10.1191/1358863x02vm428ra
Willett, W.C., Sacks, F., Trichopoulou, A., Drescher, G., Ferro-Luzzi, A., Helsing, E., Trichopoulos, D., 1995. Mediterranean diet pyramid: a cultural model for healthy eating. The American Journal of Clinical Nutrition 61, 1402S-1406S. https://doi.org/10.1093/ajcn/61.6.1402S
Wilson, P.W.F., D’Agostino, R.B., Levy, D., Belanger, A.M., Silbershatz, H., Kannel, W.B., 1998. Prediction of Coronary Heart Disease Using Risk Factor Categories. Circulation 97, 1837–1847. https://doi.org/10.1161/01.CIR.97.18.1837
Woodman, R.J., Playford, D.A., Watts, G.F., Cheetham, C., Reed, C., Taylor, R.R., Puddey, I.B., Beilin, L.J., Burke, V., Mori, T.A., Green, D., 2001. Improved analysis of brachial artery ultrasound using a novel edge-detection software system. Journal of Applied Physiology 91, 929–937. https://doi.org/10.1152/jappl.2001.91.2.929
World Health Organization (WHO), 2021. Factsheet - Cardiovascular Diseases (CVDs) [WWW Document]. URL https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds) (accessed 10.13.21).
World Health Organization (WHO), 2018. Factsheet - Cardiovascular Diseases (CVDs) [WWW Document]. URL https://www.who.int/en/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds) (accessed 4.4.20).
Yasuda, A., Natsume, M., Sasaki, K., Baba, S., Nakamura, Y., Kanegae, M., Nagaoka, S., 2008. Cacao procyanidins reduce plasma cholesterol and increase fecal steroid excretion in rats fed a high-cholesterol diet. BioFactors 33, 211–223. https://doi.org/10.1002/biof.5520330307
Zhang, T., Niu, C., Hu, J., Liu, H., Jing, H., 2008. [Vasorelaxational effects of procyanidins on rabbit aorta in vitro and decreasing arterial blood pressure in vivo]. Zhongguo Zhong Yao Za Zhi 33, 1720–1723.
Lizenz:Creative Commons Lizenzvertrag
Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz
Bezug:2013-2022
Fachbereich / Einrichtung:Medizinische Fakultät
Dokument erstellt am:14.11.2022
Dateien geändert am:14.11.2022
Promotionsantrag am:18.07.2022
Datum der Promotion:10.11.2022
english
Benutzer
Status: Gast
Aktionen