Dietary Flavanols: A Review of Select Effects on Vascular Function, Blood Pressure, and Exercise Performance

References

• Eyre H, Kahn R, Robertson RM, Clark NG, Doyle C, Hong Y, Gansler T, Glynn T, Smith RA, Taubert K, Thun MJ. Preventing cancer, cardiovascular disease, and diabetes: a common agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association. Circulation. 2004;109:3244–55. doi:10.1161/01.CIR.0000133321.00456.00. PMID:15198946.
   PubMed Web of Science ®Google Scholar
• Mozaffarian D. Dietary and policy priorities for cardiovascular disease, diabetes, and obesity: a comprehensive review. Circulation. 2016;133:187–225. doi:10.1161/circulationaha.115.018585. PMID:26746178.
   PubMed Web of Science ®Google Scholar
• He FJ, Nowson CA, Lucas M, MacGregor GA. Increased consumption of fruit and vegetables is related to a reduced risk of coronary heart disease: meta-analysis of cohort studies. J Hum Hypertens. 2007;21:717–28. doi:10.1038/sj.jhh.1002212. PMID:17443205.
   PubMed Web of Science ®Google Scholar
• Mursu J, Virtanen JK, Tuomainen TP, Nurmi T, Voutilainen S. Intake of fruit, berries, and vegetables and risk of type 2 diabetes in Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study. Am J Clin Nutr. 2014;99:328–33. doi:10.3945/ajcn.113.069641. PMID:24257723.
   PubMed Web of Science ®Google Scholar
• Liu RH. Health-promoting components of fruits and vegetables in the diet. Adv Nutr. 2013;4:384s–92s. doi:10.3945/an.112.003517. PMID:23674808.
   PubMed Web of Science ®Google Scholar
• Dauchet L, Amouyel P, Dallongeville J. Fruits, vegetables and coronary heart disease. Nat Rev Cardiol. 2009;6:599–608. doi:10.1038/nrcardio.2009.131. PMID:19652655.
   PubMed Web of Science ®Google Scholar
• Mink PJ, Scrafford CG, Barraj LM, Harnack L, Hong CP, Nettleton JA, Jacobs DR Jr. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr. 2007;85:895–909. doi:10.1093/ajcn/85.3.895. PMID:17344514.
   PubMed Web of Science ®Google Scholar
• Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D. Dietary antioxidant flavonoids and risk of coronary heart disease: the Zutphen Elderly Study. Lancet. 1993;342:1007–11. doi:10.1016/0140-6736(93)92876-U. PMID:8105262.
   PubMed Web of Science ®Google Scholar
• Mulvihill EE, Huff MW. Antiatherogenic properties of flavonoids: implications for cardiovascular health. Can J Cardiol. 2010;26(Suppl A):17a–21a. doi:10.1016/S0828-282X(10)71056-4. PMID:20386755.
   PubMedGoogle Scholar
• Erdman JW Jr, Balentine D, Arab L, Beecher G, Dwyer JT, Folts J, Harnly J, Hollman P, Keen CL, Mazza G, et al. Flavonoids and heart health: proceedings of the ILSI North America Flavonoids Workshop, May 31–June 1, 2005, Washington, DC. J Nutr. 2007;137:718s–37s. doi:10.1093/jn/137.3.718S. PMID:17311968.
   PubMed Web of Science ®Google Scholar
• Grassi D, Desideri G, Necozione S, Lippi C, Casale R, Properzi G, Blumberg JB, Ferri C. Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate. J Nutr. 2008;138:1671–6. doi:10.1093/jn/138.9.1671. PMID:18716168.
   PubMed Web of Science ®Google Scholar
• Taubert D, Roesen R, Lehmann C, Jung N, Schomig E. Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. JAMA. 2007;298:49–60. doi:10.1001/jama.298.1.49. PMID:17609490.
   PubMed Web of Science ®Google Scholar
• Heiss C, Jahn S, Taylor M, Real WM, Angeli FS, Wong ML, Amabile N, Prasad M, Rassaf T, Ottaviani JI, et al. Improvement of endothelial function with dietary flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease. J Am Coll Cardiol. 2010;56:218–24. doi:10.1016/j.jacc.2010.03.039. PMID:20620742.
   PubMed Web of Science ®Google Scholar
• Murphy KJ, Chronopoulos AK, Singh I, Francis MA, Moriarty H, Pike MJ, Turner AH, Mann NJ, Sinclair AJ. Dietary flavanols and procyanidin oligomers from cocoa (Theobroma cacao) inhibit platelet function. Am J Clin Nutr. 2003;77:1466–73. doi:10.1093/ajcn/77.6.1466. PMID:12791625.
   PubMed Web of Science ®Google Scholar
• Gasper A, Hollands W, Casgrain A, Saha S, Teucher B, Dainty JR, Venema DP, Hollman PC, Rein MJ, Nelson R, et al. Consumption of both low and high (−)-epicatechin apple puree attenuates platelet reactivity and increases plasma concentrations of nitric oxide metabolites: a randomized controlled trial. Arch Biochem Biophys. 2014;559:29–37. doi:10.1016/j.abb.2014.05.026. PMID:24929184.
   PubMed Web of Science ®Google Scholar
• Schini-Kerth VB, Auger C, Kim JH, Etienne-Selloum N, Chataigneau T. Nutritional improvement of the endothelial control of vascular tone by polyphenols: role of NO and EDHF. Pflugers Arch. 2010;459:853–62. doi:10.1007/s00424-010-0806-4. PMID:20224869.
   PubMed Web of Science ®Google Scholar
• Cooper CE, Giulivi C. Nitric oxide regulation of mitochondrial oxygen consumption II: molecular mechanism and tissue physiology. Am J Physiol Cell Physiol. 2007;292:C1993–2003. doi:10.1152/ajpcell.00310.2006. PMID:17329402.
   PubMed Web of Science ®Google Scholar
• Corti R, Flammer AJ, Hollenberg NK, Luscher TF. Cocoa and cardiovascular health. Circulation. 2009;119:1433–41. doi:10.1161/circulationaha.108.827022. PMID:19289648.
   PubMed Web of Science ®Google Scholar
• Stamler JS, Meissner G. Physiology of nitric oxide in skeletal muscle. Physiol Rev. 2001;81:209–37. doi:10.1152/physrev.2001.81.1.209. PMID:11152758.
   PubMed Web of Science ®Google Scholar
• Larsen FJ, Weitzberg E, Lundberg JO, Ekblom B. Effects of dietary nitrate on oxygen cost during exercise. Acta Physiol (Oxf). 2007;191:59–66. doi:10.1111/j.1748-1716.2007.01713.x. PMID:17635415.
   PubMed Web of Science ®Google Scholar
• Jimenez R, Duarte J. Perez-Vizcaino F. Epicatechin: endothelial function and blood pressure. J Agric Food Chem. 2012;60:8823–30. doi:10.1021/jf205370q. PMID:22440087.
   PubMed Web of Science ®Google Scholar
• Holt RR, Heiss C, Kelm M, Keen CL. The potential of flavanol and procyanidin intake to influence age-related vascular disease. J Nutr Gerontol Geriatr. 2012;31:290–323. doi:10.1080/21551197.2012.702541. PMID:22888843.
   PubMedGoogle Scholar
• Gomez-Guzman M, Jimenez R, Sanchez M, Zarzuelo MJ, Galindo P, Quintela AM, Lopez-Sepulveda R, Romero M, Tamargo J, Vargas F, et al. Epicatechin lowers blood pressure, restores endothelial function, and decreases oxidative stress and endothelin-1 and NADPH oxidase activity in DOCA-salt hypertension. Free Radic Biol Med. 2012;52:70–79. doi:10.1016/j.freeradbiomed.2011.09.015. PMID:22001745.
   PubMed Web of Science ®Google Scholar
• Loke WM, Hodgson JM, Proudfoot JM, McKinley AJ, Puddey IB, Croft KD. Pure dietary flavonoids quercetin and (−)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men. Am J Clin Nutr. 2008;88:1018–25. doi:10.1093/ajcn/88.4.1018. PMID:18842789.
   PubMed Web of Science ®Google Scholar
• Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007;115:1285–95. PMID:17353456.
   PubMed Web of Science ®Google Scholar
• Igarashi K, Honma K, Yoshinari O, Nanjo F, Hara Y. Effects of dietary catechins on glucose tolerance, blood pressure and oxidative status in Goto-Kakizaki rats. J Nutr Sci Vitaminol (Tokyo). 2007;53:496–500. doi:10.3177/jnsv.53.496. PMID:18202537.
   PubMed Web of Science ®Google Scholar
• Actis-Goretta L, Ottaviani JI, Fraga CG. Inhibition of angiotensin converting enzyme activity by flavanol-rich foods. J Agric Food Chem. 2006;54:229–34. doi:10.1021/jf052263o. PMID:16390204.
   PubMed Web of Science ®Google Scholar
• Persson IA, Persson K, Hagg S, Andersson RG. Effects of cocoa extract and dark chocolate on angiotensin-converting enzyme and nitric oxide in human endothelial cells and healthy volunteers—a nutrigenomics perspective. J Cardiovasc Pharmacol. 2011;57:44–50. doi:10.1097/FJC.0b013e3181fe62e3. PMID:20966764.
   PubMed Web of Science ®Google Scholar
• Manach C, Scalbert A, Morand C, Remesy C, Jimenez L. Polyphenols: food sources and bioavailability. Am J Clin Nutr. 2004;9:727–47. doi:10.1093/ajcn/79.5.727.
   Google Scholar
• Hollman PC, Cassidy A, Comte B, Heinonen M, Richelle M, Richling E, Serafini M, Scalbert A, Sies H, Vidry S. The biological relevance of direct antioxidant effects of polyphenols for cardiovascular health in humans is not established. J Nutr. 2011;141:989s–1009s. doi:10.3945/jn.110.131490. PMID:21451125.
   PubMed Web of Science ®Google Scholar
• Ottaviani JI, Borges G, Momma TY, Spencer JP, Keen CL, Crozier A, Schroeter H. The metabolome of [2-(14)C](−)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives. Sci Rep. 2016;6:29034. doi:10.1038/srep29034. PMID:27363516.
   PubMed Web of Science ®Google Scholar
• Gielen S, Schuler G, Adams V. Cardiovascular effects of exercise training: molecular mechanisms. Circulation. 2010;122:1221–38. doi:10.1161/circulationaha.110.939959. PMID:20855669.
   PubMed Web of Science ®Google Scholar
• Blumenthal JA, Babyak MA, Hinderliter A, Watkins LL, Craighead L, Lin PH, Caccia C, Johnson J, Waugh R, Sherwood A. Effects of the DASH diet alone and in combination with exercise and weight loss on blood pressure and cardiovascular biomarkers in men and women with high blood pressure: the ENCORE study. Arch Intern Med. 2010;170:126–35. doi:10.1001/archinternmed.2009.470. PMID:20101007.
   PubMed Web of Science ®Google Scholar
• James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, Lackland DT, LeFevre ML, MacKenzie TD, Ogedegbe O, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311:507–20. doi:10.1001/jama.2013.284427. PMID:24352797.
   PubMed Web of Science ®Google Scholar
• Appel LJ, Brands MW, Daniels SR, Karanja N, Elmer PJ, Sacks FM. Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association. Hypertension. 2006;47:296–308. doi:10.1161/01.HYP.0000202568.01167.B6. PMID:16434724.
   PubMed Web of Science ®Google Scholar
• Macready AL, George TW, Chong MF, Alimbetov DS, Jin Y, Vidal A, Spencer JP, Kennedy OB, Tuohy KM, Minihane AM, et al. Flavonoid-rich fruit and vegetables improve microvascular reactivity and inflammatory status in men at risk of cardiovascular disease—FLAVURS: a randomized controlled trial. Am J Clin Nutr. 2014;99:479–89. doi:10.3945/ajcn.113.074237. PMID:24452238.
   PubMed Web of Science ®Google Scholar
• Sies H, Hollman PC, Grune T, Stahl W, Biesalski HK, Williamson G. Protection by flavanol-rich foods against vascular dysfunction and oxidative damage: 27th Hohenheim Consensus Conference. Adv Nutr. 2012;3:217–21. doi:10.3945/an.111.001578. PMID:22516731.
   PubMed Web of Science ®Google Scholar
• Williamson G, Dionisi F, Renouf M. Flavanols from green tea and phenolic acids from coffee: critical quantitative evaluation of the pharmacokinetic data in humans after consumption of single doses of beverages. Mol Nutr Food Res. 2011;55:864–73. doi:10.1002/mnfr.201000631. PMID:21538847.
   PubMed Web of Science ®Google Scholar
• Margalef M, Pons Z, Bravo FI, Muguerza B. Arola-Arnal A. Tissue distribution of rat flavanol metabolites at different doses. J Nutr Biochem. 2015;26:987–95. doi:10.1016/j.jnutbio.2015.04.006. PMID:26026838.
   PubMed Web of Science ®Google Scholar
• Lupton JR, Atkinson SA, Chang N, Fraga CG, Levy J, Messina M, Richardson DP, van Ommen B, Yang Y, Griffiths JC, Hathcock J. Exploring the benefits and challenges of establishing a DRI-like process for bioactives. Eur J Nutr. 2014;3(Suppl 1):1–9.
   Google Scholar
• Borges G, van der Hooft JJ, Crozier A. A comprehensive evaluation of the [2–14C](−)-epicatechin metabolome in rats. Free Radic Biol Med. 2016;99:128–38. doi:10.1016/j.freeradbiomed.2016.08.001. PMID:27495388.
   PubMed Web of Science ®Google Scholar
• Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, Das SR, de Ferranti S, Despres JP, Fullerton HJ, et al. Heart disease and stroke statistics-2016 Update: a report from the American Heart Association. Circulation. 2016;133:e38–360. doi:10.1161/CIR.0000000000000350. PMID:26673558.
   PubMed Web of Science ®Google Scholar
• Eckel RH, Jakicic JM, Ard JD, de Jesus JM, Houston Miller N, Hubbard VS, Lee IM, Lichtenstein AH, Loria CM, Millen BE, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014;3:2960–84. doi:10.1016/j.jacc.2013.11.003.
   Google Scholar
• Rudolf J, Lewandrowski KB. Cholesterol, lipoproteins, high-sensitivity c-reactive protein, and other risk factors for atherosclerosis. Clin Lab Med. 2014;34:113–27. vii. doi:10.1016/j.cll.2013.11.003. PMID:24507791.
   PubMed Web of Science ®Google Scholar
• Weber MA, Schiffrin EL, White WB, Mann S, Lindholm LH, Kenerson JG, Flack JM, Carter BL, Materson BJ, Ram CV, et al. Clinical practice guidelines for the management of hypertension in the community: a statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich). 2014;16:14–26. doi:10.1111/jch.12237. PMID:24341872.
   PubMed Web of Science ®Google Scholar
• Carretero OA, Oparil S. Essential hypertension. Part I: definition and etiology. Circulation. 2000;101:329–35.
   PubMed Web of Science ®Google Scholar
• Beevers G, Lip GY, O'Brien E. ABC of hypertension: The pathophysiology of hypertension. BMJ. 2001;322:912–6. doi:10.1136/bmj.322.7291.912. PMID:11302910.
   PubMed Web of Science ®Google Scholar
• Kurtel H, Rodrigues SF, Yilmaz CE, Yildirim A, Granger DN. Impaired vasomotor function induced by the combination of hypertension and hypercholesterolemia. J Am Soc Hypertens. 2013;7:14–23. doi:10.1016/j.jash.2012.11.005. PMID:23321401.
   PubMed Web of Science ®Google Scholar
• Feletou M. Integrated systems physiology: from molecule to function to disease. In: The endothelium: part 2: EDHF-mediated responses “the classical pathway”. San Rafael (CA): Morgan & Claypool Life Sciences Publisher; 2011.
   Google Scholar
• Ikemura M, Sasaki Y, Giddings JC, Yamamoto J. Preventive effects of hesperidin, glucosyl hesperidin and naringin on hypertension and cerebral thrombosis in stroke-prone spontaneously hypertensive rats. Phytother Res. 2011;26:1272–7. doi:10.1002/ptr.3724.
   Web of Science ®Google Scholar
• Vanhoutte PM, Shimokawa H, Tang EH, Feletou M. Endothelial dysfunction and vascular disease. Acta Physiol (Oxf). 2009;196:193–222. doi:10.1111/j.1748-1716.2009.01964.x. PMID:19220204.
   PubMed Web of Science ®Google Scholar
• Lim PO, MacFadyen RJ, Clarkson PB, MacDonald TM. Impaired exercise tolerance in hypertensive patients. Ann Intern Med. 1996;124:41–55. doi:10.7326/0003-4819-124-1_Part_1-199601010-00008. PMID:7503477.
   PubMed Web of Science ®Google Scholar
• Lowry JL, Brovkovych V, Zhang Y, Skidgel RA. Endothelial nitric-oxide synthase activation generates an inducible nitric-oxide synthase-like output of nitric oxide in inflamed endothelium. J Biol Chem. 2013;288:4174–93. doi:10.1074/jbc.M112.436022. PMID:23255592.
   PubMed Web of Science ®Google Scholar
• Fernandez Vallinas S, Lopez Carreras N, Miguel M, Aleixandre A. Nitric oxide mediates the antihypertensive and vascular relaxing effects of a soluble cocoa fiber product in spontaneously hypertensive rats. Nitric Oxide. 2013;29:1–3. doi:10.1016/j.niox.2012.10.006. PMID:23142352.
   PubMed Web of Science ®Google Scholar
• Lockette W, McCurdy R, Aronow H, Butler B. Effect of 8-bromo-cyclic guanosine monophosphate on intracellular pH and calcium in vascular smooth muscle. Hypertension. 1989;13:865–9. doi:10.1161/01.HYP.13.6.865. PMID:2544526.
   PubMed Web of Science ®Google Scholar
• Intengan HD, Schiffrin EL. Structure and mechanical properties of resistance arteries in hypertension: role of adhesion molecules and extracellular matrix determinants. Hypertension. 2000;36:312–8. doi:10.1161/01.HYP.36.3.312. PMID:10988257.
   PubMed Web of Science ®Google Scholar
• Nogueira Lde P, Knibel MP, Torres MR, Nogueira Neto JF, Sanjuliani AF. Consumption of high-polyphenol dark chocolate improves endothelial function in individuals with stage 1 hypertension and excess body weight. Int J Hypertens. 2012;2012:147321. PMID:23209885.
   PubMedGoogle Scholar
• Bleakley C, Hamilton PK, Pumb R, Harbinson M, McVeigh GE. Endothelial function in hypertension: victim or culprit? J Clin Hypertens (Greenwich). 2015;17:651–4. doi:10.1111/jch.12546. PMID:25857326.
   PubMed Web of Science ®Google Scholar
• Puddu P, Puddu GM, Zaca F, Muscari A. Endothelial dysfunction in hypertension. Acta Cardiol. 2000;5:221–32. doi:10.2143/AC.55.4.2005744.
   Google Scholar
• Flammer AJ, Anderson T, Celermajer DS, Creager MA, Deanfield J, Ganz P, Hamburg NM, Luscher TF, Shechter M, Taddei S, et al. The assessment of endothelial function: from research into clinical practice. Circulation. 2012;126:753–67. doi:10.1161/circulationaha.112.093245. PMID:22869857.
   PubMed Web of Science ®Google Scholar
• Matsuzawa Y, Kwon TG, Lennon RJ, Lerman LO, Lerman A. Prognostic value of flow-mediated vasodilation in brachial artery and fingertip artery for cardiovascular events: a systematic review and meta-analysis. J Am Heart Assoc. 2015;4. doi:10.1161/JAHA.115.002270. PMID:26567372.
   PubMed Web of Science ®Google Scholar
• Schnabel RB, Wild PS, Schulz A, Zeller T, Sinning CR, Wilde S, Kunde J, Lubos E, Lackner KJ, Warnholtz A, et al. Multiple endothelial biomarkers and noninvasive vascular function in the general population: the Gutenberg Health Study. Hypertension. 2012;60:288–95. doi:10.1161/hypertensionaha.112.191874. PMID:22689741.
   PubMed Web of Science ®Google Scholar
• Wilson DE, Van Vlack T, Schievink BP, Doak EB, Shane JS, Dean E. Lifestyle factors in hypertension drug research: systematic analysis of articles in a leading Cochrane report. Int J Hypertens. 2014;2014:835716. doi:10.1155/2014/835716. PMID:24678418.
   PubMedGoogle Scholar
• Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, DePalma SM, Gidding S, Jamerson KA, Jones DW, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol epub. November 2017;13.
   Google Scholar
• Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, Chen J, He J. Global disparities of hypertension prevalence and control: a systematic analysis of population-based studies from 90 countries. Circulation. 2016;134:441–50. doi:10.1161/circulationaha.115.018912. PMID:27502908.
   PubMed Web of Science ®Google Scholar
• Shiina Y, Funabashi N, Lee K, Murayama T, Nakamura K, Wakatsuki Y, Daimon M, Komuro I. Acute effect of oral flavonoid-rich dark chocolate intake on coronary circulation, as compared with non-flavonoid white chocolate, by transthoracic doppler echocardiography in healthy adults. Int J Cardiol. 2009;131:424–9. doi:10.1016/j.ijcard.2007.07.131. PMID:18045712.
   PubMed Web of Science ®Google Scholar
• Grassi D, Desideri G, Necozione S, di Giosia P, Barnabei R, Allegaert L, Bernaert H, Ferri C. Cocoa consumption dose-dependently improves flow-mediated dilation and arterial stiffness decreasing blood pressure in healthy individuals. J Hypertens. 2015;33:294–303. doi:10.1097/HJH.0000000000000412. PMID:25380152.
   PubMed Web of Science ®Google Scholar
• Grassi D, Necozione S, Lippi C, Croce G, Valeri L, Pasqualetti P, Desideri G, Blumberg JB, Ferri C. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives. Hypertension. 2005;46:398–405. doi:10.1161/01.HYP.0000174990.46027.70. PMID:16027246.
   PubMed Web of Science ®Google Scholar
• Parichatikanond W, Pinthong D, Mangmool S. Blockade of the renin-angiotensin system with delphinidin, cyanin, and quercetin. Planta Med. 2012;78:1626–32. doi:10.1055/s-0032-1315198. PMID:22872589.
   PubMed Web of Science ®Google Scholar
• Gomolak JR, Didion SP. Angiotensin II-induced endothelial dysfunction is temporally linked with increases in interleukin-6 and vascular macrophage accumulation. Front Physiol. 2014;5:396. doi:10.3389/fphys.2014.00396. PMID:25400581.
   PubMed Web of Science ®Google Scholar
• Flammer AJ, Hermann F, Sudano I, Spieker L, Hermann M, Cooper KA, Serafini M, Luscher TF, Ruschitzka F, Noll G, Corti R. Dark chocolate improves coronary vasomotion and reduces platelet reactivity. Circulation. 2007;116:2376–82. doi:10.1161/circulationaha.107.713867. PMID:17984375.
   PubMed Web of Science ®Google Scholar
• Hermann F, Spieker LE, Ruschitzka F, Sudano I, Hermann M, Binggeli C, Luscher TF, Riesen W, Noll G, Corti R. Dark chocolate improves endothelial and platelet function. Heart. 2006;92:119–20. doi:10.1136/hrt.2005.063362. PMID:16365364.
   PubMed Web of Science ®Google Scholar
• Wang-Polagruto JF, Villablanca AC, Polagruto JA, Lee L, Holt RR, Schrader HR, Ensunsa JL, Steinberg FM, Schmitz HH, Keen CL. Chronic consumption of flavanol-rich cocoa improves endothelial function and decreases vascular cell adhesion molecule in hypercholesterolemic postmenopausal women. J Cardiovasc Pharmacol. 2006;47(Suppl 2):S177–186. discussion S206–179. doi:10.1097/00005344-200606001-00013. PMID:16794456.
   PubMed Web of Science ®Google Scholar
• Balzer J, Rassaf T, Heiss C, Kleinbongard P, Lauer T, Merx M, Heussen N, Gross HB, Keen CL, Schroeter H, Kelm M. Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial. J Am Coll Cardiol. 2008;51:2141–9. doi:10.1016/j.jacc.2008.01.059. PMID:18510961.
   PubMed Web of Science ®Google Scholar
• Heiss C, Dejam A, Kleinbongard P, Schewe T, Sies H, Kelm M. Vascular effects of cocoa rich in flavan-3-ols. JAMA. 2003;290:1030–1. doi:10.1001/jama.290.8.1030. PMID:12941674.
   PubMed Web of Science ®Google Scholar
• Hooper L, Kay C, Abdelhamid A, Kroon PA, Cohn JS, Rimm EB, Cassidy A. Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. Am J Clin Nutr. 2012;95:740–51. doi:10.3945/ajcn.111.023457. PMID:22301923.
   PubMed Web of Science ®Google Scholar
• Ried K, Sullivan TR, Fakler P, Frank OR, Stocks NP. Effect of cocoa on blood pressure. Cochrane Database Syst Rev. 2012;8:CD008893. PMID:22895979.
   PubMedGoogle Scholar
• Sansone R, Rodriguez-Mateos A, Heuel J, Falk D, Schuler D, Wagstaff R, Kuhnle GG, Spencer JP, Schroeter H, Merx MW, et al. 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. 2015;114:1246–55. doi:10.1017/S0007114515002822. PMID:26348767.
   PubMed Web of Science ®Google Scholar
• Hooper L, Kroon PA, Rimm EB, Cohn JS, Harvey I, Le Cornu KA, Ryder JJ, Hall WL, Cassidy A. Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2008;8:38–50. doi:10.1093/ajcn/88.1.38.
   Google Scholar
• Davison K, Berry NM, Misan G, Coates AM, Buckley JD, Howe PR. Dose-related effects of flavanol-rich cocoa on blood pressure. J Hum Hypertens. 2010;24:568–76. doi:10.1038/jhh.2009.105. PMID:20090776.
   PubMed Web of Science ®Google Scholar
• Desch S, Kobler D, Schmidt J, Sonnabend M, Adams V, Sareban M, Eitel I, Bluher M, Schuler G, Thiele H. Low vs. higher-dose dark chocolate and blood pressure in cardiovascular high-risk patients. Am J Hypertens. 2010;23:694–700. doi:10.1038/ajh.2010.29. PMID:20203627.
   PubMed Web of Science ®Google Scholar
• Ried K, Fakler P, Stocks NP. Effect of cocoa on blood pressure. Cochrane Database Syst Rev. 2017;4:CD008893. PMID:28439881.
   PubMedGoogle Scholar
• Turnbull F. Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials. Lancet. 2003;362:1527–35. doi:10.1016/S0140-6736(03)14739-3. PMID:14615107.
   PubMed Web of Science ®Google Scholar
• Smit HJ. Theobromine and the pharmacology of cocoa. Handb Exp Pharmacol. 2011;201–34. doi:10.1007/978-3-642-13443-2_7. PMID:20859797.
   PubMedGoogle Scholar
• Sansone R, Ottaviani JI, Rodriguez-Mateos A, Heinen Y, Noske D, Spencer JP, Crozier A, Merx MW, Kelm M, Schroeter H, Heiss C. Methylxanthines enhance the effects of cocoa flavanols on cardiovascular function: randomized, double-masked controlled studies. Am J Clin Nutr. 2016;105:352–60. doi:10.3945/ajcn.116.140046. PMID:28003203.
   PubMed Web of Science ®Google Scholar
• Schroeter H, Heiss C, Balzer J, Kleinbongard P, Keen CL, Hollenberg NK, Sies H, Kwik-Uribe C, Schmitz HH, Kelm M. (−)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci USA. 2006;103:1024–9. doi:10.1073/pnas.0510168103. PMID:16418281.
   PubMed Web of Science ®Google Scholar
• Shi J, Yu J, Pohorly JE, Kakuda Y. Polyphenolics in grape seeds-biochemistry and functionality. J Med Food. 2003;6:291–9. doi:10.1089/109662003772519831. PMID:14977436.
   PubMedGoogle Scholar
• Sivaprakasapillai B, Edirisinghe I, Randolph J, Steinberg F, Kappagoda T. Effect of grape seed extract on blood pressure in subjects with the metabolic syndrome. Metabolism. 2009;58:1743–6. doi:10.1016/j.metabol.2009.05.030.
   PubMed Web of Science ®Google Scholar
• Ras RT, Zock PL, Zebregs YE, Johnston NR, Webb DJ, Draijer R. Effect of polyphenol-rich grape seed extract on ambulatory blood pressure in subjects with pre- and stage I hypertension. Br J Nutr. 2013;110:2234–41. doi:10.1017/S000711451300161X. PMID:23702253.
   PubMed Web of Science ®Google Scholar
• Park E, Edirisinghe I, Choy YY, Waterhouse A, Burton-Freeman B. Effects of grape seed extract beverage on blood pressure and metabolic indices in individuals with pre-hypertension: a randomised, double-blinded, two-arm, parallel, placebo-controlled trial. Br J Nutr. 2016;115:226–38. doi:10.1017/S0007114515004328. PMID:26568249.
   PubMed Web of Science ®Google Scholar
• Barona J, Aristizabal JC, Blesso CN, Volek JS, Fernandez ML. Grape polyphenols reduce blood pressure and increase flow-mediated vasodilation in men with metabolic syndrome. J Nutr. 2012;42:1626–32. doi:10.3945/jn.112.162743.
   Google Scholar
• Edirisinghe I, Burton-Freeman B, Tissa Kappagoda C. Mechanism of the endothelium-dependent relaxation evoked by a grape seed extract. Clin Sci (Lond). 2008;114:331–7. doi:10.1042/CS20070264. PMID:17927567.
   PubMed Web of Science ®Google Scholar
• Brat P, George S, Bellamy A, Du Chaffaut L, Scalbert A, Mennen L, Arnault N, Amiot MJ. Daily polyphenol intake in France from fruit and vegetables. J Nutr. 2006;136:2368–73. doi:10.1093/jn/136.9.2368. PMID:16920856.
   PubMed Web of Science ®Google Scholar
• Kitadate K, Homma K, Roberts A, Maeda T. Thirteen-week oral dose toxicity study of Oligonol containing oligomerized polyphenols extracted from lychee and green tea. Regul Toxicol Pharmacol. 2014;68:140–6. doi:10.1016/j.yrtph.2013.12.001. PMID:24326174.
   PubMed Web of Science ®Google Scholar
• Werner N, Kosiol S, Schiegl T, Ahlers P, Walenta K, Link A, Bohm M, Nickenig G. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005;353:999–1007. doi:10.1056/NEJMoa043814. PMID:16148285.
   PubMed Web of Science ®Google Scholar
• Lee JS, Stebbins CL, Jung E, Nho H, Kim JK, Chang MJ, Choi HM. Effects of chronic dietary nitrate supplementation on the hemodynamic response to dynamic exercise. Am J Physiol Regul Integr Comp Physiol. 2015;309:R459–466. doi:10.1152/ajpregu.00099.2015. PMID:26084693.
   PubMed Web of Science ®Google Scholar
• Bailey SJ, Wilkerson DP, Dimenna FJ, Jones AM. Influence of repeated sprint training on pulmonary O2 uptake and muscle deoxygenation kinetics in humans. J Appl Physiol. 2009;106(1985):1875–87. doi:10.1152/japplphysiol.00144.2009. PMID:19342439.
   PubMedGoogle Scholar
• Lansley KE, Winyard PG, Fulford J, Vanhatalo A, Bailey SJ, Blackwell JR, DiMenna FJ, Gilchrist M, Benjamin N, Jones AM. Dietary nitrate supplementation reduces the O2 cost of walking and running: a placebo-controlled study. J Appl Physiol. 2011;110(1985):591–600. doi:10.1152/japplphysiol.01070.2010. PMID:21071588.
   PubMedGoogle Scholar
• Flanagan SD, Looney DP, Miller MJ, DuPont WH, Pryor L, Creighton BC, Sterczala AJ, Szivak TK, Hooper DR, Maresh CM, et al. The effects of nitrate-rich supplementation on neuromuscular efficiency during heavy resistance exercise. J Am Coll Nutr. 2016;35:100–7. doi:10.1080/07315724.2015.1081572. PMID:26885762.
   PubMed Web of Science ®Google Scholar
• Schewe T, Steffen Y, Sies H. How do dietary flavanols improve vascular function? A position paper. Arch Biochem Biophys. 2008;476:102–6. doi:10.1016/j.abb.2008.03.004. PMID:18358827.
   PubMed Web of Science ®Google Scholar
• Steffen Y, Schewe T, Sies H. (−)-Epicatechin elevates nitric oxide in endothelial cells via inhibition of NADPH oxidase. Biochem Biophys Res Commun. 2007;359:828–33. doi:10.1016/j.bbrc.2007.05.200. PMID:17560937.
   PubMed Web of Science ®Google Scholar
• Bondonno CP, Yang X, Croft KD, Considine MJ, Ward NC, Rich L, Puddey IB, Swinny E, Mubarak A, Hodgson JM. Flavonoid-rich apples and nitrate-rich spinach augment nitric oxide status and improve endothelial function in healthy men and women: a randomized controlled trial. Free Radic Biol Med. 2012;52:95–102. doi:10.1016/j.freeradbiomed.2011.09.028. PMID:22019438.
   PubMed Web of Science ®Google Scholar
• Rodriguez-Mateos A, Hezel M, Aydin H, Kelm M, Lundberg JO, Weitzberg E, Spencer JP, Heiss C. Interactions between cocoa flavanols and inorganic nitrate: additive effects on endothelial function at achievable dietary amounts. Free Radic Biol Med. 2015;80:121–8. doi:10.1016/j.freeradbiomed.2014.12.009. PMID:25530151.
   PubMed Web of Science ®Google Scholar
• Hord NG, Tang Y, Bryan NS. Food sources of nitrates and nitrites: the physiologic context for potential health benefits. Am J Clin Nutr. 2009;90:1–10. doi:10.3945/ajcn.2008.27131. PMID:19439460.
   PubMed Web of Science ®Google Scholar
• Murase T, Haramizu S, Shimotoyodome A, Nagasawa A, Tokimitsu I. Green tea extract improves endurance capacity and increases muscle lipid oxidation in mice. Am J Physiol Regul Integr Comp Physiol. 2005;288:R708–715. doi:10.1152/ajpregu.00693.2004. PMID:15563575.
   PubMed Web of Science ®Google Scholar
• Sae-Tan S, Grove KA, Kennett MJ, Lambert JD. (−)-Epigallocatechin-3-gallate increases the expression of genes related to fat oxidation in the skeletal muscle of high fat-fed mice. Food Funct. 2011;2:111–6. doi:10.1039/c0fo00155d. PMID:21779555.
   PubMed Web of Science ®Google Scholar
• Dulloo AG, Duret C, Rohrer D, Girardier L, Mensi N, Fathi M, Chantre P, Vandermander J. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr. 1999;70:1040–5. doi:10.1093/ajcn/70.6.1040. PMID:10584049.
   PubMed Web of Science ®Google Scholar
• Venables MC, Hulston CJ, Cox HR, Jeukendrup AE. Green tea extract ingestion, fat oxidation, and glucose tolerance in healthy humans. Am J Clin Nutr. 2008;87:778–84. doi:10.1093/ajcn/87.3.778. PMID:18326618.
   PubMed Web of Science ®Google Scholar
• Richards JC, Lonac MC, Johnson TK, Schweder MM, Bell C. Epigallocatechin-3-gallate increases maximal oxygen uptake in adult humans. Med Sci Sports Exerc. 2010;42:739–44. doi:10.1249/MSS.0b013e3181bcab6c. PMID:19952844.
   PubMed Web of Science ®Google Scholar
• Dean S, Braakhuis A, Paton C. The effects of EGCG on fat oxidation and endurance performance in male cyclists. Int J Sport Nutr Exerc Metab. 2009;19:624–44. doi:10.1123/ijsnem.19.6.624. PMID:20175431.
   PubMed Web of Science ®Google Scholar
• Eichenberger P, Colombani PC, Mettler S. Effects of 3-week consumption of green tea extracts on whole-body metabolism during cycling exercise in endurance-trained men. Int J Vitam Nutr Res. 2009;79:24–33. doi:10.1024/0300-9831.79.1.24. PMID:19839000.
   PubMed Web of Science ®Google Scholar
• Turkozu D, Tek NA. A minireview of effects of green tea on energy expenditure. Crit Rev Food Sci Nutr. 2017;57:254–8. doi:10.1080/10408398.2014.986672. PMID:26091183.
   PubMed Web of Science ®Google Scholar
• Zhu BT, Shim JY, Nagai M, Bai HW. Molecular modelling study of the mechanism of high-potency inhibition of human catechol-O-methyltransferase by (−)-epigallocatechin-3-O-gallate. Xenobiotica. 2008;38:130–46. doi:10.1080/00498250701744641. PMID:18197555.
   PubMed Web of Science ®Google Scholar
• Murase T, Haramizu S, Shimotoyodome A, Tokimitsu I, Hase T. Green tea extract improves running endurance in mice by stimulating lipid utilization during exercise. Am J Physiol Regul Integr Comp Physiol. 2006;290:R1550–6. doi:10.1152/ajpregu.00752.2005. PMID:16410398.
   PubMed Web of Science ®Google Scholar
• Cameron-Smith D, Burke LM, Angus DJ, Tunstall RJ, Cox GR, Bonen A, Hawley JA, Hargreaves M. A short-term, high-fat diet up-regulates lipid metabolism and gene expression in human skeletal muscle. Am J Clin Nutr. 2003;77:313–8. doi:10.1093/ajcn/77.2.313. PMID:12540388.
   PubMed Web of Science ®Google Scholar
• Berry NM, Davison K, Coates AM, Buckley JD, Howe PR. Impact of cocoa flavanol consumption on blood pressure responsiveness to exercise. Br J Nutr. 2010;103:1480–4. doi:10.1017/S0007114509993382. PMID:20082737.
   PubMed Web of Science ®Google Scholar
• Allgrove J, Farrell E, Gleeson M, Williamson G, Cooper K. Regular dark chocolate consumption's reduction of oxidative stress and increase of free-fatty-acid mobilization in response to prolonged cycling. Int J Sport Nutr Exerc Metab. 2011;21:113–23. doi:10.1123/ijsnem.21.2.113. PMID:21558573.
   PubMed Web of Science ®Google Scholar
• Patel RK, Brouner J, Spendiff O. Dark chocolate supplementation reduces the oxygen cost of moderate intensity cycling. J Int Soc Sports Nutr. 2015;12:47. doi:10.1186/s12970-015-0106-7. PMID:26674253.
   PubMed Web of Science ®Google Scholar
• Affourtit C, Bailey SJ, Jones AM, Smallwood MJ, Winyard PG. On the mechanism by which dietary nitrate improves human skeletal muscle function. Front Physiol. 2015;6:211. doi:10.3389/fphys.2015.00211. PMID:26283970.
   PubMed Web of Science ®Google Scholar
• Bailey SJ, Fulford J, Vanhatalo A, Winyard PG, Blackwell JR, DiMenna FJ, Wilkerson DP, Benjamin N, Jones AM. Dietary nitrate supplementation enhances muscle contractile efficiency during knee-extensor exercise in humans. J Appl Physiol. 2010;109(1985):135–48. doi:10.1152/japplphysiol.00046.2010. PMID:20466802.
   PubMedGoogle Scholar
• Haramizu S, Ota N, Hase T, Murase T. Catechins attenuate eccentric exercise-induced inflammation and loss of force production in muscle in senescence-accelerated mice. J Appl Physiol. 2011;111(1985):1654–63. doi:10.1152/japplphysiol.01434.2010. PMID:21903878.
   PubMedGoogle Scholar
• McBrier NM, Vairo GL, Bagshaw D, Lekan JM, Bordi PL, Kris-Etherton PM. Cocoa-based protein and carbohydrate drink decreases perceived soreness after exhaustive aerobic exercise: a pragmatic preliminary analysis. J Strength Cond Res. 2010;24:2203–10. doi:10.1519/JSC.0b013e3181e4f7f9. PMID:20634742.
   PubMed Web of Science ®Google Scholar
• Jowko E, Sacharuk J, Balasinska B, Wilczak J, Charmas M, Ostaszewski P, Charmas R. Effect of a single dose of green tea polyphenols on the blood markers of exercise-induced oxidative stress in soccer players. Int J Sport Nutr Exerc Metab. 2012;22:486–96. doi:10.1123/ijsnem.22.6.486. PMID:22805286.
   PubMed Web of Science ®Google Scholar
• Peschek K, Pritchett R, Bergman E, Pritchett K. The effects of acute post exercise consumption of two cocoa-based beverages with varying flavanol content on indices of muscle recovery following downhill treadmill running. Nutrients. 2014;6:50–62. doi:10.3390/nu6010050.
   Web of Science ®Google Scholar
• Lee JB, Shin YO, Min YK, Yang HM. The effect of Oligonol intake on cortisol and related cytokines in healthy young men. Nutr Res Pract. 2010;4:203–7. doi:10.4162/nrp.2010.4.3.203. PMID:20607065.
   PubMed Web of Science ®Google Scholar
• Nishizawa M, Hara T, Miura T, Fujita S, Yoshigai E, Ue H, Hayashi Y, Kwon AH, Okumura T, Isaka T. Supplementation with a flavanol-rich lychee fruit extract influences the inflammatory status of young athletes. Phytother Res. 2011;25:1486–93. doi:10.1002/ptr.3430. PMID:21780209.
   PubMed Web of Science ®Google Scholar
• Pedersen BK, Akerstrom TC, Nielsen AR, Fischer CP. Role of myokines in exercise and metabolism. J Appl Physiol. 2007;103(1985):1093–8. doi:10.1152/japplphysiol.00080.2007. PMID:17347387.
   PubMedGoogle Scholar
• Powers SK, Duarte J, Kavazis AN, Talbert EE. Reactive oxygen species are signalling molecules for skeletal muscle adaptation. Exp Physiol. 2010;95:1–9. doi:10.1113/expphysiol.2009.050526. PMID:19880534.
   PubMed Web of Science ®Google Scholar
• Kang SW, Hahn S, Kim JK, Yang SM, Park BJ, Chul Lee S. Oligomerized lychee fruit extract (OLFE) and a mixture of vitamin C and vitamin E for endurance capacity in a double blind randomized controlled trial. J Clin Biochem Nutr. 2012;50:106–13. doi:10.3164/jcbn.11-46. PMID:22448090.
   PubMed Web of Science ®Google Scholar
• Jones AM. Dietary nitrate supplementation and exercise performance. Sports Med. 2014;44(Suppl 1):S35–45. doi:10.1007/s40279-014-0149-y. PMID:24791915.
   PubMed Web of Science ®Google Scholar
• Wilkerson DP, Hayward GM, Bailey SJ, Vanhatalo A, Blackwell JR, Jones AM. Influence of acute dietary nitrate supplementation on 50 mile time trial performance in well-trained cyclists. Eur J Appl Physiol. 2012;112:4127–34. doi:10.1007/s00421-012-2397-6. PMID:22526247.
   PubMed Web of Science ®Google Scholar
• Trewin CB, Hopkins WG, Pyne DB. Relationship between world-ranking and Olympic performance of swimmers. J Sports Sci. 2004;22:339–45. doi:10.1080/02640410310001641610. PMID:15161107.
   PubMed Web of Science ®Google Scholar
• Mladenka P, Zatloukalova L, Filipsky T, Hrdina R. Cardiovascular effects of flavonoids are not caused only by direct antioxidant activity. Free Radic Biol Med. 2010;49:963–75. doi:10.1016/j.freeradbiomed.2010.06.010. PMID:20542108.
   PubMed Web of Science ®Google Scholar
• Sies H. Polyphenols and health: update and perspectives. Arch Biochem Biophys. 2010;501:2–5. doi:10.1016/j.abb.2010.04.006. PMID:20398620.
   PubMed Web of Science ®Google Scholar
• Heiss C, Finis D, Kleinbongard P, Hoffmann A, Rassaf T, Kelm M, Sies H. Sustained increase in flow-mediated dilation after daily intake of high-flavanol cocoa drink over 1 week. J Cardiovasc Pharmacol. 2007;49:74–80. doi:10.1097/FJC.0b013e31802d0001. PMID:17312446.
   PubMed Web of Science ®Google Scholar
• Steffen Y, Jung T, Klotz LO, Schewe T, Grune T, Sies H. Protein modification elicited by oxidized low-density lipoprotein (LDL) in endothelial cells: protection by (−)-epicatechin. Free Radic Biol Med. 2007;42: 955–70. doi:10.1016/j.freeradbiomed.2006.12.024. PMID:17349924.
   PubMed Web of Science ®Google Scholar
• Francis SH, Sekhar KR, Ke H, Corbin JD. Inhibition of cyclic nucleotide phosphodiesterases by methylxanthines and related compounds. Handb Exp Pharmacol. 2011;93–133.
   PubMedGoogle Scholar
• Chen JF, Chern Y. Impacts of methylxanthines and adenosine receptors on neurodegeneration: human and experimental studies. Handb Exp Pharmacol. 2011;267–310.
   PubMedGoogle Scholar
• Cifuentes-Gomez T, Rodriguez-Mateos A, Gonzalez-Salvador I, Alanon ME, Spencer JP. Factors affecting the absorption, metabolism, and excretion of cocoa flavanols in humans. J Agric Food Chem. 2015;63:7615–23. doi:10.1021/acs.jafc.5b00443. PMID:25711140.
   PubMed Web of Science ®Google Scholar
• Milenkovic D, Morand C, Cassidy A, Konic-Ristic A, Tomas-Barberan F, Ordovas JM, Kroon P, De Caterina R, Rodriguez-Mateos A. Interindividual variability in biomarkers of cardiometabolic health after consumption of major plant-food bioactive compounds and the determinants involved. Adv Nutr. 2017;8:558–70. PMID:28710143.
   PubMed Web of Science ®Google Scholar
• Schisterman EF, Mumford SL, Sjaarda LA. Failure to consider the menstrual cycle phase may cause misinterpretation of clinical and research findings of cardiometabolic biomarkers in premenopausal women. Epidemiol Rev. 2014;36:71–82. doi:10.1093/epirev/mxt007. PMID:24042431.
   PubMed Web of Science ®Google Scholar
• Sorkin BC, Kuszak AJ, Williamson JS, Hopp DC, Betz JM. The challenge of reproducibility and accuracy in nutrition research: resources and pitfalls. Adv Nutr. 2016;7:383–9. doi:10.3945/an.115.010595. PMID:26980822.
   PubMed Web of Science ®Google Scholar
• Ross JA, Kasum CM. Dietary flavonoids: bioavailability, metabolic effects, and safety. Annu Rev Nutr. 2002;22:19–34. doi:10.1146/annurev.nutr.22.111401.144957. PMID:12055336.
   PubMed Web of Science ®Google Scholar
• Mazzanti G, Menniti-Ippolito F, Moro PA, Cassetti F, Raschetti R, Santuccio C, Mastrangelo S. Hepatotoxicity from green tea: a review of the literature and two unpublished cases. Eur J Clin Pharmacol. 2009;65:331–41. doi:10.1007/s00228-008-0610-7. PMID:19198822.
   PubMed Web of Science ®Google Scholar
• Teschke R, Wolff A, Frenzel C, Schulze J, Eickhoff A. Herbal hepatotoxicity: a tabular compilation of reported cases. Liver Int. 2012;32:1543–56. doi:10.1111/j.1478-3231.2012.02864.x. PMID:22928722.
   PubMed Web of Science ®Google Scholar
• Vogiatzoglou A, Mulligan AA, Luben RN, Lentjes MA, Heiss C, Kelm M, Merx MW, Spencer JP, Schroeter H, Kuhnle GG. Assessment of the dietary intake of total flavan-3-ols, monomeric flavan-3-ols, proanthocyanidins and theaflavins in the European Union. Br J Nutr. 2014;111:1463–73. doi:10.1017/S0007114513003930. PMID:24331295.
   PubMed Web of Science ®Google Scholar
• Ottaviani JI, Balz M, Kimball J, Ensunsa JL, Fong R, Momma TY, Kwik-Uribe C, Schroeter H, Keen CL. Safety and efficacy of cocoa flavanol intake in healthy adults: a randomized, controlled, double-masked trial. Am J Clin Nutr. 2015;102:1425–35. doi:10.3945/ajcn.115.116178. PMID:26537937.
   PubMed Web of Science ®Google Scholar
• Lin X, Zhang I, Li A, Manson JE, Sesso HD, Wang L, Liu S. Cocoa flavanol intake and biomarkers for cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials. J Nutr. 2016;146:2325–33. doi:10.3945/jn.116.237644. PMID:27683874.
   PubMed Web of Science ®Google Scholar
• Djurica D, Holt RR, Ren J, Shindel AW, Hackman RM, Keen CL. Effects of a dietary strawberry powder on parameters of vascular health in adolescent males. Br J Nutr. 2016;116:639–47. doi:10.1017/S0007114516002348. PMID:27464461.
   PubMed Web of Science ®Google Scholar
• Clark AL, Poole-Wilson PA, Coats AJ. Exercise limitation in chronic heart failure: central role of the periphery. J Am Coll Cardiol. 1996;28:1092–102. doi:10.1016/S0735-1097(96)00323-3. PMID:8890800.
   PubMed Web of Science ®Google Scholar
• Egashira K, Suzuki S, Hirooka Y, Kai H, Sugimachi M, Imaizumi T, Takeshita A. Impaired endothelium-dependent vasodilation of large epicardial and resistance coronary arteries in patients with essential hypertension. Different responses to acetylcholine and substance P. Hypertension. 1995;5:201–6.
   Google Scholar
• Mittleman MA, Maclure M, Tofler GH, Sherwood JB, Goldberg RJ, Muller JE. Triggering of acute myocardial infarction by heavy physical exertion. Protection against triggering by regular exertion. Determinants of myocardial infarction onset study investigators. N Engl J Med. 1993;329:1677–83. doi:10.1056/NEJM199312023292301. PMID:8232456.
   PubMed Web of Science ®Google Scholar