Effect of Cocoa and Its Flavonoids on Biomarkers of Inflammation: Studies of Cell Culture, Animals and Humans

Luis Goya, María Ángeles Martín, Beatriz Sarriá, Sonia Ramos, Raquel Mateos, Laura Bravo, Luis Goya, María Ángeles Martín, Beatriz Sarriá, Sonia Ramos, Raquel Mateos, Laura Bravo

Abstract

Chronic inflammation has been identified as a necessary step to mediate atherosclerosis and cardiovascular disease and as a relevant stage in the onset and progression of several types of cancer. Considerable attention has recently been focused on the identification of dietary bioactive compounds with anti-inflammatory activities as an alternative natural source for prevention of inflammation-associated diseases. The remarkable capacity of cocoa flavanols as antioxidants, as well as to modulate signaling pathways involved in cellular processes, such as inflammation, metabolism and proliferation, has encouraged research on this type of polyphenols as useful bioactive compounds for nutritional prevention of cardiovascular disease and cancer. Data from numerous studies suggest that cocoa and cocoa-derived flavanols can effectively modify the inflammatory process, and thus potentially provide a benefit to individuals with elevated risk factors for atherosclerosis/cardiovascular pathology and cancer. The present overview will focus on the most recent findings about the effects of cocoa, its main constituents and cocoa derivatives on selected biomarkers of the inflammatory process in cell culture, animal models and human cohorts.

Keywords: anti-inflammatory flavonoids; anti-inflammatory-polyphenols; cardiovascular disease; chocolate; colon cancer; colon inflammation; flavanols.

References

    1. Ricordi C., García-Contreras M., Farnetti S. Diet and inflammation: Possible effects on immunity, chronic diseases, and life span. J. Am. Coll. Nutr. 2015;34(Suppl. S1):10–13. doi: 10.1080/07315724.2015.1080101.
    1. Khan N., Khymenets O., Urpí-Sardá M., Tulipani S., Garcia-Aloy M., Monagas M., Mora-Cubillos X., Llorach R., Andrés-Lacueva C. Cocoa polyphenols and inflammatory markers of cardiovascular disease. Nutrients. 2014;6:844–880. doi: 10.3390/nu6020844.
    1. Osiecki H. The role of chronic inflammation in cardiovascular disease and its regulation by nutrients. Alter. Med. Rev. 2004;9:32–53.
    1. Packard R.R., Libby P. Inflammation in atherosclerosis: From vascular biology to biomarker discovery and risk prediction. Clin. Chem. 2008;54:24–38. doi: 10.1373/clinchem.2007.097360.
    1. Willerson J.T., Ridker P.M. Inflammation as a cardiovascular risk factor. Circulation. 2004;109:II2–II10. doi: 10.1161/01.CIR.0000129535.04194.38.
    1. Hansson G.K. Inflammatory mechanisms in atherosclerosis. J. Thromb. Haemost. 2009;7:328–331. doi: 10.1111/j.1538-7836.2009.03416.x.
    1. Maeda S., Omata M. Inflammation and cancer: Role of nuclear factor-kappaB activation. Cancer Sci. 2008;99:836–842. doi: 10.1111/j.1349-7006.2008.00763.x.
    1. Kashfi K. Anti-inflammatory agents as cancer therapeutics. Adv. Pharmacol. 2009;57:31–89.
    1. Grivennikov S.I., Greten F.R., Karin M. Immunity, inflammation, and cancer. Cell. 2010;140:883–899. doi: 10.1016/j.cell.2010.01.025.
    1. Grivennikov S.I., Karin M. Inflammatory cytokines in cancer: Tumour necrosis factor and interleukin 6 take the stage. Ann. Rheum. Dis. 2011;70(Suppl. S1):104–108. doi: 10.1136/ard.2010.140145.
    1. Gosslau A., Li S., Ho C.-T., Chen K.Y., Rawson N.E. The importance of natural product characterization in studies of their anti-inflammatory activity. Mol. Nutr. Food Res. 2011;55:74–82. doi: 10.1002/mnfr.201000455.
    1. Cooper K.A., Donovan J.L., Waterhouse A.L., Williamson G. Cocoa and health: A decade of research. Br. J. Nutr. 2008;99:1–11. doi: 10.1017/S0007114507795296.
    1. Pan M.-H., Lai C.-S., Wu J.-C., Ho C.T. Molecular mechanisms for chemoprevention of colorectal cancer by natural dietary compounds. Mol. Nutr. Food Res. 2011;55:32–45.
    1. Lee K.W., Kim Y.J., Lee H.J., Lee C.Y. Cocoa has more phenolic phytochemicals and a higher antioxidant capacity than teas and red wine. J. Agric. Food Chem. 2003;51:7292–7295. doi: 10.1021/jf0344385.
    1. Rusconi M., Conti A. Theobroma cacao L., the food of the gods: A scientific approach beyond myths and claims. Pharmacol. Res. 2010;61:5–13. doi: 10.1016/j.phrs.2009.08.008.
    1. Vinson J.A., Proch J., Zubik L. Phenol antioxidant quantity and quality in foods: Cocoa, dark chocolate, and milk chocolate. J. Agric. Food Chem. 2009;47:4821–4824. doi: 10.1021/jf990312p.
    1. Halvorsen B.L., Carlsen M.H., Phillips K.M., Bohn S.K., Holte K., Jacobs D.R.J., Blomhoff R. Content of redox-active compounds (i.e., antioxidants) in foods consumed in the United States. Am. J. Clin. Nutr. 2006;84:95–135.
    1. Sánchez-Rabaneda F., Jáuregui O., Casals I., Andrés-Lacueva C., Izquierdo-Pulido M., Lamuela-Raventós R.M. Liquid chromatographic/electrospray ionization tandem mass spectrometric study of the phenolic composition of cocoa (Theobroma cacao) J. Mass Spectrom. 2003;38:35–42. doi: 10.1002/jms.395.
    1. Ramiro-Puig E., Castell M. Cocoa: Antioxidant and immunomodulator. Br. J. Nutr. 2009;101:931–940. doi: 10.1017/S0007114508169896.
    1. Arts C., Holmann P., Bueno de Mesquita H., Feskens E., Kromhout D. Dietary catechins and epithelial cancer incidence: The Zutphen elderly study. Int. J. Cancer. 2001;92:298–302. doi: 10.1002/1097-0215(200102)9999:9999<::AID-IJC1187>;2-8.
    1. Tabernero M., Serrano J., Saura-Calixto F. The antioxidant capacity of cocoa products: Contribution to the Spanish diet. Int. J. Food Sci. Tech. 2006;41:28–32. doi: 10.1111/j.1365-2621.2006.01239.x.
    1. Gu L., Kelm M.A., Hammerstone J.F., Beecher G., Holden J., Haytowitz D., Gebhardt S., Prior R.L. Concentrations of proanthocyanidins in common foods and estimations of normal consumption. J. Nutr. 2004;134:613–617.
    1. Manach C., Williamson G., Morand C., Scalbert A., Rémésy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. Am. J. Clin. Nutr. 2005;81:230S–242S.
    1. Lamuela-Raventós R.M., Romero-Pérez A.I., Andrés-Lacueva C., Tornero A. Health effects of cocoa flavonoids. Food Sci. Tech. Int. 2005;11:159–176. doi: 10.1177/1082013205054498.
    1. Urpí-Sardá M., Monagas M., Khan N., Lamuela-Raventós R.M., Santos-Buelga C., Sacanella E., Castell M., Permanyer J., Andrés-Lacueva C. Epicatechin, procyanidins, and phenolic microbial metabolites after cocoa intake in humans and rats. Anal. Bioanal. Chem. 2009;394:1545–1556. doi: 10.1007/s00216-009-2676-1.
    1. Baba S., Osakabe N., Yasuda A., Natsume M., Takizawa T., Nakamura T., Terao J. Bioavailability of (2)-epicatechin upon intake of chocolate and cocoa in human volunteers. Free Radic. Res. 2000;33:635–641. doi: 10.1080/10715760000301151.
    1. Holt R.R., Lazarus S.A., Sullards M.C., Zhu Q.Y., Schramm D.D., Hammerstone J.F., Fraga C.G., Schmitz H.H., Keen C.L. Procyanidin dimer B2 [epicatechin-(4b-8)-epicatechin] in human plasma after the consumption of a flavanol-rich cocoa. Am. J. Clin. Nutr. 2002;76:798–804.
    1. Roura E., Andrés-Lacueva C., Jauregui O., Badía E., Estruch R., Izquierdo-Pulido M., Lamuela-Raventós R.M. Rapid liquid chromatography tandem mass spectrometry assay to quantify plasma (2)-epicatechin metabolites after ingestion of a standard portion of cocoa beverage in humans. J. Agric. Food Chem. 2005;53:6190–6194. doi: 10.1021/jf050377u.
    1. Tsang C., Auger C., Mullen W., Bornet A., Rouanet J.M., Crozier A., Teissedre P.L. The absorption, metabolism and excretion of flavan-3-ols and procyanidins following the ingestion of a grape seed extract by rats. Br. J. Nutr. 2005;94:170–181. doi: 10.1079/BJN20051480.
    1. Urpí-Sardá M., Ramiro-Puig E., Khan N., Ramos-Romero S., Llorach R., Castell M., González-Manzano S., Santos-Buelga C., Andrés-Lacueva C. Distribution of epicatechin metabolites in lymphoid tissues and testes of young rats with a cocoa-enriched diet. Br. J. Nutr. 2010;103:1393–1397. doi: 10.1017/S0007114509993473.
    1. Serra A., Macia A., Romero M.P., Valls J., Bladé C., Arola L., Motilva M.J. Bioavailability of procyanidin dimers and trimers and matrix food effects in in vitro and in vivo models. Br. J. Nutr. 2010;103:944–952. doi: 10.1017/S0007114509992741.
    1. Rodríguez-Ramiro I., Ramos S., López-Oliva E., Agís-Torres A., Gómez-Juaristi M., Mateos R., Bravo L., Goya L., Martín M.A. Cocoa-rich diet prevents azoxymethane-induced colonic preneoplastic lesions in rats by restraining oxidative stress and cell proliferation and inducing apoptosis. Mol. Nutr. Food Res. 2011;55:1895–1899. doi: 10.1002/mnfr.201100363.
    1. Monagas M., Urpí-Sardá M., Sánchez-Patán F., Llorach R., Garrido I., Gómez-Cordovés C., Andrés-Lacueva C., Bartolomé B. Insights into the metabolism and microbial biotransformation of dietary flavan-3-ols and the bioactivity of their metabolites. Food Funct. 2010;1:233–253. doi: 10.1039/c0fo00132e.
    1. Fernández-Millán E., Ramos S., Álvarez C., Bravo L., Goya L., Martín M.A. Microbial phenolic metabolites improve glucose-stimulated insulin secretion and protect pancreatic beta cells against oxidative stress via ERKs and PKC pathways. Food Chem. Toxicol. 2014;66:245–253. doi: 10.1016/j.fct.2014.01.044.
    1. Selmi C., Cocchi C.A., Lanfredini M., Keen C.L., Gershwin M.E. Chocolate at heart: The anti-inflammatory impact of cocoa flavanols. Mol. Nutr. Food Res. 2008;52:1340–1348. doi: 10.1002/mnfr.200700435.
    1. Martín M.A., Goya L., Ramos R. Potential for preventive effects of cocoa and cocoa polyphenols in cancer. Food Chem. Toxicol. 2013;56:336–351. doi: 10.1016/j.fct.2013.02.020.
    1. Martín M.A., Goya L., Ramos S. Preventive effects of cocoa and cocoa antioxidants in colon cancer. Diseases. 2016;4 doi: 10.3390/diseases4010006.
    1. Uhlenhut K., Högger P. Facilitated cellular uptake and suppression of inducible nitric oxide synthase by a metabolite of maritime pine bark extract (Pycnogenol) Free Radic. Biol. Med. 2012;53:305–313. doi: 10.1016/j.freeradbiomed.2012.04.013.
    1. Ramos S. Cancer chemoprevention and chemotherapy: Dietary polyphenols and signaling pathways. Mol. Nutr. Food Res. 2008;52:507–526. doi: 10.1002/mnfr.200700326.
    1. Sies H., Schewe T., Heiss C., Kelm M. Cocoa polyphenols and inflammatory mediators. Am. J. Clin. Nutr. 2005;81:3045–3125.
    1. Erlejman A.G., Jaggers G., Fraga C.G., Oteiza P.I. TNF-α-induced NF-κB activation and cell oxidant production are modulated by hexameric procyanidins in Caco-2 cells. Arch. Biochem. Biophys. 2008;476:186–195. doi: 10.1016/j.abb.2008.01.024.
    1. Bitzer Z.T., Glisan S.L., Dorenkott M.R., Goodrich K.M., Ye L., O’Keefe S.F., Lambert J.D., Neilson A.P. Cocoa procyanidins with different degrees of polymerization possess distinct activities in models of colonic inflammation. J. Nutr. Biochem. 2015;26:827–831. doi: 10.1016/j.jnutbio.2015.02.007.
    1. Romier-Crouzet B., Van De Walle J., During A., Joly A., Rousseau C., Henry O., Larondelle Y., Schneider Y.J. Inhibition of inflammatory mediators by polyphenolic plant extracts in human intestinal Caco-2 cells. Food Chem. Toxicol. 2009;47:1221–1230. doi: 10.1016/j.fct.2009.02.015.
    1. Rodríguez-Ramiro I., Ramos S., López-Oliva E., Agís-Torres A., Bravo L., Goya L., Martín M.A. Cocoa polyphenols prevent inflammation in the colon of 2 azoxymethane-treated rats and in TNF-α-stimulated Caco-2 cells. Br. J. Nutr. 2013;110:206–215. doi: 10.1017/S0007114512004862.
    1. Kim J.E., Son J.E., Jung S.K., Kang N.J., Lee C.Y., Lee K.W., Lee H.J. Cocoa polyphenols suppress TNF-α-induced vascular endothelial growth factor expression by inhibiting phosphoinositide 3-kinase (PI3K) and mitogen activated protein kinase kinase-1 (MEK1) activities in mouse epidermal cells. Br. J. Nutr. 2010;104:957–964. doi: 10.1017/S0007114510001704.
    1. Guruvayoorappan C., Kuttan G. (+)-Catechin inhibits tumour angiogenesis and regulates the production of nitric oxide and TNF-α in LPS-stimulated macrophages. Innate Immun. 2008;14:160–174. doi: 10.1177/1753425908093295.
    1. Schroeder P., Klotz L.O., Buchczyk D.P., Sadik C.D., Schewe T., Sies H. Epicatechin selectively prevents nitration but not oxidation reactions of peroxynitrite. Biochem. Biophys. Res. Comm. 2001;285:782–787. doi: 10.1006/bbrc.2001.5210.
    1. Andújar M.I., Recio C., Giner R.M., Cienfuegos-Jovellanos E., Laghi S., Muguerza B., Ríos J.L. Inhibition of ulcerative colitis in mice after oral administration of a polyphenol-enriched cocoa extract is mediated by the inhibition of STAT1 and STAT3 phosphorylation in colon cells. J. Agric. Food Chem. 2011;59:6474–6483. doi: 10.1021/jf2008925.
    1. Nicod N., Chiva-Blanch G., Giordano E., Dávalos A., Parker R.S., Visioli F. Green tea, cocoa, and red wine polyphenols moderately modulate intestinal inflammation and do not increase high-density lipoprotein (HDL) production. J. Agric. Food Chem. 2014;62:2228–2232. doi: 10.1021/jf500348u.
    1. Granado-Serrano A.B., Martín M.A., Haegeman G., Goya L., Bravo L. Epicatechin induces NF-κB, activator protein-1 (AP-1) and nuclear transcription factor erythroid 2p45-related factor-2 (Nrf2) via phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) and extracellular regulated kinase (ERK) signalling in HepG2 cells. Br. J. Nutr. 2010;103:168–179. doi: 10.1017/S0007114509991747.
    1. Rodríguez-Ramiro I., Martín M.A., Ramos S., Bravo L., Goya L. Comparative effects of dietary flavanols on antioxidant defences and their response to oxidant-induced stress on Caco2 cells. Eur. J. Nutr. 2011;50:313–322. doi: 10.1007/s00394-010-0139-2.
    1. Ruijters E.J.B., Haenen G.R.M.M., Weseler A.R., Bast A. The cocoa flavanol (−)-epicatechin protects the cortisol response. Pharmacol. Res. 2014;79:28–33. doi: 10.1016/j.phrs.2013.11.004.
    1. Tarka S.M., Morrissey R.B., Apgar J.L., Hostetler K.A., Shively C.A. Chronic toxicity/carcinogenicity studies of cocoa powder in rats. Food Chem. Toxicol. 1991;29:7–19. doi: 10.1016/0278-6915(91)90057-E.
    1. Pérez-Berezo T., Ramírez-Santana C., Franch A., Ramos-Romero S., Castellote C., Pérez-Cano F.J., Castell M. Effects of a cocoa diet on an intestinal inflammation model in rats. Exp. Biol. Med. 2012;237:1181–1188. doi: 10.1258/ebm.2012.012083.
    1. Ramos-Romero S., Pérez-Cano F.J., Pérez-Berezo T., Castellote C., Franch A., Castell M. Effect of a cocoa flavonoid-enriched diet on experimental autoimmune arthritis. Br. J. Nutr. 2012;107:523–532. doi: 10.1017/S000711451100328X.
    1. Gu Y., Yu S., Lambert J.D. Dietary cocoa ameliorates obesity-related inflammation in high fat-fed mice. Eur. J. Nutr. 2014;53:149–158. doi: 10.1007/s00394-013-0510-1.
    1. Gu Y., Yu S., Park J.Y., Harvatine K., Lambert J.D. Dietary cocoa reduces metabolic endotoxemia and adipose tissue inflammation in high-fat fed mice. J. Nutr. Biochem. 2014;25:439–445. doi: 10.1016/j.jnutbio.2013.12.004.
    1. Fidaleo M., Fracassi A., Zuorro A., Lavecchia R., Morenoc S., Sartoria C. Cocoa protective effects against abnormal fat storage and oxidative stress induced by a high-fat diet involve PPARα signalling activation. Food Funct. 2014;5:2931–2939. doi: 10.1039/C4FO00616J.
    1. Osakabe N., Hoshi J., Kudo N., Shibata M. The flavan-3-ol fraction of cocoa powder suppressed changes associated with early-stage metabolic syndrome in high-fat diet-fed rats. Life Sci. 2014;114:51–56. doi: 10.1016/j.lfs.2014.07.041.
    1. Zempo H., Suzuki J.I., Watanabe R., Wakayama K., Kumagai H., Ikeda Y., Akazawa H., Komuro I., Isobe M. Cacao polyphenols ameliorate autoimmune myocarditis in mice. Hypertens. Res. 2016;39:203–209. doi: 10.1038/hr.2015.136.
    1. Quiñones M., Margalef M., Arola-Arnal A., Muguerza B., Miguel M., Aleixandre A. The blood pressure effect and related plasma levels of flavan-3-ols in spontaneously hypertensive rats. Food Funct. 2015;6:3479–3489. doi: 10.1039/C5FO00547G.
    1. Yakala G.K., Wielinga P.Y., Suárez M., Bunschoten A., Van Golde J.M., Arola L., Keijer J., Kleemann R., Kooistra T., Heeringa P. Effects of chocolate supplementation on metabolic and cardiovascular parameters in ApoE3L mice fed a high-cholesterol atherogenic diet. Mol. Nutr. Food Res. 2013;57:2039–2048. doi: 10.1002/mnfr.201200858.
    1. Pérez-Cano F.J., Massot-Cladera M., Franch A., Castellote C., Castell M. The effects of cocoa on the immune system. Front. Pharmacol. 2013;4:1–12. doi: 10.3389/fphar.2013.00071.
    1. Pandurangan A.K., Saadatdoust Z., Esa N.M., Hamzah H., Ismail A. Dietary cocoa protects against colitis-associated cancer by activating the Nrf2/Keap1 pathway. Biofactors. 2015;41:1–14. doi: 10.1002/biof.1195.
    1. Saadatdoust Z., Pandurangan A.K., Sadagopan S.K.A., Esa N.M., Ismail A., Mustafa M.R. Dietary cocoa inhibits colitis associated cancer: A crucial involvement of the IL-6/STAT3 pathway. J. Nutr. Biochem. 2015;26:1547–1558. doi: 10.1016/j.jnutbio.2015.07.024.
    1. Weyant M.J., Carothers A.M., Dannenberg A.J., Bertagnoll M.M. (+)-Catechin inhibits intestinal tumor formation and suppresses focal adhesion kinase activation in the Min/1 mouse. Cancer Res. 2001;61:118–125.
    1. Mahmoud N.N., Kucherlapati R., Bilinski R.T., Churchill M.R., Chadburn A., Bertagnolli M.M. Genotype-phenotype correlation in murine Apc mutation: Differences in enterocyte migration and response to sulindac. Cancer Res. 1999;59:353–359.
    1. Pritchard C.C., Grady W.M. Colorectal cancer molecular biology moves into clinical practice. Gut. 2011;60:116–129. doi: 10.1136/gut.2009.206250.
    1. Hong M.Y., Nulton E., Shelechi M., Hernández L.M., Nemoseck T. Effects of dark chocolate on azoxymethane-induced colonic aberrant crypt foci. Nutr. Cancer. 2013;65:677–685. doi: 10.1080/01635581.2013.789542.
    1. Milner J.A. Diet and cancer: Facts and controversies. Nutr. Cancer. 2006;56:216–224. doi: 10.1207/s15327914nc5602_13.
    1. Maskarinec G. Cancer protective properties of cocoa: A review of the epidemiologic evidence. Nutr. Cancer. 2009;61:573–579. doi: 10.1080/01635580902825662.
    1. Gasper A., Hollands W., Casgrain A., Saha S., Teucher B., Dainty J.R., Venema D.P., Hollman P.C., Rein M.J., 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.
    1. Sarriá B., Martínez-López S., Sierra-Cinos J.L., García-Diz L., Mateos R., Bravo L. Regular consumption of a cocoa product improves the cardiometabolic profile in healthy and moderately hypercholesterolaemic adults. Br. J. Nutr. 2014;111:122–134. doi: 10.1017/S000711451300202X.
    1. Lakoski S.G., Liu Y., Brosnihan K.B., Herrington D.M. Interleukin-10 concentration and coronary heart disease (CHD) event risk in the estrogen replacement and atherosclerosis (ERA) study. Atherosclerosis. 2008;197:443–447. doi: 10.1016/j.atherosclerosis.2007.06.033.
    1. Heiskanen M., Kahonen M., Hurme M., Lehtimäki T., Mononen N., Juonala M., Hutri-Kähönen N., Viikari J., Raitakari O., Hulkkonen J. Polymorphism in the IL10 promoter region and early markers of atherosclerosis: The Cardiovascular Risk in Young Finns Study. Atherosclerosis. 2010;208:190–196. doi: 10.1016/j.atherosclerosis.2009.06.032.
    1. Martínez-López S., Sarriá B., Sierra-Cinos J.L., Goya L., Mateos R., Bravo L. Realistic intake of a flavanol-rich soluble cocoa product increases HDL-cholesterol without inducing anthropometric changes in healthy and moderately hypercholesterolemic subjects. Food Funct. 2014;5:364–374. doi: 10.1039/c3fo60352k.
    1. Sarriá B., Martínez-López S., Sierra-Cinos J.L., García-Diz L., Goya L., Mateos R., Bravo L. Effects of bioactive constituents in functional cocoa products on cardiovascular health in humans. Food Chem. 2015;174:214–218. doi: 10.1016/j.foodchem.2014.11.004.
    1. Kwok C., Boekholdt S.M., Lentjes M.A., Loke Y.K., Luben R.N., Yeong J.K., Wareham N.J., Myint P.K., Khaw K.T. Habitual chocolate consumption and risk of cardiovascular disease among healthy men and women. Heart. 2015;101:1279–1287. doi: 10.1136/heartjnl-2014-307050.
    1. Dower J.I., Geleijnse J.M., Gijsbers L., Schalkwijk C., Kromhout D., Hollman P.C. Supplementation of the pure flavonoids epicatechin and quercetin affects some biomarkers of endothelial dysfunction and inflammation in (pre)hypertensive adults: A randomized double-blind, placebo-controlled, crossover trial. J. Nutr. 2015;145:1459–1463. doi: 10.3945/jn.115.211888.
    1. Grassi D., Lippi C., Necozione S., Desideri G., Ferri C. Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons. Am. J. Clin. Nutr. 2005;81:611–614.
    1. Muniyappa R., Hall G., Kolodziej T.L., Karne R.J., Crandon S.K., Quon M.J. Cocoa consumption for 2 weeks enhances insulin-mediated vasodilatation without improving blood pressure or insulin resistance in essential hypertension. Am. J. Clin. Nutr. 2008;88:1685–1696. doi: 10.3945/ajcn.2008.26457.
    1. Monagas M., Khan N., Andrés-Lacueva C., Casas R., Urpí-Sardá M., Llorach R., Lamuela-Raventós R.M., Estruch R. Effect of cocoa powder on the modulation of inflammatory biomarkers in patients at high risk of cardiovascular disease. Am. J. Clin. Nutr. 2009;90:1144–1150. doi: 10.3945/ajcn.2009.27716.
    1. Netea S.A., Janssen S.A., Jaeger M., Jansen T., Jacobs L., Miller-Tomaszewska G., Plantinga T.S., Netea M.G., Joosten L.A.B. Chocolate consumption modulates cytokine production in healthy individuals. Cytokine. 2013;62:40–43. doi: 10.1016/j.cyto.2013.02.003.
    1. Gu L., House S.E., Wu X., Ou B., Prior R.L. Procyanidin and catechin contents and antioxidant capacity of cocoa and chocolate products. J. Agric. Food Chem. 2006;54:4057–4061. doi: 10.1021/jf060360r.
    1. 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. Chronic consumption of flavanol-rich cocoa improves endothelial function and decreases vascular cell adhesion molecule in hypercholesterolemic postmenopausal women. J. Cardiovasc. Pharmacol. 2006;47:S177–S186. doi: 10.1097/00005344-200606001-00013.
    1. Esser D., Mars M., Oosterink E., Stalmach A., Müller M., Afman L.A. Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men. FASEB J. 2014;28:1464–1473. doi: 10.1096/fj.13-239384.
    1. Stote K.S., Clevidence B.A., Novotny J.A., Henderson T., Radecki S.V., Baer D.J. Effect of cocoa and green tea on biomarkers of glucose regulation, oxidative stress, inflammation and hemostasis in obese adults at risk for insulin resistance. Eur. J. Clin. Nutr. 2012;66:1153–1159. doi: 10.1038/ejcn.2012.101.
    1. Arranz S., Valderas-Martínez P., Chiva-Blanch G., Casas R., Urpí-Sardá M., Lamuela-Raventós R.M., Estruch R. Cardioprotective effects of cocoa: Clinical evidence from randomized clinical intervention trials in humans. Mol. Nutr. Food Res. 2013;57:936–947. doi: 10.1002/mnfr.201200595.
    1. Ellam S., Williamson G. Cocoa and human health. Ann. Rev. Nutr. 2013;33:105–128. doi: 10.1146/annurev-nutr-071811-150642.
    1. Du H., Boshuizen H.C., Forouhi N.G., Wareham N.J., Halkjær J., Tjønneland A., Overvad K., Jakobsen M.U., Boeing H., Buijsse B., et al. Dietary fiber and subsequent changes in body weight and waist circumference in European men and women. Am. J. Clin. Nutr. 2010;91:329–336. doi: 10.3945/ajcn.2009.28191.
    1. Qi L., Van Dam R.M., Liu S., Franz M., Mantzoros C., Hu F.B. Whole-grain, bran, and cereal fiber intakes and markers of systemic inflammation in diabetic women. Diabetes Care. 2006;29:207–211. doi: 10.2337/diacare.29.02.06.dc05-1903.
    1. Jensen M.K., Koh-Banerjee P., Franz M., Sampson L., Gronbaek M., Rimm E.B. Whole grains, bran, and germ in relation to homocysteine and markers of glycemic control, lipids, and inflammation. Am. J. Clin. Nutr. 2006;83:275–283.
    1. Lutsey P.L., Jacobs D.R., Kori S., Mayer-Davis E., Shea S., Steffen L.M., Szklo M., Tracy R. Whole grain intake and its cross-sectional association with obesity, insulin resistance, inflammation, diabetes and subclinical CVD: The MESA Study. Br. J. Nutr. 2007;98:397–405. doi: 10.1017/S0007114507700715.
    1. Katcher H.I., Legro R.S., Kunselman A.R., Gillies P.J., Demers L.M., Bagshaw D.M., Kris-Etherton P.M. The effects of a whole grain-enriched hypocaloric diet on cardiovascular disease risk factors in men and women with metabolic syndrome. Am. J. Clin. Nutr. 2008;87:79–90.
    1. Jonnalagadda S.S., Harnack L., Liu R.H., McKeown N., Seal C., Liu S., Fahey G.C. Putting the whole grain puzzle together: Health benefits associated with whole grains—Summary of American Society for Nutrition 2010 Satellite Symposium. J. Nutr. 2011;141:1011S–1022S. doi: 10.3945/jn.110.132944.
    1. Ma Y., Hebert J.R., Li W., Bertone-Johnson E.R., Olendzki B., Pagoto S.L., Tinker L., Rosal M.C., Ockene I.S., Ockene J.K., et al. Association between dietary fiber and markers of systemic inflammation in the Women’s Health Initiative Observational Study. Nutrition. 2008;24:941–949. doi: 10.1016/j.nut.2008.04.005.
    1. Khan N., Monagas M., Andrés-Lacueva C., Casas R., Urpí-Sardá M., Lamuela-Raventós R.M., Estruch R. Regular consumption of cocoa powder with milk increases HDL cholesterol and reduces oxidized LDL levels in subjects at high-risk of cardiovascular disease. Nutr. Metab. Cardiovasc. Dis. 2012;22:1046–1053.
    1. Jenkins D.J.A., Kendall C.W.C., Vuksan V., Vidgen E., Wong E., Augustin L.S.A., Fulgoni V. Effect of cocoa bran on low-density lipoprotein oxidation and fecal bulking. Arch. Intern. Med. 2000;160:2374–2379. doi: 10.1001/archinte.160.15.2374.
    1. Sarriá B., Mateos R., Sierra-Cinos J.L., Goya L., García-Diz L., Bravo L. Hypotensive, hypoglycaemic and antioxidant effects of consuming a cocoa product in moderately hypercholesterolemic humans. Food Funct. 2012;3:867–874. doi: 10.1039/c2fo10267f.
    1. Neufingerl N., Zebregs Y.E.M.P., Schuring E.A.H., Trautwein E.A. Effect of cocoa and theobromine consumption on serum HDL-cholesterol concentrations: A randomized controlled trial. Am. J. Clin. Nutr. 2013;97:1201–1209. doi: 10.3945/ajcn.112.047373.
    1. Almoosawi S., Tsang C., Ostertag L.M., Fyfe L., Al-Dujaili E.A.S. Differential effect of polyphenol-rich dark chocolate on biomarkers of glucose metabolism and cardiovascular risk factors in healthy, overweight and obese subjects: A randomized clinical trial. Food Funct. 2012;3:1035–1043. doi: 10.1039/c2fo30060e.
    1. Grassi D., Desideri G., Necozione S., Lippi C., Casale R., Properzi G., Blumberg J.B., 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;138:1671–1676.
    1. Kelly C.J. Effects of theobromine should be considered in future studies. Am. J. Clin. Nutr. 2005;82:483–489.
    1. Visioli F., Bernaert H., Corti R., Ferri C., Heptinstall S., Molinari E., Poli A., Serafini M., Smit H.J., Vinson J.A., et al. Chocolate, lifestyle, and health. Crit. Rev. Food Sci. Nutr. 2009;49:299–312. doi: 10.1080/10408390802066805.
    1. Matsui N., Itoa R., Nishimura E., Kato M., Kamei M., Shibata H., Kamei M., Shibata H., Matsumoto I., Abe K., et al. Ingested cocoa can prevent high-fat diet–induced obesity by regulating the expression of genes for fatty acid metabolism. Nutrition. 2005;21:594–601. doi: 10.1016/j.nut.2004.10.008.
    1. Farhat G., Drummond S., Fyfe L., Al-Dujaili E.A.S. Dark Chocolate: An Obesity Paradox or a Culprit for Weight Gain? Phytother. Res. 2014;28:791–797. doi: 10.1002/ptr.5062.
    1. Fernández-Millán E., Cordero-Herrera I., Ramos S., Escrivá F., Álvarez C., Goya L., Martín M.A. Cocoa-rich diet attenuates beta cell mass loss and function in young Zucker diabetic fatty rats by preventing oxidative stress and beta cell apoptosis. Mol. Nutr. Food Res. 2015;59:820–824. doi: 10.1002/mnfr.201400746.
    1. European Food Safety Authority Scientific Opinion on the substantiation of health claims related to cocoa flavanols and protection of lipids from oxidative damage and maintenance of normal blood pressure. EFSA J. 2010;8:1792.
    1. European Food Safety Authority Scientific opinion on the substantiation of a health claim related to cocoa flavanols and maintenance of normal endothelium-dependent vasodilation. EFSA J. 2012;10:2809.
    1. Higginbotham E., Taub P.R. Cardiovascular benefits of dark chocolate? Curr. Treat. Options Cardiovasc. Med. 2015;17:54–65. doi: 10.1007/s11936-015-0419-5.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅