Flavan-3-ols, theobromine, and the effects of cocoa and chocolate on cardiometabolic risk factors

Current Opinion in Lipidology

Volumn 26, Issue 1, 2015, Pages 10-19

  Berends, Lindsey M ^a   Van Der Velpen, Vera ^a   Cassidy, Aedin ^a  

^a UNIVERSITY OF EAST ANGLIA   (United Kingdom)

Author keywords

cardiometabolic; chocolate; flavan 3 ols; procyanidins; theobromine

Indexed keywords

BIOLOGICAL MARKER; FLAVAN 3 OL DERIVATIVE; FLAVANOL DERIVATIVE; LIPOPROTEIN; THEOBROMINE; UNCLASSIFIED DRUG; FLAVAN-3-OL; FLAVONOID;

BLOOD PRESSURE; CACAO; CARDIOMETABOLIC RISK; CARDIOVASCULAR DISEASE; DILATATION; DOSE RESPONSE; FLOW MEDIATED DILATATION; FOOD INTAKE; HUMAN; INSULIN RESISTANCE; META ANALYSIS (TOPIC); METABOLITE; OBSERVATIONAL STUDY; OPTIMAL DRUG DOSE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; RISK FACTOR; CARDIOVASCULAR SYSTEM; CHEMISTRY; DRUG EFFECTS; MEDICAL RESEARCH; METABOLISM; TRENDS;

THEOBROMA CACAO;

BIOMEDICAL RESEARCH; CACAO; CARDIOVASCULAR SYSTEM; FLAVONOIDS; HUMANS; RISK FACTORS; THEOBROMINE;

EID: 84920859921     PISSN: 09579672     EISSN: 14736535     Source Type: Journal    
DOI: 10.1097/MOL.0000000000000144     Document Type: Review

References (79)

1. Hurst WJ, Tarka SM Jr, Powis TG, et al. Cacao usage by the earliest Maya civilization. Nature 2002; 418:289-290.
2. Trognitz B, Cros E, Assemat S, et al. Diversity of cacao trees in Waslala, Nicaragua: associations between genotype spectra, product quality and yield potential. PLoS One 2013; 8:e54079.
3. Khan N, Khymenets O, Urpi-Sarda M, et al. Cocoa polyphenols and inflammatory markers of cardiovascular disease. Nutrients 2014; 6:844-880.
4. Miller KB, Hurst WJ, Payne MJ, et al. Impact of alkalization on the antioxidant and flavanol content of commercial cocoa powders. J Agric Food Chem 2008; 56:8527-8533.
5. U.S. Food and Drug Administration. CFR title 21; part 163 Cacao Products 2014. [cited 12 September 2014]. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?CFRPart=163&showFR=1. [Accessed 1 September 2014].
6. Langer S, Marshall LJ, Day AJ, Morgan MR. Flavanols and methylxanthines in commercially available dark chocolate: a study of the correlation with nonfat cocoa solids. J Agric Food Chem 2011; 59:8435-8441.
7. USDA Database for the flavonoid content of selected foods, release 3.1. [Internet]. Nutrient Data Laboratory; 2014. http://www.ars.usda.gov/nutrientdata/flav. [Accessed 1 September 2014].
8. Rothwell JA, Perez-Jimenez J, Neveu V, et al. Phenol-Explorer 3.0: a major update of the Phenol-Explorer database to incorporate data on the effects of food processing on polyphenol content. Database (Oxford) 2013.
9. Pereira-Caro G, Borges G, Nagai C, et al. Profiles of phenolic compounds and purine alkaloids during the development of seeds of Theobroma cacao cv. Trinitario. J Agric Food Chem 2013; 61:427-434.
10. USDA. USDA national nutrient database. http://ndb.nal.usda.gov/ndb/. [Accessed 1 September 2014].
11. UK Joint Food Safety and Standards Group - survey of caffeine and other methylxanthines in energy drinks and other caffeine-containing products. London: 1998. Contract No.: Food Surveillance Information Sheet 144.
12. Buitrago-Lopez A, Sanderson J, Johnson L, et al. Chocolate consumption and cardiometabolic disorders: systematic review and meta-analysis. BMJ 2011; 343:d4488.
13. Buijsse B, Feskens EJ, Kok FJ, Kromhout D. Cocoa intake, blood pressure, and cardiovascular mortality: the Zutphen Elderly Study. Arch Intern Med 2006; 166:411-417.
14. Djousse L, Hopkins PN, Arnett DK, et al. Chocolate consumption is inversely associated with calcified atherosclerotic plaque in the coronary arteries: the NHLBI Family Heart Study. Clin Nutr 2011; 30:38-43.
15. Buijsse B, Weikert C, Drogan D, et al. Chocolate consumption in relation to blood pressure and risk of cardiovascular disease in German adults. Eur Heart J 2010; 31:1616-1623.
16. Oba S, Nagata C, Nakamura K, et al. Consumption of coffee, green tea, oolong tea, black tea, chocolate snacks and the caffeine content in relation to risk of diabetes in Japanese men and women. Br J Nutr 2010; 103:453-459.
17. Larsson SC, Virtamo J, Wolk A. Chocolate consumption and risk of stroke: a prospective cohort of men and meta-analysis. Neurology 2012; 79:1223-1229.
18. Wang X, Ouyang YY, Liu J, Zhao G. Flavonoid intake and risk of CVD: a systematic review and meta-analysis of prospective cohort studies. Br J Nutr 2014; 111:1-11.
19. Zhang Z, Xu G, Liu X. Chocolate intake reduces risk of cardiovascular disease: evidence from 10 observational studies. Int J Cardiol 2013; 168:5448-5450.
20. Ried K, Sullivan TR, Fakler P, et al. Effect of cocoa on blood pressure. Cochrane Database Syst Rev 2012; 8:CD008893.
21. Shrime MG, Bauer SR, McDonald AC, et al. Flavonoid-rich cocoa consumption affects multiple cardiovascular risk factors in a meta-analysis of short-term studies. J Nutr 2011; 141:1982-1988.
22. Hooper L, Kay C, Abdelhamid A, et al. 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; 95:740-751.
23. Grassi D, Desideri G, Necozione S, et al. 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.
24. Balzer J, Rassaf T, Heiss C, et al. Sustained benefits in vascular function through flavanol-containing cocoa in medicated diabetic patients a double-masked, randomized, controlled trial. J Am Coll Cardiol 2008; 51:2141-2149.
25. Davison K, Coates AM, Buckley JD, Howe PR. Effect of cocoa flavanols and exercise on cardiometabolic risk factors in overweight and obese subjects. Int J Obes 2008; 32:1289-1296.
26. Grassi D, Lippi C, Necozione S, et al. 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 JClin Nutr 2005; 81:611-614.
27. Wang-Polagruto JF, Villablanca AC, Polagruto JA, et al. 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-S186; discussion S206-S209.
28. Wan Y, Vinson JA, Etherton TD, et al. Effects of cocoa powder and dark chocolate on LDL oxidative susceptibility and prostaglandin concentrations in humans. Am J Clin Nutr 2001; 74:596-602.
29. Njike VY, Faridi Z, Shuval K, et al. Effects of sugar-sweetened and sugar-free cocoa on endothelial function in overweight adults. Int J Cardiol 2011; 149:83-88.
30. Allen RR, Carson L, Kwik-Uribe C, et al. Daily consumption of a dark chocolate containing flavanols and added sterol esters affects cardiovascular risk factors in a normotensive population with elevated cholesterol. J Nutr 2008; 138:725-731.
31. Esser D, Mars M, Oosterink E, et al. Dark chocolate consumption improves leukocyte adhesion factors and vascular function in overweight men. FASEB J 2014; 28:1464-1473.
32. Sarria B, Martinez-Lopez S, Sierra-Cinos JL, et al. Regular consumption of a cocoa product improves the cardiometabolic profile in healthy and moderately hypercholesterolaemic adults. Br J Nutr 2014; 111:122-134.
33. Martinez-Lopez S, Sarria B, Sierra-Cinos JL, et al. Realistic intake of a flavanolrich soluble cocoa product increases HDL-cholesterol without inducing anthropometric changes in healthy and moderately hypercholesterolemic subjects. Food Funct 2014; 5:364-374.
34. West SG, McIntyre MD, Piotrowski MJ, et al. Effects of dark chocolate and cocoa consumption on endothelial function and arterial stiffness in overweight adults. Br J Nutr 2014; 111:653-661.
35. Hammer A, Koppensteiner R, Steiner S, et al. Dark chocolate and vascular function in patients with peripheral artery disease: a randomized, controlled cross-over trial. Clin Hemorheol Microcirc 2014. [Epub ahead of print]
36. Curtis PJ, Potter J, Kroon PA, et al. Vascular function and atherosclerosis progression after 1 y of flavonoid intake in statin-treated postmenopausal women with type 2 diabetes: a double-blind randomized controlled trial. Am J Clin Nutr 2013; 97:936-942.
37. Curtis PJ, Sampson M, Potter J, et al. Chronic ingestion of flavan-3-ols and isoflavones improves insulin sensitivity and lipoprotein status and attenuates estimated 10-year CVD risk in medicated postmenopausal women with type 2 diabetes: a 1-year, double-blind, randomized, controlled trial. Diabetes Care 2012; 35:226-232.
38. Inaba Y, Chen JA, Bergmann SR. Prediction of future cardiovascular outcomes by flow-mediated vasodilatation of brachial artery: a meta-analysis. Int J Cardiovasc Imaging 2010; 26:631-640.
39. Del Rio D, Rodriguez-Mateos A, Spencer JP, et al. Dietary (poly)phenolics in human health: structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid Redox Signal 2013; 18:1818-1892.
40. Knaze V, Zamora-Ros R, Lujan-Barroso L, et al. Intake estimation of total and individual flavan-3-ols, proanthocyanidins and theaflavins, their food sources and determinants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Br J Nutr 2012; 108:1095-1108.
41. Wang Y, Chung SJ, Song WO, Chun OK. Estimation of daily proanthocyanidin intake and major food sources in the U.S. diet. J Nutr 2011; 141:447-452.
42. Vogiatzoglou A, Mulligan AA, Luben RN, et al. 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; 111:1463-1473.
43. Mullen W, Borges G, Donovan JL, et al. Milk decreases urinary excretion but not plasma pharmacokinetics of cocoa flavan-3-ol metabolites in humans. Am J Clin Nutr 2009; 89:1784-1791.
44. Spadafranca A, Martinez Conesa C, Sirini S, Testolin G. Effect of dark chocolate on plasma epicatechin levels, DNA resistance to oxidative stress and total antioxidant activity in healthy subjects. Br J Nutr 2010; 103:1008-1014.
45. Actis-Goretta L, Leveques A, Giuffrida F, et al. Elucidation of (-)-epicatechin metabolites after ingestion of chocolate by healthy humans. Free Radic Biol Med 2012; 53:787-795.
46. Holt RR, Lazarus SA, Sullards MC, et al. Procyanidin dimer B2 [epicatechin- (4beta-8)-epicatechin] in human plasma after the consumption of a flavanolrich cocoa. Am J Clin Nutr 2002; 76:798-804.
47. Ottaviani JI, Kwik-Uribe C, Keen CL, Schroeter H. Intake of dietary procyanidins does not contribute to the pool of circulating flavanols in humans. Am J Clin Nutr 2012; 95:851-858.
48. Urpi-Sarda M, Monagas M, Khan N, et al. Epicatechin, procyanidins, and phenolic microbial metabolites after cocoa intake in humans and rats. Anal Bioanal Chem 2009; 394:1545-1556.
49. Stoupi S, Williamson G, Drynan JW, et al. A comparison of the in vitro biotransformation of (-)-epicatechin and procyanidin B2 by human faecal microbiota. Mol Nutr Food Res 2010; 54:747-759.
50. Appeldoorn MM, Vincken JP, Aura AM, et al. Procyanidin dimers are metabolized by human microbiota with 2-(3,4-dihydroxyphenyl)acetic acid and 5- (3,4-dihydroxyphenyl)-gamma-valerolactone as the major metabolites. J Agric Food Chem 2009; 57:1084-1092.
51. Ou K, Sarnoski P, Schneider KR, et al. Microbial catabolism of procyanidins by human gut microbiota. Mol Nutr Food Res 2014; 58:2196-2205.
52. Rodriguez-Mateos A, Vauzour D, Krueger CG, et al. Bioavailability, bioactivity and impact on health of dietary flavonoids and related compounds: an update. Arch Toxicol 2014; 88:1803-1853.
53. Blumberg JB, Camesano TA, Cassidy A, et al. Cranberries and their bioactive constituents in human health. Adv Nutr 2013; 4:618-632.
54. Mink PJ, Scrafford CG, Barraj LM, et al. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr 2007; 85:895-909.
55. Mursu J, Voutilainen S, Nurmi T, et al. Flavonoid intake and the risk of ischaemic stroke and CVD mortality in middle-aged Finnish men: the Kuopio Ischaemic Heart Disease Risk Factor Study. Br J Nutr 2008; 100:890-895.
56. McCullough ML, Peterson JJ, Patel R, et al. Flavonoid intake and cardiovascular disease mortality in a prospective cohort of US adults. Am J Clin Nutr 2012; 95:454-464.
57. Cassidy A, Rimm EB, O'Reilly EJ, et al. Dietary flavonoids and risk of stroke in women. Stroke 2012; 43:946-951.
58. Cassidy A, Mukamal KJ, Liu L, et al. High anthocyanin intake is associated with a reduced risk of myocardial infarction in young and middle-aged women. Circulation 2013; 127:188-196.
59. Ivey KL, Lewis JR, Prince RL, Hodgson JM. Tea and nontea flavonol intakes in relation to atherosclerotic vascular disease mortality in older women. Br J Nutr 2013; 110:1648-1655.
60. Zamora-Ros R, Jimenez C, Cleries R, et al. Dietary flavonoid and lignan intake and mortality in a Spanish cohort. Epidemiology 2013; 24:726-733.
61. Tresserra-Rimbau A, Medina-Remon A, Perez-Jimenez J, et al. Dietary intake and major food sources of polyphenols in a Spanish population at high cardiovascular risk: the PREDIMED study. Nutr Metab Cardiovasc Dis 2013; 23:953-959.
62. Kay CD, Hooper L, Kroon PA, et al. Relative impact of flavonoid composition, dose and structure on vascular function: a systematic review of randomised controlled trials of flavonoid-rich food products. Mol Nutr Food Res 2012; 56:1605-1616.
63. Hollman PC. Unravelling of the health effects of polyphenols is a complex puzzle complicated by metabolism. Arch Biochem Biophys 2014; 559:100-105.
64. Tousoulis D, Kampoli AM, Tentolouris C, et al. The role of nitric oxide on endothelial function. Curr Vasc Pharmacol 2012; 10:4-18.
65. Schroeter H, Heiss C, Balzer J, et al. (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans. Proc Natl Acad Sci USA 2006; 103:1024-1029.
66. Claude S, Boby C, Rodriguez-Mateos A, et al. Flavanol metabolites reduce monocyte adhesion to endothelial cells through modulation of expression of genes via p38-MAPK and p65-Nf-kB pathways. Mol Nutr Food Res 2014; 58:1016-1027.
67. Vazquez-Agell M, Urpi-Sarda M, Sacanella E, et al. Cocoa consumption reduces NF-kappaB activation in peripheral blood mononuclear cells in humans. Nutr Metab Cardiovasc Dis 2013; 23:257-263.
68. Ostertag LM, Kroon PA, Wood S, et al. Flavan-3-ol-enriched dark chocolate and white chocolate improve acute measures of platelet function in a genderspecific way - a randomized-controlled human intervention trial. Mol Nutr Food Res 2013; 57:191-202.
69. Horn P, Amabile N, Angeli FS, et al. Dietary flavanol intervention lowers the levels of endothelial microparticles in coronary artery disease patients. Br J Nutr 2014; 111:1245-1252.
70. Rodriguez-Mateos A, Toro-Funes N, Cifuentes-Gomez T, et al. Uptake and metabolism of (-)-epicatechin in endothelial cells. Arch Biochem Biophys 2014; 559:17-23.
71. Zamora-Ros R, Touillaud M, Rothwell JA, et al. Measuring exposure to the polyphenol metabolome in observational epidemiologic studies: current tools and applications and their limits. Am J Clin Nutr 2014; 100:11-26.
72. Neufingerl N, Zebregs YE, Schuring EA, Trautwein EA. Effect of cocoa and theobromine consumption on serum HDL-cholesterol concentrations: a randomized controlled trial. Am J Clin Nutr 2013; 97:1201-1209.
73. Tzounis X, Rodriguez-Mateos A, Vulevic J, et al. Prebiotic evaluation of cocoa-derived flavanols in healthy humans by using a randomized, controlled, double-blind, crossover intervention study. Am J Clin Nutr 2011; 93:62-72.
74. Baba S, Osakabe N, Kato Y, et al. Continuous intake of polyphenolic compounds containing cocoa powder reduces LDL oxidative susceptibility and has beneficial effects on plasma HDL-cholesterol concentrations in humans. Am J Clin Nutr 2007; 85:709-717.
75. Baggott MJ, Childs E, Hart AB, et al. Psychopharmacology of theobromine in healthy volunteers. Psychopharmacology 2013; 228:109-118.
76. Van den Bogaard B, Draijer R, Westerhof BE, et al. Effects on peripheral and central blood pressure of cocoa with natural or high-dose theobromine: a randomized, double-blind crossover trial. Hypertension 2010; 56: 839-846.
77. Franco R, Onatibia-Astibia A, Martinez-Pinilla E. Health benefits of methylxanthines in cacao and chocolate. Nutrients 2013; 5:4159-4173.
78. Yamamoto T, Takahashi H, Suzuki K, et al. Theobromine enhances absorption of cacao polyphenol in rats. Biosci Biotechnol Biochem 2014; 78:2059-2063.
79. Rodriguez-Mateos A, Oruna-Concha MJ, Kwik-Uribe C, et al. Influence of sugar type on the bioavailability of cocoa flavanols. Br J Nutr 2012; 108:2243-2250.