Top

Trials

Published in:

Open Access 01-12-2017 | Study protocol

The Pocket-4-Life project, bioavailability and beneficial properties of the bioactive compounds of espresso coffee and cocoa-based confectionery containing coffee: study protocol for a randomized cross-over trial

Authors: Pedro Mena, Michele Tassotti, Daniela Martini, Alice Rosi, Furio Brighenti, Daniele Del Rio

Published in: Trials | Issue 1/2017

Abstract

Background

Coffee is an important source of bioactive compounds, including caffeine, phenolic compounds (mainly chlorogenic acids), trigonelline, and diterpenes. Several studies have highlighted the preventive effects of coffee consumption on major cardiometabolic diseases, but the impact of coffee dosage on markers of cardiometabolic risk is not well understood. Moreover, the pool of coffee-derived circulating metabolites and the contribution of each metabolite to disease prevention still need to be evaluated in real-life settings. The aim of this study will be to define the bioavailability and beneficial properties of coffee bioactive compounds on the basis of different levels of consumption, by using an innovative experimental design. The contribution of cocoa-based products containing coffee to the pool of circulating metabolites and their putative bioactivity will also be investigated.

Methods

A three-arm, crossover, randomized trial will be conducted. Twenty-one volunteers will be randomly assigned to consume three treatments in a random order for 1 month: 1 cup of espresso coffee/day, 3 cups of espresso coffee/day, and 1 cup of espresso coffee plus 2 cocoa-based products containing coffee twice per day. The last day of each treatment, blood and urine samples will be collected at specific time points, up to 24 hours following the consumption of the first product. At the end of each treatment the same protocol will be repeated, switching the allocation group. Besides the bioavailability of the coffee/cocoa bioactive compounds, the effect of the coffee/cocoa consumption on several cardiometabolic risk factors (anthropometric measures, blood pressure, inflammatory markers, trimethylamine N-oxide, nitric oxide, blood lipids, fasting indices of glucose/insulin metabolism, DNA damage, eicosanoids, and nutri-metabolomics) will be investigated.

Discussion

Results will provide information on the bioavailability of the main groups of phytochemicals in coffee and on their modulation by the level of consumption. Findings will also show the circulating metabolites and their bioactivity when coffee consumption is substituted with the intake of cocoa-based products containing coffee. Finally, the effect of different levels of 1-month coffee consumption on cardiometabolic risk factors will be elucidated, likely providing additional insights on the role of coffee in the protection against chronic diseases.

Trial registration

ClinicalTrials.gov, NCT03166540. Registered on May 21, 2017.

Available only for authorised users

Tresserra-Rimbau A, Rimm EB, Medina-Remón A, Martínez-González MA, de la Torre R, Corella D, et al. Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study. Nutr Metab Cardiovasc Dis. 2014;24:639–47.CrossRefPubMed

Ludwig IA, Clifford MN, Lean MEJ, Ashihara H, Crozier A. Coffee: biochemistry and potential impact on health. Food Funct. 2014;5:1695–717.CrossRefPubMed

Van Dam RM, Hu FB. Coffee consumption and risk of type 2 diabetes: a systematic review. J Am Med Assoc. 2005;294:97–104.CrossRef

Ding M, Bhupathiraju SN, Satija A, van Dam RM, Hu FB. Long-term coffee consumption and risk of cardiovascular disease: a systematic review and a dose-response meta-analysis of prospective cohort studies. Circulation. 2013;129:643–59.CrossRefPubMedPubMedCentral

Malerba S, Turati F, Galeone C, Pelucchi C, Verga F, La Vecchia C, Tavani A. A meta-analysis of prospective studies of coffee consumption and mortality for all causes, cancers and cardiovascular diseases. Eur J Epidemiol. 2013;28:527–39.CrossRefPubMed

Huxley R, Lee CMY, Barzi F, Timmermeister L, Czernichow S, Perkovic V, et al. Coffee, decaffeinated coffee, and tea consumption in relation to incident type 2 diabetes mellitus: A systematic review with meta-analysis. Arch Intern Med. 2009;169:2053–63.CrossRefPubMed

Grosso G, Godos J, Galvano F, Giovannucci EL. Coffee, caffeine, and health outcomes: an umbrella review. Annu Rev Nutr. 2017;37:131–56.CrossRefPubMed

Grosso G, Micek A, Godos J, Sciacca S, Pajak A, Martinez-Gonzalez MA, et al. Coffee consumption and risk of all-cause, cardiovascular, and cancer mortality in smokers and non-smokers: a dose-response meta-analysis. Eur J Epidemiol. 2016;31:1191–205.CrossRefPubMed

Marventano S, Salomone F, Godos J, Pluchinotta F, Del Rio D, Mistretta A, Grosso G. Coffee and tea consumption in relation with non-alcoholic fatty liver and metabolic syndrome: a systematic review and meta-analysis of observational studies. Clin Nutr. 2016;35:1269–81.CrossRefPubMed

10.

de Lau LM, Breteler MM. Epidemiology of Parkinson’s disease. Lancet Neurol. 2006;5:525–35.CrossRefPubMed

11.

Lindsay J, Laurin D, Verreault R, Hébert R, Helliwell B, Hill GB, McDowell I. Risk factors for Alzheimer’s disease: a prospective analysis from the Canadian Study of Health and Aging. Am J Epidemiol. 2002;156:445–53.CrossRefPubMed

12.

Bidel S, Tuomilehto J. The emerging health benefits of coffee with an emphasis on type 2 diabetes and cardiovascular disease. Eur Endocrinol. 2013;9:99–106.CrossRef

13.

Larsson SC. Coffee, tea, and cocoa and risk of stroke. Stroke. 2014;45:309–14.CrossRefPubMed

14.

Mostofsky E, Rice MS, Levitan EB, Mittleman MA. Habitual coffee consumption and risk of heart failure a dose-response meta-analysis. Circ Heart Fail. 2012;5:401–5.CrossRefPubMedPubMedCentral

15.

Nordestgaard AT, Thomsen M, Nordestgaard BG. Coffee intake and risk of obesity, metabolic syndrome and type 2 diabetes: a Mendelian randomization study. Int J Epidemiol. 2015;44:551–65.CrossRefPubMed

16.

Shang F, Li X, Jiang X. Coffee consumption and risk of the metabolic syndrome: A meta-analysis. Diabetes Metab. 2016;42:80–7.CrossRefPubMed

17.

Kempf K, Kolb H, Gärtner B, Bytof G, Stiebitz H, Lantz I, et al. Cardiometabolic effects of two coffee blends differing in content for major constituents in overweight adults: a randomized controlled trial. Eur J Nutr. 2015;54:845–54.CrossRefPubMed

18.

Gavrieli A, Fragopoulou E, Mantzoros CS, Yannakoulia M. Gender and body mass index modify the effect of increasing amounts of caffeinated coffee on postprandial glucose and insulin concentrations; a randomized, controlled, clinical trial. Metabolism. 2013;62:1099–106.CrossRefPubMed

19.

Rakvaag E, Dragsted LO. Acute effects of light and dark roasted coffee on glucose tolerance: a randomized, controlled crossover trial in healthy volunteers. Eur J Nutr. 2016;55:2221–30.CrossRefPubMed

20.

Rodriguez-Mateos A, Vauzour D, Krueger CG, Shanmuganayagam D, Reed J, Calani L, et al. Bioavailability, bioactivity and impact on health of dietary flavonoids and related compounds: an update. Arch Toxicol. 2014;88:1803–53.CrossRefPubMed

21.

Del Rio D, Rodriguez-Mateos A, Spencer JPE, Tognolini M, Borges G, Crozier A. Dietary (poly)phenolics in human health: Structures, bioavailability, and evidence of protective effects against chronic diseases. Antioxid Redox Signal. 2013;18:1818–92.CrossRefPubMedPubMedCentral

22.

Landberg R, Sun Q, Rimm EB, Cassidy A, Scalbert A, Mantzoros CS, et al. Selected dietary flavonoids are associated with markers of inflammation and endothelial dysfunction in U.S. women. J Nutr. 2011;141:618–25.CrossRefPubMedPubMedCentral

23.

Chiva-Blanch G, Badimon L, Estruch R. Latest evidence of the effects of the Mediterranean diet in prevention of cardiovascular disease. Curr Atheroscler Rep. 2014;16:446.CrossRefPubMed

24.

Zamora-Ros R, Forouhi NG, Sharp SJ, González CA, Buijsse B, Guevara M, et al. Dietary intakes of individual flavanols and flavonols are inversely associated with incident type 2 diabetes in European populations. J Nutr. 2014;144:335–43.CrossRefPubMed

25.

Rodriguez-Mateos A, Cifuentes-Gomez T, Gonzalez-Salvador I, Ottaviani JI, Schroeter H, Kelm M, et al. Influence of age on the absorption, metabolism, and excretion of cocoa flavanols in healthy subjects. Mol Nutr Food Res. 2015;59:1504–12.CrossRefPubMed

26.

Vogiatzoglou A, Mulligan AA, Bhaniani A, Lentjes MAH, McTaggart A, Luben RN, et al. Associations between flavan-3-ol intake and CVD risk in the Norfolk cohort of the European Prospective Investigation into Cancer (EPIC-Norfolk). Free Radic Biol Med. 2015;84:1–10.CrossRefPubMedPubMedCentral

27.

Sansone R, Rodriguez-Mateos A, Heuel J, Falk D, Schuler D, Wagstaff R, 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.CrossRefPubMedPubMedCentral

28.

EFSA. Scientific Opinion on the substantiation of a health claim related to cocoa flavanols and maintenance of normal endothelium-dependent vasodilation pursuant to Article 13(5) of Regulation (EC) No 1924/2006. EFSA J. 2012;10:2809–29.

29.

Kwok CS, Boekholdt SM, Lentjes MAH, Loke YK, Luben RN, Yeong JK, et al. Habitual chocolate consumption and risk of cardiovascular disease among healthy men and women. Heart. 2015;101:1279–87.CrossRefPubMed

30.

Kim J, Shim J, Lee CY, Lee KW, Lee HJ. Cocoa phytochemicals: recent advances in molecular mechanisms on health. Crit Rev Food Sci Nutr. 2014;54:1458–72.CrossRefPubMed

31.

Welch RW, Antoine JM, Berta JL, Bub A, de Vries J, Guarner F, et al. Guidelines for the design, conduct and reporting of human intervention studies to evaluate the health benefits of foods. Br J Nutr. 2011;106 Suppl 2:S3–15.CrossRefPubMed

32.

Bianco G, Abate S, Labella C, Cataldi TRI. Identification and fragmentation pathways of caffeine metabolites in urine samples via liquid chromatography with positive electrospray ionization coupled to a hybrid quadrupole linear ion trap (LTQ) and Fourier transform ion cyclotron resonance mass spectrometry and tandem mass spectrometry. Rapid Commun Mass Spectrom. 2009;23:1065–74.CrossRefPubMed

33.

Lang R, Dieminger N, Beusch A, Lee YM, Dunkel A, Suess B, et al. Bioappearance and pharmacokinetics of bioactives upon coffee consumption. Anal Bioanal Chem. 2013;405:8487–503.CrossRefPubMed

34.

Marmet C, Actis-Goretta L, Renouf M, Giuffrida F. Quantification of phenolic acids and their methylates, glucuronides, sulfates and lactones metabolites in human plasma by LC-MS/MS after oral ingestion of soluble coffee. J Pharm Biomed Anal. 2014;88:617–25.CrossRefPubMed

35.

Van Cruchten STJ, De Waart DR, Kunne C, Hooiveld GJEJ, Boekschoten MV, Katan MB, et al. Absorption, distribution, and biliary excretion of cafestol, a potent cholesterol-elevating compound in unfiltered coffees, in mice. Drug Metab Dispos. 2010;38:635–40.CrossRefPubMed

36.

Renouf M, Marmet C, Giuffrida F, Lepage M, Barron D, Beaumont M, et al. Dose-response plasma appearance of coffee chlorogenic and phenolic acids in adults. Mol Nutr Food Res. 2014;58:301–9.CrossRefPubMed

37.

Pellegrini N, Salvatore S, Valtueña S, Bedogni G, Porrini M, Pala V, et al. Development and validation of a food frequency questionnaire for the assessment of dietary total antioxidant capacity. J Nutr. 2007;137:93–8.PubMed

38.

Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE, et al. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003;35:1381–95.CrossRefPubMed

39.

Zhang Y, Mehrotra N, Budha NR, Christensen ML, Meibohm B. A tandem mass spectrometry assay for the simultaneous determination of acetaminophen, caffeine, phenytoin, ranitidine, and theophylline in small volume pediatric plasma specimens. Clin Chim Acta. 2008;398:105–12.CrossRefPubMed

40.

Curti C, Brindani N, Battistini L, Sartori A, Pelosi G, Mena P, et al. Catalytic, enantioselective vinylogous mukaiyama aldol reaction of furan-based dienoxy silanes: a chemodivergent approach to γ-valerolactone flavan-3-ol metabolites and δ-lactone analogues. Adv Synt Catal. 2015;357:4082–92.CrossRef

41.

Brindani N, Mena P, Calani L, Benzie I, Choi SW, Brighenti F, et al. Synthetic and analytical strategies for the quantification of phenyl-gamma-valerolactone conjugated metabolites in human urine. Mol Nutr Food Res. 2017. doi: 10.1002/mnfr.201700077.

42.

Klick DE, Hines RN. Mechanisms regulating human FMO3 transcription. Drug Metab Rev. 2007;39:419–42.CrossRefPubMed

43.

Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472:57–63.CrossRefPubMedPubMedCentral

44.

Miller CA, Corbin KD, da Costa KA, Zhang S, Zhao X, Galanko JA, et al. Effect of egg ingestion on trimethylamine-N-oxide production in humans: a randomized, controlled, dose-response study. Am J Clin Nutr. 2014;100:778–86.CrossRefPubMedPubMedCentral

45.

Forstermann U, Munzel T. Endothelial nitric oxide synthase in vascular disease: from marvel to menace. Circulation. 2006;113:1708–14.CrossRefPubMed

46.

Pacini G, Mari A. Methods for clinical assessment of insulin sensitivity and beta-cell function. Best Pract Res Clin Endocrinol Metab. 2003;17:305–22.CrossRefPubMed

47.

Stadler M, Pacini G, Petrie J, Luger A, Anderwald C. Beta cell (dys)function in non-diabetic offspring of diabetic patients. Diabetologia. 2009;52:2435–44.CrossRefPubMed

48.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.CrossRefPubMed

49.

Del Bo C, Fracassetti D, Lanti C, Porrini M, Riso P. Comparison of DNA damage by the comet assay in fresh versus cryopreserved peripheral blood mononuclear cells obtained following dietary intervention. Mutagenesis. 2015;30:29–35.CrossRefPubMed

50.

Garcia-Flores LA, Medina S, Cejuela-Anta R, Martinez-Sanz JM, Abellan A, Genieser HG, et al. DNA catabolites in triathletes: effects of supplementation with an aronia-citrus juice (polyphenols-rich juice). Food Funct. 2016;7:2084–93.CrossRefPubMed

51.

Medina S, Domínguez-Perles R, Moreno DA, García-Viguera C, Ferreres F, Gil JI, Gil-Izquierdo Á. The intake of broccoli sprouts modulates the inflammatory and vascular prostanoids but not the oxidative stress-related isoprostanes in healthy humans. Food Chem. 2015;173:1187–94.CrossRefPubMed

52.

Llorach R, Urpi-Sarda M, Tulipani S, Garcia-Aloy M, Monagas M, Andres-Lacueva C. Metabolomic fingerprint in patients at high risk of cardiovascular disease by cocoa intervention. Mol Nutr Food Res. 2013;57:962–73.CrossRefPubMed

53.

Urpi-Sarda M, Boto-Ordóñez M, Queipo-Ortuño MI, Tulipani S, Corella D, Estruch R, et al. Phenolic and microbial-targeted metabolomics to discovering and evaluating wine intake biomarkers in human urine and plasma. Electrophoresis. 2015;36:2259–68.CrossRef

54.

Matyash V, Liebisch G, Kurzchalia TV, Shevchenko A, Schwudke D. Lipid extraction by methyl-terf-butyl ether for high-throughput lipidomics. J Lipid Res. 2008;49:1137–46.CrossRefPubMedPubMedCentral

55.

Lenth RV. Some practical guidelines for effective sample size determination. Am Stat. 2001;55:187–93.CrossRef

56.

Stalmach A, Mullen W, Barron D, Uchida K, Yokota T, Cavin C, et al. Metabolite profiling of hydroxycinnamate derivatives in plasma and urine after the ingestion of coffee by humans: identification of biomarkers of coffee consumption. Drug Metab Dispos. 2009;37:1749–58.CrossRefPubMed

57.

Freedman ND, Park Y, Abnet CC, Hollenbeck AR, Sinha R. Association of coffee drinking with total and cause-specific mortality. New Eng J Med. 2012;366:1891–904.CrossRefPubMedPubMedCentral

58.

Saito E, Inoue M, Sawada N, Shimazu T, Yamaji T, Iwasaki M, et al. Association of coffee intake with total and cause-specific mortality in a Japanese population: the Japan Public Health Center-based Prospective Study. Am J Clin Nutr. 2015;101:1029–37.CrossRefPubMed

59.

Andersen LF, Jacobs Jr DR, Carlsen MH, Blomhoff R. Consumption of coffee is associated with reduced risk of death attributed to inflammatory and cardiovascular diseases in the Iowa Women’s Health Study. Am J Clin Nutr. 2006;83:1039–46.PubMed

60.

Jiang X, Zhang D, Jiang W. Coffee and caffeine intake and incidence of type 2 diabetes mellitus: a meta-analysis of prospective studies. Eur J Nutr. 2014;53:25–38.CrossRefPubMed

61.

Sartorelli DS, Fagherazzi G, Balkau B, Touillaud MS, Boutron-Ruault MC, De Lauzon-Guillain B, Clavel-Chapelon F. Differential effects of coffee on the risk of type 2 diabetes according to meal consumption in a French cohort of women: The E3N/EPIC cohort study. Am J Clin Nutr. 2010;91:1002–12.CrossRefPubMed

62.

Pereira MA, Parker ED, Folsom AR. Coffee consumption and risk of type 2 diabetes mellitus: an 11-year prospective study of 28 812 postmenopausal women. Arch Intern Med. 2006;166:1311–6.CrossRefPubMed

63.

Salazar-Martinez E, Willett WC, Ascherio A, Manson JE, Leitzmann MF, Stampfer MJ, Hu FB. Coffee consumption and risk for type 2 diabetes mellitus. Ann Intern Med. 2004;140:1–8.CrossRefPubMed

64.

Grosso G, Stepaniak U, Micek A, Topor-Madry R, Pikhart H, Szafraniec K, Pajak A. Association of daily coffee and tea consumption and metabolic syndrome: results from the Polish arm of the HAPIEE study. Eur J Nutr. 2015;54:1129–37.CrossRefPubMed

65.

Koloverou E, Panagiotakos DB, Pitsavos C, Chrysohoou C, Georgousopoulou EN, Laskaris A, Stefanadis C. The evaluation of inflammatory and oxidative stress biomarkers on coffee-diabetes association: results from the 10-year follow-up of the ATTICA Study (2002-2012). Eur J Clin Nutr. 2015;69:1220–5.CrossRefPubMed

66.

Crippa A, Discacciati A, Larsson SC, Wolk A, Orsini N. Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: a dose-response meta-analysis. Am J Epidemiol. 2014;180:763–75.CrossRefPubMed

67.

Zhao Y, Wu K, Zheng J, Zuo R, Li D. Association of coffee drinking with all-cause mortality: a systematic review and meta-analysis. Public Health Nutr. 2015;18:1282–91.CrossRefPubMed

68.

Boekschoten MV, Engberink MF, Katan MB, Schouten EG. Reproducibility of the serum lipid response to coffee oil in healthy volunteers. Nutr J. 2003;2:1–8.CrossRef

69.

De Roos B, Meyboom S, Kosmeijer-Schuil TG, Katan MB. Absorption and urinary excretion of the coffee diterpenes cafestol and kahweol in healthy ileostomy volunteers. J Intern Med. 1998;244:451–60.CrossRefPubMed

70.

Guertin KA, Loftfield E, Boca SM, Sampson JN, Moore SC, Xiao Q, et al. Serum biomarkers of habitual coffee consumption may provide insight into the mechanism underlying the association between coffee consumption and colorectal cancer. Am J Clin Nutr. 2015;101:1000–11.CrossRefPubMedPubMedCentral

71.

Lof M, Sandin S, Yin L, Adami HO, Weiderpass E. Prospective study of coffee consumption and all-cause, cancer, and cardiovascular mortality in Swedish women. Eur J Epidemiol. 2015;30:1027–34.CrossRefPubMed

72.

Cornelis MC, Byrne EM, Esko T, Nalls MA, Ganna A, Paynter N, et al. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. Mol Psychiatry. 2015;20:647–56.CrossRefPubMed

73.

Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H. Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA. 2006;295:1135–41.CrossRefPubMed

74.

Salonen JT, Happonen P, Salonen R, Korhonen H, Nissinen A, Puska P, et al. Interdependence of associations of physical activity, smoking, and alcohol and coffee consumption with serum high-density lipoprotein and non-high-density lipoprotein cholesterol--a population study in eastern Finland. Prev Med. 1987;16:647–58.CrossRefPubMed

75.

Cotillard A, Kennedy SP, Kong LC, Prifti E, Pons N, Le Chatelier E, et al. Dietary intervention impact on gut microbial gene richness. Nature. 2013;500:585–8.CrossRefPubMed

76.

Anhe FF, Varin TV, Le Barz M, Desjardins Y, Levy E, Roy D, Marette A. Gut microbiota dysbiosis in obesity-linked metabolic diseases and prebiotic potential of polyphenol-rich extracts. Curr Obes Rep. 2015;4:389–400.CrossRefPubMed

77.

Wong JM. Gut microbiota and cardiometabolic outcomes: influence of dietary patterns and their associated components. Am J Clin Nutr. 2014;100 Suppl 1:369S–77S.CrossRefPubMed

78.

Mills CE, Tzounis X, Oruna-Concha MJ, Mottram DS, Gibson GR, Spencer JP. In vitro colonic metabolism of coffee and chlorogenic acid results in selective changes in human faecal microbiota growth. Br J Nutr. 2015;113:1220–7.CrossRefPubMed

79.

Neves AL, Chilloux J, Sarafian MH, Rahim MB, Boulange CL, Dumas ME. The microbiome and its pharmacological targets: therapeutic avenues in cardiometabolic diseases. Curr Opin Pharmacol. 2015;25:36–44.CrossRefPubMed

80.

Minihane AM, Vinoy S, Russell WR, Baka A, Roche HM, Tuohy KM, et al. Low-grade inflammation, diet composition and health: current research evidence and its translation. Br J Nutr. 2015;114:999–1012.CrossRefPubMedPubMedCentral

81.

Tomas-Barberan F, García-Villalba R, Quartieri A, Raimondi S, Amaretti A, Leonardi A, Rossi M. In vitro transformation of chlorogenic acid by human gut microbiota. Mol Nutr Food Res. 2013;58:1122–31.CrossRefPubMed

82.

Ludwig IA, Paz De Peña M, Concepción C, Alan C. Catabolism of coffee chlorogenic acids by human colonic microbiota. BioFactors. 2013;39:623–32.CrossRefPubMed

83.

Cowan TE, Palmnas MS, Yang J, Bomhof MR, Ardell KL, Reimer RA, et al. Chronic coffee consumption in the diet-induced obese rat: impact on gut microbiota and serum metabolomics. J Nutr Biochem. 2014;25:489–95.CrossRefPubMed

Title: The Pocket-4-Life project, bioavailability and beneficial properties of the bioactive compounds of espresso coffee and cocoa-based confectionery containing coffee: study protocol for a randomized cross-over trial
Authors: Pedro Mena
Michele Tassotti
Daniela Martini
Alice Rosi
Furio Brighenti
Daniele Del Rio
Publication date: 01-12-2017
Publisher: BioMed Central
Published in: Trials / Issue 1/2017
Electronic ISSN: 1745-6215
DOI: https://doi.org/10.1186/s13063-017-2271-2

Keynote webinar | Spotlight on medication adherence

Springer Medicine

The Pocket-4-Life project, bioavailability and beneficial properties of the bioactive compounds of espresso coffee and cocoa-based confectionery containing coffee: study protocol for a randomized cross-over trial

Abstract

Background

Methods

Discussion

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Discussion

Trial registration

Please log in to get access to this content

Other articles of this Issue 1/2017

The efficacy and safety of Danggui-Sayuk-Ga-Osuyu-Saenggang-tang on Korean patients with cold hypersensitivity in the hands: study protocol for a pilot, double-blind, randomized, placebo-controlled, parallel-group clinical trial

App-based serious gaming for training of chest tube insertion: study protocol for a randomized controlled trial

Intrapleural Dornase and Tissue Plasminogen Activator in pediatric empyema (DTPA): a study protocol for a randomized controlled trial

The efficacy of varenicline in achieving abstinence among waterpipe tobacco smokers – study protocol for a randomized controlled trial

Effects of high-frequency transcranial magnetic stimulation on functional performance in individuals with incomplete spinal cord injury: study protocol for a randomized controlled trial

Optimizing veteran-centered prostate cancer survivorship care: study protocol for a randomized controlled trial