European Journal of Nutrition

, Volume 58, Issue 2, pp 865–878 | Cite as

Moderate consumption of a soluble green/roasted coffee rich in caffeoylquinic acids reduces cardiovascular risk markers: results from a randomized, cross-over, controlled trial in healthy and hypercholesterolemic subjects

  • Sara Martínez-López
  • Beatriz SarriáEmail author
  • R. Mateos
  • Laura Bravo-ClementeEmail author
Original Contribution



Coffee is rich in bioactive compounds with health beneficial properties, with green coffee presenting higher phenol content than roasted. We evaluated the effects of regularly consuming realistic amounts of a green/roasted coffee blend on cardiovascular health-related biomarkers.


A randomized, cross-over, controlled study was carried out in 25 normocholesterolemic [total cholesterol (TC) < 200 mg/dL] and 27 hypercholesterolemic (TC 200–240 mg/dL) subjects. During 8 weeks, volunteers consumed 6 g/day of soluble green/roasted (35:65) coffee or a control beverage (water or an isotonic drink). Blood pressure, heart rate and body weight were monitored at the end of each intervention, and serum lipids [TC, HDL-C, LDL-C, VLDL-C, triglycerides and phospholipids], cytokines and chemokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, MCP-1, MIP-1β, TNF-α, INF-γ), adhesion molecules (ICAM-1, VCAM-1), and C-reactive protein were measured. Plasma antioxidant capacity (FRAP, ORAC and ABTS methods), and lipid (malondialdehyde, MDA) and protein (carbonyl groups, CG) oxidation were also determined.


Attending to the general lineal model of variance for repeated measures, after the green/roasted coffee intervention significant reductions in TC, LDL-C, VLDL-C and triglycerides levels (p = 0.006, 0.001, 0.003 and 0.017, respectively), and a significant group effect were observed (0.001, < 0.001, 0.019 and 0.027, respectively). Only within the hypercholesterolemic group, attending to the Bonferroni test, the aforementioned lipid parameters were significantly lower after regular green/roasted coffee intake compared to baseline values. Moreover, after the coffee stage, plasma antioxidant capacity improved, according to the increase in ORAC and FRAP values (p < 0.001 and p < 0.001, respectively) and decrease of MDA (p = 0.015) and CG (p < 0.001) levels, without differences between groups. Systolic (p = 0.001) and diastolic (p < 0.001) blood pressure, heart rate (p = 0.035), and body weight (p = 0.017) were reduced in both normo- and hypercholesterolemic groups.


Regular consumption of moderate amounts of a soluble green/roasted (35:65) coffee blend may contribute to improve cardiovascular health in moderately hypercholesterolemic people, as reducing serum lipids, blood pressure and body weight effects, as well as increasing plasma antioxidant capacity, have been observed. Moreover, positive influences on blood pressure, body weight, and plasma antioxidant capacity were obtained in the healthy group. Therefore, incorporation of green coffee beans into the coffee brew can be recommended as part of a dietary strategy to protect from cardiovascular disease.


Green coffee Antioxidant Chlorogenic acid Cardiovascular health Inflammation Weight control 



2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)


Body mass index


Blood pressure


Carbonyl groups


Caffeoylquinic acids


C-reactive protein


Diastolic blood pressure


Ferric reducing/antioxidant power


Granulocyte colony-stimulating factor


Intercellular cell adhesion molecule-1


Interferon gamma




Liquid chromatography–mass spectrometry


Monocyte chemoattractant protein-1




Macrophage inflammatory protein-1 beta


Oxygen radical absorbance capacity


Randomized clinical trial


Systolic blood pressure


Total cholesterol




Tumor necrosis factor alpha


Vascular cell adhesion molecule-1



The financial support of projects AGL2010-18269 and AGL2015-69986-R from the Spanish Ministry of Economy, Industry and Competitivity is acknowledged. We want to thank the volunteers who participated in the study, J. L. Sierra Cinos and L. García-Diz for their assistance in anthropometric measurements, M. Jimenez and L. T. Cayuelas for their assistance in dietary records analysis and M. Barba and C. Oeo for their assistance in lab analysis. Nestle, S. A. provided and packed the soluble coffee product for free. S. M.-L. thanks the Spanish National Research Council for her pre-doctoral fellowship under the JAE-Pre programme co-funded by CSIC and the European Social Fund. L.B. designed the trial and has the primary responsibility for final content. B.S. and S.M.-L carried out the statistical analysis of data. B.S., R.M. and S.M.-L. conducted the research and interpreted the results. S.M.-L wrote the initial draft and all authors revised and approved the final version of the manuscript.


This study was funded by Projects AGL2010-18269 and AGL2015-69986-R from the Spanish Ministry of Economy and Competitivity and approved by Ethical Committee Hospital Puerta de Hierro (Majadahonda, Madrid).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest.


  1. 1.
    Farah A (2012) Coffee constituents. In: Chu YF (ed) Coffee: emerging health effects and disease prevention. Blackwell Publishing Ltd, Oxford, pp 21–58CrossRefGoogle Scholar
  2. 2.
    Jaiswal R, Matei MF, Subedi P, Kuhnert N (2014) Does roasted coffee contain chlorogenic acid lactones or/and cinnamoylshikimate esters? Food Res Int 61:214–227CrossRefGoogle Scholar
  3. 3.
    Alonso-Salces RM, Serra F, Reniero F, Heberger K (2009) Botanical and geographical characterization of green coffee (Coffea arabica and Coffea canephora): chemometric evaluation of phenolic and methylxanthine contents. J Agric Food Chem 57:4224–4235CrossRefGoogle Scholar
  4. 4.
    Baeza G, Sarriá B, Bravo L, Mateos R (2016) Exhaustive qualitative LC-DAD-MSn analysis of Arabica green coffee beans: cinnamoyl-glycosides and cinnamolyshikimic acids as new polyphenols in green coffee. J Agric Food Chem 64:9663–9674CrossRefGoogle Scholar
  5. 5.
    Morales FJ, Somoza V, Fogliano V (2012) Physiological relevance of dietary melanoidins. Amino Acids 42:1097–1109CrossRefGoogle Scholar
  6. 6.
    Ochiai R, Chikama A, Kataoka K, Tokimitsu I, Maekawa Y, Ohishi M, Rakugi M, Mikami H (2009) Effects of hydroxyhydroquinone-reduced coffee on vasoreactivity and blood pressure. Hypertens Res 32:969–974CrossRefGoogle Scholar
  7. 7.
    Bakuradze T, Boehm N, Janzowski C, Lang R, Hofmann T, Stockis JP, Albert FW, Stiebitz H, Bytof G, Lantz I et al (2011) Antioxidant-rich coffee reduces DNA damage, elevates glutathione status and contributes to weight control: results from an intervention study. Mol Nutr Food Res 55:793–797CrossRefGoogle Scholar
  8. 8.
    Lopez-Garcia E, Guallar-Castillon P, Leon-Muñoz L, Graciani A, Rodriguez-Artalejo F (2014) Coffee consumption and health-related quality of life. Clin Nutr 33:143–149CrossRefGoogle Scholar
  9. 9.
    Ohnaka K, Ikeda M, Maki T, Okada T, Shimazoe T, Adachi M, Nomura M, Takayanagi R, Kono S (2012) Effects of 16-week consumption of caffeinated and decaffeinated instant coffee on glucose metabolism in a randomized controlled trial. J Nutr Metab 207426Google Scholar
  10. 10.
    Sarriá B, Martínez-López S, Sierra-Cinos JL, García-Diz L, Mateos R, Bravo L (2016) Regularly consuming a green/roasted coffee blend reduces the risk of metabolic syndrome. Eur J Nutr. Google Scholar
  11. 11.
    Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Drazner MH, Fonarow GC, Gerazi SA, Horwich T, Januzzi JL et al (2013) ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 128:e240–e327Google Scholar
  12. 12.
    Bravo L, Mateos R, Sarriá B (2017) Preventive effect of coffee against cardiovascular diseases. In: Farah A (ed) Coffee: chemistry, quality and health implications. Royal Society of Chemistry, OxfordGoogle Scholar
  13. 13.
    Jee SH, He J, Appel LJ, Whelton PK, Suh I, Klag MJ (2001) Coffee consumption and serum lipids: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol 153:353–362CrossRefGoogle Scholar
  14. 14.
    Cai L, Ma D, Zhang Y, Liu Z, Wang P (2012) The effect of coffee consumption on serum lipids: a meta-analysis of randomized controlled trials. Eur J Clin Nutr 66:872–877CrossRefGoogle Scholar
  15. 15.
    Jee SH, He J, Whelton PK, Suh I, Klag MJ (1999) The effect of chronic coffee drinking on blood pressure. A meta-analysis of controlled clinical trials. Hypertension 33:647–652CrossRefGoogle Scholar
  16. 16.
    Noordzij M, Uiterwaal CS, Arends LR, Kok FJ, Grobbee DE, Geleijnse JM (2005) Blood pressure response to chronic intake of coffee and caffeine: a meta-analysis of randomized controlled trials. J Hypertens 23:921–928CrossRefGoogle Scholar
  17. 17.
    Nurminen M-L, Niittyenen L, Korpela R, Vapaatalo V (1999) Coffee, caffeine and blood pressure: a critical review. Eur J Clin Nutr 53:831–839CrossRefGoogle Scholar
  18. 18.
    Mesas AE, Leon-Muñoz LM, Rodriguez-Artalejo F, Lopez-Garcia E (2011) The effect of coffee on blood pressure and cardiovascular disease in hypertensive individuals: a systematic review and meta-analysis. Am J Clin Nutr 94:1113–1126CrossRefGoogle Scholar
  19. 19.
    Steffen M, Kuhle C, Hensrud D, Erwin PJ, Murad MH (2012) The effect of coffee consumption on blood pressure and the development of hypertension: a systematic review and meta-analysis. J Hypertens 30:2245–2254CrossRefGoogle Scholar
  20. 20.
    Zhang Z, Hu G, Caballero B, Apple L, Chen L (2011) Habitual coffee consumption and risk of hypertension: a systematic review and meta-analysis of prospective observational studies. Am J Clin Nutr 93:1212–1219CrossRefGoogle Scholar
  21. 21.
    Karatzis E, Papaioannou TG, Aznaouridis K, Karatzi K, Stamatelopoulos K, Zampelas A, Papamichael C, Lekakis J, Mavrikakis M (2005) Acute effects of caffeine on blood pressure and wave reflections in healthy subjects: should we consider monitoring central blood pressure? Int J Cardiol 98:425–430CrossRefGoogle Scholar
  22. 22.
    Papamichael CM, Aznaouridis KA, Karatzis EN, Karatzi KN, Stamatelopoulos KS, Vamvakou G, Lekakis JP, Mavrikakis ME (2005) Effect of coffee on endothelial function in healthy subjects: the role of caffeine. Clin Sci 109:55–60CrossRefGoogle Scholar
  23. 23.
    Buscemi S, Verga S, Batsis JA, Donatelli M, Tranchina MR, Belmonte S, Mattina A, Re A, Cerasola G (2010) Acute effects of coffee on endothelial function in healthy subjects. Eur J Clin Nutr 64:483–489CrossRefGoogle Scholar
  24. 24.
    Ochiai R, Sugiura Y, Otsuka K, Katsuragi Y, Hashiguchi T (2014) Coffee polyphenols improve peripheral endothelial function after glucose loading in healthy male adults. Nutr Res 34:155–159CrossRefGoogle Scholar
  25. 25.
    Ludwig IA, Clifford MN, Lean ME, Ashihara H, Crozier A (2014) Coffee: biochemistry and potential impact on health. Food Funct 5:1695–1717CrossRefGoogle Scholar
  26. 26.
    Cho AS, Jeon SM, Kim MJ, Yeo J, Seo KI, Choi MS, Lee MK (2010) Chlorogenic acid exhibits anti-obesity property and improves lipid metabolism in high-fat diet-induce-obese mice. Food Chem Toxicol 48:937–943CrossRefGoogle Scholar
  27. 27.
    Vinson JA, Burnham BR, Nagendran MV (2012) Randomized, double-blind, placebo-controlled, linear dose, crossover study to evaluate the efficacy and safety of a green coffee bean extract in overweight subjects. Diabetes Metab Syndr Obes Target Ther 5:21–27CrossRefGoogle Scholar
  28. 28.
    Agudelo-Ochoa GM, Pulgarín-Zapata IC, Velásquez-Rodríguez CM, Duqye-Ramírez M, Naranjo-Cano M, Quintero-Ortiz MM, Lara-Guzmán OJ, Muñoz-Durango K (2016) Coffee consumption increases the antioxidant capacity of plasma and has no effect on the lipid profile or vascular function in healthy adults in a randomized controlled trial. J Nutr 146:524–531CrossRefGoogle Scholar
  29. 29.
    Meng S, Cao J, Feng Q, Peng J, Hu Y (2013) Roles of chlorogenic acid on regulating glucose and lipids metabolism: a review. Evid Based Complem Alt Med 2013:801457Google Scholar
  30. 30.
    Kozuma K, Tsuchiya S, Kohori J, Hase T, Tokimitsu I (2005) Antihypertensive effect of green coffee bean extract on mildly hypertensive subjects. Hypertens Res 28:711–718CrossRefGoogle Scholar
  31. 31.
    Watanabe T, Arai Y, Mitsui Y, Kusaura T, Okawa W, Kajihara Y, Saito I (2006) The blood pressure-lowering effect and safety of chlorogenic acid from green coffee bean extract in essential hypertension. Clin Exper Hypert 28:439–449CrossRefGoogle Scholar
  32. 32.
    Revuelta-Iniesta R, Al-Dujaili EAS (2014) Consumption of green coffee reduces blood pressure and body composition by influencing 11β-HSD1 enzyme activity in healthy individuals: a pilot crossover study using green and black coffee. Bio Med Res Int 482704Google Scholar
  33. 33.
    Ochiai R, Jokura H, Suzuki A, Tokimitsu I, Ohishi M, Komai N, Rakugi H, Ogihara T (2004) Green coffee bean extract improves human vasoreactivity. Hypertens Res 27:731–737CrossRefGoogle Scholar
  34. 34.
    Ward NC, Hodgson JM, Woodman RJ, Zimmermann D, Poquet L, Leveques A, Actis-Goretta L, Puddey IB, Croft KD (2016) Acute effects of chlorogenic acids on endothelial function and blood pressure in healthy men and women. Food Funct 7:2197–2203CrossRefGoogle Scholar
  35. 35.
    Sarriá B, Martínez-López S, Mateos R, Bravo L (2016) Long-term consumption of a green/roasted coffee blend positively affects glucose and insulin resistance in humans. Food Res Int 89:1023–1028CrossRefGoogle Scholar
  36. 36.
    Martinez-Lopez S, Sarria B, Baeza G, Mateos R, Bravo-Clemente L (2014) Theobromine, caffeine, and theophylline metabolites in human plasma and urine after consumption of soluble cocoa products with different methylxanthine contents. Food Res Int 63:446–455CrossRefGoogle Scholar
  37. 37.
    Olthof MR, Hollman PC, Zock PL, Katan MK (2001) Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans. Am J Clin Nutr 73:532–538CrossRefGoogle Scholar
  38. 38.
    Kempf K, Kolb H, Gärtner B, Bytof G, Stiebitz H, Lantz I, Lang R, Hofmann T, Martin S (2015) Cardiometabolic effects of two coffee blends differing in content form major constituents in overweight adults: a randomized controlled trial. Eur J Nutr 54:845–854CrossRefGoogle Scholar
  39. 39.
    Hoelzl C, Knasmüller S, Wagner KH, Elbling L, Huber W, Kager N, Ferk F, Ehrlich V, Nersesyan A, Neubauer O et al (2010) Instant coffee with high chlorogenic acid levels protects humans against oxidative damage of macromolecules. Mol Nutr Food Res 54:1722–1733CrossRefGoogle Scholar
  40. 40.
    Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C (1999) Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Bio Med 26:1231–1237CrossRefGoogle Scholar
  41. 41.
    Huang D, Ou B, Hampsch-Woodill M, Flanagan JA, Prior RL (2002) High-throughput assay of oxygen radical absorbance capacity (ORAC) using a multichannel liquid handling system coupled with a microplate fluorescence reader in 96-well format. J Agric Food Chem 50:4437–4444CrossRefGoogle Scholar
  42. 42.
    Pulido R, Bravo L, Saura-Calixto F (2000) Antioxidant activity of dietary polyphenols as determined by a modified FRAP assay. J Agric Food Chem 48:3396–3402CrossRefGoogle Scholar
  43. 43.
    Mateos R, Lecumberri E, Ramos S, Goya L, Bravo L (2005) Determination of malondialdehyde (MDA) by high-performance liquid chromatography in serum and liver as a biomarker for oxidative stress. Application to a rat model for hypercholesterolemia and evaluation of the effect of diets rich in phenolic antioxidants from fruits. J Chrom B 827:76–82CrossRefGoogle Scholar
  44. 44.
    Ritcher S, Wehr NB, Stadtman ER, Levine RL (2002) Assessment of skin carbonyl content as a noninvasive measure of biological age. Arch Biochem Biophys 397:430–432CrossRefGoogle Scholar
  45. 45.
    Moreiras O, Carbajal A, Cabrera L, Cuadrado C (2016) Ingestas diarias recomendadas de energía y nutrientes para la población española. Tablas de Composición de Alimentos. Ed. Pirámide (Grupo Anaya, SA), 18th edn. MadridGoogle Scholar
  46. 46.
    FAO/WHO/UNU (1985) Expert Consultation Report. Energy and Protein Requirements. Technical Report Series 724. WHO, GenevaGoogle Scholar
  47. 47.
    Greenberg JA, Boozer CN, Geliebter A (2006) Coffee, diabetes, and weight control. Am J Clin Nutr 84:682–693CrossRefGoogle Scholar
  48. 48.
    Riksen NP, Rongen GA, Smits P (2009) Acute and long-term cardiovascular effects of coffee: implications for coronary heart disease. Pharmacol Ther 121:185–191CrossRefGoogle Scholar
  49. 49.
    Mubarak A, Bondonno CP, Liu AH, Considine MJ, Rich L, Mas E, Croft KD, Hodgson JM (2012) Acute effects of chlorogenic acid on nitric oxide status, endothelial function, and blood pressure in healthy volunteers: a randomized trial. J Agric Food Chem 60:9130–9136CrossRefGoogle Scholar
  50. 50.
    Kempf K, Herder C, Erlund I, Kolb H, Martin S, Cartensen M, Koenig W, Sundvall J, Bidel S, Kuha S, Tuomilehto J (2010) Effects of coffee consumption on subclinical inflammation and other risk factors for type 2 diabetes: a clinical trial. Am J Clin Nutr 91:950–957CrossRefGoogle Scholar
  51. 51.
    Koh KK, Quon MJ, Han SH, Chung W-J, Ahn JY, Seo Y-H, Kang MH, Ahn TH, Choi IS, Shin EK (2004) Additive beneficial effects of losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients. Circulation 110:3687–3692CrossRefGoogle Scholar
  52. 52.
    Panahi Y, Hosseini MS, Khalili N, Naimi E, Simental.Mendia LE, Majeed M, Sahebkar A (2016) Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: a post-hoc analysis of a randomized controlled trial. Biomed Pharmacother 82:578–582CrossRefGoogle Scholar
  53. 53.
    Correa TAF, Rogero MM, Mioto BM, Tarasoutchi D, Tuda VL, Cesar LAM, Torres EAFS. (2013) Paper-filtered coffee increases cholesterol and inflammation biomarkers independent of roasting degree: a clinical trial. Nutrition 29:977–981CrossRefGoogle Scholar
  54. 54.
    Therkelsen SP, Hetland G, Lyberg T, Lygren I, Johnson E (2016) Cytokine levels after consumption of a medicinal Agaricus blazei Murill-based mushroom extract, AndoSanTM, in patients with Chron’s disease and ulcerative colitis in a randomized single-blinded placebo-controlled study. Human Immunol 84:323–331Google Scholar
  55. 55.
    Chang WC, Chen CH, Lee MF, Chang T, Yu YM (2010) Chlorogenic acid attenuates adhesion molecules up-regulation in IL-1β-treated endothelial cells. Eur J Nutr 49:267–275CrossRefGoogle Scholar
  56. 56.
    Hwang SJ, Kim Y-W, Park Y, Lee H-J, Kim K-W (2014) Anti-inflammatory effects of chlorogenic acid in lipopolysaccharide-stimulated RWA 264.7 cells. Inflamm Res 63:81–90CrossRefGoogle Scholar
  57. 57.
    Lee E-S, Park S-H, Kim MS, Han S-Y, Kim H-S, Kang Y-H (2012) Caffeic acid disturbs monocyte adhesion onto cultured endothelial cells stimulated by adipokine resistin. J Agric Food Chem 60:2730–2739CrossRefGoogle Scholar
  58. 58.
    Ma Z-C, Hong Q, Wang Y-G, Tan H-L, Xiao C-R, Liang Q-D, Cai S-H, Gao Y (2010) Ferulic acid attenuates adhesion molecule expression in gamma-radiated human umbilical vascular endothelial cells. Biol Pharm Bull 33:752–758CrossRefGoogle Scholar
  59. 59.
    Pellegrini N, Serafini M, Colombi B, Del Rio D, Salvatore S, Bianchi M, Brighenti F (2003) Total antioxidant capacity of plant foods, beverages and oils consumed in Italy assessed by three different in vitro assays. J Nutr 133:2812–2819CrossRefGoogle Scholar
  60. 60.
    Svilaas A, Sakhi AK, Andersen LF, Svilaas T, Ström EC, Jacobs DR, Ose L, Bloomhoff R (2004) Intakes of antioxidants in coffee, wine, and vegetables are correlated with plasma carotenoids in humans. J Nutr 134:562–567CrossRefGoogle Scholar
  61. 61.
    Baeza G, Amigo-Benavent M, Sarria B, Goya L, Mateos R, Bravo L (2014) Green coffee hydroxycinnamic acids but not caffeine protect human HepG2 cells against oxidative stress. Food Res Int 62:1038–1046CrossRefGoogle Scholar
  62. 62.
    Gómez-Juaristi M, Martínez-López S, Sarria B, Bravo L, Mateos R (2018) Bioavailability of hydroxycinnamates in an instant green/roasted coffee blend in humans. Identification of novel colonic metabolites. Food Funct 9:313–334CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN)Spanish National Research Council (CSIC)MadridSpain

Personalised recommendations