Skip to main content Accessibility help
×
Home

Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-)hypertension: a randomised double-blinded placebo-controlled cross-over trial

  • Verena Brüll (a1), Constanze Burak (a1), Birgit Stoffel-Wagner (a2), Siegfried Wolffram (a3), Georg Nickenig (a4), Cornelius Müller (a4), Peter Langguth (a5), Birgit Alteheld (a1), Rolf Fimmers (a6), Stefanie Naaf (a7), Benno F. Zimmermann (a7) (a8), Peter Stehle (a1) and Sarah Egert (a1)...

Abstract

The polyphenol quercetin may prevent CVD due to its antihypertensive and vasorelaxant properties. We investigated the effects of quercetin after regular intake on blood pressure (BP) in overweight-to-obese patients with pre-hypertension and stage I hypertension. In addition, the potential mechanisms responsible for the hypothesised effect of quercetin on BP were explored. Subjects (n 70) were randomised to receive 162 mg/d quercetin from onion skin extract powder or placebo in a double-blinded, placebo-controlled cross-over trial with 6-week treatment periods separated by a 6-week washout period. Before and after the intervention, ambulatory blood pressure (ABP) and office BP were measured; urine and blood samples were collected; and endothelial function was measured by EndoPAT technology. In the total group, quercetin did not significantly affect 24 h ABP parameters and office BP. In the subgroup of hypertensives, quercetin decreased 24 h systolic BP by −3·6 mmHg (P=0·022) when compared with placebo (mean treatment difference, −3·9 mmHg; P=0·049). In addition, quercetin significantly decreased day-time and night-time systolic BP in hypertensives, but without a significant effect in inter-group comparison. In the total group and also in the subgroup of hypertensives, vasoactive biomarkers including endothelin-1, soluble endothelial-derived adhesion molecules, asymmetric dimethylarginine, angiotensin-converting enzyme activity, endothelial function, parameters of oxidation, inflammation, lipid and glucose metabolism were not affected by quercetin. In conclusion, supplementation with 162 mg/d quercetin from onion skin extract lowers ABP in patients with hypertension, suggesting a cardioprotective effect of quercetin. The mechanisms responsible for the BP-lowering effect remain unclear.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-)hypertension: a randomised double-blinded placebo-controlled cross-over trial
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-)hypertension: a randomised double-blinded placebo-controlled cross-over trial
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-)hypertension: a randomised double-blinded placebo-controlled cross-over trial
      Available formats
      ×

Copyright

This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.

Corresponding author

* Corresponding author: S. Egert, fax +49 228 733217, email s.egert@uni-bonn.de

References

Hide All
1. Crozier, A, Jaganath, IB & Clifford, MN (2009) Dietary phenolics: chemistry, bioavailability and effects on health. Nat Prod Rep 26, 10011043.
2. Erdman, JW Jr, Balentine, D, Arab, L, et al. (2007) Flavonoids and Heart Health: Proceedings of the ILSI North America Flavonoids Workshop, May 31-June 1, 2005, Washington, DC. J Nutr 137, 718S737S.
3. Scalbert, A & Williamson, G (2000) Dietary intake and bioavailability of polyphenols. J Nutr 130, 2073S2085S.
4. Wang, X, Ouyang, YY, Liu, J, et al. (2013) Flavonoid intake and risk of CVD: a systematic review and meta-analysis of prospective cohort studies. Br J Nutr 111, 111.
5. Hubbard, GP, Wolffram, S, Lovegrove, JA, et al. (2004) Ingestion of quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in humans. J Thromb Haemost 2, 21382145.
6. Hubbard, GP, Wolffram, S, de Vos, R, et al. (2006) Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study. Br J Nutr 96, 482488.
7. Egert, S, Bosy-Westphal, A, Seiberl, J, et al. (2009) Quercetin reduces systolic blood pressure and plasma oxidised low-density lipoprotein concentrations in overweight subjects with a high-cardiovascular disease risk phenotype: a double-blinded, placebo-controlled cross-over study. Br J Nutr 102, 10651074.
8. Boots, AW, Wilms, LC, Swennen, EL, et al. (2008) In vitro and ex vivo anti-inflammatory activity of quercetin in healthy volunteers. Nutrition 24, 703710.
9. Nair, MP, Mahajan, S, Reynolds, JL, et al. (2006) The flavonoid quercetin inhibits proinflammatory cytokine (tumor necrosis factor alpha) gene expression in normal peripheral blood mononuclear cells via modulation of the NF-kappa beta system. Clin Vaccine Immunol 13, 319328.
10. Rivera, L, Moron, R, Sanchez, M, et al. (2008) Quercetin ameliorates metabolic syndrome and improves the inflammatory status in obese zucker rats. Obesity (Silver Spring) 16, 20812087.
11. Jeong, SM, Kang, MJ, Choi, HN, et al. (2012) Quercetin ameliorates hyperglycemia and dyslipidemia and improves antioxidant status in type 2 diabetic db/db mice. Nutr Res Pract 6, 201207.
12. Kobori, M, Masumoto, S, Akimoto, Y, et al. (2011) Chronic dietary intake of quercetin alleviates hepatic fat accumulation associated with consumption of a Western-style diet in C57/BL6J mice. Mol Nutr Food Res 55, 530540.
13. Edwards, RL, Lyon, T, Litwin, SE, et al. (2007) Quercetin reduces blood pressure in hypertensive subjects. J Nutr 137, 24052411.
14. Zahedi, M, Ghiasvand, R, Feizi, A, et al. (2013) Does quercetin improve cardiovascular risk factors and inflammatory biomarkers in women with type 2 diabetes: a double-blind randomized controlled clinical trial. Int J Prev Med 4, 777785.
15. Larson, AJ, Symons, JD & Jalili, T (2012) Therapeutic potential of quercetin to decrease blood pressure: review of efficacy and mechanisms. Adv Nutr 3, 3946.
16. Zawadzki, MJ, Graham, JW & Gerin, W (2012) Increasing the validity and efficiency of blood pressure estimates using ambulatory and clinic measurements and modern missing data methods. Am J Hypertens 25, 764769.
17. Myers, MG & Godwin, M (2007) Automated measurement of blood pressure in routine clinical practice. J Clin Hypertens (Greenwich) 9, 267270.
18. Chobanian, AV, Bakris, GL, Black, HR, et al. (2003) The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 289, 25602572.
19. Alberti, KG, Zimmet, P & Shaw, J (2005) The metabolic syndrome--a new worldwide definition. Lancet 366, 10591062.
20. Linseisen, J, Radtke, J & Wolfram, G (1997) Flavonoid intake of adults in a Bavarian subgroup of the national food consumption survey. Z Ernahrungswiss 36, 403412.
21. Zamora-Ros, R, Forouhi, NG, Sharp, SJ, et al. (2014) Dietary intakes of individual flavanols and flavonols are inversely associated with incident type 2 diabetes in European populations. J Nutr 144, 335343.
22. Egert, S, Wolffram, S, Schulze, B, et al. (2012) Enriched cereal bars are more effective in increasing plasma quercetin compared with quercetin from powder-filled hard capsules. Br J Nutr 107, 539546.
23. Egert, S, Wolffram, S, Bosy-Westphal, A, et al. (2008) Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans. J Nutr 138, 16151621.
24. Egert, S, Boesch-Saadatmandi, C, Wolffram, S, et al. (2010) Serum lipid and blood pressure responses to quercetin vary in overweight patients by apolipoprotein E genotype. J Nutr 140, 278284.
25. Pickering, TG, Hall, JE, Appel, LJ, et al. (2005) Recommendations for blood pressure measurement in humans and experimental animals: Part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension 45, 142161.
26. Axtell, AL, Gomari, FA & Cooke, JP (2010) Assessing endothelial vasodilator function with the Endo-PAT 2000. J Vis Exp, issue 44, 2167.
27. Kuvin, JT, Patel, AR, Sliney, KA, et al. (2003) Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J 146, 168174.
28. Nohria, A, Gerhard-Herman, M, Creager, MA, et al. (2006) Role of nitric oxide in the regulation of digital pulse volume amplitude in humans. J Appl Physiol (1985) 101, 545548.
29. Bonetti, PO, Pumper, GM, Higano, ST, et al. (2004) Noninvasive identification of patients with early coronary atherosclerosis by assessment of digital reactive hyperemia. J Am Coll Cardiol 44, 21372141.
30. Hamburg, NM, Keyes, MJ, Larson, MG, et al. (2008) Cross-sectional relations of digital vascular function to cardiovascular risk factors in the Framingham Heart Study. Circulation 117, 24672474.
31. Sun, SS, Chumlea, WC, Heymsfield, SB, et al. (2003) Development of bioelectrical impedance analysis prediction equations for body composition with the use of a multicomponent model for use in epidemiologic surveys. Am J Clin Nutr 77, 331340.
32. Matthews, DR, Hosker, JP, Rudenski, AS, et al. (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28, 412419.
33. Fürst, P, Pollack, L, Graser, TA, et al. (1990) Appraisal of four pre-column derivatization methods for the high-performance liquid chromatographic determination of free amino acids in biological materials. J Chromatogr 499, 557569.
34. Bieger, J, Cermak, R, Blank, R, et al. (2008) Tissue distribution of quercetin in pigs after long-term dietary supplementation. J Nutr 138, 14171420.
35. U.S.Department of Agriculture (2013) USDA database for the flavonoid content of selected foods, release 3.1 http://www ars usda gov/Services/docs htm?docid=6231
36. Kenward, MG & Jones, B (1987) The analysis of data from 2×2 cross-over trials with baseline measurements. Stat Med 6, 911926.
37. Appel, LJ, Brands, MW, Daniels, SR, et al. (2006) Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association. Hypertension 47, 296308.
38. Whelton, PK, Appel, LJ, Sacco, RL, et al. (2012) Sodium, blood pressure, and cardiovascular disease: further evidence supporting the American Heart Association sodium reduction recommendations. Circulation 126, 28802889.
39. Lewington, S, Clarke, R, Qizilbash, N, et al. (2002) Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 360, 19031913.
40. Ellinger, S, Reusch, A, Stehle, P, et al. (2012) Epicatechin ingested via cocoa products reduces blood pressure in humans: a nonlinear regression model with a Bayesian approach. Am J Clin Nutr 95, 13651377.
41. Hooper, L, Kay, C, Abdelhamid, A, et al. (2012) Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials. Am J Clin Nutr 95, 740751.
42. Loke, WM, Hodgson, JM, Proudfoot, JM, et al. (2008) Pure dietary flavonoids quercetin and (−)-epicatechin augment nitric oxide products and reduce endothelin-1 acutely in healthy men. Am J Clin Nutr 88, 10181025.
43. Duarte, J, Jimenez, R, O’Valle, F, et al. (2002) Protective effects of the flavonoid quercetin in chronic nitric oxide deficient rats. J Hypertens 20, 18431854.
44. Galindo, P, Rodriguez-Gomez, I, Gonzalez-Manzano, S, et al. (2012) Glucuronidated quercetin lowers blood pressure in spontaneously hypertensive rats via deconjugation. PLOS ONE 7, e32673.
45. Sanchez, M, Galisteo, M, Vera, R, et al. (2006) Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats. J Hypertens 24, 7584.
46. Ruef, J, Moser, M, Kubler, W, et al. (2001) Induction of endothelin-1 expression by oxidative stress in vascular smooth muscle cells. Cardiovasc Pathol 10, 311315.
47. Zhao, X, Gu, Z, Attele, AS, et al. (1999) Effects of quercetin on the release of endothelin, prostacyclin and tissue plasminogen activator from human endothelial cells in culture. J Ethnopharmacol 67, 279285.
48. Ying, B, Yang, T, Song, X, et al. (2008) Quercetin inhibits IL-1 beta-induced ICAM-1 expression in pulmonary epithelial cell line A549 through the MAPK pathways. Mol Biol Rep 36, 18251832.
49. Kleemann, R, Verschuren, L, Morrison, M, et al. (2011) Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models. Atherosclerosis 218, 4452.
50. Boesch-Saadatmandi, C, Wagner, AE, Wolffram, S, et al. (2012) Effect of quercetin on inflammatory gene expression in mice liver in vivo - role of redox factor 1, miRNA-122 and miRNA-125b. Pharmacol Res 65, 523530.
51. Mahmoud, MF, Hassan, NA, El Bassossy, HM, et al. (2013) Quercetin protects against diabetes-induced exaggerated vasoconstriction in rats: effect on low grade inflammation. PLOS ONE 8, e63784.
52. Pfeuffer, MA, Auinger, A, Bley, U, et al. (2013) Effect of quercetin on traits of the metabolic syndrome, endothelial function and inflammatory parameters in men with different APOE isoforms. Nutr Metab Cardiovasc Dis 23, 403409.
53. Loizzo, MR, Said, A, Tundis, R, et al. (2007) Inhibition of angiotensin converting enzyme (ACE) by flavonoids isolated from Ailanthus excelsa (Roxb) (Simaroubaceae). Phytother Res 21, 3236.
54. Mackraj, I, Govender, T & Ramesar, S (2008) The antihypertensive effects of quercetin in a salt-sensitive model of hypertension. J Cardiovasc Pharmacol 51, 239245.
55. Hackl, LP, Cuttle, G, Dovichi, SS, et al. (2002) Inhibition of angiotesin-converting enzyme by quercetin alters the vascular response to brandykinin and angiotensin I. Pharmacology 65, 182186.
56. Larson, A, Witman, MA, Guo, Y, et al. (2012) Acute, quercetin-induced reductions in blood pressure in hypertensive individuals are not secondary to lower plasma angiotensin-converting enzyme activity or endothelin-1: nitric oxide. Nutr Res 32, 557564.
57. Conquer, JA, Maiani, G, Azzini, E, et al. (1998) Supplementation with quercetin markedly increases plasma quercetin concentration without effect on selected risk factors for heart disease in healthy subjects. J Nutr 128, 593597.
58. Lee, KH, Park, E, Lee, HJ, et al. (2011) Effects of daily quercetin-rich supplementation on cardiometabolic risks in male smokers. Nutr Res Pract 5, 2833.
59. Castilla, P, Echarri, R, Davalos, A, et al. (2006) Concentrated red grape juice exerts antioxidant, hypolipidemic, and antiinflammatory effects in both hemodialysis patients and healthy subjects. Am J Clin Nutr 84, 252262.
60. Zern, TL, Wood, RJ, Greene, C, et al. (2005) Grape polyphenols exert a cardioprotective effect in pre- and postmenopausal women by lowering plasma lipids and reducing oxidative stress. J Nutr 135, 19111917.
61. Gnoni, GV, Paglialonga, G & Siculella, L (2009) Quercetin inhibits fatty acid and TAG synthesis in rat-liver cells. Eur J Clin Invest 39, 761768.
62. Glasser, G, Graefe, EU, Struck, F, et al. (2002) Comparison of antioxidative capacities and inhibitory effects on cholesterol biosynthesis of quercetin and potential metabolites. Phytomedicine 9, 3340.
63. Wiczkowski, W, Romaszko, J, Bucinski, A, et al. (2008) Quercetin from shallots (Allium cepa L. var. aggregatum) is more bioavailable than its glucosides. J Nutr 138, 885888.
64. Rothman, KJ (1990) No adjustments are needed for multiple comparisons. Epidemiology 1, 4346.

Keywords

Effects of a quercetin-rich onion skin extract on 24 h ambulatory blood pressure and endothelial function in overweight-to-obese patients with (pre-)hypertension: a randomised double-blinded placebo-controlled cross-over trial

  • Verena Brüll (a1), Constanze Burak (a1), Birgit Stoffel-Wagner (a2), Siegfried Wolffram (a3), Georg Nickenig (a4), Cornelius Müller (a4), Peter Langguth (a5), Birgit Alteheld (a1), Rolf Fimmers (a6), Stefanie Naaf (a7), Benno F. Zimmermann (a7) (a8), Peter Stehle (a1) and Sarah Egert (a1)...

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed