The Effects of Quercetin Supplementation on Blood Pressures and Endothelial Function Among Patients with Metabolic Syndrome and Related Disorders: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Author(s): Omid R. Tamtaji, Alireza Milajerdi, Ehsan Dadgostar, Fariba Kolahdooz, Maryam Chamani, Elaheh Amirani, Hamed Mirzaei, Zatollah Asemi*.

Journal Name: Current Pharmaceutical Design

Volume 25 , Issue 12 , 2019


Abstract:

Background: This systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to determine the effect of quercetin administration on blood pressures and endothelial function among patients with metabolic syndrome (MetS) and related disorders.

Methods: We searched systematically online databases including Cochrane Library, EMBASE, MEDLINE, and Web of Science to identify the relevant RCTs until December 2018. Q-test and I2 statistics were applied to assess heterogeneity among the included studies. Data were pooled using a random-effects model and weighted mean difference (WMD) was considered as the overall effect size.

Results: Out of 284 citations, 8 RCTs were included in the meta-analysis. We found a significant reduction in systolic blood pressure (SBP) (WMD: -1.69; 95% CI: -3.22, -0.17) following the intake of quercetin supplements. However, quercetin supplementation did not significantly affect diastolic blood pressure (DBP) (WMD: -3.14; 95% CI: -8.24, 1.95), vascular cell adhesion molecule 1 (VCAM-1) (WMD: -24.49; 95% CI: -53.74, 4.77) and intercellular adhesion molecule 1 (ICAM-1) (WMD: -5.78; 95% CI: -12.93, 1.38).

Conclusion: In summary, the current meta-analysis demonstrated that quercetin supplementation significantly reduced SBP, yet did not affect DBP, VCAM-1 and ICAM-1 among patients with MetS and related disorders.

Keywords: Quercetin, blood pressures, endothelial function, meta-analysis, randomized controlled trials, metabolic syndrome.

[1]
Atkins GB, Jain MK, Hamik A. Endothelial differentiation: molecular mechanisms of specification and heterogeneity. Arterioscler Thromb Vasc Biol 2011; 31(7): 1476-84. [http://dx.doi.org/10.1161/ATVBAHA.111.228999]. [PMID: 21677290].
[2]
Félétou M, Köhler R, Vanhoutte PM. Endothelium-derived vasoactive factors and hypertension: possible roles in pathogenesis and as treatment targets. Curr Hypertens Rep 2010; 12(4): 267-75. [http://dx.doi.org/10.1007/s11906-010-0118-2]. [PMID: 20532699].
[3]
Dharmashankar K, Widlansky ME. Vascular endothelial function and hypertension: insights and directions. Curr Hypertens Rep 2010; 12(6): 448-55. [http://dx.doi.org/10.1007/s11906-010-0150-2]. [PMID: 20857237].
[4]
van den Hoogen PC, Feskens EJ, Nagelkerke NJ, Menotti A, Nissinen A, Kromhout D. The relation between blood pressure and mortality due to coronary heart disease among men in different parts of the world. N Engl J Med 2000; 342(1): 1-8. [http://dx.doi.org/10.1056/NEJM200001063420101]. [PMID: 10620642].
[5]
Wong ND, Pio JR, Franklin SS, L’Italien GJ, Kamath TV, Williams GR. Preventing coronary events by optimal control of blood pressure and lipids in patients with the metabolic syndrome. Am J Cardiol 2003; 91(12): 1421-6. [http://dx.doi.org/10.1016/S0002-9149(03)00392-8]. [PMID: 12804727].
[6]
Higashi Y, Maruhashi T, Noma K, Kihara Y. Oxidative stress and endothelial dysfunction: clinical evidence and therapeutic implications. Trends Cardiovasc Med 2014; 24(4): 165-9. [http://dx.doi.org/10.1016/j.tcm.2013.12.001]. [PMID: 24373981].
[7]
Förstermann U, Xia N, Li H. Roles of vascular oxidative stress and nitric oxide in the pathogenesis of atherosclerosis. Circ Res 2017; 120(4): 713-35. [http://dx.doi.org/10.1161/CIRCRESAHA.116.309326]. [PMID: 28209797].
[8]
Korsholm AS, Kjær TN, Ornstrup MJ, Pedersen SB. Comprehensive metabolomic analysis in blood, urine, fat, and muscle in men with metabolic syndrome: a randomized, placebo-controlled clinical trial on the effects of resveratrol after four months’ treatment. Int J Mol Sci 2017; 18(3): 18. [http://dx.doi.org/10.3390/ijms18030554]. [PMID: 28273841].
[9]
Boyer J, Brown D, Liu RH. Uptake of quercetin and quercetin 3-glucoside from whole onion and apple peel extracts by Caco-2 cell monolayers. J Agric Food Chem 2004; 52(23): 7172-9. [http://dx.doi.org/10.1021/jf030733d]. [PMID: 15537334].
[10]
Pfeuffer M, Auinger A, Bley U, et al. Effect of quercetin on traits of the metabolic syndrome, endothelial function and inflammation in men with different APOE isoforms. Nutr Metab Cardiovasc Dis 2013; 23(5): 403-9. [http://dx.doi.org/10.1016/j.numecd.2011.08.010]. [PMID: 22118955].
[11]
Lotito SB, Frei B. Dietary flavonoids attenuate tumor necrosis factor alpha-induced adhesion molecule expression in human aortic endothelial cells. Structure-function relationships and activity after first pass metabolism. J Biol Chem 2006; 281(48): 37102-10. [http://dx.doi.org/10.1074/jbc.M606804200]. [PMID: 16987811].
[12]
Mamani-Matsuda M, Kauss T, Al-Kharrat A, et al. Therapeutic and preventive properties of quercetin in experimental arthritis correlate with decreased macrophage inflammatory mediators. Biochem Pharmacol 2006; 72(10): 1304-10. [http://dx.doi.org/10.1016/j.bcp.2006.08.001]. [PMID: 16959220].
[13]
Sanders RA, Rauscher FM, Watkins JB III. Effects of quercetin on antioxidant defense in streptozotocin-induced diabetic rats. J Biochem Mol Toxicol 2001; 15(3): 143-9. [http://dx.doi.org/10.1002/jbt.11]. [PMID: 11424224].
[14]
Egert S, Bosy-Westphal A, Seiberl J, et al. 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 2009; 102(7): 1065-74. [http://dx.doi.org/10.1017/S0007114509359127]. [PMID: 19402938].
[15]
Perez-Vizcaino F, Duarte J, Andriantsitohaina R. Endothelial function and cardiovascular disease: effects of quercetin and wine polyphenols. Free Radic Res 2006; 40(10): 1054-65. [http://dx.doi.org/10.1080/10715760600823128]. [PMID: 17015250].
[16]
Serban MC, Sahebkar A, Zanchetti A, et al. Effects of quercetin on blood pressure: a systematic review and meta‐analysis of randomized controlled trials. J Am Heart Assoc 2016; 5(7)e002713 [http://dx.doi.org/10.1161/JAHA.115.002713]. [PMID: 27405810].
[17]
Edwards RL, Lyon T, Litwin SE, Rabovsky A, Symons JD, Jalili T. Quercetin reduces blood pressure in hypertensive subjects. J Nutr 2007; 137(11): 2405-11. [http://dx.doi.org/10.1093/jn/137.11.2405]. [PMID: 17951477].
[18]
Clifton PM. Effect of grape seed extract and quercetin on cardiovascular and endothelial parameters in high-risk subjects. J Biomed Biotechnol 2004; 2004(5): 272-8. [http://dx.doi.org/10.1155/S1110724304403088]. [PMID: 15577189].
[19]
Pfeuffer M, Auinger A, Bley U, et al. Effect of quercetin on traits of the metabolic syndrome, endothelial function and inflammation in men with different APOE isoforms. Nutr Metab Cardiovasc Dis 2013; 23(5): 403-9. [http://dx.doi.org/10.1016/j.numecd.2011.08.010]. [PMID: 22118955].
[20]
Brüll V, Burak C, Stoffel-Wagner B, et al. 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. Br J Nutr 2015; 114(8): 1263-77. [http://dx.doi.org/10.1017/S0007114515002950]. [PMID: 26328470].
[21]
Brüll V, Burak C, Stoffel-Wagner B, et al. Acute intake of quercetin from onion skin extract does not influence postprandial blood pressure and endothelial function in overweight-to-obese adults with hypertension: a randomized, double-blind, placebo-controlled, crossover trial. Eur J Nutr 2017; 56(3): 1347-57. [http://dx.doi.org/10.1007/s00394-016-1185-1]. [PMID: 26924303].
[22]
Schulz E, Gori T, Münzel T. Oxidative stress and endothelial dysfunction in hypertension. Hypertens Res 2011; 34(6): 665-73. [http://dx.doi.org/10.1038/hr.2011.39]. [PMID: 21512515].
[23]
Valente AJ, Irimpen AM, Siebenlist U, Chandrasekar B. OxLDL induces endothelial dysfunction and death via TRAF3IP2: inhibition by HDL3 and AMPK activators. Free Radic Biol Med 2014; 70: 117-28. [http://dx.doi.org/10.1016/j.freeradbiomed.2014.02.014]. [PMID: 24561578].
[24]
Bhaskar S, Sudhakaran PR, Helen A. Quercetin attenuates atherosclerotic inflammation and adhesion molecule expression by modulating TLR-NF-κB signaling pathway. Cell Immunol 2016; 310: 131-40. [http://dx.doi.org/10.1016/j.cellimm.2016.08.011]. [PMID: 27585526].
[25]
Hung CH, Chan SH, Chu PM, Tsai KL. Quercetin is a potent anti-atherosclerotic compound by activation of SIRT1 signaling under oxLDL stimulation. Mol Nutr Food Res 2015; 59(10): 1905-17. [http://dx.doi.org/10.1002/mnfr.201500144]. [PMID: 26202455].
[26]
Barona J, Aristizabal JC, Blesso CN, Volek JS, Fernandez ML. Grape polyphenols reduce blood pressure and increase flow-mediated vasodilation in men with metabolic syndrome. J Nutr 2012; 142(9): 1626-32. [http://dx.doi.org/10.3945/jn.112.162743]. [PMID: 22810991].
[27]
Kim KA, Yim JE. Antioxidative activity of onion peel extract in obese women: a randomized, double-blind, placebo controlled study. J Cancer Prev 2015; 20(3): 202-7. [http://dx.doi.org/10.15430/JCP.2015.20.3.202]. [PMID: 26473159].
[28]
Frostegård J, Wu R, Lemne C, Thulin T, Witztum JL, de Faire U. Circulating oxidized low-density lipoprotein is increased in hypertension. Clin Sci (Lond) 2003; 105(5): 615-20. [http://dx.doi.org/10.1042/CS20030152]. [PMID: 12837127].
[29]
Bergmark C, Wu R, de Faire U, Lefvert AK, Swedenborg J. Patients with early-onset peripheral vascular disease have increased levels of autoantibodies against oxidized LDL. Arterioscler Thromb Vasc Biol 1995; 15(4): 441-5. [http://dx.doi.org/10.1161/01.ATV.15.4.441]. [PMID: 7749854].
[30]
Sánchez M, Galisteo M, Vera R, et al. Quercetin downregulates NADPH oxidase, increases eNOS activity and prevents endothelial dysfunction in spontaneously hypertensive rats. J Hypertens 2006; 24(1): 75-84. [http://dx.doi.org/10.1097/01.hjh.0000198029.22472.d9]. [PMID: 16331104].
[31]
Tribolo S, Lodi F, Connor C, et al. Comparative effects of quercetin and its predominant human metabolites on adhesion molecule expression in activated human vascular endothelial cells. Atherosclerosis 2008; 197(1): 50-6. [http://dx.doi.org/10.1016/j.atherosclerosis.2007.07.040]. [PMID: 17880982].
[32]
Panicker SR, Sreenivas P, Babu MS, Karunagaran D, Kartha CC. Quercetin attenuates monocyte chemoattractant protein-1 gene expression in glucose primed aortic endothelial cells through NF-kappaB and AP-1. Pharmacol Res 2010; 62(4): 328-36. [http://dx.doi.org/10.1016/j.phrs.2010.06.003]. [PMID: 20542118].
[33]
Chen P, Shi Q, Xu X, Wang Y, Chen W, Wang H. Quercetin suppresses NF-κB and MCP-1 expression in a high glucose-induced human mesangial cell proliferation model. Int J Mol Med 2012; 30(1): 119-25. [PMID: 22469745].
[34]
Peet GW, Li J. IkappaB kinases alpha and beta show a random sequential kinetic mechanism and are inhibited by staurosporine and quercetin. J Biol Chem 1999; 274(46): 32655-61. [http://dx.doi.org/10.1074/jbc.274.46.32655]. [PMID: 10551820].
[35]
Yoshizumi M, Tsuchiya K, Suzaki Y, et al. Quercetin glucuronide prevents VSMC hypertrophy by angiotensin II via the inhibition of JNK and AP-1 signaling pathway. Biochem Biophys Res Commun 2002; 293(5): 1458-65. [http://dx.doi.org/10.1016/S0006-291X(02)00407-2]. [PMID: 12054679].
[36]
Häckl LP, Cuttle G, Dovichi SS, Lima-Landman MT, Nicolau M. Inhibition of angiotesin-converting enzyme by quercetin alters the vascular response to brandykinin and angiotensin I. Pharmacology 2002; 65(4): 182-6. [http://dx.doi.org/10.1159/000064341]. [PMID: 12174832].
[37]
Duarte J, Pérez-Palencia R, Vargas F, et al. Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats. Br J Pharmacol 2001; 133(1): 117-24. [http://dx.doi.org/10.1038/sj.bjp.0704064]. [PMID: 11325801].
[38]
Mackraj I, Govender T, Ramesar S. The antihypertensive effects of quercetin in a salt-sensitive model of hypertension. J Cardiovasc Pharmacol 2008; 51(3): 239-45. [http://dx.doi.org/10.1097/FJC.0b013e318162011f]. [PMID: 18356687].
[39]
Zahedi M, Ghiasvand R, Feizi A, Asgari G, Darvish L. 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 2013; 4(7): 777-85. [PMID: 24049596].
[40]
Egert S, Boesch-Saadatmandi C, Wolffram S, Rimbach G, Müller MJ. Serum lipid and blood pressure responses to quercetin vary in overweight patients by apolipoprotein E genotype. J Nutr 2010; 140(2): 278-84. [http://dx.doi.org/10.3945/jn.109.117655]. [PMID: 20032478].
[41]
Biesinger S, Michaels HA, Quadros AS, et al. A combination of isolated phytochemicals and botanical extracts lowers diastolic blood pressure in a randomized controlled trial of hypertensive subjects. Eur J Clin Nutr 2016; 70(1): 10-6. [http://dx.doi.org/10.1038/ejcn.2015.88]. [PMID: 26059745].


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Article Details

VOLUME: 25
ISSUE: 12
Year: 2019
Page: [1372 - 1384]
Pages: 13
DOI: 10.2174/1381612825666190513095352
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