Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Effects of supplementation with quercetin on plasma C-reactive protein concentrations: a systematic review and meta-analysis of randomized controlled trials

European Journal of Clinical Nutrition volume 71, pages 1033–1039 (2017)Cite this article

Subjects

Abstract

Promising experimental studies suggest that quercetin has potential anti-inflammatory effects. However, the results of current clinical trials on quercetin’s effects on the C-reactive protein (CRP), a sensitive inflammatory biomarker, are ambiguous. We conducted a meta-analysis of available randomized controlled trials (RCTs) to resolve this inconsistency and quantify the net effect of quercetin on circulating CRP concentrations. A systematic search was performed in several databases including SCOPUS, PubMed–Medline and Google Scholar until 16 June 2016. We used a random-effects model in combination with weight mean difference (WMD) and 95% confidence intervals (CI) for data analysis. Standard methods were used for the assessment of heterogeneity, meta-regression, sensitivity analysis and publication bias. The meta-analysis of seven RCTs (10 treatment arms) showed a significant reduction of circulating CRP levels (WMD: −0.33 mg/l; 95% CI: −0.50 to −0.15; P<0.001) following quercetin supplementation. In the subgroup analysis, a significant reducing effect was observed in trials with ⩾500 mg/day dosage (WMD: −0.34 mg/l; 95% CI: −0.52, −0.16; P⩽0.001) and in those with CRP <3 mg/l (WMD: −0.34 mg/l; 95% CI: −0.51, −0.18; P⩽0.001). In meta-regression, there was no association between changes in CRP concentrations, dose of supplementation and CRP baseline values. Our findings showed a significant effect of quercetin supplementation on the C-reactive protein—especially at doses above 500 mg/day and in patients with CRP <3 mg/l.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Knekt P, Jarvinen R, Reunanen A, Maatela J . Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ 1996; 312: 478–481.

    Article  CAS  Google Scholar 

  2. Ferreyra MLF, Rius SP, Casati P . Flavonoids: biosynthesis, biological functions, and biotechnological applications. Front Plant Sci 2012; 3: 222.

    Google Scholar 

  3. Erlund I . Review of the flavonoids quercetin, hesperetin, and naringenin. Dietary sources, bioactivities, bioavailability, and epidemiology. Nutr Res 2004; 24: 851–874.

    Article  CAS  Google Scholar 

  4. D'Andrea G . Quercetin: a flavonol with multifaceted therapeutic applications? Fitoterapia 2015; 106: 256–271.

    Article  CAS  Google Scholar 

  5. Guillermo Gormaz J, Quintremil S, Rodrigo R . Cardiovascular disease: a target for the pharmacological effects of quercetin. Curr Top Med Chem 2015; 15: 1735–1742.

    Article  Google Scholar 

  6. Kleemann R, Verschuren L, Morrison M, Zadelaar S, van Erk MJ, Wielinga PY et al. Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models. Atherosclerosis 2011; 218: 44–52.

    Article  CAS  Google Scholar 

  7. Lakhanpal P, Rai DK . Quercetin: a versatile flavonoid. Internet J Med Update 2007; 2: 22–37.

    Google Scholar 

  8. Sanchez M, Lodi F, Vera R, Villar IC, Cogolludo A, Jimenez R et al. Quercetin and isorhamnetin prevent endothelial dysfunction, superoxide production, and overexpression of p47phox induced by angiotensin II in rat aorta. J Nutr 2007; 137: 910–915.

    Article  CAS  Google Scholar 

  9. Hubbard G, Stevens J, Cicmil M, Sage T, Jordan P, Williams C et al. Quercetin inhibits collagen‐stimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway. J Thromb Haemost 2003; 1: 1079–1088.

    Article  CAS  Google Scholar 

  10. Alam MM, Meerza D, Naseem I . Protective effect of quercetin on hyperglycemia, oxidative stress and DNA damage in alloxan induced type 2 diabetic mice. Life Sci 2014; 109: 8–14.

    Article  CAS  Google Scholar 

  11. Nabavi SF, Russo GL, Daglia M, Nabavi SM . Role of quercetin as an alternative for obesity treatment: you are what you eat!. Food Chem 2015; 179: 305–310.

    Article  CAS  Google Scholar 

  12. Men K, Duan X, Wei X, Ling Gou M, Juan Huang M, Juan Chen L et al. Nanoparticle-delivered quercetin for cancer therapy. Anti-Cancer Agents Med Chem 2014; 14: 826–832.

    Article  CAS  Google Scholar 

  13. Bischoff SC . Quercetin: potentials in the prevention and therapy of disease. Curr Opin Clin Nutr Metab Care 2008; 11: 733–740.

    Article  CAS  Google Scholar 

  14. Collaboration ERF. C-reactive protein, fibrinogen, and cardiovascular disease prediction. N Engl J Med 2012; 2012: 1310–1320.

    Article  Google Scholar 

  15. Venugopal SK, Devaraj S, Jialal I . Effect of C-reactive protein on vascular cells: evidence for a proinflammatory, proatherogenic role. Curr Opin Nephrol Hypertens 2005; 14: 33–37.

    Article  CAS  Google Scholar 

  16. Pasceri V, Willerson JT, Yeh ET . Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 2000; 102: 2165–2168.

    Article  CAS  Google Scholar 

  17. Das N, Sikder K, Bhattacharjee S, Majumdar SB, Ghosh S, Majumdar S et al. Quercetin alleviates inflammation after short-term treatment in high-fat-fed mice. Food Funct 2013; 4: 889–898.

    Article  CAS  Google Scholar 

  18. González-Segovia R, Quintanar JL, Salinas E, Ceballos-Salazar R, Aviles-Jiménez F, Torres-López J . Effect of the flavonoid quercetin on inflammation and lipid peroxidation induced by Helicobacter pylori in gastric mucosa of guinea pig. J Gastroenterol 2008; 43: 441–447.

    Article  Google Scholar 

  19. Askari G, Ghiasvand R, Feizi A, Ghanadian SM, Karimian J . The effect of quercetin supplementation on selected markers of inflammation and oxidative stress. J Res Med Sci 2012; 17: 637–641.

    PubMed  PubMed Central  Google Scholar 

  20. 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: 278–284.

    Article  CAS  Google Scholar 

  21. Egert S, Bosy-Westphal A, Seiberl J, Kürbitz C, Settler U, Plachta-Danielzik S 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: 1065–1074.

    Article  CAS  Google Scholar 

  22. Javadi F, Eghtesadi S, Ahmadzadeh A, Aryaeian N, Zabihiyeganeh M, Foroushani AR et al. The effect of quercetin on plasma oxidative status, C-reactive protein and blood pressure in women with rheumatoid arthritis. Int J Prev Med 2014; 5: 293–301.

    PubMed  PubMed Central  Google Scholar 

  23. 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: 777–785.

    PubMed  PubMed Central  Google Scholar 

  24. Dower JI, Geleijnse JM, Gijsbers L, Schalkwijk C, Kromhout D, Hollman PC . Supplementation of the pure flavonoids epicatechin and quercetin affects some biomarkers of endothelial dysfunction and inflammation in (pre) hypertensive adults: a randomized double-blind, placebo-controlled, crossover trial. J Nutr 2015; 145: 1459–1463.

    Article  CAS  Google Scholar 

  25. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev 2015; 4: 1.

    Article  Google Scholar 

  26. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJM, Gavaghan DJ et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Controlled Clin Trials 1996; 17: 1–12.

    Article  CAS  Google Scholar 

  27. Moher D, Cook D, Jadad A, Tugwell P, Moher M, Jones A et al. Assessing the quality of reports of randomised trials: implications for the conduct of meta-analyses. Health Technol Assess 1999; 3: 1–98. i.

    Article  Google Scholar 

  28. Borenstein M, Hedges L, Higgins J, Rothstein H . Comprehensive Meta-Analysis Version 2. Biostat: Englewood, NJ, 2005, pp 104.

    Google Scholar 

  29. Brüll V, Burak C, Stoffel-Wagner B, Wolffram S, Nickenig G, Müller C 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: 1263–1277.

    Article  Google Scholar 

  30. Pfeuffer M, Auinger A, Bley U, Kraus-Stojanowic I, Laue C, Winkler P 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: 403–409.

    Article  CAS  Google Scholar 

  31. Erdman JW, Balentine D, Arab L, Beecher G, Dwyer JT, Folts J et al. Flavonoids and heart health: proceedings of the ILSI North America flavonoids workshop, May 31–June 1, 2005, Washington, DC. J Nutr 2007; 137: 718S–737S.

    Article  CAS  Google Scholar 

  32. Bhaskar S, Kumar KS, Krishnan K, Antony H . Quercetin alleviates hypercholesterolemic diet induced inflammation during progression and regression of atherosclerosis in rabbits. Nutrition 2013; 29: 219–229.

    Article  CAS  Google Scholar 

  33. García-Mediavilla V, Crespo I, Collado PS, Esteller A, Sánchez-Campos S, Tuñón MJ et al. The anti-inflammatory flavones quercetin and kaempferol cause inhibition of inducible nitric oxide synthase, cyclooxygenase-2 and reactive C-protein, and down-regulation of the nuclear factor kappaB pathway in Chang Liver cells. Eur J Pharmacol 2007; 557: 221–229.

    Article  Google Scholar 

  34. Zahedi M, Ghiasvand R, Feizi A, Asgari G, Darvishi 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: 777–785.

    PubMed  PubMed Central  Google Scholar 

  35. Boots AW, Wilms LC, Swennen EL, Kleinjans JC, Bast A, Haenen GR . In vitro and ex vivo anti-inflammatory activity of quercetin in healthy volunteers. Nutrition 2008; 24: 703–710.

    Article  CAS  Google Scholar 

  36. Rivera L, Morón R, Sánchez M, Zarzuelo A, Galisteo M . Quercetin ameliorates metabolic syndrome and improves the inflammatory status in obese Zucker rats. Obesity 2008; 16: 2081–2087.

    Article  CAS  Google Scholar 

  37. Loke WM, Proudfoot JM, Stewart S, McKinley AJ, Needs PW, Kroon PA et al. Metabolic transformation has a profound effect on anti-inflammatory activity of flavonoids such as quercetin: lack of association between antioxidant and lipoxygenase inhibitory activity. Biochem Pharmacol 2008; 75: 1045–1053.

    Article  CAS  Google Scholar 

  38. Kumazawa Y, Kawaguchi K, Takimoto H . Immunomodulating effects of flavonoids on acute and chronic inflammatory responses caused by tumor necrosis factor alpha. Curr Pharm Des 2006; 12: 4271–4279.

    Article  CAS  Google Scholar 

  39. Harwood M, Danielewska-Nikiel B, Borzelleca J, Flamm G, Williams G, Lines T . A critical review of the data related to the safety of quercetin and lack of evidence of in vivo toxicity, including lack of genotoxic/carcinogenic properties. Food Chem Toxicol 2007; 45: 2179–2205.

    Article  CAS  Google Scholar 

  40. Ambrose AM, Robbins DJ, Deeds F . Comparative toxicities of quercetin and quercitrin. J Am Pharmaceut Assoc 1952; 41: 119–122.

    Article  CAS  Google Scholar 

  41. Saito D, Shirai A, Matsushima T, Sugimura T, Hirono I . Test of carcinogenicity of quercetin, a widely distributed mutagen in food. Teratog Carcinog Mutagen 1980; 1: 213–221.

    Article  CAS  Google Scholar 

  42. Hirono I, Ueno I, Hosaka S, Takanashi H, Matsushima T, Sugimura T et al. Carcinogenicity examination of quercetin and rutin in ACI rats. Cancer Lett 1981; 13: 15–21.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

    M Mohammadi-Sartang, Z Mazloom, S Sherafatmanesh & Donya Firoozi

  2. Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

    M Ghorbani

Authors
  1. M Mohammadi-Sartang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Z Mazloom
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S Sherafatmanesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Ghorbani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Donya Firoozi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Z Mazloom.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Author contributions

MMS and ZM conceived the study. MMS carried out the literature search and wrote the manuscript. SSH and DF carried out data extraction and independent reviewing. MMS and ZM assessed the quality of included studies. MMS and MGH performed data analysis and interpretation. ZM revised the manuscript. The manuscript has been read and approved by all authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mohammadi-Sartang, M., Mazloom, Z., Sherafatmanesh, S. et al. Effects of supplementation with quercetin on plasma C-reactive protein concentrations: a systematic review and meta-analysis of randomized controlled trials. Eur J Clin Nutr 71, 1033–1039 (2017). https://doi.org/10.1038/ejcn.2017.55

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2017.55

This article is cited by

Search

Advanced search

Quick links