Effect of quercetin supplementation on serum CRP levels: a systematic review and meta-analysis of randomized controlled trials
Abstract
Background: Several studies have investigated the effect of quericitn supplementation on serum C - reactive protein (CRP). However, results were inconsistent. This systematic review and meta-analysis was designed to assess the effect of quercetin supplementation on CRP levels in randomize control trials (RCTs).
Method: We searched PubMed and Scopus up to July 2016 to identify RCTs investigating the effect of quercetin on serum CRP. Meta-analysis was performed using either a fixed-effects or random-effect model according to I² statistic. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) were calculated for net changes in CRP levels.
Results: Seven trials with eight data sets and 346 participants met the inclusion criteria. There was no significant differences for CRP reduction between subjects with quercetin supplementation and placebo control [WMD, 0.01 mg/L; 95% CI: -0.18 to 0.21, p =0.88] with significant heterogeneity (I²=48.9%; p=0.05). Subgroup analyses showed that dose, duration and country were not the potential sources of heterogeneity.
Conclusion: Our results suggest that quercetin supplementation does not reduce serum CRP. Further large and well-designed studies are necessary to confirm this conclusion.
1. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105(9):1135-43.
2. Pradhan A, Ridker P. Do atherosclerosis and type 2 diabetes share a common inflammatory basis? European Heart Journal. 2002;23(11):831-4.
3. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. New England Journal of Medicine. 2005;352(16):1685-95.
4. Kontogianni M, Zampelas A, Tsigos C. Nutrition and inflammatory load. Annals of the New York Academy of Sciences. 2006;1083(1):214-38.
5. Haffner SM. The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease. The American journal of cardiology. 2006;97(2):3-11.
6. Malik S, Wong ND, Franklin S, Pio J, Fairchild C, Chen R. Cardiovascular disease in US patients with metabolic syndrome, diabetes, and elevated C-reactive protein. Diabetes care. 2005;28(3):690-3.
7. Bhaskar S, Sudhakaran P, Helen A. Quercetin attenuates atherosclerotic inflammation and adhesion molecule expression by modulating TLR-NF-κB signaling pathway. Cellular Immunology. 2016;310:131-40.
8. Carullo G, Cappello AR, Frattaruolo L, Badolato M, Armentano B, Aiello F. Quercetin and derivatives: useful tools in inflammation and pain management. Future Medicinal Chemistry. 2017;9(1):79-93.
9. Li Y, Yao J, Han C, Yang J, Chaudhry MT, Wang S, et al. Quercetin, inflammation and immunity. Nutrients. 2016;8(3):167.
10. Overman A, Chuang C, McIntosh M. Quercetin attenuates inflammation in human macrophages and adipocytes exposed to macrophage-conditioned media. International Journal of Obesity. 2011;35(9):1165-72.
11. Formica J, Regelson W. Review of the biology of quercetin and related bioflavonoids. Food and chemical toxicology. 1995;33(12):1061-80.
12. Justesen U, Knuthsen P, Leth T. Determination of plant polyphenols in Danish foodstuffs by HPLC-UV and LC-MS detection. Cancer letters. 1997;114(1-2):165-7.
13. Sampson L, Rimm E, Hollman PC, de VRIES JH, Katan MB. Flavonol and flavone intakes in US health professionals. Journal of the American Dietetic Association. 2002;102(10):1414-20.
14. Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. European journal of pharmacology. 2008;585(2):325-37.
15. 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 and chemical toxicology. 2007;45(11):2179-205.
16. Scalbert A, Williamson G. Dietary intake and bioavailability of polyphenols. The Journal of nutrition. 2000;130(8):2073S-85S.
17. Cermak R, Landgraf S, Wolffram S. The bioavailability of quercetin in pigs depends on the glycoside moiety and on dietary factors. The Journal of nutrition. 2003;133(9):2802-7.
18. Jullian C, Moyano L, Yanez C, Olea-Azar C. Complexation of quercetin with three kinds of cyclodextrins: an antioxidant study. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2007;67(1):230-4.
19. 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 sciences. 2014;109(1):8-14.
20. Kim J-H, Kang M-J, Choi H-N, Jeong S-M, Lee Y-M, Kim J-I. Quercetin attenuates fasting and postprandial hyperglycemia in animal models of diabetes mellitus. Nutrition research and practice. 2011;5(2):107-11.
21. Kelly GS. Quercetin. Altern Med Rev. 2011;16(2):172-94.
22. Lee K-H, Park E, Lee H-J, Kim M-O, Cha Y-J, Kim J-M, et al. Effects of daily quercetin-rich supplementation on cardiometabolic risks in male smokers. Nutrition research and practice. 2011;5(1):28-33.
23. 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. The Journal of nutrition. 2007;137(4):910-5.
24. Mackraj I, Govender T, Ramesar S. The antihypertensive effects of quercetin in a salt-sensitive model of hypertension. Journal of cardiovascular pharmacology. 2008;51(3):239-45.
25. Nabavi SF, Russo GL, Daglia M, Nabavi SM. Role of quercetin as an alternative for obesity treatment: you are what you eat! Food chemistry. 2015;179:305-10.
26. Monori-Kiss A, Monos E, Nádasy GL. Quantitative analysis of vasodilatory action of quercetin on intramural coronary resistance arteries of the rat in vitro. PloS one. 2014;9(8):e105587.
27. Chun OK, Chung S-J, Claycombe KJ, Song WO. Serum C-reactive protein concentrations are inversely associated with dietary flavonoid intake in US adults. The Journal of nutrition. 2008;138(4):753-60.
28. 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. International journal of preventive medicine. 2014;5(3).
29. Nieman DC, Henson DA, Maxwell KR, Williams AS, Mcanulty SR, Jin F, et al. Effects of quercetin and EGCG on mitochondrial biogenesis and immunity. Med Sci Sports Exerc. 2009;41(7):1467-75.
30. 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. The Journal of nutrition. 2010;140(2):278-84.
31. O’Fallon KS, Kaushik D, Michniak-Kohn B, Dunne CP, Zambraski EJ, Clarkson PM. Effects of quercetin supplementation on markers of muscle damage and inflammation after eccentric exercise. International journal of sport nutrition and exercise metabolism. 2012;22(6):430-7.
32. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS med. 2009;6(7):e1000097.
33. 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 clinical trials. 1996;17(1):1-12.
34. Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions: John Wiley & Sons; 2011.
35. Brüll V, Burak C, Stoffel-Wagner B, Wolffram S, Nickenig G, Müller C, 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. European journal of nutrition. 2016:1-11.
36. Nieman DC, Henson DA, Davis JM, Dumke CL, Gross SJ, Jenkins DP, et al. Quercetin ingestion does not alter cytokine changes in athletes competing in the Western States Endurance Run. Journal of Interferon & Cytokine Research. 2007;27(12):1003-12.
37. 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. International journal of preventive medicine. 2013;4(7).
38. Askari G, Ghiasvand R, Feizi A, Ghanadian SM, Karimian J. The effect of quercetin supplementation on selected markers of inflammation and oxidative stress. Journal of Research in Medical Sciences. 2012;17(7).
39. Cochain C, Zernecke A. Macrophages in vascular inflammation and atherosclerosis. Pflügers Archiv-European Journal of Physiology. 2017:1-15.
40. Knekt P, Kumpulainen J, Järvinen R, Rissanen H, Heliövaara M, Reunanen A, et al. Flavonoid intake and risk of chronic diseases. The American journal of clinical nutrition. 2002;76(3):560-8.
41. Nair MP, Mahajan S, Reynolds JL, Aalinkeel R, Nair H, Schwartz SA, et al. The flavonoid quercetin inhibits proinflammatory cytokine (tumor necrosis factor alpha) gene expression in normal peripheral blood mononuclear cells via modulation of the NF-κβ system. Clinical and Vaccine Immunology. 2006;13(3):319-28.
42. Neuhouser ML. Review: Dietary flavonoids and cancer risk: Evidence from human population studies. Nutrition and cancer. 2004;50(1):1-7.
43. Theodoratou E, Kyle J, Cetnarskyj R, Farrington SM, Tenesa A, Barnetson R, et al. Dietary flavonoids and the risk of colorectal cancer. Cancer Epidemiology and Prevention Biomarkers. 2007;16(4):684-93.
44. Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free radical biology and medicine. 1996;20(7):933-56.
45. Wang L, Tu Y-C, Lian T-W, Hung J-T, Yen J-H, Wu M-J. Distinctive antioxidant and antiinflammatory effects of flavonols. Journal of Agricultural and Food Chemistry. 2006;54(26):9798-804.
46. Gardi C, Bauerova K, Stringa B, Kuncirova V, Slovak L, Ponist S, et al. Quercetin reduced inflammation and increased antioxidant defense in rat adjuvant arthritis. Archives of biochemistry and biophysics. 2015;583:150-7.
47. Mahmoud MF, Hassan NA, El Bassossy HM, Fahmy A. Quercetin protects against diabetes-induced exaggerated vasoconstriction in rats: effect on low grade inflammation. PloS one. 2013;8(5):e63784.
48. Manach C, Williamson G, Morand C, Scalbert A, Rémésy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. The American journal of clinical nutrition. 2005;81(1):230S-42S.
49. Perez‐Vizcaino F, Duarte J, Santos‐Buelga C. The flavonoid paradox: conjugation and deconjugation as key steps for the biological activity of flavonoids. Journal of the Science of Food and Agriculture. 2012;92(9):1822-5.
50. Shimoi K, Saka N, Nozawa R, Sato M, Amano I, Nakayama T, et al. Deglucuronidation of a flavonoid, luteolin monoglucuronide, during inflammation. Drug metabolism and disposition. 2001;29(12):1521-4.
51. Hubacek JA, Peasey A, Pikhart H, Stavek P, Kubinova R, Marmot M, et al. APOE polymorphism and its effect on plasma C-reactive protein levels in a large general population sample. Human immunology. 2010;71(3):304-8.
52. Sterne JA, Gavaghan D, Egger M. Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. Journal of clinical epidemiology. 2000;53(11):1119-29.
2. Pradhan A, Ridker P. Do atherosclerosis and type 2 diabetes share a common inflammatory basis? European Heart Journal. 2002;23(11):831-4.
3. Hansson GK. Inflammation, atherosclerosis, and coronary artery disease. New England Journal of Medicine. 2005;352(16):1685-95.
4. Kontogianni M, Zampelas A, Tsigos C. Nutrition and inflammatory load. Annals of the New York Academy of Sciences. 2006;1083(1):214-38.
5. Haffner SM. The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease. The American journal of cardiology. 2006;97(2):3-11.
6. Malik S, Wong ND, Franklin S, Pio J, Fairchild C, Chen R. Cardiovascular disease in US patients with metabolic syndrome, diabetes, and elevated C-reactive protein. Diabetes care. 2005;28(3):690-3.
7. Bhaskar S, Sudhakaran P, Helen A. Quercetin attenuates atherosclerotic inflammation and adhesion molecule expression by modulating TLR-NF-κB signaling pathway. Cellular Immunology. 2016;310:131-40.
8. Carullo G, Cappello AR, Frattaruolo L, Badolato M, Armentano B, Aiello F. Quercetin and derivatives: useful tools in inflammation and pain management. Future Medicinal Chemistry. 2017;9(1):79-93.
9. Li Y, Yao J, Han C, Yang J, Chaudhry MT, Wang S, et al. Quercetin, inflammation and immunity. Nutrients. 2016;8(3):167.
10. Overman A, Chuang C, McIntosh M. Quercetin attenuates inflammation in human macrophages and adipocytes exposed to macrophage-conditioned media. International Journal of Obesity. 2011;35(9):1165-72.
11. Formica J, Regelson W. Review of the biology of quercetin and related bioflavonoids. Food and chemical toxicology. 1995;33(12):1061-80.
12. Justesen U, Knuthsen P, Leth T. Determination of plant polyphenols in Danish foodstuffs by HPLC-UV and LC-MS detection. Cancer letters. 1997;114(1-2):165-7.
13. Sampson L, Rimm E, Hollman PC, de VRIES JH, Katan MB. Flavonol and flavone intakes in US health professionals. Journal of the American Dietetic Association. 2002;102(10):1414-20.
14. Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. European journal of pharmacology. 2008;585(2):325-37.
15. 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 and chemical toxicology. 2007;45(11):2179-205.
16. Scalbert A, Williamson G. Dietary intake and bioavailability of polyphenols. The Journal of nutrition. 2000;130(8):2073S-85S.
17. Cermak R, Landgraf S, Wolffram S. The bioavailability of quercetin in pigs depends on the glycoside moiety and on dietary factors. The Journal of nutrition. 2003;133(9):2802-7.
18. Jullian C, Moyano L, Yanez C, Olea-Azar C. Complexation of quercetin with three kinds of cyclodextrins: an antioxidant study. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy. 2007;67(1):230-4.
19. 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 sciences. 2014;109(1):8-14.
20. Kim J-H, Kang M-J, Choi H-N, Jeong S-M, Lee Y-M, Kim J-I. Quercetin attenuates fasting and postprandial hyperglycemia in animal models of diabetes mellitus. Nutrition research and practice. 2011;5(2):107-11.
21. Kelly GS. Quercetin. Altern Med Rev. 2011;16(2):172-94.
22. Lee K-H, Park E, Lee H-J, Kim M-O, Cha Y-J, Kim J-M, et al. Effects of daily quercetin-rich supplementation on cardiometabolic risks in male smokers. Nutrition research and practice. 2011;5(1):28-33.
23. 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. The Journal of nutrition. 2007;137(4):910-5.
24. Mackraj I, Govender T, Ramesar S. The antihypertensive effects of quercetin in a salt-sensitive model of hypertension. Journal of cardiovascular pharmacology. 2008;51(3):239-45.
25. Nabavi SF, Russo GL, Daglia M, Nabavi SM. Role of quercetin as an alternative for obesity treatment: you are what you eat! Food chemistry. 2015;179:305-10.
26. Monori-Kiss A, Monos E, Nádasy GL. Quantitative analysis of vasodilatory action of quercetin on intramural coronary resistance arteries of the rat in vitro. PloS one. 2014;9(8):e105587.
27. Chun OK, Chung S-J, Claycombe KJ, Song WO. Serum C-reactive protein concentrations are inversely associated with dietary flavonoid intake in US adults. The Journal of nutrition. 2008;138(4):753-60.
28. 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. International journal of preventive medicine. 2014;5(3).
29. Nieman DC, Henson DA, Maxwell KR, Williams AS, Mcanulty SR, Jin F, et al. Effects of quercetin and EGCG on mitochondrial biogenesis and immunity. Med Sci Sports Exerc. 2009;41(7):1467-75.
30. 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. The Journal of nutrition. 2010;140(2):278-84.
31. O’Fallon KS, Kaushik D, Michniak-Kohn B, Dunne CP, Zambraski EJ, Clarkson PM. Effects of quercetin supplementation on markers of muscle damage and inflammation after eccentric exercise. International journal of sport nutrition and exercise metabolism. 2012;22(6):430-7.
32. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS med. 2009;6(7):e1000097.
33. 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 clinical trials. 1996;17(1):1-12.
34. Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions: John Wiley & Sons; 2011.
35. Brüll V, Burak C, Stoffel-Wagner B, Wolffram S, Nickenig G, Müller C, 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. European journal of nutrition. 2016:1-11.
36. Nieman DC, Henson DA, Davis JM, Dumke CL, Gross SJ, Jenkins DP, et al. Quercetin ingestion does not alter cytokine changes in athletes competing in the Western States Endurance Run. Journal of Interferon & Cytokine Research. 2007;27(12):1003-12.
37. 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. International journal of preventive medicine. 2013;4(7).
38. Askari G, Ghiasvand R, Feizi A, Ghanadian SM, Karimian J. The effect of quercetin supplementation on selected markers of inflammation and oxidative stress. Journal of Research in Medical Sciences. 2012;17(7).
39. Cochain C, Zernecke A. Macrophages in vascular inflammation and atherosclerosis. Pflügers Archiv-European Journal of Physiology. 2017:1-15.
40. Knekt P, Kumpulainen J, Järvinen R, Rissanen H, Heliövaara M, Reunanen A, et al. Flavonoid intake and risk of chronic diseases. The American journal of clinical nutrition. 2002;76(3):560-8.
41. Nair MP, Mahajan S, Reynolds JL, Aalinkeel R, Nair H, Schwartz SA, et al. The flavonoid quercetin inhibits proinflammatory cytokine (tumor necrosis factor alpha) gene expression in normal peripheral blood mononuclear cells via modulation of the NF-κβ system. Clinical and Vaccine Immunology. 2006;13(3):319-28.
42. Neuhouser ML. Review: Dietary flavonoids and cancer risk: Evidence from human population studies. Nutrition and cancer. 2004;50(1):1-7.
43. Theodoratou E, Kyle J, Cetnarskyj R, Farrington SM, Tenesa A, Barnetson R, et al. Dietary flavonoids and the risk of colorectal cancer. Cancer Epidemiology and Prevention Biomarkers. 2007;16(4):684-93.
44. Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free radical biology and medicine. 1996;20(7):933-56.
45. Wang L, Tu Y-C, Lian T-W, Hung J-T, Yen J-H, Wu M-J. Distinctive antioxidant and antiinflammatory effects of flavonols. Journal of Agricultural and Food Chemistry. 2006;54(26):9798-804.
46. Gardi C, Bauerova K, Stringa B, Kuncirova V, Slovak L, Ponist S, et al. Quercetin reduced inflammation and increased antioxidant defense in rat adjuvant arthritis. Archives of biochemistry and biophysics. 2015;583:150-7.
47. Mahmoud MF, Hassan NA, El Bassossy HM, Fahmy A. Quercetin protects against diabetes-induced exaggerated vasoconstriction in rats: effect on low grade inflammation. PloS one. 2013;8(5):e63784.
48. Manach C, Williamson G, Morand C, Scalbert A, Rémésy C. Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies. The American journal of clinical nutrition. 2005;81(1):230S-42S.
49. Perez‐Vizcaino F, Duarte J, Santos‐Buelga C. The flavonoid paradox: conjugation and deconjugation as key steps for the biological activity of flavonoids. Journal of the Science of Food and Agriculture. 2012;92(9):1822-5.
50. Shimoi K, Saka N, Nozawa R, Sato M, Amano I, Nakayama T, et al. Deglucuronidation of a flavonoid, luteolin monoglucuronide, during inflammation. Drug metabolism and disposition. 2001;29(12):1521-4.
51. Hubacek JA, Peasey A, Pikhart H, Stavek P, Kubinova R, Marmot M, et al. APOE polymorphism and its effect on plasma C-reactive protein levels in a large general population sample. Human immunology. 2010;71(3):304-8.
52. Sterne JA, Gavaghan D, Egger M. Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. Journal of clinical epidemiology. 2000;53(11):1119-29.
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| Issue | Vol 2, No 3 (Summer 2016) | |
| Section | Review Article(s) | |
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| Quercitin C-reactive protein Meta-analysis | ||
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How to Cite
1.
Khorshidi M, Shab-Bidar S, Kord-Varkaneh H, Djafarian K. Effect of quercetin supplementation on serum CRP levels: a systematic review and meta-analysis of randomized controlled trials. J Nutr Sci & Diet. 2017;2(3).
