Evaluation of the Effects of a Supplement Composed by Quercetin, Rutin, Bromelain and L-Carnosine in Patients with Borderline Uricemia

Giuseppe Derosa^{1, 2,} , Angela D’Angelo^{1, 3} and Pamela Maffioli^{1, 4}

¹Centre of Diabetes and Metabolic Diseases, Department of Internal Medicine and Therapeutics, University of Pavia and Fondazione IRCCS Policlinico San Matteo, PAVIA, Italy.

²Laboratory of Molecular Medicine, University of Pavia, PAVIA, Italy;Centre for Prevention, Surveillance, Diagnosis and Treatment of Rare Diseases, Fondazione IRCCS Policlinico San Matteo, PAVIA, Italy

³Laboratory of Molecular Medicine, University of Pavia, PAVIA, Italy

⁴Centre for Prevention, Surveillance, Diagnosis and Treatment of Rare Diseases, Fondazione IRCCS Policlinico San Matteo, PAVIA, Italy

Cite this paper:
Giuseppe Derosa, Angela D’Angelo and Pamela Maffioli. Evaluation of the Effects of a Supplement Composed by Quercetin, Rutin, Bromelain and L-Carnosine in Patients with Borderline Uricemia. Journal of Food and Nutrition Research. 2020; 8(10):550-555. doi: 10.12691/jfnr-8-10-2

Abstract

The aim of this study was to evaluate if a nutraceutical containing quercetin, rutin, bromelain and L-carnosine (Uricemin®) can reduce uric acid levels in subjects with values between ≥ 6 and < 7 mg/dl after 3 months of therapy. Patients were randomized to Uricemin® or placebo for three months. We evaluated body weight, fasting plasma glucose (FPG), lipid profile, uricemia (UA), high-sensitivity C-reactive protein (Hs-CRP) at baseline and after 3 months since the study start. Treatment tolerability was assessed evaluating transaminases, and creatinine, and all adverse events were recorded. A total of 116 patients were enrolled in the trial. Of these, 59 were randomized to the nutraceutical and 57 to placebo. One hundred and seven subjects completed the study, and were included in the analysis. We did not record any change in glycemia, or lipid profile in neither group. We observed a reduction of uricemia, and Hs-CRP in the group treated with Uricemin®, compared to baseline and to placebo (p < 0.05 for both). The results of this study suggested that a combination of quercetin, rutin, bromelain and L-carnosine can be useful in reducing uricemia in patients with borderline uricemia.

Keywords:
bromelain hyperuricemia L-carnosine quercetin rutin

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Dincer, H.E., Dincer, A.P., Levinson, D.J., “Asymptomatic hyperuricemia: to treat or not to treat”, Cleve Clin J Med, 69(8). 594-608. Aug.2002.
[2]	Neogi, T., “Clinical practice: gout”, N Engl J Med, 364(5). 443-452. Feb.2011.
[3]	Khanna, D., Fitzgerald, J.D., Khanna, P.P., Bae, S., Singh, M.K., Neogi, T., Pillinger, M.H., Merill, J., Lee, S., Prakash, S., Kaldas, M., Gogia, M., Perez-Ruiz, F., Taylor, W., Lioté, F., Choi, H., Singh, J.A., Dalbeth, N., Kaplan, S., Niyyar, V., Jones, D., Yarows, S.A., Roessler, B., Kerr, G., King, C., Levy, G., Furst, D.E., Edwards, N.L., Mandell, B., Schumacher, H.R., Robbins, M., Wenger, N., Terkeltaub, R.; American College of Rheumatology., “2012 American College of Rheumatology guidelines for management of gout. Part 1: systematic nonpharmacologic and pharmacologic therapeutic approaches to hyperuricemia”, Arthritis Care Res, 64(10). 1431-1446. Oct.2012.
[4]	Choi, H.K., Mount, D.B., Reginato, A.M., “Pathogenesis of gout”, Ann Intern Med, 143(7). 499-516. Oct.2005.
[5]	Chen, C., Lu, J.M., Yao, Q., “Hyperuricemia-related diseases and xanthine oxidoreductase (XOR) inhibitors: an overview”, Med Sci Monit, 22. 2501-2512. Jul.2016.
[6]	Lippi, G., Montagnana, M., Franchini, M., Favaloro, E.J., Targher, G., “The paradoxical relationship between serum uric acid and cardiovascular disease”, Clin Chim Acta, 392(1.2). 1-7. Jun.2008.
[7]	Borghi, C., Desideri, G., “Urate-lowering drugs and prevention of cardiovascular disease: the emerging role of xanthine oxidase inhibition”, Hypertension, 67(3). 496-498. Mar.2016.
[8]	Feig, D.I., Kang, D.H., Johnson, R.J., “Uric acid and cardiovascular risk”, N Engl J Med, 359(17). 1811-1821. Oct.2008.
[9]	Borghi, C., Rosei, E.A., Bardin, T., Dawson, J., Dominiczak, A., Kielstein, J.T., Manolis, A.J., Perez-Ruiz, F., Mancia, G., “Serum uric acid and the risk of cardiovascular and renal disease”, J Hypertens, 33(9). 1729-1741. Sep. 2015.
[10]	Shah, A., Keenan, R.T., “Gout, hyperuricemia and the risk of cardiovascular disease: cause and effect?”, Curr Rheumatol Rep, 12(2). 118-124. Apr.2010.
[11]	Katsiki, N., Karagiannis, A., Athyros, V.G., Mikhailidis, D.P., “Hyperuricaemia: more than just a cause of gout?”, J Cardiovasc Med, 14(6). 397-402. Jun.2013.
[12]	Pontremoli, R., “The role of urate-lowering treatment on cardiovascular and renal disease: evidence from CARES, FAST, ALL-HEART, and FEATHER studies”, Curr Med Res Opin, 33(3). 27-32. Nov.2017.
[13]	The Council for International Organisation of Medical Sciences, “Proposed International Guidelines for Biomedical Research Involving Human Subjects, Geneva,” 1982.
[14]	European Diabetes Policy Group 1999., “A desktop guide to type 2 diabetes mellitus,” Diabet Med, 16(9). 716-730. Sep.1999.
[15]	Klose, S., Borner, K., “Enzymatische Bestimmung des Gesamtcholesterins mit dem [Enzymatic dosage of total cholesterolemia by Greiner Selective Analyzer (GSA II)]”, J Clin Chem Clin Biochem 15(3). 121-130. Mar.1978.
[16]	Wahlefeld, A.W., Triglycerides determination after enzymatic hydrolysis, In: Methods of Enzymatic Analysis. Ed. H. U. Bergmeyer, 2nd English ed. Academic Press, New York (USA) 1974; pp. 18-31.
[17]	Havel, R.J., Eder, H.A., Bragdon, J.H., “The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum”, J Clin Invest 34(9). 1345-1353. Sep.1955.
[18]	Friedewald, W.T., Levy, R.I., Fredrickson, D.S., “Estimation of the concentration of low density lipoprotein in plasma, without use of the preparative ultracentrifuge”, Clin Chem, 18(6). 499-502. Jun.1972.
[19]	Cicero, A.F., Rosticci, M., Fogacci, F., Grandi, E., D’Addato, S., Borghi, C.; Brisighella Heart Study Group, “High serum uric acid is associated to poorly controlled blood pressure and higher arterial stiffness in hypertensive subjects”, Eur J Intern Med, 37. 38-42. Jan.2017.
[20]	Rifai, N., Tracy, R.P., Ridker, P.M., “Clinical Efficacy of an Automated High-Sensitivity C-Reactive Protein Assay”, Clin Chem, 45(12). 2136-2141. Dec.1999.
[21]	Winer, B.J., Statistical Principles in Experimental Design. 2nd ed., McGraw-Hill, New York (USA) 1971.
[22]	Day, A.J., Bao, Y., Morgan, M.R., Williamson, G., “Conjugation position of quercetin glucuronides and effect on biological activity”, Free Radic Biol Med, 29(12). 1234-1243. Dec.2000
[23]	Haidari, F., Rashidi, M.R., Eshraghian, M.R., Mahboob, S.A., Shahi, M.M., Keshavarz, S.A., “Hypouricemic and antioxidant activities of Allium cepa Lilliaceae and quercetin in normal and hyperuricemic rats”, Saudi Med J, 29(11). 1573-1579. Nov.2008.
[24]	Mo, S.F., Zhou, F., Lv, Y.Z., Hu, Q.H., Zhang, D.M., Kong, L.D., “Hypouricemic action of selected flavonoids in mice: structure-activity relationships”, Biol Pharm Bull, 30(8). 1551-1556. Aug.2007.
[25]	Auclair, S., Silberberg, M., Gueux, E., Morand, C., Mazur, A., Milenkovic, D., Scalbert, A., “Apple polyphenols and fibers attenuate atherosclerosis in apolipoprotein E-deficient mice.” J Agric Food Chem, 56(14). 5558-5563. Jul.2008.
[26]	Hu, Q.H., Zhang, X., Wang, X., Jiao, R.Q., Kong, L.D., “Quercetin regulates organic ion transporter and uromodulin expression and improves renal function in hyperuricemic mice”, Eur J Nutr, 51(5). 593-606. Aug.2012.
[27]	Egert, S., Wolffram, S., Bosy-Westphal, A., Boesch-Saadatmandi, C., Wagner, A.E., Frank, J., Rimbach, G., Mueller, M.J., “Daily quercetin supplementation dose-dependently increases plasma quercetin concentrations in healthy humans”, J Nutr, 138(9). 1615-1621. Sep.2008.
[28]	Boots, A.W., Wilms, L.C., Swennen, E.L., Kleinjans, J.C., Bast, A., Haenen, G.R., “In vitro and ex vivo anti-inflammatory activity of quercetin in healthy volunteers”, Nutrition, 24(7-8). 703-710. Jul-Aug.2008.
[29]	Lean, M.E., Noroozi, M., Kelly, I., Burns, J., Talwar, D., Sattar, N., Crozier, A., “Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA”, Diabetes, 48(1). 176-181. Jan.1999.
[30]	Princen, H.M., van Duyvenvoorde, W., Buytenhek, R., Blonk, C., Tijburg, L.B., Langius, J.A., Meinders, A.E., Pijl, H., “No effect of consumption of green and black tea on plasma lipid and antioxidant levels and on LDL oxidation in smokers”, Arterioscler Thromb Vasc Biol, 18(5). 833-841. May.1998.
[31]	Castilla, P., Echarri, R., Davalos, A., Cerrato, F., Ortega, H., Teruel, J.L., Lucas, M.F., Gómez-Coronado, D., Ortuño, J., Lasunción, M.A., “Concentrated red grape juice exerts antioxidant, hypolipidemic, and anti-inflammatory effects in both hemodialysis patients and healthy subjects”, Am J Clin Nutr, 84(1). 252-262. Jul.2006.
[32]	Kimira, M., Arai, Y., Shimoi, K., Watanabe, S., “Japanese intake of flavonoids and isoflavonoids from foods”, J Epidemiol, 8(3). 168-175. Aug.1998.
[33]	Shi, Y., Williamson, G., “Quercetin lowers plasma uric acid in pre-hyperuricaemic males: a randomised, double-blinded, placebo-controlled, cross-over trial”, Br J Nutr, 115(5). 800-806. Mar.2016.
[34]	Anyachuckwu Irondi, E., Olalekan Agboola, S., Oboh, G., Boligon, A.A., Athayde, M.L., Shode, F.O., “Guava leaves polyphenolics-rich extract inhibits vital enzymes implicated in gout and hypertension in vitro.” J Intercult Ethnopharmacol, 5(2). 122-130. Mar.2016.
[35]	Rozza, F., Trimarco, V., Izzo, R., Grassi, D., Ferri, C., “Effects of a novel fixed combination of nutraceuticals on serum uric acid concentrations and the lipid profile in asymptomatic hyperuricemic patients: results from the PICONZ-UA Study”, High Blood Press Cardiovasc Prev, 23(4). 381-386. Dec.2016.
[36]	Taussig, S.J., Batkin, S., “Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application: an update”, J Ethnopharmacol, 22(2). 191-203. Feb.1988.
[37]	Seligman, B., “Bromelain: an anti-inflammatory agent” Angiology, 13. 508-510. Nov.1962.
[38]	Maurer, H.R., “Bromelain: biochemistry, pharmacology and medical use”, Cell Mol Life Sci, 58(9). 1234-1245. Aug.2001.
[39]	Cohen, A., Goldman, J., “Bromelain therapy in rheumatoid arthritis” Pa Med J, 67. 27-30. Feb.1964.
[40]	Brien, S., Lewith, G., Walker, A., Hicks, S.M., Middleton, D., “Bromelain as a treatment for osteoarthritis: a review of clinical studies”, Evid Based Complement Alternat Med. 1(3). 251-257. Dec.2004.
[41]	Akhtar, N., Haqqi, T.M., “Current nutraceuticals in the management of osteoarthritis: a review”, Ther Adv Musculoskelet Dis, 4(3). 181-207.Jun.2012.
[42]	Severin, S.E., Skolysheva, L.K., Shur, S.A., Vulfson, P.L., “The pH-dependent conformational transition in glycogen phosphorylase b. The effect of carnosine and anserine on its activity”, Biochem Int, 20(2). 227-238. Feb.1990.
[43]	Ikeda, T., Kimura, K., Hama, T., Tamaki, N., “Activation of rabbit muscle fructose 1,6-bisphosphatase by histidine and carnosine”, J Biochem, 87(1). 179-185. Jan.1980.
[44]	Kubomura, D., Yamada, M., Masui, A., “Tuna extract reduces serum uric acid in gout-free subjects with insignificantly high serum uric acid: A randomized controlled trial”, Biomed Rep, 5(2). 254-258. Aug.2016.
[45]	Sato, M., Karasawa, N., Shimizu, M., Morimatsu, F., Yamada, R., “Safety evaluation of chicken breast extract containing carnosine and anserine”, Food Chem Toxicol, 46(2). 480489. Feb.2008.
[46]	Aoyagi, S., Sugino, T., Kajimoto, Y., Nishitani, M., “Safety of excess administration of CBEXDrcontaining drink on healthy people”, Jpn Pharmacol Ther, 36(3). 225-235. Mar.2008.
[47]	Perez-Ruiz, F., Becker, M.A., “Inflammation: a possible mechanism for a causative role of hyperuricemia/gout in cardiovascular disease”, Curr Med Res Opin, 31(2). 9-14. Sep.2015.