Hostname: page-component-797576ffbb-pxgks Total loading time: 0 Render date: 2023-12-09T22:02:56.063Z Has data issue: false Feature Flags: { "corePageComponentGetUserInfoFromSharedSession": true, "coreDisableEcommerce": false, "useRatesEcommerce": true } hasContentIssue false

Serum Urate and the Risk of Parkinson's Disease: Results From a Meta-Analysis

Published online by Cambridge University Press:  23 September 2014

Chunhong Shen
Department of Neurology, Second Affiliated Hospital, Zhejiang University, Hangzhou, China
Yi Guo
Department of Neurology, Second Affiliated Hospital, Zhejiang University, Hangzhou, China
Wei Luo
Department of Neurology, Second Affiliated Hospital, Zhejiang University, Hangzhou, China
Chen Lin
School of Medicine, Zhejiang University, Hangzhou, China
Meiping Ding*
Department of Neurology, Second Affiliated Hospital, Zhejiang University, Hangzhou, China
Department of Neurology, Second Affiliated Hospital, School of Medicine, Zhejiang University, No. 88, Jiefang Road, Hangzhou 310009, China. email address:
Rights & Permissions [Opens in a new window]


Core share and HTML view are not possible as this article does not have html content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

Serum urate may exert protective effects against Parkinson's disease (PD) through its antioxidant capacities. In this article, we examine the hypothesis that high serum urate levels are associated with lower risk of PD.


We searched NCBI (PubMed), ISI Web of Science and EMBASE for studies that reported the risk of PD associated with serum urate. Fixed or random effects meta-analysis was used to pool results across studies, and further analysis was used to assess the effects by gender.


Six studies met the inclusion criteria involving a total of 33 185 participants. Overall, we found a 33% reduction in PD incidence among persons with high serum urate level (relative risk [RR]=0.67; 95% confidence interval [CI], 0.50-0.91). Subgroup analysis was performed with 20 641 men and 12 544 women included, indicating statistically significant protective effects of serum urate in men (RR=0.60; 95% CI, 0.40-0.90) but not in women. A dose-response trend of serum urate to reduce PD risk was also observed involving 11 795 participants (RR=0.77; 95% CI, 0.68-0.88). Additionally, high serum urate levels seemed to slow the clinical decline of PD patients (RR=0.56; 95% CI, 0.43-0.72).


In light of these findings, our study confirms previous findings of a robust association between high serum urate level and PD risk, especially in men. It also suggests that long-term exposure to high serum urate may be linked to the delay of PD progression, however more well-designed investigations are needed.

Original Article
Copyright © The Canadian Journal of Neurological 2013


1. Driver, JA, Kurth, T, Buring, JE, Gaziano, JM, Logroscino, G. Parkinson disease and risk of mortality: a prospective comorbidity-matched cohort study. Neurology. 2008;70(pt 2):1423–30.Google Scholar
2. Dorsey, ER, Constantinescu, R, Thompson, JP, et al. Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030. Neurology. 2007;68:384–6.Google Scholar
3. Schlesinger, I, Schlesinger, N. Uric acid in Parkinson's disease. Mov Disord. 2008;23:1653–7.Google Scholar
4. Jenner, P. Oxidative stress and Parkinson's disease. Handb Clin Neurol. 2007;83:507–20.Google Scholar
5. Lotharius, J, Brundin, P. Pathogenesis of Parkinson's disease: dopamine, vesicles and alpha-synuclein. Nat Rev Neurosci. 2002;3(12):932–42.Google Scholar
6. Ames, BN, Cathcart, R, Schwiers, E, Hochstein, P. Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis. Proc Natl Acad Sci. 1981;78:6858–62.Google Scholar
7. Gao, X, Chen, H, Choi, HK, Curhan, G, Schwarzschild, MA, Ascherio, A. Diet, urate, and Parkinson's disease risk in men. Am J Epidemiol. 2008;167(7):831–8.Google Scholar
8. De Lau, LM, Koudstaal, PJ, Hofman, A, Breteler, MMB. Serum uric acid levels and the risk of Parkinson disease. Ann Neurol. 2005;58(5):797800.Google Scholar
9. Davis, JW, Grandinetti, A, Waslien, CI, Ross, GW, White, LR, Morens, DM. Observations on serum uric acid levels and the risk of idiopathic Parkinson's disease. Am J Epidemiol. 1996;144(5):480–4.Google Scholar
10. O’Reilly, ÉJ, Gao, X, Weisskopf, MG, et al. Plasma urate and Parkinson's disease in women. Am J Epidemiol. 2010;172(6):666–70.Google Scholar
11. Alonso, A, Rodríguez, LAG, Logroscino, G, Hernán, MA. Gout and risk of Parkinson disease: a prospective study. Neurology. 2007;69(17):1696–700.Google Scholar
12. Stroup, DF, Berlin, JA, Morton, SC, et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. meta-analysis of observational studies in epidemiology (MOOSE) group. JAMA. 2000;283:2008–12.Google Scholar
13. Wells, G, Shea, B, O’Connell, D, et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Ottawa Health Research Institute.Google Scholar
14. Wilcox, WR, Khalaf, A, Weinberger, A, et al. Solubility of uric acid and monosodium urate. Med Biol Eng. 1972;10(4):522–31.Google Scholar
15. Winquist, A, Steenland, K, Shankar, A. High serum uric acid associated with decreased Parkinson's disease prevalence in a large community-based survey. Mov Disord. 2010;25:932–6.Google Scholar
16. Schwarzschild, MA, Schwid, SR, Marek, K, et al. Serum urate as a predictor of clinical and radiographic progression in Parkinson disease. Arch Neurol. 2008;65(6):716–23.Google Scholar
17. Ascherio, A, LeWitt, PA, Xu, K, et al. Urate as a predictor of the rate of clinical decline in Parkinson disease. Arch Neurol. 2009;66(12):1460–8.Google Scholar
18. De Vera, M, Rahman, MM, Rankin, J, Kopec, J, Gao, X, Choi, H. Gout and the risk of Parkinson's disease: a cohort study. Arthritis Rheum. 2008;59(11):1549–54.Google Scholar
19. Chen, H, Mosley, TH, Alonso, A, Huang, X. Plasma urate and Parkinson's disease in the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol. 2009;169(9):1064–9.Google Scholar
20. Jain, S, Ton, TG, Boudreau, RM, et al. The risk of Parkinson disease associated with urate in a community-based cohort of older adults. Neuroepidemiology. 2011;36(4):223–9.Google Scholar
21. Weisskopf, MG, O’reilly, ÉJ, Chen, H, Schwarzschild, MA, Ascherio, A. Plasma urate and risk of Parkinson's disease. Am J Epidemiol. 2007;166(5):561–7.Google Scholar
22. Zhang, HN, Guo, JF, He, D, et al. Lower serum UA levels in Parkinson's disease patients in the Chinese population. Neurosci Lett. 2012;514:152–5Google Scholar
23. Sun, CC, Luo, FF, Wei, L, et al. Association of serum uric acid levels with the progression of Parkinson's disease in Chinese patients. Chinese Med J-Peking. 2012;125(4):583–7Google Scholar
24. Jesús, S, Pérez, I, Cáceres-Redondo, MT, et al. Low serum uric acid concentration in Parkinson's disease in southern Spain. Eur J Neurol. 2012 May 12. doi: 10.1111/j.14681331.2012.03745.x. [Epub ahead of print]Google Scholar
25. Ascherio, A, Weisskopf, MG, O’Reilly, ÉJ, et al. Coffee consumption, gender, and Parkinson's disease mortality in the Cancer Prevention Study II cohort: the modifying effects of estrogen. Am J Epidemiol. 2004;160(10):977–84.Google Scholar
26. Nilsen, J, Brinton, RD. Mitochondria as therapeutic targets of estrogen action in the central nervous system. Curr Drug Targets Neurol Disord. 2004;3:297313.Google Scholar
27. Ikeda, K, Nakamura, Y, Kiyozuka, T, et al. Serological profiles of urate, paraoxonase-1, ferritin and lipid in Parkinson's disease: changes linked to disease progression. Neurodegener Dis. 2011;8(4):252–8.Google Scholar
28. Andreadou, E, Nikolaou, C, Gournaras, F, et al. Serum uric acid levels in patients with Parkinson's disease: their relationship to treatment and disease duration. Clin Neurol Neurosur. 2009;111(9):724–8.Google Scholar
29. Duan, W, Ladenheim, B, Cutler, RG, Kruman, II, Cadet, JL, Mattson, MP. Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson's disease. J. Neurochem. 2002;80(1):101–10.Google Scholar
30. Whiteman, M, Ketsawatsakul, U, Halliwell, B. A reassessment of the peroxynitrite scavenging activity of uric acid. Ann NY Acad Sci. 2002;962:242–59.Google Scholar
31. Sies, H. Oxidative stress:oxidants and antioxidants. Exp Physiol. 1997;82:291–5.Google Scholar
32. Everse, J, Coates, PW. The cytotoxic activity of lactoperoxidase: enhancement and inhibition by neuroactive compounds. Free Radic Biol Med. 2004; 37:839–49.Google Scholar
33. Jones, DC, Gunasekar, PG, Borowitz, JL, Isom, GE. Dopamine-induced apoptosis is mediated by oxidative stress and is enhanced by cyanide in differentiated PC12 cells. J Neurochem. 2000;74:2296–304.Google Scholar
34. Church, WH, Ward, VL. Uric acid is reduced in the substantia nigra in Parkinson's disease: effect on dopamine oxidation. Brain Res Bull. 1994;33(4):419–25.Google Scholar
35. Guerreiro, S, Ponceau, A, Toulorge, D, et al. Protection of midbrain dopaminergic neurons by the end-product of purine metabolism uric acid: potentiation by low-level depolarization. J Neurochem. 2009;109(4):1118–28.Google Scholar
36. Niklasson, F, Agren, H. Brain energy metabolism and bloodbrain barrier permeability in depressive patients: analyses of creatine, creatinine, urate, and albumin in CSF and blood. Biol Psychiatry. 1984;19:1183–206.Google Scholar
37. Kortekaas, R, Leenders, KL, Van Oostrom, JC, et al. Blood-brainbarrier dysfunction in parkinsonian midbrain in vivo. Ann Neurol. 2005;57:176–9.Google Scholar
38. Hooper, DC, Kean, RB, Scott, GS, et al. The central nervous system inflammatory response to neurotropic virus infection is peroxynitrite dependent. J Immunol. 2001;167: 3470–7.Google Scholar
39. Kehrer, JP. The Haber-Weiss reaction and mechanisms of toxicity. Toxicology. 2000;149(1):4350.Google Scholar
40. Miura, T, Muraoka, S, Ogiso, T. Inhibitory effect of urate on oxidative damage induced by adriamycin-Fe3+ in the presence of H2O2 . Res Commun Chem Pathol Pharmacol. 1993;79(1):7585.Google Scholar
41. Einsele, H, Clemens, MR, Wegner, U, Waller, HD. Effect of free radical scavengers and metal ion chelators on hydrogen peroxide and phenylhydrazine induced red blood cell lipid peroxidation. Free Radical Res. 1987;3(1–5):257–63.Google Scholar
42. Spitsin, S, Hooper, DC, Leist, T, Streletz, LJ, Mikheeva, T, Koprowskiet, H. Inactivation of peroxynitrite in multiple sclerosis patients after oral administration of inosine may suggest possible approaches to therapy of the disease. Mult Scler. 2001;7(5):313–9.Google Scholar
43. Wheeler, JG, Juzwishin, KD, Eiriksdottir, G, Gudnason, V, Danesh, J. Serum uric acid and coronary heart disease in 9458 incident cases and 155084 controls: prospective study and meta-analysis. PLoS Med. 2005;2(3):e76.Google Scholar
44. Grayson, PC, Kim, SY, Valley, ML, Choi, HK. Hyperuricemia and incident hypertension: a systematic review and meta-analysis. Arthritis Care Res. 2011;63(1):102–10.Google Scholar
45. Kim, SY, Guevara, JP, Kim, KM, Choi, HK, Heitjan, DF, Albert, DA. Hyperuricemia and risk of stroke: A systematic review and meta-analysis. Arthrit Care Res. 2009;61(7):885–92.Google Scholar