Plasma Urate and Risk of Parkinson's Disease

Department of Environmental Health, Harvard School of Public Health, Boston, MA 02215, USA.
American Journal of Epidemiology (Impact Factor: 5.23). 10/2007; 166(5):561-7. DOI: 10.1093/aje/kwm127
Source: PubMed


Oxidative stress contributes to dopaminergic neuron degeneration in Parkinson's disease. Urate, a potent antioxidant, could
be neuroprotective. To determine whether higher plasma concentrations of urate predict a reduced risk of Parkinson's disease,
the authors conducted a nested case-control study among participants in the Health Professionals Follow-up Study, a cohort
comprising over 18,000 men who provided blood samples in 1993–1995. Eighty-four incident cases of Parkinson's disease were
diagnosed through 2000, and each was randomly matched to two controls by year of birth, race, and time of blood collection.
Rate ratios of Parkinson's disease according to quartile of uricemia were estimated by use of conditional logistic regression.
The mean urate concentration was 5.7 mg/dl among cases and 6.1 mg/dl among controls (p = 0.01). After adjustment for age, smoking, and caffeine, the rate ratio of Parkinson's disease for the highest quartile
of uricemia compared with the lowest was 0.43 (95% confidence interval: 0.18, 1.02; ptrend = 0.017). This association was stronger in analyses excluding cases diagnosed within 4 years (median) from blood collection
(rate ratio = 0.17, 95% confidence interval: 0.04, 0.69; ptrend = 0.010). These results suggest that high plasma urate concentrations may decrease the risk of Parkinson's disease, and they
raise the possibility that interventions to increase plasma urate may reduce the risk and delay the progression of Parkinson's

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    • "Forced exercise may also restore the dopaminergic system and increase dopaminergic neurons' availability in the striatum, possibly through functional enhancement of vesicular dopamine release (Petzinger et al., 2007) or elevation of D 2 receptors (Vuckovic et al., 2010). In humans, physical exercise has been suggested to increase plasma urate levels (Green and Fraser, 1988), which in turn has been associated with lower risk of Parkinson's disease (Weisskopf et al., 2007) and a slower clinical progression (Schwarzschild et al., 2008). Additionally, physical inactivity may lead to overweight or obesity, which has been suggested to decrease striatal D 2 receptor availability (Wang et al., 2001), in turn associated with higher Parkinson's disease risk (Hu et al., 2006;Hawkes, 2008). "
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    ABSTRACT: Physical exercise has been associated with neuroprotective effects in the nigrostriatal dopaminergic system. To examine the impact of physical activity on Parkinson's disease risk prospectively, we followed 43 368 individuals who provided extensive information on physical activity at baseline. We estimated hazard ratios with 95% confidence intervals using Cox proportional hazards regression. During an average of 12.6 years of follow-up, 286 incident Parkinson's disease cases were identified. In males, there was an inverse association with Parkinson's disease for total physical activity (hazard ratio 0.55, 95% confidence interval 0.35-0.87 for medium versus low level), for sum of household, commuting and leisure time exercise (hazard ratio 0.53, 95% confidence interval 0.33-0.85 for high versus low level), and for household and commuting physical activity specifically (hazard ratio 0.50, 95% confidence interval 0.31-0.81 for >6 versus <2 h per week). No association was observed for leisure time exercise or occupational physical activity with Parkinson's disease, among either males or females. Meta-analysis of the present study and five previous prospective studies showed a pooled hazard ratio of 0.66 (95% confidence interval 0.57-0.78) for highest versus lowest physical activity level. Our results indicate that a medium level of physical activity lowers Parkinson's disease risk. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email:
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    • "The possibility that endogenous urate may protect the integrity of the nigrostriatal dopaminergic system has been suggested by epidemiological studies that have indicated the existence of an inverse correlation between high uricemia and incidence of PD ( Davis et al . 1996 ; De Lau et al . 2005 ; Weisskopf et al . 2007 ; Ascherio et al . 2009 ; Chen et al . 2009 ) . In line with this , previous preclinical findings have demonstrated a crucial role for purinergic signaling in neurotoxicity or neuroprotection phenomena ( Gomes et al . 2011 ) 9 . By demonstrating an elevation in the striatal levels of urate in two experimental models of PD , this study e"

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    • "This conflicting result of our study could be due to the relatively small sample size. Although there is still some indistinctness over whether low serum uric acid level is a cause or a result of PD[13], the prospective studies[14][15]reporting susceptibility to PD in people with lower serum urate levels make it reasonable to consider this situation as the cause of the disease rather than the result of it. According to this opinion, examining the serum urate levels periodically, especially in people who have family history of PD, may be predictable for the disease in asymptomatic relatives. "
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    ABSTRACT: Background: The antioxidant effect of uric acid has been proposed to be involved in Parkinson’s disease. A role of lipid and cholesterol metabolism in the pathogenesis of this neurodegenerative disease has been reported. Body mass index also has been suggested as a risk factor. Objective: We aimed to determine whether serum uric acid level, body mass index (BMI) and lipid profile have any roles in the stages of Parkinson’s disease and the duration of the symptoms. Methods: Fifty-six patients diagnosed with idiopathic Parkinson’s disease and forty gender- and age-matched healthy controls were included in the study. Serum uric acid levels, total cholesterol, LDL cholesterol (LDL-c), HDL cholesterol (HDL-c), tryglyceride (TG) levels and BMI were taken into account. Statistical analysis of the data was done using the SPSS 11.5 programme. P<0.05 was accepted as significant. Results: Patients had lower serum uric acid levels and higher HDL-c levels than controls. Between the two groups, no significant differences were observed in respect to BMI, total cholesterol, LDL-c and TG. There were no statistical associations between uric acid levels, total cholesterol, LDL-c, HDL-c, TG, BMI and duration or stage of the disease. Conclusions: Lower uric acid levels may be associated with the increased risk of Parkinson’s disease; higher levels of HDL-c may accompany Parkinson’s disease; while BMI may not be related to the stage of Parkinson’s disease or the duration of the symptoms.
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