Plasma Urate and Risk of Parkinson's Disease

ArticleinAmerican Journal of Epidemiology 166(5):561-7 · October 2007with13 Reads
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 disease.
    • "Given the high metabolic demand of the neurons and their susceptibility to oxidative damage, it has been proposed that urate may prevent oxidative stress and subsequently neurodegeneration (Xu et al., 2002 ). A large body of evidence has revealed increased risk of PD among those with lower levels of plasma and CNS urate, with oxidative stress consistently implicated as a central pathogenic mechanism (Chen, Mosley, Alonso, & Huang, 2009; Jain et al., 2011; O'Reilly et al., 2010; Schwarzschild et al., 2008; Weisskopf, O'Reilly, Chen, Schwarzschild, & Ascherio, 2007). Studies have consistently reported low PD risk among those with higher serum or cerebrospinal fluid urate levels in PD patients compared with healthy controls (Tohgi, Abe, Takahashi, & Kikuchi, 1993). "
    [Show abstract] [Hide abstract] ABSTRACT: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. Although the precise pathogenetic mechanisms of PD remain undetermined, there appears to be both genetic and environmental factors that contribute to the risk of developing PD. With regard to environmental risk factors, there has been significant interest related to the role of diet, nutrition, and nutrients on the onset and progression of PD. As the current treatments are predominantly focused on symptomatic management, efforts must be directed toward prevention of the PD and identification of potentially modifiable risk and preventive factors. This comprehensive review gives an overview of studies examining the role of micronutrients in PD, and provides guidance on the value of the reported outcomes.
    Full-text · Article · Apr 2016
    • "Among men participating in a 30- year prospective study, men with elevated uric acid levels had a 40% reduction in the incidence of PD, unaffected by adjustment for age and smoking [15]. Similarly, a large nested case–control study found that higher plasma concentrations of urate predict risk of PD, with a significantly reduced rate of PD for men in the highest quartile of uricemia compared with the lowest [16]. This notion is strengthened by the finding that a diet which increases plasma urate levels is associated with a reduced PD risk, rendering it unlikely that the association is merely a consequence of shared predisposing factors [17]. "
    [Show abstract] [Hide abstract] ABSTRACT: Uric acid has antioxidant effects on neurons. Abnormally high levels of uric acid are, however, associated with gout. Previous studies have suggested that high levels of uric acid (and the presence of gout) may exert a protective effect against the risk of developing some neurological diseases. We aimed to investigate this hypothesis in a large database of hospital admissions in England. We analysed a database of linked statistical records of hospital admissions and death registrations in England (1999-2012). A cohort of people with gout was constructed and followed for development of multiple sclerosis (MS), Parkinson's disease (PD) or motor neuron disease (MND). Then, conversely, cohorts of all people in the database with MS, PD or MND were constructed and followed for subsequent gout. Rate ratios (RRs) were determined, comparing these cohorts with people in a reference cohort. In the gout cohort, we observed a modest elevation of the overall risk of subsequent MS, PD and MND (respectively, RR = 1.27 (95% confidence interval 1.03-1.55), 1.11 (1.05-1.17) and 1.28 (1.11-1.48) which was largely attributable to an increased risk observed in the early years after hospitalisation for gout. The increased risk of neurological disease did not remain after 5 years. In the cohorts of people with MS or PD, there was a significantly reduced risk of subsequent gout admission (RR = 0.79 (0.69-0.89) and 0.83 (0.79-0.87), respectively). This inverse association was sustained over time. There was also a reduced risk of MND following gout which only emerged more than five years following initial gout admission (RR at 5+ years 0.35 (0.15-0.68)). This study investigated the epidemiological evidence for a protective role of high serum concentration of uric acid, for which we used gout as a proxy, in the aetiology of MS, PD or MND. Our observations do not support this hypothesis. However, when the order was reversed, and we retrospectively followed up patients with MS, PD and MND for a number of years, we found a statistically significant deficit of gout. This suggests that there is relationship between some aspects of these neurodegenerative diseases and metabolism of uric acid.
    Full-text · Article · Dec 2015
    • "Fifth, lacking information on potential confounders, such as serum urate concentration, remains as concern. There are suggestions that hyperuricemia may increase the risk of metabolic syndrome, diabetes, obesity, hypertension and cardiovascular disorders [34], while meta-analysis of three prospective studies found an inverse association between serum uric acid and PD risk [35]. In conclusion, we found that hypertriglyceridemia and hyperglycaemia independently of each other predicted low PD incidence, even within the time frame of excluding the presumable preclinical disease phase after baseline assessment. "
    [Show abstract] [Hide abstract] ABSTRACT: Inconsistent results regarding the association between the components of metabolic syndrome and Parkinson's disease (PD) have been reported. We investigated whether the metabolic syndrome or its components, or serum total cholesterol, predict PD incidence in a prospective cohort study design. The study was based on the Mini-Finland Health Survey including 6641 individuals aged 30-79 and free from PD at baseline (1978-1980). During 30 years of follow-up, 89 incident PD cases occurred. After adjustment for sociodemographic and lifestyle factors, the relative risk (RR) of PD was 0.50 (95% confidence interval (CI): 0.30, 0.83) for individuals with the metabolic syndrome compared to those without. This association was especially due to elevated serum triglyceride concentration (≥1.7 vs.<1.7 mmol/L, RR = 0.52, 95%CI: 0.30-0.89, P for trend 0.02) and elevated plasma fasting glucose concentration (≥5.6 vs.<5.6 mmol/L, RR = 0.56 0.32, 0.98, P for trend 0.05). Elevated serum triglyceride and plasma fasting glucose concentration predicted lower PD risk even after excluding the first 10 years of follow-up. After this exclusion and further adjustment for other components of the metabolic syndrome, a suggestively increased PD risk was observed in overweight individuals (≥25 kg/m(2) vs.<25 kg/m(2), RR = 1.75, 95%CI: 1.00, 3.07, P for trend 0.22). Blood pressure, serum HDL cholesterol, or serum total cholesterol carried no prediction of PD risk. Elevated serum triglyceride and plasma fasting glucose concentrations predict low PD incidence whereas high BMI seems to be suggestively related to an increased PD risk. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Article · Jul 2015
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