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In a new, large-scale, prospective study exploring the link between levels of urate in the blood and risk of Parkinson's disease, scientists from the Harvard School of Public Health (HSPH) have observed that high levels of urate are strongly linked to a reduced risk of the disease. The findings were published online on June 20, 2007 in The American Journal of Epidemiology and will appear in an upcoming print issue of the journal.

Urate is a normal component of blood, and eventhough high levels can lead to gout, urate might also have beneficial effects because it is a potent antioxidant. Parkinson's disease is a chronic, progressive nerve disorder linked to destruction of brain cells producing dopamine, a neurotransmitter essential to the normal functioning of the central nervous system.

"This is the strongest evidence to date that urate may protect against Parkinson's disease," said lead author Marc Weisskopf, Assistant Professor of Environmental and Occupational Epidemiology at HSPH.

The scientists used the HSPH-based Health Professionals Follow-up Study, a population of male health professionals established in 1986, as the source for their data. The study cohort included more than 18,000 men without Parkinson's disease who had provided blood samples between 1993 and 1995 and whose subsequent health status was followed.

The scientists observed that men in the top quartile of blood urate concentration had 55 percent lower risk of developing Parkinson's disease than men in the bottom quartile. This difference was not explained by differences in age or other risk factors for Parkinson's disease. The results of two prior studies had suggested a possible inverse relation between blood urate and risk of Parkinson's disease, but it is only when the prior data were combined with those of this new study that the evidence became compelling.

The authors hypothesize that urate's antioxidant properties may help dampen the effects of oxidative stress, which appears to contribute to the progressive loss of the dopamine-producing brain cells that occurs in individuals with Parkinson's disease. If so, elevating blood urate could be helpful for patients with Parkinson's disease, said Alberto Ascherio, Associate Professor of Nutrition and Epidemiology at HSPH and senior author of the study. To follow-up on this clue, Ascherio, along with co-author Michael Schwarzschild, a movement disorder specialist at Massachusetts General Hospital, and his colleagues at the Parkinson Study Group, a collaborative group of Parkinson's disease scientists from the U.S. and Canada, accessed the databases of two large, randomized studies conducted among patients with early Parkinson's disease. The preliminary results, presented in abstract form at recent meetings, showed a slower progression of the disease among individuals with high blood urate.

"It is still uncertain whether urate exerts a neuroprotective effect, but approaches to elevating urate levels are nonetheless worth considering as a potential neuroprotective strategy," said Ascherio, who is now collaborating with Schwarzschild and others in the design of a clinical trial in individuals with Parkinson's disease to examine this possibility. "But elevating blood urate increases the risk of kidney stones and may have adverse cardiovascular effects and should only be attempted in the context of a closely monitored randomized trial until beneficial effects are proven," he added.

The study was supported by National Institutes of Health/National Institute of Neurological Disorders and Stroke, the Kinetics Foundation and the Intramural Research Program of the National Institutes of Health/National Institute of Environmental Health Sciences.

"Plasma Urate and Risk of Parkinson's Disease," M. G. Weisskopf, E. O'Reilly, H. Chen, M. A. Schwarzschild and A. Ascherio, American Journal of Epidemiology, published online June 20, 2007.


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