June 29, 2007 — A new study has found high levels of plasma urate are strongly associated with a reduced risk for Parkinson's disease (PD), a finding that may ultimately have implications for slowing disease progression.
In a large, prospective study, investigators at Harvard School of Public Health, in Boston, Massachusetts, found men in the top quartile of blood urate concentration had a 55% lower risk of developing PD than men in the bottom quartile.
"The data are very compelling, and if they are confirmed, urate could become the first biomarker of Parkinson's disease," principal investigator Marc Weisskopf, PhD, ScD, told Medscape.
Even more exciting, said Dr. Weisskopf, is the possibility that raising urate levels may have a therapeutic impact in individuals who already have the disease.
"We're not there yet, but it's possible we're on the verge of finding a treatment for PD. Work done by a couple of my coauthors, which has not yet been published, does seem to suggest that increased urate levels may be related to a slower rate of disease progression," he added.
The study was published online June 20 in the American Journal of Epidemiology.
Powerful Antioxidant
Urate, a powerful antioxidant, could potentially work by preventing oxidative stress, researchers speculate, which appears to play a key role in the progressive loss of dopaminergic neurons in the substantia nigra that characterizes PD.
The study cohort included 18,018 men who were participants in the Health Professionals Follow-up Study. Between April 1993 and August 1995, blood samples were collected and participants were followed for incident PD until 2002.
For each confirmed case of PD, there were 2 randomly selected controls with no PD diagnosis who were matched by age, race, and time of blood collection. Participants were then divided according to urate concentration quartiles, which were then compared with PD status.
A total of 84 incident cases of PD were diagnosed. The mean plasma urate concentration was 5.7 mg/dL for cases and 6.1 mg/dL among age-matched controls.
According to Dr. Weisskopf, there have only been 2 previous prospective studies that have investigated the relationship between plasma urate and PD risk. Both suggested that individuals with high serum levels have a lower PD risk. However, these associations were either nonsignificant or only marginally significant.
Compelling Evidence
However, as part of this study, the investigators conducted a meta-analysis of the 3 studies. "When we combined the results of all the research to date, we were surprised by the strength and consistency of the results. When you put all the data together, the evidence is very, very compelling that urate may indeed be neuroprotective," he said.
However, he added, high urate levels are associated with increased risk for overall mortality, adverse cardiovascular and kidney effects, and an increased risk for gout. As result, it is unlikely that raising urate levels would ever be adopted as a preventive PD strategy.
On the other hand, he said, in patients who already have PD, it may well offer a viable treatment strategy. However, he said, this hypothesis needs to be confirmed in a large, randomized controlled interventional trial.
"We don't want to just wantonly increase urate levels in everybody, because it is not at all clear that the risk/benefit balance will come out in a positive way. However, if you restrict this to individuals with PD, that may change the equation," he said.
Increasing Urate Easily Done
Increasing urate levels can be done relatively simply — either through a diet high in purine-rich foods, which include organ meats, legumes, mushrooms, spinach, asparagus, and cauliflower, as well as certain types of fish such as sardines and herring. Beer and other alcoholic beverages also raise urate levels. In addition, said Dr. Weisskopf, inosine, an over-the-counter supplement frequently marketed to bodybuilders to "increase energy," can also raise plasma urate levels.
In addition to an interventional trial to examine the question of disease progression, future research will also explore whether high urate levels are also protective in women, the role of diet in disease etiology as it relates to urate levels, and the possibility that genetic/environmental interactions may work to increase susceptibility to urate's potential protective effects.
Am J Epidemiol. 2007. Published online June 20, 2007.
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