Higher Urate Levels Linked to Lower PD Risk

Pauline Anderson

January 13, 2016

Men, but not women, with higher plasma concentrations of uric acid (urate) have a lower risk for Parkinson's disease (PD), a new study suggests.

The results suggest that urate, a powerful antioxidant, could protect against PD or slow its progression, said lead study author Xiang Gao, MD, PhD, associate professor and director, Nutritional Epidemiology Lab, Department of Nutritional Sciences, Pennsylvania State University, University Park.

Although it's too early to recommend that patients with PD take supplements to raise urate levels, low levels might help identify a high-risk population, Dr Gao told Medscape Medical News.

"Maybe urate can be used as a risk predictor," he speculated. "Low uric acid may suggest that those people may have a high risk of PD, so they may need to see their neurologist to do further neurological tests."

Dr Xiang Gao

The study was published online January 13 in Neurology.

The analysis included 90,214 participants from three ongoing US cohorts: the Health Professionals Follow-up Study, the Nurses' Health Study, and the Cancer Prevention Study II Nutrition.

Researchers identified 388 new incident PD cases (202 men and 186 women). For each case, they randomly selected 1267 controls matched on the basis of the cohort; sex; birth year; race; fasting status; and year, month, and time of blood draw.

The researchers found that higher baseline plasma urate concentrations were associated with lower risk for PD in men but not in women.

Compared with the lowest quartile (Q1; urate concentrations <4.9 mg/dL), the relative risk (RR) of PD for those in the highest quartile (Q4; urate concentrations of 6.3 - 9.0 mg/dL) was 0.63 (95% confidence interval [CI], 0.35 - 1.10; P for trend = .049) in men, after adjustment for age; smoking status; caffeine intake; body mass index; alcohol intake; and serum concentrations of ferritin, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol.

In women, the multivariate-adjusted RR of PD in those in Q4 compared with Q1 was 1.04 (95% CI, 0.61 - 1.78; P = .44).

Dr Gao and his colleagues initially thought that the study didn't show a protective effect of urate in women because their levels are generally lower than those in men. So they carried out a secondary analysis using the same cutoff points of plasma concentrations of urate for both men and women instead of distribution quartiles.

That analysis showed a similar sex difference for the urate-PD relationship.

"It suggests that it may not be because women have lower urate levels; it's something else, but at this time, we still don't have a very good explanation for this difference," said Dr Gao.

It could be that hormones are somehow involved, or that women need much higher levels of urate to have any protective effect, he said.

Pooled Analysis

When pooling the results of the current study with those of three previous studies with a total of 325 PD cases, the RRs comparing the two extreme categories of urate were 0.63 (95% CI, 0.42 - 0.95; P heterogeneity = .22) in men and 0.89 (95% CI, 0.57 - 1.40; P heterogeneity = .52) in women.

A recent feasibility study showed that inosine, a urate precursor, is generally safe among patients with early PD. A dietary supplement, inosine is available in health food stores and is used to enhance athletic performance.

"But I think it's too early to recommend that people use inosine to prevent PD because we still don't have strong evidence," said Dr Gao.

A larger multisite trial, funded by the National Institutes of Health, will test whether inosine can slow disease progression among male and female patients with early PD.

Marie Saint-Hilaire, MD, associate professor, neurology, Boston University School of Medicine, and director, Parkinson's Disease and Movement Disorders Center, Boston University Medical Center, Massachusetts, who was involved in the earlier feasibility study, will also participate in the multisite trial.

Asked to comment on this new study, Dr Saint-Hilaire said the results weren't surprising.

"It just confirms the fact that women might not be as sensitive as men, for whatever reason, to the effect of uric acid."

She noted that women develop PD less frequently than do men. "It's possible that they have something that's protecting them that's more potent than uric acid, and you don't see the effect of uric acid because there's something else already in play that hides the effect."

She noted that researchers have looked at estrogen possibly playing a role, but that "hasn't really panned out that well."

Only apes and humans have uric acid, Dr Saint-Hilaire pointed out. "There must be an evolutionary reason why it's advantageous for us to have urate."

Dr Saint-Hilaire also warned against using inosine without close physician supervisions because uric levels that are too high could lead to gout, kidney stones, and cardiovascular disease.

The study was supported by the National Institutes of Health. Dr Gao received funding from the National Institute of Neurological Disorders and Stroke.

Neurology. Published online January 13, 2016. Abstract

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