The dietary supplement inosine, which the body converts to urate, safely raises blood urate levels in people with early stage Parkinson's disease (PD), according to a new study. The result paves the way for testing inosine as a potential treatment for slowing PD progression. The research appears in the December 23 issue of JAMA Neurology.
Earlier studies have suggested that PD progresses more slowly in people whose natural levels of uric acid (urate), are higher than average. Research with laboratory mice has shown urate to have neuroprotective properties, meaning it has shown potential to protect the brain cells lost in Parkinson's. Too much urate, however, can cause gout and kidney stones.
The new research, called the Safety of Urate Elevation in PD (SURE-PD) study, aimed to test how well inosine raised levels of urate in blood and cerebrospinal fluid (the body fluid that bathes the brain), and whether higher levels were safe. Between 2009 and 2011, researchers at 17 clinical study sites recruited 75 people with early stage PD to participate in the study. Study participants were on average 62 years old, had been diagnosed with PD for about a year, and had blood urate levels less than 6 mg/dL. None were taking levodopa, but some used MAO-B inhibitors (selegiline or rasagiline).
Every day, for up to 24 months, one-third of the study participants took placebo capsules, one-third took enough inosine to raise urate levels to 6.1 to 7.0 mg/dL, and one-third took enough inosine to raise urate levels to 7.1 to 8.0 mg/dL. The researchers regularly tested participants' urate levels. The study was double-blinded, meaning that neither study participants nor the health care workers they interacted with knew who received inosine and who received placebo.
- Treatment with oral inosine in early PD was safe and well tolerated.
- Inosine treatment raised urate levels in blood serum and cerebrospinal fluid.
- There was no increased risk of severe adverse effects from taking inosine.
- None of the participants developed gout; however, three who took inosine developed symptomatic urolithiasis-crystals or stones in the urinary tract or kidneys.
What Does It Mean?
Epidemiological studies have shown that higher urate levels are associated with better prognosis in PD. However, it was unknown whether urate levels can be safely elevated in people with PD and whether this elevation would improve PD prognosis. In this study, scientists have shown that urate levels can be relatively safely elevated by taking the supplemental compound inosine. Taken together with previous findings, the results of this study support testing inosine in a clinical trial to investigate its ability to slow the progression of PD.
Much research points to oxidative stress as one of the molecular mechanisms that underlies PD. Urate is a potent antioxidant, which provides a rationale for looking into its potential benefits, although the details of how it may work in humans are not known.
The study authors emphasize that, although elevated from the start of the research, participants' urate levels were still within the normal range. They also caution that raising urate levels by taking inosine supplements or through diet can result in gout and kidney stones.