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Caffeine, Metabolite Levels Lower in Early Stage Parkinson Disease

January 05, 2018

By Anne Harding

NEW YORK (Reuters Health) - Serum levels of caffeine and nine of its metabolites are lower in people with Parkinson's disease (PD) than in healthy controls, regardless of caffeine intake, new findings show.

Caffeine intake correlated more strongly with serum caffeine in the control group than in the PD patients, suggesting that the PD patients were absorbing caffeine less efficiently, Dr. Shinji Saiki of Juntendo University School of Medicine in Tokyo and colleagues state in Neurology, online January 3.

Several lines of evidence suggest that caffeine protects against PD, improving motor symptoms by blocking adenosine 2A receptors, Dr. Saiki and his team note. They previously found lower levels of caffeine and four downstream metabolites in patients receiving treatment for PD.

In the new study, the researchers looked at caffeine metabolism in 31 healthy controls and 108 PD patients without dementia. Controls included patients’ spouses and hospital patients with asymptomatic brain ischemia.

Serum levels of caffeine, and 9 of 11 downstream metabolites, were significantly lower in the PD patients than the controls. PD patients with motor fluctuations had lower caffeine levels than those who did not, but patients with more severe PD did not have lower serum caffeine than those in the early stages of the disease.

ROC curve analysis showed that the area under the curve (AUC) of caffeine at a 33.04-pmol/10 microliter cutoff was 0.78, with a sensitivity of 76.9% and a specificity of 74.2%. Adding the main metabolites of caffeine improved AUC to 0.87. AUC was 0.98 when the researchers used caffeine and all measurable metabolites.

Levels of caffeine metabolites were not associated with levodopa equivalent doses.

PD patients and controls did not differ in single-nucleotide variations in genes associated with coffee metabolism.

Dr. Saiki and his team now plan to test the efficacy of caffeine and its metabolites as biomarkers in patients with preclinical or prodromal PD. “In terms of patients with REM sleep behavioral disorders, about 10% of them would have onset of PD in a year (,” he told Reuters Health by email. “Thus, around 150 patients with REM sleep behavioral disorders should be included and followed up for 3 years with annual blood sampling.”

If future research finds similar results for PD patients who are not receiving antiparkinson drugs, “the implications of the current study would take enormous importance,” Dr. David G. Munoz of the University of Toronto in Canada and Dr. Shinsuke Fujioka of Fukuoka University in Japan write in an accompanying editorial.

The findings “open the door” to diagnostic tests for early PD, Dr. Munoz told Reuters Health in a telephone interview, noting that the disease is correctly diagnosed at a patient’s first encounter just 50% of the time.

“Any test that would increase the diagnostic accuracy would be extremely good, and part of the problem is that there are several conditions that may be mistaken for Parkinson disease,” he added. Future prospective studies must look at serum caffeine in patients diagnosed with these conditions, such as progressive supranuclear palsy and multiple system atrophy, to confirm whether the effect is selective for PD, he said.

A relationship between low caffeine levels and PD in untreated patients “would point to a basic mechanism of pathogenesis of PD, one that probably would be actionable,” Dr. Munoz and Dr. Fujioka write. “These studies in drug-free patients are urgently needed.”


Neurology 2018.

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