Serum caffeine and downstream metabolites may be indicative biomarkers for early Parkinson disease, according to a study published in Neurology.

Motoki Fujimaki, MD, of the Department of Neurology, Research Institute for Diseases of Old Age at the Juntendo University School of Medicine in Tokyo, and associates conducted a series of tests to assess the kinetics and metabolism of serum caffeine in patients with and without Parkinson disease.

The researchers evaluated 31 healthy individuals (18 women) and 108 patients with Parkinson disease and without dementia (50 women). Controls were either spouses of patients or patients with asymptomatic brain ischemia. Patients were eligible if they met the Movement Disorder Society standards for idiopathic Parkinson disease diagnosis and did not show any signs of dementia.

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The concentrations of caffeine were evaluated as 60 mg per cup of coffee, 30 mg per cup of tea, and 20 mg per cup of green tea. None of the participating members had any history of cancer, aspiration pneumonia, or collagen vascular diseases.

Additionally, 51 healthy participants (82 total controls, 26 additional women) and 67 Parkinson disease patients (176 total, 34 additional women) were monitored genetically for any mutations in caffeine-affiliated genes.

Serum caffeine and 9 of the 11 associated downstream metabolites were found to be at lower levels in patients with Parkinson disease than the controls. The top 3 closest downstream metabolites, theophylline, theobromine, and paraxanthine, were found in significantly lower concentrations in Parkinson disease patients.

There was no indication of any significant genetic variations between patients with Parkinson disease and the control group. There was decreased serum caffeine levels in Parkinson disease patients with motor fluctuations in comparison with Parkinson disease patients without motor fluctuations.

“Considering disease severity differences between patients with Parkinson disease with and without motor fluctuations, lower levels of caffeine in patients with Parkinson disease may result in greater disease progression,” reported the authors.

“Furthermore, significant decreases in caffeine and metabolites were detected in patients with Parkinson disease with motor complications and more severe disease symptoms. This further indicates the neuroprotective effects of caffeine.”

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In an editorial published in Neurology, David G Munoz, MD, the Department of Laboratory Medicine and Pathobiology at the University of Toronto and Shinsuke Fujioka, MD, of the Department of Neurology at Kukuoka University in Japan, noted the benefits and impact that caffeine has on neurologic health.

“The protective effect of caffeine (found not only in coffee, but also in tea, and some sodas) has been demonstrated in large prospectively followed populations of men, with a dramatic reduction in risk (up to fivefold for persons who drank more than 4 cups of coffee a day),” Munoz and Fujioka stated. “Decaffeinated coffee afforded no protection, pointing to caffeine rather than other substances in coffee or tea as the underlying pharmacologic agent.


  1. Fujimaki M, Saiki S, Li Y, et al. Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease. Neurology. 2018 Jan 3. doi:10.1212/WNL.0000000000004888
  2. Munoz DG, Fujioka S. Caffeine and Parkinson disease: a possible diagnosis and pathogenic breakthrough. 2018 Jan 3. doi:10.1212/WNL.0000000000004898