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Christina Lau, 23 Nov 2018

In patients with severe small vessel disease (SVD), intensive blood pressure (BP) lowering does not reduce cerebral perfusion or increase the risk of falls, according to results of the ASL substudy of the PRESERVE trial.

Caffeine protects against Parkinson’s disease

Tristan Manalac
10 Jan 2018
Caffeine can cause several unwanted side effects which come with the over-stimulation of the central nervous system.

Caffeine may have a protective effect against Parkinson’s disease (PD), suggests a recent study, which shows that lower absolute serum levels of caffeine and a decreased profile of its metabolites appear to be diagnostic biomarkers for early PD.

“Serum levels of caffeine and nine related metabolites were uniformly and significantly decreased in patients with PD, despite an equivalent caffeine intake to controls,” said researchers, noting, however, that the genes involved in caffeine metabolism were not significantly altered in PD cases.

Moreover, while caffeine metabolite profiles may serve as diagnostic markers for early PD, there were “[n]o significant associations between disease severity and the levels of each of metabolite,” the researchers added.

Performing liquid chromatography-mass spectrometry on blood samples of 108 PD patients and 31 age-matched healthy controls, the research team found that significantly reduced mean levels of caffeine in PD patients than in controls (79.10±91.52 vs 23.53±22.4; p<0.0001). [Neurology 2018:doi:10.1212/WNL.0000000000004888]

The mean concentrations of the three main metabolites from caffeine were also significantly lower in PD patients: theophylline (14.40±12.1 vs 6.01±4.7; p<0.0001), theobromine (48.65±46.9 vs 24.50±32.1; p=0.0004) and paraxanthine (73.71±59.5 vs 30.70±23.9; p<0.0001). Aside from 1-methyluric acid, all other caffeine metabolites were significantly altered in PD patients relative to controls.

Notably, serum 1,3,7-trimethyluric acid levels were significantly higher in PD cases compared with controls (0.25±0.4 vs 0.69±1.3; p=0.0023). “However, 1-methyluric acid and 1,3,7-trimethyluric acid levels were under the limit of detection in 32 and 63 percent of participants, respectively,” the researchers qualified.

Serum caffeine appeared to be a good diagnostic biomarker for PD, with an area under the curve (AUC) value of 0.78 at a cut-off concentration of 33.04 pmol/10 µL. The corresponding sensitivity and specificity were 76.9 and 74.2 percent, respectively.

Inclusion of the three main metabolites of caffeine improved the AUC to 0.87, while inclusion of all measurable metabolites accurately distinguished PD cases from controls (AUC, 0.98).

Caffeine may exert its neuroprotective effects against PD on several levels, the researchers said. On a molecular level, high concentrations of caffeine have been shown to induce autophagy, the process by which cells remove defective protein. [Autophagy 2011;7:176-187]

On a physiological level, caffeine can also help prevent motor fluctuations by inhibiting the adenosine 2A receptor (A2A), explained researchers. “In this study, patients with PD with motor fluctuations had lower levels of caffeine than those without, consistent with the beneficial effects of A2A antagonism.” [Parkinsonism Relat Disord 2010;58:1154-1160]

“Also, considering disease severity differences between patients with PD with and without motor fluctuations, lower levels of caffeine in patients with PD may result in greater disease progression,” they added.

In contrast, analysis of the participants according to their Hoehn & Yahr stages showed that while most metabolites were decreased in every stage relative to controls, none reached statistical significance. Likewise, metabolite serum concentrations were not associated with scores on the Unified Parkinson’s Disease Rating Scale motor section (UPDRS-III).

The data indicate that while absolute concentrations of caffeine and its downstream metabolites may be potential diagnostic tools for early PD, they are less indicative of disease severity, according to the researchers.

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Most Read Articles
Christina Lau, 23 Nov 2018

In patients with severe small vessel disease (SVD), intensive blood pressure (BP) lowering does not reduce cerebral perfusion or increase the risk of falls, according to results of the ASL substudy of the PRESERVE trial.