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Low serum caffeine and caffeine metabolite levels after an overnight fast may be a sensitive way to detect the presence of Parkinson’s disease, according to the results of a new case-control study.
Levels of caffeine and its metabolites were also lower in Parkinson’s disease (PD) patients who had motor dysfunction, compared with those without motor dysfunction, but no differences in serum levels of caffeine metabolites could be detected between patients with mild to more severe stages of PD, reported Motoki Fujimaki, MD, of Juntendo University, Tokyo, and colleagues. The report was published online Jan. 3 in Neurology.
To test that idea, Dr. Fujimaki and associates recruited 31 healthy controls (18 women) and 108 patients with PD but no dementia (50 women). The control group’s mean caffeine intake of 115.81 mg/day (standard deviation, 69.22) was similar to PD patients’ intake of 107.50 mg/day (SD, 67.27).
Serum caffeine levels measured after an overnight fast showed that a cutoff of 33.04 pmol/10 mcL identified PD with an area under the curve (AUC) of 0.78 (sensitivity 76.9%, specificity 74.2%). Inclusion of the primary caffeine metabolites theophylline, theobromine, and paraxanthine improved the AUC to 0.87. When the researchers included all 11 measurable metabolites, the AUC jumped to 0.98.
Genetic analyses found no significant differences in the frequencies of caffeine metabolism–associated genetic variants between PD patients and controls.
The study was limited by the fact that it was conducted at a single university hospital, and the patient population did not include many severe cases. The algorithm should also be studied in other PD patient populations.
The study was funded by grants from several Japanese government agencies. Some of the authors have financial relationships with the pharmaceutical industry.
SOURCE: Fujimaki M et al. Neurology. 2018 Jan 3. doi: 10.1212/WNL.0000000000004888
A key question is what is causing the decrease in serum concentration found in patients with Parkinson’s disease? Nearly all of the patients were receiving treatment, which could have affected serum levels.
The researchers addressed this by looking for an association between serum caffeine metabolite levels and levodopa equivalent doses, and they found none.
Still, the validity of the study depends on whether caffeine metabolism may be affected by treatment. To demonstrate the utility of caffeine metabolites unequivocally, a future study will have to reproduce these results in patients with untreated PD or subjects at high risk of PD, such as those with prodromal signs of PD.
David G. Munoz, MD, is in the department of laboratory medicine and pathobiology at the University of Toronto. Shinsuke Fujioka, MD is in the department of neurology at Fukuoka (Japan) University. Dr. Munoz and Dr. Fujioka reported having no financial disclosures. Their comments are derived from an editorial accompanying the study by Dr. Fujimaki and colleagues (Neurology. 2018 Jan 3. doi: 10.1212/WNL.0000000000004898).
A key question is what is causing the decrease in serum concentration found in patients with Parkinson’s disease? Nearly all of the patients were receiving treatment, which could have affected serum levels.
The researchers addressed this by looking for an association between serum caffeine metabolite levels and levodopa equivalent doses, and they found none.
Still, the validity of the study depends on whether caffeine metabolism may be affected by treatment. To demonstrate the utility of caffeine metabolites unequivocally, a future study will have to reproduce these results in patients with untreated PD or subjects at high risk of PD, such as those with prodromal signs of PD.
David G. Munoz, MD, is in the department of laboratory medicine and pathobiology at the University of Toronto. Shinsuke Fujioka, MD is in the department of neurology at Fukuoka (Japan) University. Dr. Munoz and Dr. Fujioka reported having no financial disclosures. Their comments are derived from an editorial accompanying the study by Dr. Fujimaki and colleagues (Neurology. 2018 Jan 3. doi: 10.1212/WNL.0000000000004898).
A key question is what is causing the decrease in serum concentration found in patients with Parkinson’s disease? Nearly all of the patients were receiving treatment, which could have affected serum levels.
The researchers addressed this by looking for an association between serum caffeine metabolite levels and levodopa equivalent doses, and they found none.
Still, the validity of the study depends on whether caffeine metabolism may be affected by treatment. To demonstrate the utility of caffeine metabolites unequivocally, a future study will have to reproduce these results in patients with untreated PD or subjects at high risk of PD, such as those with prodromal signs of PD.
David G. Munoz, MD, is in the department of laboratory medicine and pathobiology at the University of Toronto. Shinsuke Fujioka, MD is in the department of neurology at Fukuoka (Japan) University. Dr. Munoz and Dr. Fujioka reported having no financial disclosures. Their comments are derived from an editorial accompanying the study by Dr. Fujimaki and colleagues (Neurology. 2018 Jan 3. doi: 10.1212/WNL.0000000000004898).
Low serum caffeine and caffeine metabolite levels after an overnight fast may be a sensitive way to detect the presence of Parkinson’s disease, according to the results of a new case-control study.
Levels of caffeine and its metabolites were also lower in Parkinson’s disease (PD) patients who had motor dysfunction, compared with those without motor dysfunction, but no differences in serum levels of caffeine metabolites could be detected between patients with mild to more severe stages of PD, reported Motoki Fujimaki, MD, of Juntendo University, Tokyo, and colleagues. The report was published online Jan. 3 in Neurology.
To test that idea, Dr. Fujimaki and associates recruited 31 healthy controls (18 women) and 108 patients with PD but no dementia (50 women). The control group’s mean caffeine intake of 115.81 mg/day (standard deviation, 69.22) was similar to PD patients’ intake of 107.50 mg/day (SD, 67.27).
Serum caffeine levels measured after an overnight fast showed that a cutoff of 33.04 pmol/10 mcL identified PD with an area under the curve (AUC) of 0.78 (sensitivity 76.9%, specificity 74.2%). Inclusion of the primary caffeine metabolites theophylline, theobromine, and paraxanthine improved the AUC to 0.87. When the researchers included all 11 measurable metabolites, the AUC jumped to 0.98.
Genetic analyses found no significant differences in the frequencies of caffeine metabolism–associated genetic variants between PD patients and controls.
The study was limited by the fact that it was conducted at a single university hospital, and the patient population did not include many severe cases. The algorithm should also be studied in other PD patient populations.
The study was funded by grants from several Japanese government agencies. Some of the authors have financial relationships with the pharmaceutical industry.
SOURCE: Fujimaki M et al. Neurology. 2018 Jan 3. doi: 10.1212/WNL.0000000000004888
Low serum caffeine and caffeine metabolite levels after an overnight fast may be a sensitive way to detect the presence of Parkinson’s disease, according to the results of a new case-control study.
Levels of caffeine and its metabolites were also lower in Parkinson’s disease (PD) patients who had motor dysfunction, compared with those without motor dysfunction, but no differences in serum levels of caffeine metabolites could be detected between patients with mild to more severe stages of PD, reported Motoki Fujimaki, MD, of Juntendo University, Tokyo, and colleagues. The report was published online Jan. 3 in Neurology.
To test that idea, Dr. Fujimaki and associates recruited 31 healthy controls (18 women) and 108 patients with PD but no dementia (50 women). The control group’s mean caffeine intake of 115.81 mg/day (standard deviation, 69.22) was similar to PD patients’ intake of 107.50 mg/day (SD, 67.27).
Serum caffeine levels measured after an overnight fast showed that a cutoff of 33.04 pmol/10 mcL identified PD with an area under the curve (AUC) of 0.78 (sensitivity 76.9%, specificity 74.2%). Inclusion of the primary caffeine metabolites theophylline, theobromine, and paraxanthine improved the AUC to 0.87. When the researchers included all 11 measurable metabolites, the AUC jumped to 0.98.
Genetic analyses found no significant differences in the frequencies of caffeine metabolism–associated genetic variants between PD patients and controls.
The study was limited by the fact that it was conducted at a single university hospital, and the patient population did not include many severe cases. The algorithm should also be studied in other PD patient populations.
The study was funded by grants from several Japanese government agencies. Some of the authors have financial relationships with the pharmaceutical industry.
SOURCE: Fujimaki M et al. Neurology. 2018 Jan 3. doi: 10.1212/WNL.0000000000004888
FROM NEUROLOGY
Key clinical point:
Major finding: Combining serum levels of caffeine and nine related metabolites identified individuals with PD with an AUC of 0.98.
Data source: Analysis of 108 Parkinson’s patients and 31 healthy controls.
Disclosures: The study was funded by grants from several Japanese government agencies. Some of the authors have financial relationships with the pharmaceutical industry.
Source: Fujimaki M et al., Neurology. 2018 Jan 3. doi: 10.1212/WNL.0000000000004888