(Tokyo, 15 February) Researchers at Juntendo University report in Neurology the potential use of blood levels of caffeine and its byproducts as biomarkers for Parkinson’s disease. The finding is promising for the development of a method enabling early identification of the disease.
Parkinson’s disease is a degenerative disorder of the central nervous system, affecting the latter’s motor system — the part controlling bodily motion. Its symptoms include shaking, rigidity and difficulty with walking. There is evidence that daily caffeine consumption reduces the risk of developing Parkinson’s. Now, a team of researchers led by Nobutaka Hattori from Juntendo University School of Medicine have studied how traces of caffeine in the blood, after drinking coffee, can be indicative of Parkinson’s disease. The researchers found that caffeine levels are significantly lower in patients with the disease; caffeine concentrations could therefore be used as an indicator of Parkinson’s, particularly in its early stages.
Video: Professor Nobutaka Hattori describing his group’s research on Parkinson’s disease.
The researchers studied a group of 139 people, both men and women, with and without Parkinson’s disease. Each person drank between 0 and 5 cups of coffee per day (except for one participant who drank more than six). Then, they checked the participants’ blood serum for traces of caffeine and its 11 so-called downstream metabolites — small molecules produced during caffeine-induced metabolic processes in the human body.

Video: Professor Shinji Saiki describing the details of the research published in Neurology, January 3, 2018.



The scientists found that the serum levels of caffeine and of almost all metabolites, including theophylline, theobromine and paraxanthine — caffeine’s main byproducts — were lower in patients with Parkinson’s disease. Although the data obtained by Hattori’s team show that there is a clear relation between a person’s caffeine (metabolite) serum levels and having Parkinson’s disease, there was no significant association between the severity of the disease and the concentration of any of the caffeine-related substances. Also, there was no significant difference in serum levels between male and female patients (males are known to suffer more often from Parkinson’s disease).
The findings of Hattori and colleagues suggest that caffeine and caffeine metabolite levels in the blood can be, quoting the researchers, “early diagnostic biomarkers for the [Parkinson’s] disease”; moreover, the results “further indicated the neuroprotective effects of caffeine”.
Parkinson’s disease
In patients suffering from Parkinson’s disease, progressive loss of the function or structure of neurons (brain cells) leads to a disorder of the central nervous system, affecting its motor system. Tremor, slowness of movement and difficulties with walking are among the main symptoms in the early stages of Parkinson’s, with dementia being common at more advanced stages.
The cause of Parkinson’s disease is unclear, but it is believed that genetic and environmental factors play a role. Men are more affected than women, and people who drink tea or coffee have a reduced risk. The latter inspired Nobutaka Hattori and colleagues from Juntendo University School of Medicine to check whether caffeine levels in the blood, and levels of the byproducts (metabolites) that caffeine intake causes, can be used as biomarkers for the diagnosis of Parkinson’s disease. They found that this is indeed the case.
Caffeine is an organic molecule that, when consumed through e.g. coffee or tea, stimulates the central nervous system. Its best-known effect is the prevention of (the onset of) drowsiness. Daily caffeine consumption has been shown to reduce the risk of developing Parkinson’s disease in men, and in women not taking hormone replacement therapy — caffeine’s neuroprotective effect.
The team of Nobutaka Hattori has now demonstrated that, following caffeine intake, the levels of caffeine and its metabolites in the blood serum are lower for people with Parkinson’s, independent of the stage of the disease, implying that these levels could be used as biomarkers for the disease in the early stage.
Motoki Fujimaki, Shinji Saiki, Yuanzhe Li, Naoko Kaga, Hikari Taka, Taku Hatano, Kei-Ichi Ishikawa, Yutaka Oji, Akio Mori, Ayami Okuzumi, Takahiro Koinuma, Shin-Ichi Ueno, Yoko Imamichi, Takashi Ueno, Yoshiki Miura, Manabu Funayama & Nobutaka Hattori. Serum caffeine and metabolites are reliable biomarkers of early Parkinson disease. Neurology, January 3, 2018.
DOI: 10.1212/WNL.0000000000004888
Figure 1. [From the Supplementary Information (page 7)]
Caffeine and its byproducts (metabolites) after intake in the human body. Levels of these molecules in the blood are lower for patients with Parkinson’s and can hence serve as biomarkers for the disease.
Correspondence to:
Further information
Juntendo University :Ayano Nagashima
Juntendo University Corporate Communications
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Website: http://www.juntendo.ac.jp/english/
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The mission of Juntendo University is to strive for advances in society through education, research, and healthcare, guided by the motto “Jin – I exist as you exist” and the principle of “Fudan Zenshin – Continuously Moving Forward”. The spirit of “Jin”, which is the ideal of all those who gather at Juntendo University, entails being kind and considerate of others. The principle of “Fudan Zenshin” conveys the belief of the founders that education and research activities will only flourish in an environment of free competition. Our academic environment enables us to educate outstanding students to become healthcare professionals patients can believe in, scientists capable of innovative discoveries and inventions, and global citizens ready to serve society.

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Juntendo was originally founded in 1838 as a Dutch School of Medicine at a time when Western medical education was not yet embedded as a normal part of Japanese society. With the creation of Juntendo, the founders hoped to create a place where people could come together with the shared goal of helping society through the powers of medical education and practices. Their aspirations led to the establishment of Juntendo Hospital, the first private hospital in Japan. Through the years the institution’s experience and perspective as an institution of higher education and a place of clinical practice has enabled Juntendo University to play an integral role in the shaping of Japanese medical education and practices. Along the way the focus of the institution has also expanded, now consisting of four undergraduate programs and three graduate programs, the university specializes in the fields of health and sports science and nursing health care and sciences, as well as medicine. Today, Juntendo University continues to pursue innovative approaches to international level education and research with the goal of applying the results to society.