Association of Coffee Consumption and Prediagnostic Caffeine Metabolites With Incident Parkinson Disease in a
Yujia Zhao1, Yunjia Lai1, Hilde Konijnenberg1
1From the Institute for Risk Assessment Sciences (Y.Z., H.K., S. Peters, R.V.), Utrecht University, the Netherlands; Department of Environmental Health Sciences (Y.L., G.W.M.), Mailman School of Public Health, Columbia University, New York, NY; Department of Epidemiology (J.M.H.), Murcia Regional Health Council-IMIB, Murcia; CIBER Epidemiología y Salud Pública (CIBERESP) (J.M.H., M.G.), Madrid; Movement Disorders Unit (A.V.-A.), Department of Neurology, University Hospital Donostia; BioDonostia Health Research Institute (A.V.-A.), Neurodegenerative Diseases Area, San Sebastián, Spain; Division of Cancer Epidemiology (J.A.S.), German Cancer Research Center (DKFZ), Heidelberg, Germany; Danish Cancer Institute (J.H.), Danish Cancer Society, Copenhagen, Denmark; Escuela Andaluza de Salud Pública (EASP) (D.P.); Instituto de Investigación Biosanitaria-ibs.GRANADA (D.P.), Granada; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP) (D.P.), Madrid, Spain; Unit of Cancer Epidemiology (C.S.), Città della Salute e della Scienza University-Hospital, Turin, Italy; Unit of Nutrition and Cancer (R.Z.-R.), Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain; Epidemiology and Prevention Unit (V.P.), Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Italy; Department of Epidemiology and Biostatistics (A.K.H., M.G.), School of Public Health, Imperial College London, United Kingdom; School of Medicine (S. Panico), Federico II University, Naples, Italy; de Salud Pública y Laboral de Navarra (M.G.), Pamplona; Navarra Institute for Health Research (IdiSNA) (M.G.), Pamplona, Spain; Institute for Cancer Research (G.M.), Prevention and Clinical Network (ISPRO), Florence, Italy; Institute of Epidemiology and Social Medicine (C.M.L.), University of Münster, Germany; Ageing Epidemiology Research Unit (AGE) (C.M.L.), School of Public Health, Imperial College London, United Kingdom; and University Medical Centre Utrecht (R.V.), the Netherlands.
Background And Objectives:
Inverse associations between caffeine intake and Parkinson disease (PD) have been frequently implicated in human studies. However, no studies have quantified biomarkers of caffeine intake years before PD onset and investigated whether and which caffeine metabolites are related to PD.
Methods:
Associations between self-reported total coffee consumption and future PD risk were examined in the EPIC4PD study, a prospective population-based cohort including 6 European countries. Cases with PD were identified through medical records and reviewed by expert neurologists. Hazard ratios (HRs) and 95% CIs for coffee consumption and PD incidence were estimated using Cox proportional hazards models. A case-control study nested within the EPIC4PD was conducted, recruiting cases with incident PD and matching each case with a control by age, sex, study center, and fasting status at blood collection. Caffeine metabolites were quantified by high-resolution mass spectrometry in baseline collected plasma samples. Using conditional logistic regression models, odds ratios (ORs) and 95% CIs were estimated for caffeine metabolites and PD risk.
Results:
In the EPIC4PD cohort (comprising 184,024 individuals), the multivariable-adjusted HR comparing the highest coffee intake with nonconsumers was 0.63 (95% CI 0.46-0.88, p = 0.006). In the nested case-control study, which included 351 cases with incident PD and 351 matched controls, prediagnostic caffeine and its primary metabolites, paraxanthine and theophylline, were inversely associated with PD risk. The ORs were 0.80 (95% CI 0.67-0.95, p = 0.009), 0.82 (95% CI 0.69-0.96, p = 0.015), and 0.78 (95% CI 0.65-0.93, p = 0.005), respectively. Adjusting for smoking and alcohol consumption did not substantially change these results.
Discussion:
This study demonstrates that the neuroprotection of coffee on PD is attributed to caffeine and its metabolites by detailed quantification of plasma caffeine and its metabolites years before diagnosis.
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