Original ArticlesCaffeine and Progression of Parkinson Disease A Deleterious Interaction With CreatineSimon, David K. MD, PhD*; Wu, Cai MS†; Tilley, Barbara C. PhD†; Wills, Anne-Marie MD, MPH‡; Aminoff, Michael J. MD, DSc§; Bainbridge, Jacquelyn BSPharm, PharmD∥; Hauser, Robert A. MD, MBA¶; Schneider, Jay S. PhD#; Sharma, Saloni MBBS**; Singer, Carlos MD††; Tanner, Caroline M. MD, PhD§‡‡; Truong, Daniel MD§§; Wong, Pei Shieen PharmD∥∥∥Author Information *Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; †Department of Biostatistics, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX; ‡Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, MA; §Department of Neurology, University of California, San Francisco, CA; ∥Department of Clinical Pharmacy and Neurology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO; ¶Department of Neurology, University of South Florida, Tampa, FL; #Department of Pathology, Anatomy and Cell Biology, Parkinson's Disease Research Unit, Thomas Jefferson University, Philadelphia, PA; **Clinical Trials Coordination Center, University of Rochester Medical Center, Rochester, NY; ††Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL; ‡‡Parkinson's Disease Research Education and Clinical Center, San Francisco Veteran's Affairs Medical Center, San Francisco, CA; §§The Parkinson's and Movement Disorder Institute, Fountain Valley, CA; and ∥∥Singapore General Hospital, Singapore. Address correspondence and reprint requests to David K. Simon, MD, PhD, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215; E-mail: email@example.com The study sponsor, the National Institute of Neurological Disorders and Stroke, approved the study protocol and had oversight role in the collection, analysis, and interpretation of data. D.K.S. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conflicts of Interest and Source of Funding: The study was funded by the National Institute of Neurological Disorders and Stroke. Dr Wills participated as a site investigator in the Preladenant clinical trials funded by Merck. Other authors have no relevant conflicts of interest. Clinical Neuropharmacology: September/October 2015 - Volume 38 - Issue 5 - p 163-169 doi: 10.1097/WNF.0000000000000102 Buy Metrics Abstract Objective Increased caffeine intake is associated with a lower risk of Parkinson disease (PD) and is neuroprotective in mouse models of PD. However, in a previous study, an exploratory analysis suggested that, in patients taking creatine, caffeine intake was associated with a faster rate of progression. In the current study, we investigated the association of caffeine with the rate of progression of PD and the interaction of this association with creatine intake. Methods Data were analyzed from a large phase 3 placebo-controlled clinical study of creatine as a potentially disease-modifying agent in PD. Subjects were recruited for this study from 45 movement disorders centers across the United States and Canada. A total of 1741 subjects with PD participated in the primary clinical study, and caffeine intake data were available for 1549 of these subjects. The association of caffeine intake with rate of progression of PD as measured by the change in the total Unified Parkinson Disease Rating Scale score and the interaction of this association with creatine intake were assessed. Results Caffeine intake was not associated with the rate of progression of PD in the main analysis, but higher caffeine intake was associated with significantly faster progression among subjects taking creatine. Conclusions This is the largest and longest study conducted to date that addresses the association of caffeine with the rate of progression of PD. These data indicate a potentially deleterious interaction between caffeine and creatine with respect to the rate of progression of PD. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.