Caffeine and Progression of Parkinson Disease: A Deleterious Interaction With Creatine

ObjectiveIncreased 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. MethodsData 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. ResultsCaffeine 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. ConclusionsThis 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.

[1]  P. Laurienti,et al.  Methodological considerations for the quantification of self-reported caffeine use , 2009, Psychopharmacology.

[2]  W. Willett,et al.  Prospective study of caffeine consumption and risk of Parkinson's disease in men and women , 2001, Annals of neurology.

[3]  Connie Marras,et al.  Occupation and risk of parkinsonism: a multicenter case-control study. , 2009, Archives of neurology.

[4]  C. Tanner,et al.  Association of coffee and caffeine intake with the risk of Parkinson disease. , 2000, JAMA.

[5]  Beate Ritz,et al.  Genome-Wide Gene-Environment Study Identifies Glutamate Receptor Gene GRIN2A as a Parkinson's Disease Modifier Gene via Interaction with Coffee , 2011, PLoS genetics.

[6]  Masahiko Watanabe,et al.  Uncovering Caffeine’s Adenosine A2A Receptor Inverse Agonism in Experimental Parkinsonism , 2014, ACS chemical biology.

[7]  J. Sullivan,et al.  Creatine Supplementation in High School Football Players , 2001, Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine.

[8]  Hyon K. Choi,et al.  Coffee, tea, and caffeine consumption and serum uric acid level: the third national health and nutrition examination survey. , 2007, Arthritis and rheumatism.

[9]  J. Elm.  Design innovations and baseline findings in a long‐term Parkinson's trial: The national institute of neurological disorders and stroke exploratory trials in Parkinson's Disease Long‐Term Study–1 , 2012, Movement disorders : official journal of the Movement Disorder Society.

[10]  I. Litvan.  Faculty Opinions recommendation of A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. , 2006 .

[11]  R. Elble,et al.  A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease , 2006, Neurology.

[12]  J. A. Swanson,et al.  Caffeine and nicotine: a review of their joint use and possible interactive effects in tobacco withdrawal. , 1994, Addictive behaviors.

[13]  L. Wilkins.  Caffeine for treatment of Parkinson disease: A randomized controlled trial , 2012, Neurology.

[14]  M. Morelli,et al.  Pathophysiological roles for purines: adenosine, caffeine and urate. , 2010, Progress in brain research.

[15]  P. Hespel,et al.  Opposite actions of caffeine and creatine on muscle relaxation time in humans. , 2002, Journal of applied physiology.

[16]  Tanya Simuni,et al.  Effect of creatine monohydrate on clinical progression in patients with Parkinson disease: a randomized clinical trial. , 2015, JAMA.

[17]  M. Aminoff,et al.  Caffeine and Progression of Parkinson Disease , 2008, Clinical neuropharmacology.

[18]  M. Schwarzschild,et al.  Adenosine A2A receptor gene disruption protects in an α‐synuclein model of Parkinson's disease , 2012, Annals of neurology.

[19]  J. Jankovic,et al.  A randomized clinical trial of coenzyme Q10 and GPI-1485 in early Parkinson disease , 2007, Neurology.

[20]  M. Schwarzschild,et al.  Urate in Parkinson’s Disease: More Than a Biomarker? , 2012, Current Neurology and Neuroscience Reports.

[21]  S. Wood,et al.  Rare POLG1 CAG variants do not influence Parkinson's disease or polymerase gamma function. , 2014, Mitochondrion.

[22]  P. van Hecke,et al.  Caffeine counteracts the ergogenic action of muscle creatine loading. , 1996, Journal of applied physiology.