Caffeine, creatine, GRIN2A and Parkinson's disease progression

David K. Simon, Cai Wu, Barbara C. Tilley, Katja Lohmann, Christine Klein, Haydeh Payami, Anne Marie Wills, Michael J. Aminoff, Jacquelyn Bainbridge, Richard Dewey, Robert A. Hauser, Susen Schaake, Jay S. Schneider, Saloni Sharma, Carlos Singer, Caroline M. Tanner, Daniel Truong, Peng Wei, Pei Shieen Wong, Tianzhong Yang

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


Caffeine is neuroprotective in animal models of Parkinson's disease (PD) and caffeine intake is inversely associated with the risk of PD. This association may be influenced by the genotype of GRIN2A, which encodes an NMDA-glutamate-receptor subunit. In two placebo-controlled studies, we detected no association of caffeine intake with the rate of clinical progression of PD, except among subjects taking creatine, for whom higher caffeine intake was associated with more rapid progression. We now have analyzed data from 420 subjects for whom DNA samples and caffeine intake data were available from a placebo-controlled study of creatine in PD. The GRIN2A genotype was not associated with the rate of clinical progression of PD in the placebo group. However, there was a 4-way interaction between GRIN2A genotype, caffeine, creatine and the time since baseline. Among subjects in the creatine group with high levels of caffeine intake, but not among those with low caffeine intake, the GRIN2A T allele was associated with more rapid progression (p = 0.03). These data indicate that the deleterious interaction between caffeine and creatine with respect to rate of progression of PD is influenced by GRIN2A genotype. This example of a genetic factor interacting with environmental factors illustrates the complexity of gene-environment interactions in the progression of PD.

Original languageEnglish (US)
Pages (from-to)355-359
Number of pages5
JournalJournal of the Neurological Sciences
StatePublished - Apr 15 2017


  • Caffeine
  • Coffee
  • Creatine
  • GRIN2A
  • Parkinson's disease
  • Progression

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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