Dataset Information

Caffeine, creatine, GRIN2A and Parkinson's disease progression.

ABSTRACT: 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.

SUBMITTER: Simon DK

PROVIDER: S-EPMC5386398 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Caffeine, creatine, GRIN2A and Parkinson's disease progression.

Simon David K DK Wu Cai C Tilley Barbara C BC Lohmann Katja K Klein Christine C Payami Haydeh H Wills Anne-Marie AM Aminoff Michael J MJ Bainbridge Jacquelyn J Dewey Richard R Hauser Robert A RA Schaake Susen S Schneider Jay S JS Sharma Saloni S Singer Carlos C Tanner Caroline M CM Truong Daniel D Wei Peng P Wong Pei Shieen PS Yang Tianzhong T

Journal of the neurological sciences 20170217

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 ha ...[more]

PMID: 28320167

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Project description:BackgroundParkinson's disease is one of the most common neurodegenerative disorders and mitochondrial dysfunction plays an important role in its pathogenesis. Creatine is effective in improving mitochondrial function. It may therefore be useful for slowing the progression of Parkinson's disease.ObjectivesTo assess the efficacy and safety of creatine used alone or as an adjuvant treatment for Parkinson's disease.Search methodsWe searched the Cochrane Movement Disorders Group Trials Register, CENTRAL (The Cochrane Library 2013, November Issue 4), MEDLINE (January 1966 to 10 November 2013), EMBASE (1974 to 10 November 2013) and two Chinese databases. We searched ongoing trials registers and conference proceedings, checked reference lists and contacted authors of included trials.Selection criteriaRandomized controlled trials (RCTs) comparing creatine versus placebo for Parkinson's disease.Data collection and analysisTwo review authors independently selected the trials for inclusion, assessed trial quality and extracted data.Main resultsWe included two RCTs with a total of 194 patients. Both trials compared creatine with placebo for Parkinson's disease and both had methodological limitations. There was no clear evidence of an effect on motor function (MD -0.26; 95% confidence interval (CI) -4.39 to 3.88, low quality evidence), activities of daily living (MD 0.37; 95% CI -1.28 to 2.02, low quality evidence) or quality of life after one or two years of treatment. One trial reported serious adverse events that were not attributed to creatine. Also, one trial observed higher rates of gastrointestinal effects at two years follow-up.Authors' conclusionsThe evidence base on the effects of creatine in Parkinson's disease is limited by risk of bias, small sample sizes and short duration of the eligible trials. It does not provide a reliable basis on which treatment decisions can be made. Future well-designed RCTs with larger sample size and long-term follow-up are needed to assess creatine for Parkinson's disease.

Dataset Information

Caffeine, creatine, GRIN2A and Parkinson's disease progression.

Publications

Caffeine, creatine, GRIN2A and Parkinson's disease progression.

Similar Datasets

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