The principal research question was whether caffeine could be a symptomatic treatment for PD. RCTs can be considered definitive when they are large enough and well conducted. Although this study seems to have been well conducted, the are some differences in the groups at baseline, such as smoking, gender and l-dopa doses, which may have relevance, and suggest that randomisation wasn’t perfect. The trial was halted early when an independent data monitoring committee agreed that it could not achieve its primary outcome. This was appropriate given what was seen in the interim analysis and the confidence intervals did not include the estimated treatment differences that they were expecting. The authors list a number of other limitations too.
Much of the epidemiological literature is undertaken with risk of PD as the outcome. First it is important to note that the factors that affect progression may not be the same as those affect risk and secondly whether we are talking about risk or progression, the current study was only really (at least at the first stage) designed to assess symptomatic benefit, not disease modification. For that reason, I think further work is required before one can rule out caffeine as a potential neuroprotective agent.
Neurology. 2017 Sep 27. pii: 10.1212/WNL.0000000000004568. doi: 10.1212/WNL.0000000000004568. [Epub ahead of print]
Postuma RB, Anang J, Pelletier A, Joseph L, Moscovich M, Grimes D, Furtado S, Munhoz RP, Appel-Cresswell S, Moro A, Borys A, Hobson D, Lang AE.
http://www.neurology.org/content/early/2017/09/27/WNL.0000000000004568.abstract
OBJECTIVE: To assess effects of caffeine on Parkinson disease (PD).
METHODS: In this multicenter parallel-group controlled trial, patients with PD with 1-8 years disease duration, Hoehn & Yahr stages I-III, on stable symptomatic therapy were randomized to caffeine 200 mg BID vs matching placebo capsules for 6-18 months. The primary research question was whether objective motor scores would differ at 6 months (Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale [MDS-UPDRS]-III, Class I evidence). Secondary outcomes included safety and tolerability, motor symptoms (MDS-UPDRS-II), motor fluctuations, sleep, nonmotor symptoms (MDS-UPDRS-I), cognition (Montreal Cognitive Assessment), and quality of life.
RESULTS: Sixty patients received caffeine and 61 placebo. Caffeine was well-tolerated with similar prevalence of side effects as placebo. There was no improvement in motor parkinsonism (the primary outcome) with caffeine treatment compared to placebo (difference between groups -0.48 [95% confidence interval -3.21 to 2.25] points on MDS-UPDRS-III). Similarly, on secondary outcomes, there was no change in motor signs or motor symptoms (MDS-UPDRS-II) at any time point, and no difference on quality of life. There was a slight improvement in somnolence over the first 6 months, which attenuated over time. There was a slight increase in dyskinesia with caffeine (MDS-UPDRS-4.1+4.2 = 0.25 points higher), and caffeine was associated with worse cognitive testing scores (average Montreal Cognitive Assessment = 0.66 [0.01, 1.32] worse than placebo).
CONCLUSION: Caffeine did not provide clinically important improvement of motor manifestations of PD (Class I evidence). Epidemiologic links between caffeine and lower PD risk do not appear to be explained by symptomatic effects.
CLINICALTRIALSGOV IDENTIFIER: NCT01738178.
CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with PD, caffeine does not significantly improve motor manifestations.
In conversation with a Malaysian doctor some years ago he observed that a treatment of PD consisting of Intestinal washouts as far up as possible (by irrigation)and followed by irrigation with a very strong coffee solution and then fasting for a few days is regarded as a good method. One presumes it removes some of the gut microbiota which may be responsible for PD in the first place. The interesting observation that strong coffee is in some way antibiotic/antifungal?/antiviral? might coincide with some of the reasoning behind this study.
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