Thoughts on the possibility that the conclusions of the "Ghana trial" could be flawed
 

The Ghana trial [1] compared data from a group of Ghanaian PwPs, with data from a group of Italian PwPs. The trial demonstrated that the time from diagnosis to the onset of dyskinesia was similar in the two groups, even though the Ghanaian PwPs started levodopa therapy a few years later than the Italian PwPs. The major recommendation from the trial was that the common practice of delaying the start of levodopa therapy (in order to delay the time-of-onset-of-dyskinesia) was not justified.

The research paper titled "The impact of early versus late levodopa administration" [2] currently has 3 "cites" in Google Scholar (i.e. 3 later-publication-date papers make reference to it). In one of them [3] the following text appears: " ... protein-restricted diets may also contribute to several side effects, including dyskinesia ...". Assuming that this is correct, and assuming that Ghanaians have a protein-restricted diet (at least compared to Italians) then this seems to me to invalidate the major result of the Ghana trial (i.e. a protein-restricted diet might have caused the Ghanaian PwPs to get dyskinesia "artificially" early, in a timeframe similar to the Italian PwPs).

Here is a quote from [2]: " ... [the Ghana trial] compared two different populations with very different ethnic, genetic and environmental characteristics ... ". To that list perhaps could be added the word "diet" (i.e. pull it out from the general area of "environment").

When I had my first visit to my MDS neurologist (almost 3 years ago) I told him that I had read about the common practice of delaying the start of levodopa therapy (in order to delay the time-of-onset-of-dyskinesia). He assured me that this had now been disproven, and gave me a reference to the Ghana trial. I Googled it and was duly convinced by its clarity and simplicity.

Today I am no longer so sure.

[1] Cilia R, et al. (2014) The modern prelevodopa era of Parkinson's disease: insights into motor complications from sub-Saharan Africa. Brain 137(Pt 10):2731-2742

The modern pre-levodopa era of Parkinson’s disease: insights into motor complications from sub-Saharan Africa

[2] Yahalom G, et al. (2016) The impact of early versus late levodopa administration. J.Neural Transm. 24, 471-476. doi: 10.1007/s00702-016-1669-4

The impact of early versus late levodopa administration (PDF Download Available)

[3] Wang L, et al. (2017) Protein-Restricted Diets for Ameliorating Motor Fluctuations in Parkinson's Disease. Front. Aging Neurosci. 9:206. doi: 10.3389/fnagi.2017.00206

Protein-Restricted Diets for Ameliorating Motor Fluctuations in Parkinson's Disease

Rytary
 

If people are having problems with dyskinesia and they are taking regular sinemet, they may want to try Rytary. My wife was taking sinemet then stelevo and had bad dyskinesia. She went over to Rytary about 2 years ago and dyskinesia is not nearly as bad now, maybe even rare.

I've done a bit more reading, particularly of some of the "cites" associated with the "Ghana trial" report [1]. What I found was that, even as recently as 2017 (maybe even 2018), clinical trial results have been published which support both sides of this debate.

I think the following (short) articles give a fairly good summary of the current state of play.

[4] Espay A. J., Lang A. E., Common Myths in the Use of Levodopa in Parkinson Disease - When Clinical Trials Misinform Clinical Practice, JAMA Neurology, June 2017, Volume 74, Number 6.
Common Myths in the Use of Levodopa in Parkinson Disease: When Clinical Trials Misinform Clinical Practice (PDF Download Available)

[5] Lim SY, Poewe W., Tan A. H., Levodopa and Parkinson Disease - Myths Revisited, JAMA Neurology, October 2017, Volume 74, Number 10.
[6] Espay A. J., Lang A. E., Levodopa and Parkinson Disease - Myths Revisited - Reply, JAMA Neurology, October 2017, Volume 74, Number 10.
Levodopa and Parkinson Disease—Myths Revisited—Reply (PDF Download Available)

Jeffreyn,

Fascinating. Thanks for identifying these papers.

I think both sides of the argument make sense. This suggests to me that either the differences between the two regimens are small or they affect different people differently. There is probably no one size fits all strategy.

It would be interesting to know how drug costs and drug marketing affect what is prescribed.

I'm in the middle of writing a post on how my drug regimen is constructed.

John