Parkinson's Disease Tulip


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Old 11-26-2019, 10:42 AM #1
soccertese soccertese is offline
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soccertese soccertese is offline
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Join Date: Nov 2007
Posts: 2,531
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Quote:
Originally Posted by johnt View Post
First my thanks go to pdinva on HU for pointing me to this paper [1].

Probably most of the PwP on this forum rely on levodopa based drugs, such as Sinemet and Stalevo, to have a reasonable quality of life. It is important, therefore, that large amounts of each dose gets through to the brain. Even more important is that the absorbtion is consistent from dose to dose.

In the early days post diagnosis, you are probably producing enough dopamine yourself (endogenous) and have enough dopamine reservoirs in the surviving dopaminergic neurons to not be affected much by any variability of absorbtion.

Unfortunately as time goes by this changes: gastric emptying slows, protein competition becomes more important. This manifests itself by more "off" time, even lost doses, and declining performance in the afternoon. And, if the PwP takes more levodopa to account for the low bioavailability, when things go well and an unexpected high amount of levodopa is absorbed, this can lead to more levodopa induced dyskinesia.

Guebila and Thiele built a mathematical model that predicted:

" ... an improvement in bioavailability, as reflected by blood concentrations of levodopa with protein redistribution diet by 34% compared with a low-protein diet and by 11% compared with the a.c [before food] administration. These results are consistent with the reported better outcome in late-stage patients. A systematic analysis of the effect of different amino acids in the diet suggested that a serine-rich diet could improve the bioavailability by 22% compared with the a.c. administration."

This possible effect of serine is new to me.

Reference:

[1] "Model-based dietary optimization for late-stage, levodopa-treated, Parkinson’s disease patients"
Marouen Ben Guebila and Ines Thiele
npj Systems Biology and Applications (2016)
https://www.nature.com/articles/npjsba201613.pdf

John
noticed this in the article
"We found that threonine, serine, and asparagine resulted in the highest brain bioavailability of levodopa (Figure 5). To our knowledge, these amino acids have not been reported to compete with levodopa in the small intestine and in the brain. Moreover, the amino acids were predicted to compete with levodopa for elimination in the kidneys and trans-stimulate levodopa secretion from the intestinal lumen. It has been shown that serine improves dopamine production.25 Consequently, we ranked serine as the amino acid with the highest contribution to levodopa bioavailability."
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