Parkinson's Disease Tulip


advertisement
Reply
 
Thread Tools Display Modes
Old 11-17-2019, 08:44 PM #1
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
Default Serine may increase the bioavailability of levodopa by 22%

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
__________________
Born 1955. Diagnosed PD 2005.
Meds 2010-Nov 2016: Stalevo(75 mg) x 4, ropinirole xl 16 mg, rasagiline 1 mg
Current meds: Stalevo(75 mg) x 5, ropinirole xl 8 mg, rasagiline 1 mg
johnt is offline   Reply With QuoteReply With Quote
"Thanks for this!" says:
eds195 (11-24-2019), jeffreyn (11-18-2019), made it up (11-26-2019), moondaughter (11-20-2019), soccertese (11-25-2019)

advertisement
Old 11-25-2019, 05:09 PM #2
soccertese soccertese is offline
Magnate
 
Join Date: Nov 2007
Posts: 2,531
15 yr Member
soccertese soccertese is offline
Magnate
 
Join Date: Nov 2007
Posts: 2,531
15 yr Member
Default this paper on soybeans increasing ON time was referenced

Effects of soybean ingestion on pharmacokinetics of levodopa and motor symptoms of Parkinson's disease--In relation to the effects of Mucuna pruriens. - PubMed - NCBI


J Neurol Sci. 2016 Feb 15;361:229-34. doi: 10.1016/j.jns.2016.01.005. Epub 2016 Jan 6.
Effects of soybean ingestion on pharmacokinetics of levodopa and motor symptoms of Parkinson's disease--In relation to the effects of Mucuna pruriens.
Nagashima Y1, Kondo T2, Sakata M3, Koh J3, Ito H3.
Author information

1
Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-shi, Wakayama 641-8509, Japan. Electronic address: y_naga@wakayama-med.ac.jp.
2
Hana-no-Ie Hospital, 1218-1 Minamiakatsuka, Nogimachi, Shimotsuka-gun, Tochigi 329-0112, Japan.
3
Department of Neurology, Wakayama Medical University, 811-1 Kimiidera, Wakayama-shi, Wakayama 641-8509, Japan.

Abstract

Mucuna pruriens is a levodopa-containing legume and its favorable effects on motor complications in Parkinson disease patients have been reported. The aim of this study was to investigate the effects of another legume, soybeans, on the pharmacokinetics and metabolism of levodopa. Seven parkinsonian patients with the wearing-off phenomenon and dyskinesia and five healthy volunteers participated in this study. We conducted a crossover study of the clinical effects on the participants before and after taking either levodopa (100mg)/carbidopa (10mg) only (LD/CD) or levodopa/carbidopa with 11 g of ground soybeans (LD/CD/soy). Parkinsonism and dyskinesia before and after ingestion of these substances were evaluated using UPDRS part III, the modified Abnormal Involuntary Movement Scale (mAIMS) and a self-rating scale. The concentrations of plasma levodopa and its major metabolites were measured by high-performance liquid chromatography. Clinical assessment and blood sampling were conducted before and three hours after the ingestion of ground soybeans. When the patients took LD/CD/soy, they had a significantly longer on-period (p=0.028) and a lower mAIMS score (p<0.001). From the comparison of the results of pharmacokinetic study before and after taking LD/CD or LD/CD/soy, the estimated marginal mean (EMM) of HVA after LD/CD/soy increased in the PD group. EMMs of 3-OMD after LD/CD/soy significantly decreased both in PD patients and healthy controls. These results indicate that soy partly increased the bioavailability of levodopa and suppressed levodopa degradation through COMT. Soybeans may have favorable effects on the motor complications occurring under current levodopa therapy. Further investigation to clarify the mechanism underlying such effects is required.
soccertese is offline   Reply With QuoteReply With Quote
"Thanks for this!" says:
eds195 (11-26-2019), jeffreyn (11-25-2019), johnt (11-25-2019), moondaughter (11-26-2019)
Old 11-25-2019, 07:07 PM #3
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
Default

Thanks for the reference Soccertese. It looks like soybean is a COMT inhibitor.

Entacapone is another COMT inhibitor. Stalevo = L/C/E.

John
__________________
Born 1955. Diagnosed PD 2005.
Meds 2010-Nov 2016: Stalevo(75 mg) x 4, ropinirole xl 16 mg, rasagiline 1 mg
Current meds: Stalevo(75 mg) x 5, ropinirole xl 8 mg, rasagiline 1 mg
johnt is offline   Reply With QuoteReply With Quote
"Thanks for this!" says:
eds195 (11-26-2019), soccertese (11-27-2019)
Old 11-25-2019, 07:40 PM #4
soccertese soccertese is offline
Magnate
 
Join Date: Nov 2007
Posts: 2,531
15 yr Member
soccertese soccertese is offline
Magnate
 
Join Date: Nov 2007
Posts: 2,531
15 yr Member
Default

Quote:
Originally Posted by johnt View Post
Thanks for the reference Soccertese. It looks like soybean is a COMT inhibitor.

Entacapone is another COMT inhibitor. Stalevo = L/C/E.

John
going to try some TOFU
soccertese is offline   Reply With QuoteReply With Quote
Old 11-25-2019, 09:51 PM #5
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
johnt johnt is offline
Senior Member
 
Join Date: Apr 2009
Location: Stafford, UK
Posts: 1,059
10 yr Member
Default

Be careful when playing with soybean.

According to [1]:

"soy isoflavones have been found to inhibit CYP3A4 metabolism"

At least to me, the meaning of this is unclear: "inhibit CYP3A4 metabolism" could mean slowing the destruction of CYP3A4 itself, or it could mean slowing the speed of the the metabolism caused by CYP3A4. I've followed some of the papers cited in [1] and I think that the second meaning is correct. So, in that case soybean is a CYP3A4 inhibitor.

Similar to grapefruit juice, this has the advantage of increasing the AUC of levodopa, which is good. But, it can also lead to increasing the effect of other drugs (e.g. statins), which can result in an overdose.

Reference:

[1] "Interactions between CYP3A4 and Dietary Polyphenols
Loai Basheer and Zohar Kerem"
Oxid Med Cell Longev, 2015
Interactions between CYP3A4 and Dietary Polyphenols

John
__________________
Born 1955. Diagnosed PD 2005.
Meds 2010-Nov 2016: Stalevo(75 mg) x 4, ropinirole xl 16 mg, rasagiline 1 mg
Current meds: Stalevo(75 mg) x 5, ropinirole xl 8 mg, rasagiline 1 mg

Last edited by johnt; 11-26-2019 at 05:12 AM. Reason: paying to playing
johnt is offline   Reply With QuoteReply With Quote
"Thanks for this!" says:
eds195 (11-26-2019), jeffreyn (11-27-2019), made it up (11-26-2019), soccertese (11-26-2019)
Old 11-26-2019, 10:42 AM #6
soccertese soccertese is offline
Magnate
 
Join Date: Nov 2007
Posts: 2,531
15 yr Member
soccertese soccertese is offline
Magnate
 
Join Date: Nov 2007
Posts: 2,531
15 yr Member
Default

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."
soccertese is offline   Reply With QuoteReply With Quote
"Thanks for this!" says:
eds195 (11-26-2019), made it up (11-26-2019)
Reply

Tags
bioavailability, compared, diet, dose, levodopa

Thread Tools
Display Modes

Posting Rules
You may not post new threads
You may not post replies
You may not post attachments
You may not edit your posts

BB code is On
Smilies are On
[IMG] code is On
HTML code is Off


Similar Threads
Thread Thread Starter Forum Replies Last Post
Bioavailability of Mucuna vs Standard Levodopa Formulations lab rat Parkinson's Disease 0 10-07-2015 01:47 PM
Does exercise increase the effectiveness of levodopa? johnt Parkinson's Disease 1 04-14-2015 10:58 AM
Phosphatidyl Serine / Complex? mxmxmxmxmxmx Peripheral Neuropathy 1 09-19-2013 01:45 PM
Curcumin bioavailability GerryW Parkinson's Disease 0 12-15-2012 01:02 PM
SPRITE- to help bioavailability? VICTORIALOU Parkinson's Disease 2 09-05-2012 03:50 PM


All times are GMT -5. The time now is 09:36 AM.

Powered by vBulletin • Copyright ©2000 - 2024, Jelsoft Enterprises Ltd.

vBulletin Optimisation provided by vB Optimise v2.7.1 (Lite) - vBulletin Mods & Addons Copyright © 2024 DragonByte Technologies Ltd.
 

NeuroTalk Forums

Helping support those with neurological and related conditions.

 

The material on this site is for informational purposes only,
and is not a substitute for medical advice, diagnosis or treatment
provided by a qualified health care provider.


Always consult your doctor before trying anything you read here.