[Niggs]

Hi

I've been reading about cdp choline, papers and past posts on here ( Ron H and Rick E in particular).
Below is what I've come up with, confusion mainly ! So I am hoping somone can
correct,add to or comment on the following.

It's a precursor to acetylcholine
But is also possibly a dopamine agonist in a round about way.
There's only one study of note which suggests a therapeutic benefit in Parkinson's
Ron H felt it helped him reduce L.dopa.

I wonder if those it helps are over medicated, that the dopamine/acetylcholine balance is slanted towards too much dopamine.
Perhaps some PWP's are acetylcholine rich not dopamine poor. Dopamine replacement therapy would still work by restoring balance but give rise to a situation where levels of both neurotransmitters are high.
Maybe this is why some people are Parkinsonian yet have negative dat.scans.
????
Nigel

[johnt]

Niggs,

I do so miss Ron and Rick.

Thanks for raising this topic. It's a mistake that many of us make, me included, in seeing PD as a one factor, dopamine, disease. Anyway, CDP-choline passes the alpha-synuclein sanity check.

Hurtado et al. report [1]:

"Citicoline (CDP-choline) increases Sirtuin 1 expression concomitant to neuroprotection in experimental stroke".

Donmez et al. write [2]:

"our findings suggest that therapeutic strategies to activate SIRT1 in the brain may be useful in treating α-synuclein aggregation and related toxicity. The synthetic effect of α-synuclein induced stress and SIRT1 activation in the induction of the heat shock response may also inform treatment. SIRT1 activating drugs may be effective after disease onset and function to mitigate progression of α-synuclein aggregation and related toxicity. Our findings further support the notion that genes activated by calorie restriction to mediate physiological adaptations, such as sirtuins, may be broadly beneficial in combating diseases of aging"

References

[1] http://onlinelibrary.wiley.com/doi/1.../jnc.12269/pdf

[2] J Neurosci. 2012 Jan 4; 32(1): 124–132.
SIRT1 protects against α-synuclein aggregation by activating molecular chaperones
Gizem Donmez,1,* Anirudh Arun,1 Chee-Yeun Chung,3 Pamela J. McLean,2 Susan Lindquist,3 and Leonard Guarente1
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3263206/

John

[Niggs]

Hi John

I think Rick & Ron were onto something, I'm wondering, given it's broad and varied actions wether it smooths out the peaks/troughs of the various neurotransmitters.



Citicoline has been shown to act as a dopaminergic agonist, and has a particularly significant effect on
levels of dopamine and its metabolites in the striatum. The results obtained suggest that, with citicoline
administration, striatal dopamine synthesis is increased, probably through tyrosine hydroxylase activation.
Increase in dopamine levels would partly result from inhibition of dopamine reuptake, possibly related to
citicoline action upon phospholipid synthesis. In addition, citicoline also has some effects upon the other
monoamines, serotonin and norepinephrine, muscarinic receptors, and glutamate and GABA (Secades,
2006).
Citicoline stimulates dopamine synthesis in nigrostriatal areas and antagonizes changes in CNS
dopamine and norepinephrine levels caused by various toxins. Citicoline stimulates cholinergic
neurotransmission. In various brain disease models, citicoline has improved or normalized biochemical
and functional parameters of the central nervous system. Citicoline stimulates the synthesis and inhibits
catabolism of cerebral phospholipids, and also has a protective effect upon membrane ATPase and
enzymes involved in brain energy metabolism, particularly succinyl dehydrogenase and citrate
synthetase, as well as protein and nucleic acid metabolism, increasing RNA biosynthesis at certain brain
regions (Secades, 2006).

http://www.ninds.nih.gov/research/pa...%20dossier.pdf


Nigel

[Canna]

I was listening to an online program on PD treatments and one of the doctors said that citicoline/cdp choline was effective and underutilized. I took a note and will ask my MDS about it in a couple of weeks. Why would it be underutilized? The studies I looked at used subcutaneous delivery. I guess that could be one reason. What do you think from what you have read?

[Niggs]

Originally Posted by Canna

I was listening to an online program on PD treatments and one of the doctors said that citicoline/cdp choline was effective and underutilized. I took a note and will ask my MDS about it in a couple of weeks. Why would it be underutilized? The studies I looked at used subcutaneous delivery. I guess that could be one reason. What do you think from what you have read?

Hi Canna,

I'm very intrigued and some what confused by CDP-CHOLINE. I believe it possibly, may be a partial Agonist + DRI ( dopamine re-uptake inhibitor). It seems to act on other neurotransmitters as well, most notably Serotonin and of course it is a precursor to Acetylcholine. My pet interest is that there is a PD subset where the trigger is chronic stress, hence I'm interested due to the neutotransmitters involved.
It crosses the blood/brain barrier and seems to have different effects at different levels of ingestion. Ron H, took 250mg 2 x daily.

I intend to do a bit of citizen science soon but I'm on the point of swapping
sinemet cr for stalevo and as I'm very sensitive to psychotropic drugs I'm holding back.
However, in a prime example of 'impulse control disorder' I took 500mg 1 x daily for 6 days three weeks ago. Understand also that since 22/12/15 I'v upped my requip xl from 10mg to 12mg. But days 3-6 were the best I'v had for 3 years !
Then I had a bad day, stopped abruptly and things have been dreadful for the last 2 weeks ? There are a number of possible conclusions.

1. The CDP Chol worked, the down turn being due to me not taking it properly,
ie.stopping abruptly, timings etc or the usual fluctuations due to hydration,sleep. It could also have been (the 2 following bad weeks) due to me incubating a virus as I'm now suffering from Man Flu.

2. It was nothing to do with CDP Chol. and all to do with the requip increase.
I doubt this as I know the feeling of DA titration well.

3. At the level I was taking as the CDP Chol built up, it's primary action, Acetylcholine, reached a level where Dopamine/Acetylcholine were in perfect
balance, days 3-6, but by day 7 that had shifted in favour of Acetylcholine.
I have to say these last couple of weeks have felt like I'v just increased Ropinirole, worsening Parkinsonian symptoms and dyskinesia.
Against this is the fact that I only noticed improvement when on CDP C.

Whatever the reasons for the above experience, there is certainly, I feel,some kind of effect on PD and I had 'no' side effects, though on a longer trial this may change.
When I say improvement on 3-6 days I mean dramatically. After a summer of failed requip titrations leaving me more or less house bound, it was a shock to my family and myself to suddenly walk 1 mile, watch a band, walk 1 mile back
with such fluidity that my Daughter (17) asked me to slow down and apologised for remarking on my near normal gait so often.

So, conclusion, my gut feeling is It's worth a few pounds/dollars/euro's for some Jarrow cdp-choline 250mg's to try, as Ron H used. BUT, this time I'll do it properly and post back.
One final point, we have no idea of dose requirement or L.E.D or it's precise
method of action however,
thank you Ron and Rick for this legacy.

Nigel