citicoline as an adjunct therapy in PD - Cure Parkinson's

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citicoline as an adjunct therapy in PD

PDConscience profile image
PDConscience

“A total of 7 studies (2 crossover, 3 randomized controlled, and 2 open prospective studies) were included. Despite the varied outcome tools, this review found that patients with PD who were taking citicoline had significant improvement in rigidity, akinesia, tremor, handwriting, and speech. Citicoline allowed effective reduction of levodopa by up to 50%. Significant improvement in cognitive status evaluation was also noted with citicoline adjunctive therapy.” sciencedirect.com/science/a...!

68 Replies

I’ve taken it over a month. 2 times a day 250 mg a dose. Feel it is effective but not enough to reduce c/l dosage.

chartist profile image
chartist in reply to ParlePark

In one of the studies, they used 500 mg/day, but it was delivered intramuscularly. The study is behind a paywall. The study dose produced a 23% reduction of bradykinesia and a 33% reduction in rigidity. A total of 20 days of administration suggesting a fairly rapid onset of action.

The other study was a PD rat model (Rotenone)study that also showed improvement in rigidity.

Art

House2 profile image
House2 in reply to chartist

I take it, it reduced my C/L and helped with brain fog.

chartist profile image
chartist in reply to House2

House2,

Thank you for your important feedback!

If you wouldn't mind sharing, could you share your dosing schedule for Citicoline?

Art

House2 profile image
House2 in reply to chartist

I took it, in a supplement called Brain. Vitale, 3 pills per day for 3 months. Stopped it. When I had dental surgery.

chartist profile image
chartist in reply to House2

Thank you for the reply!Brain Vitale has some good supplements in it, but it comes at a price premium of $135 per month. If it gets good results, it may be worth it?

Each serving (2 capsules) contains :

500 mg of Acetyl L Carnitine which is known to have neuroprotective effects.

250 mg of Citicoline which is shown to be neuroprotective and neuroregenerative

200 mg of Glycerophosphocholine

100mg Coffee Fruit Extract

100 mg Phosphatidylserine

100 mg Ginkgo

Looking at the components, this supplement seems to be targeted toward memory improvement. I would expect to see at least 500 mg per serving of Citicoline if it were targeted toward PD, rigidity, bradykinesia and reduction of C/L. You got the added benefit of reduced brain fog. You also used 3 capsules per serving or one more capsule than the recommended dose which means you were getting 375 mg of Citicoline total per day and pushing the monthly cost up to around $200. Interesting! Thank you again, House2 for sharing your experience!

Since you stopped for the dental surgery, did you notice how long the effects lasted after you stopped taking the supplement?

Art

House2 profile image
House2 in reply to chartist

Brain fog is still pretty good, about six weeks out, I had to increase C/L how ever.I chose that formula because it also has ginkgo which may raise glial derived growth factor, which may also help PD

chartist profile image
chartist in reply to House2

House2,

On the subject of the reduction of C/L intake related to Citicoline, how did you know that a reduction in C/L was needed and how did you know how much C/L to subtract? I am sorry for all of the questions, but I know other members will want to know these answers and thank you very much for taking the time to answer these questions! The study suggested as much as a 50% reduction, but that study used 500 mg intramuscularly, so it may be different with oral dosing, even though Citicoline is extremely well absorbed.

Art

House2 profile image
House2 in reply to chartist

I was Rx’d 25/100ER three times a day, after taking citicholine I started to feel “normal”. So I broke the 25/100s. In half. Felt good. So then I tried stopping C/L completely. BIG MISTAKE!!!! I lasted about three days.

chartist profile image
chartist in reply to House2

House2,

Now that is cutting right to the chase!!

Very helpful to me and I am sure to others! I have always wondered how people know how much to cut their C/L dose with B1 and now Citicoline. If too much levodopa causes dyskinesia, I wonder if adding Citicoline and decreasing levodopa can resolve the dyskinesia while keeping the levodopa effective enough for symptom control?

Art

ParlePark profile image
ParlePark in reply to chartist

Thanks Art!

parkie13 profile image
parkie13 in reply to chartist

What I remember about the dosage, from couple years ago, it was 1250 mg per day. I took it for a while, noticed good benefit till I started having headaches. Stopped till now. About 3 weeks ago started again since I am not getting the same time on. So far no headache. Seems to be helping. Mary

chartist profile image
chartist in reply to parkie13

Thank you for the additional dosing information, Mary! Its seems like most of the supplements are 500 mg capsules or 250 mg capsules. Even the bottles that say 1,000 mg, are mostly 500 mg capsules and it requires 2 - 500 mg capsules to get the 1,000 mg level listed on the front of the label. So are you taking 2 of the 500 mg capsules plus one of the 250 mg capsules to reach the 1250 mg dose?

Mary, are you saying that this 1,250 mg dose is increasing your on time? If so, by how much time? What other benefits have you noticed? Citicoline seems to impart its effects in a month or less.

Art

parkie13 profile image
parkie13 in reply to chartist

Hi Art, They are 250 mg caps. I have been taking 2 or 3 caps per day. Always first one 5 or 6 am. I'm scarred I'll start getting a headache so that is why I'm taking a smaller amount. I think it's better, not as good as before. I'll report in a while. Mary

chartist profile image
chartist in reply to parkie13

Thank you, Mary!

Art

parkie13 profile image
parkie13 in reply to chartist

I am staying at the same dosage which is between 7 and 6 pills a day of 25/100 CL. It seems like I really need more C / L to function now, after nine years.

Citicoline should be a critical component of every PD patient’s symptom-busting arsenal.

"Citicoline was reported to effective in reducing levodopa by up to 50%, with improvement in the patient's rigidity, akinesia, tremor, habwriting and speech." (sic)

Some things inspire confidence. Some things caution.

The day-to-day existence of the compulsive pedant must be painfully dull. My sympathies.

Yes. Much easier to see a headline on another thread and copy it , without looking at the detail. Try another morsel from the blurb

"Recent studies have found that citicoline could increase brain dopamine levels and synthesis rate and may also inhibit dopamine reuptake.6,7"

Reference 6 - as "recent" as 1989 - "Choline increases acetylcholine release and protects against the stimulation-induced decrease in phosphatide levels within membranes of rat corpus striatum" - you can read the article but no mention of dopamine

Reference 7 - "W.D. Killgore, A.J. Ross, T. Kamiya, Y. Kawada, P.F. Renshaw, D.A. Yurgelun-Todd

Citicoline affects appetite and cortico-limbic responses to images of high-calorie foods"

7 studies. Mostly short duration, small numbers of participants, and 1000mg per day im or iv injections (not 250mg orally)

6 of them between 1973 & 1991. The 7th, in 2016 was in China, comrade Con.

I found Art's (chartist) comment to Parle Park and cclemonade on Roy's B1 fundraising post, interesting. Something to investigate further.

But "Citicoline should be a critical component of every PD patient’s symptom-busting arsenal."

Well, obviously, if you say so.

What did Art say to Parle Park and cc lemonade on Roy's B1 fundraising post?

This was Art's comment

ParlePark & ccl

This is an important reply regarding CDP Choline in PwP!

You made me look and CDP Choline is essentially the same as Citicoline as discussed here:

edu.emersonecologics.com/20....

Here is a quote from the article link :

>>> ' Citicoline is the ingredient name for a compound that’s chemically identical to cytidine-diphosphocholine (CDP-choline). The only difference is that CDP-choline is naturally occurring in humans, and citicoline is the form found in nutritional supplements.

CDP-choline is a nucleotide composed of choline, cytosine, ribose, and pyrophosphate. ' <<<

Based on that information, the following newer systematic review of studies (January/2021 ) came up that discusses the benefits of Citicoline in PwP and though it is only a brief abstract, it says a mouthful. Here is a link to the review abstract which I would describe as worth reading by anyone with PD!

pubmed.ncbi.nlm.nih.gov/332...

Here is an important quote from that review :

>>> 'Despite the varied outcome tools, this review found that patients with PD who were taking citicoline had significant improvement in rigidity, akinesia, tremor, handwriting, and speech. Citicoline allowed effective reduction of levodopa by up to 50%. Significant improvement in cognitive status evaluation was also noted with citicoline adjunctive therapy. ' <<<

I will look into this further, but anyone with PD should do the same, imo!

ParlePark & ccl, thank you for sharing!!!

Art

@cclemonade

Much appreciated, thanks Richard. I'm betwixt and between. Was thinking of asking Glen's Dr if he could perhaps try a drug for his anxiety but as most of these drugs are anti depressants which are anticholinergic, as well as increased risk of brain fog, not to mention possible serotonin syndrome.......it's a minefield and, ultimately, a trade off I guess......any advice?

Not really, I'm afraid. I think Glen's a bit further down the track than me. I would ask his doctor about citicoline - in case you get interactions with other drugs

Pity I can't loan him Keisha. She loves a cuddle, and its hard to be anxious with a big German Shepherd looking after you.

I can't remember if you've tried the red light hats? They appear to work best for pwp in the early stages, and I'm still cautious about enthusing too much about mine. But I'm planning to keep using it every day.

No, haven’t tried the red light hat. Several years ago tried a red light headband which I imported from the US but like everything else, Glen does not apply himself or stick with it I’m afraid

I guess I'm lucky with the red light hat that it is quite easy for me to fit in at least one session a day. Often 2 sessions. I have my log cabin office where I disturb nobody and can look as ridiculous as I please. And I feel good at the moment. I have been shadowing my wife on a 12 week diet plan, which has involved a short exercise routine for the last 6 weeks, so that muddies the water for the red light hat. It will be interesting to see over the longer term whether I sustain my enthusiasm for it

But I can understand why Glen would find it irritating.

hido you take 1000mg then?

thx

No. I don't take Citicoline at all at the moment. I am just starting to look at it. The trial information is hardly overwhelming. Mostly they used injections. I believe Citocoline is reasonably well absorbed orally, so unlike B1 there may be a near equivalence of oral to IV injection. But if that's the case it makes you wonder why they opted for IV in the trials

I note I read a warning somewhere (can't find it atm - maddening) that excess dosage of citocoline (and / or combined with C/L) can provoke diskynesias - similar to C/L in that respect

Also WebMD has the oral dose at 1000-2000mg daily, and says it is POSSIBLY SAFE for up to 90 days

webmd.com/vitamins/ai/ingre...

Quote from your WebMD article, “How does it work ?Citicoline seems to increase a brain chemical called phosphatidylcholine. This brain chemical is important for brain......”

Why not take phosphatidylcholne instead?

Thx

My husband takes 1 a day of 250mg. Probably not enough but being an overreactor to drugs I usually give him less of things in case he has side effects. He has been taking it for a few years with a few breaks. I’m not sure how much effect it has as he takes many things. One of his main problems is rigidity in shoulders and hands.

Other than the one mentioned below (pretty pricey) are there other brands people recommend? Thanks.

In my experience as a rigidity dominat PD, anything that increases the acetylcholine level in my body makes me become stiffer including Citicoline which acts as a choline donor for the synthesis of Acetylcholine.

healthunlocked.com/cure-par...

Thanks for sharing! My husband is restarting CDP Choline, and I’m pretty sure dosing will be tricky and require a reduction in other supplements that affect dopamine levels. Last time he tried it over a year ago, after a week or so he started hallucinating, which is what happens when his dopamine levels are too high. But prior to that, his memory and speech were suddenly really clear for a couple of days.

So dosing everything is a house of cards, but I really feel he needs a cognitive boost, so we’re gonna try it again.

Well, that had an intense effect.

Hubby took one 300mg dose Sunday, and tolerated it fine (we skipped all other dopamine enhancing supplements that day ....mannitol and B1). Then waited 2 days and tried another 300 mg dose on Wednesday, also skipping mannitol and B1 on Wednesday. Wednesday night he had vivid dreams and didn't sleep much, then woke Thursday morning hallucinating, and high energy. So we skipped mannitol and B1 Thursday and today, though today he's mentally normal, and moving quite well.

So, the big question is, do we push through and try it again, maybe even a lower dose or more spread out? Or give up on CDP Choline and maybe try a different acetylcholine booster like Panang Ginseng, Rosemary or Alpha GPC, which I read may be more calming rather than excitatory?

I'm pretty sure it's the citicholine that put him over the edge, most likely raising his dopamine levels, as he had been on the lower side of his dopamine levels prior, and nothing else changed.

LL62,

I don't know how long your husband has been taking B1, but if it is over 6 months, the effects of B1 will remain for days to weeks depending on the individual, so B1 effects are probably still in play. Both B1 and Citicoline are likely to have Levodopa enhancing effects in one way or another.

Art

Thanks! I’m pretty sure it’s mainly the mannitol that has built up his dopamine levels, as we paused B1 for 5 months or so to get the mannitol dosing, and too much mannitol during that time could also trigger this kind of high anxiety hallucinating. Just restarted B1 in March, but at a much reduced dose so far, so it’s a factor too.

He no longer takes c/l or any dopamine agonists, so it’s pretty fascinating the impact he can get just from supplements.

He had another episode just now, by the way, and we walked for a mile to burn off the energy! Pretty amazing that he could walk that far at this stage. Anyway, we definitely need to pause these supplements for a few days until he resets, and get back to baseline.

For anyone who missed this Dr. Mischley webinar from earlier this year.

youtube.com/watch?v=qWwzETa...

25:20 mark - CDP Choline. Makes l-dopa 30-50% stronger.

1:36:08 mark - You need at least 3-4 pills a day to fully appreciate the benefits and potentiate l-dopa - A patient noticed a huge difference on 4 pills while 3 pills did nothing for years.

gaga1958 profile image
gaga1958 in reply to rescuema

Thanks for posting

chartist profile image
chartist in reply to rescuema

That was a long video at 2 hours! She brings up interesting points, but also many questions that still need to be answered through research and testing.

Art

rescuema profile image
rescuema in reply to chartist

I don’t agree with everything said on the video but yes good observational data to draw from.

chartist profile image
chartist in reply to rescuema

I agree, I do not agree with all that she said.

Art

Despe profile image
Despe in reply to rescuema

This is what our homeopathic doctor asked my husband to take:

amazon.com/BodyBio-Phosphat...

rescuema profile image
rescuema in reply to Despe

That seems unnecessarily pricey but I hope it works for him. I'm curious to see if you notice any beneficial effects on top of the citicoline he has been taking.

Despe profile image
Despe in reply to rescuema

He stopped Citicoline and started phospholipids. We are thinking about going back to Citicoline as it gets really expensive.

rescuema profile image
rescuema in reply to Despe

I understand. I'd probably do the same if one bottle doesn't show an appreciable effect.

gaga1958 profile image
gaga1958 in reply to Despe

What is the difference between phospholipids and phosphatidylcholne ?

Despe profile image
Despe in reply to gaga1958

I am not sure but phospholipids cover more than just citicoline.

Despe profile image
Despe in reply to Despe

Here is another link:

bodybio.com/blogs/blog/what...

Despe profile image
Despe in reply to gaga1958

thoughtco.com/phospholipids...

This link answers your question.

gaga1958 profile image
gaga1958 in reply to rescuema

From WebMD.....

Citicoline seems to increase a brain chemical called phosphatidylcholine. This brain chemical is important for brain......”

Why not take phosphatidylcholne instead?

rescuema profile image
rescuema in reply to gaga1958

Choline is a methyl donor and it has other important health contributions such as lipid metabolism, managing liver functions, homocysteine conversion, etc. Unlike choline, citicoline is less likely to worsen TMAO metabolites which may increase the risk of cardiovascular events. Also, see The Gut Metabolite Trimethylamine N-oxide Is Associated With Parkinson's Disease Severity and Progression researchgate.net/publicatio...

Citicoline is also a source of cytidine which gives citicoline an advantage over choline. The cytidine component of citicoline converts to uridine before crossing the blood-brain barrier.

The uridine component is required for the rate-limiting step of phosphatidylcholine production and that uridine also promotes neuronal growth. Uridine is the molecule responsible for increasing brain levels of norepinephrine and dopamine, improving mitochondrial function, and boosting energy production in the brain. accurateclinic.com/accurate....

Because phosphatidylcholine metabolism is a source of endogenous choline, the nutrient was not initially classified as essential. Yet, de novo choline synthesis in humans is not sufficient to meet their metabolic needs such that healthy humans fed choline-deficient diets develop fatty liver, liver damage, and/or muscle damage

lpi.oregonstate.edu/mic/oth...

Is it over the counter or prescription? I'm not on any meds yet. Would this be something to start with to reduce symptoms? What dosage would you recommend starting with,? I'm taking 1000 mg of b1 plus many supplements. Thanks for your help

From Wikipedia:

"Citicoline (INN), also known as cytidine diphosphate-choline (CDP-Choline) or cytidine 5'-diphosphocholine is an intermediate in the generation of phosphatidylcholine from choline, a common biochemical process in cell membranes. Citicoline is naturally occurring in the cells of human and animal tissue, in particular the organs. Studies suggest that CDP-choline supplements increase dopamine receptor densities."

Source: en.wikipedia.org/wiki/Citic...

*Readily available as a supplement online (typically in multiples of 250mg):

amazon.com/s?k=citicoline+s...

What is the difference between Citicholine and Choline Dihydrogen Citrate found in B-Complex pills?

JayPwP profile image
JayPwP in reply to JayPwP

No responses?

CaseyInsights profile image
CaseyInsights in reply to JayPwP

Jay see if this helps, to differentiate between choline supplements and their effectiveness.

mindlabpro.com/blogs/nootro...

As per my experience, my spouse supplementation includes

1. One softgel capsule of Phosphatidylcholine (420mg)

2. One capsule Acetyl L Carnitine (800mg)

3. One capsule Citicoline (250mg)

Got to this place trying to deal with balance issues. Got the idea from here

parkinsons.org.uk/news/comm...

....Common dementia drug could improve Parkinson's symptoms

All three items boost Acetylcholine production 🌺

...just in case you missed the connection Rivastigmine is a cholinesterase inhibitor, it therefore prevents the breakdown of acetylcholine.

JayPwP profile image
JayPwP in reply to CaseyInsights

Thanks Casey

Dr Mischley appears to confirm that citicoline produces dyskinesias - when dosing is excessive. The early studies, a bit like the Macuna studies, were about the potential for a substance in countries where levadopa therapy was unavailable. It acts like levadopa, it interacts with levadopa. What is the benefit in replacing levadopa with a substance which produces the same relief, and has the same side effects, as levadopa but costs north of £60 a month for an effective 4 capsule a day dose?

It made my dyskinesia worse, but pretty much anything pitched to extend levodopa does that.

Ola, Ricardo,

Not much in the way of human studies for Citicoline and PD, but this very brief abstract offers one possibility as to why Citicoline in combination with levodopa might offer some benefit over levodopa alone, which seems to be how most PwP use it, in combination with levodopa. This abstract is looking at a longer term usage potential benefit of Citicoline which could be of value in later stages of PD if instituted now

pubmed.ncbi.nlm.nih.gov/228...

Another consideration is that Levodopa is known from previous studies to create oxidative stress in the brain, something that PwP absolutely do not need more of, whereas Citicoline has neuroprotective effects which could be beneficial for PwP in the longer term.

To my way of thinking about Levodopa, it is a drug that can improve motor symptoms in the majority of PwP, but offers nothing in the way of actual health improvement. My feeling about Citicoline is that the evidence for utility in PwP has plenty of room for further testing, but when you look at Citicoline in terms of other health issues such as memory, dementia or cognitive decline, three symptoms seen in PwP, Citicoline seems to have more to offer than Levodopa alone.

Here is a link to an October 2020 review of Citicoline studies :

With what is currently known about Citicoline, in my opinion, is that it offers more than levodopa alone and may confer longer term benefit for PwP, but more studies are needed in order to better define the potential of Citicoline in PwP. I am a fan of supplements which have multiple health benefits in humans and is why I appreciate melatonin so much and melatonin has an abundance of studies to prove some of its health benefits. If I had to choose between Citicoline and melatonin as an adjunctive treatment for multiple health issues including PD, I would opt for melatonin by a very significant margin, because of its broader health effects compared to Citicoline as well as significantly more studies to support its health benefits. If my choice was limited to levodopa with or without Citicoline, I would opt for the combination until such time as I found something better.

Art

Art

The point that citicoline MIGHT offer benefits beyond the levadopa amplification benefit, and in particular neuroprotective ones, is a good one.

Your link to the 2020 review is missing but I think I've read it.

Your link which wasn't missing to the Eberhardt trial is typically underwhelming for this substance

1990

Open label

4 weeks duration

Citicoline enabled levadopa dose to be halved without deterioration in motor skills

It suggests possibilities and begs for further studies, but is hardly a slam dunk. Over multiple 4 week periods since diagnosis I have experienced all sorts of symptom fluctuations

And over the last 3 years on here I have watched people load up with a multitude of supplements and be unsure which if any might be responsible for what slight improvement in a parkinson's disease which nonetheless continues to trouble them greatly.

Worse, some appear to suffer more as their quest for a natural solution causes them to miss out on the benefits of conventional medication.

Having said all that, I've ordered a pot for a quick try out ahead of my next neurologists appointment in July.

kevowpd profile image
kevowpd in reply to WinnieThePoo

Which product did you buy?

WinnieThePoo profile image
WinnieThePoo in reply to kevowpd

amazon.fr/dp/B093Z7N9DG/ref...

But even now I'm wondering what I think I'm going to achieve. It would probably be a better experiment after the trip to the neuro

Sorry about that, Ricardo. That's what happens when I do this stuff when I'm half asleep. Here is the missing link :

ncbi.nlm.nih.gov/pmc/articl...

Art

Thanks. I'd seen it.

What if one were to take CDP one day and Alpha GPC the other day?

mindlabpro.com/blogs/nootro...

Very interesting but did I miss the dose amount?

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