Citicoline: "patients treated with citicoline experienced a significant worsening 45 days after the medication was discontinued". Updated.

[park_bear]

This statement appears in a review that was published here: ncbi.nlm.nih.gov/pmc/articl... It is attributed to a study published in a book on citicoline in 1985. I've been unable to locate a copy of this book either online, for sale or to borrow from a library.

Book: Zappia V, Kennedy EP, Nilsson BI, Galletti P, eds. Novel biochemical,pharmacological and clinical aspects of cytidinediphosphocholine. Amsterdam: Elsevier Science Publishing; 1985.

Study: Loeb C, Albano C, Caraceni T, Caraffa T, Coppi R, Di Perri R, et al. CDP-choline in the treatment of Parkinson’s disease: a multicenter controlled trial. p. 339-46.

Be that as it may, this has been my experience: I started citicoline in January of this year, and stopped around the second or third week of January. Since then I've experienced an increasing need for more levodopa medication, now considerably more than my prior baseline, approximately 45 days later.

My advice: if you have not started citicoline, don't. If you are taking citicoline, don't quit.

Additional Detail

What citicoline does is to improve the efficiency with which the brain converts levodopa into dopamine. It enabled me was able to reduce my levodopa dosage from baseline to something less. It does not treat the underlying disease process as far as I know. I was not taking very much levodopa to begin with so reducing levodopa was not very important to me. I stopped due to concern about its affect upon circulation which I detailed towards the end of my post here: healthunlocked.com/cure-par...

Now, subsequent to quitting citicoline, it appears I'm needing about considerably more than the original baseline amount of levodopa in order to have "on" time. I have restarted citicoline at half the prior dosage, 250 mg twice daily instead of 500, and plan to taper very slowly.

Thanks to       JayPwP for bringing this review to my attention. Further discussion of this review in his post here: healthunlocked.com/cure-par...

[Missy0202]

Can I ask why you stopped? and if you are going to start again?? Hope you can get your symptoms under control again!

[park_bear in reply to Missy0202]

I stopped due to concern about it's affect upon circulation which I detailed towards the end of my post here: healthunlocked.com/cure-par...

I have now restarted at half the prior dosage, 250 mg twice daily instead of 500

[chartist in reply to park_bear]

park_bear,

Berberine will significantly lower TMA and TMAO into a safer range and vitamin D will be additive in that process. I know you can't take melatonin, but you can get sun exposure to get melatonin without problem and for those who can take melatonin, it will further lower TMAO while working against TMAOs negative effects on the cardiovascular system and organs. Berberine , vitamin D and melatonin are all beneficial for PD too and have studies to support many other health benefits. Berberine also works against insulin resistance that is a common health issue in PwP.

Citicoline is thought to increase dopamine receptor density in the brain to make the most of the available dopamine and that is thought to be the reason why some people are able to lower their Sinemet dose if they are taking higher dose citicoline. I imagine if the density of dopamine receptors begins to decline toward where they were when you started using citicoline, there will be a delay in the time it takes to see the results of that decline, as you are reporting.

If you are looking for an alternative to melatonin to lower your TMAO levels, you can consider the probiotic, Lactobacillus rhamnosus GG.

Art

[MarionP in reply to chartist]

Please what do the acronyms mean! "TMA"

"TMAO" an enzyme? Or what?

trimethylamine?

What is TMAO?

[park_bear in reply to MarionP]

Yes, TMA = trimethylamine, which is rapidly oxidized by the liver to TMAO. TMA is cardiotoxic and TMAO is a marker for TMA.

[MarionP in reply to park_bear]

TMAO is Trimethylamine-N-oxide?

[park_bear in reply to MarionP]

Yes. To get started with additional information see my writing here: tinyurl.com/bdz5cy3u

[MarionP in reply to park_bear]

Thanks! Will do that.

[JayPwP in reply to MarionP]

TMAO is not cardiotoxic

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

[MarionP in reply to JayPwP]

I wouldn't know, others may know better, like you. I just found the articles interesting maybe we can get some discussion out of them. I was thinking of the possible weight benefits definitely the blood sugar and cholesterol benefits. On the other hand I also noticed on TV a TV ad for berberine, which is unusual to see in our neck of the woods, I mean are groups neck of the woods somebody is latched on to the possibility of an alternative to the GLP-1 drugs.

That said I looked at WebMD and they're not quite as, shall we say, enthusiastic about berberine demonstrated benefits.

[chartist in reply to JayPwP]

Although citicoline is hypothesized to produce less TMA/TMAO than choline, it is thought that it still produces both. In any case, both TMA and TMAO can have a negative impact in multiple areas of our heath. TMAO is considered to be proatherogenic and if that is correct, then it can have a negative impact on the major organs, including the heart over the mid to longer term.

Vitamin D, Lactobacillus rhamnosus GG, berberine, Folate, FMT, vitamin B2/riboflavin, Curcumin, Ginkgo Biloba, Resveratrol, Beta Sitosterol and melatonin will all work to reduce TMA/TMAO while also fighting against the negative effects of these two in humans while also working against the multitude of negative effects involved in the second most common neurodegenerative disease, PD.

The bold supplements seem likely to be the most active with Berberine and Folate likely leading the pack followed by LrGG.

Art

[JayPwP in reply to chartist]

Thank you 🙏

[park_bear in reply to chartist]

Thanks. Will check into berberine. Have some Lactobacillus rhamnosus. Was wondering why

[chartist in reply to park_bear]

The berberine is also antiatherosclerotic, heart protective , anti inflammatory and has antioxidant effects while improving insulin resistance.

Art

[chartist in reply to park_bear]

This brand of Lactobacillus rhamnosus GG is fairly highly rated and contains 12 billion colony forming units (CFUs). Many other GGs are 10 billion CFUs. Of the tested probiotics, GG was shown to be the most effective at reducing TMAO.

Here is a link to the systematic review, that pertains to humans and animals :

pubmed.ncbi.nlm.nih.gov/355....

Here is a relevant study quote :

' The body of evidence on the use of probiotics to reduce TMAO concentrations shows that only a few strains have this beneficial effect. This review can conclude that Lactobacillus rhamnosus GG were the most efficient strains in reducing the plasma TMAO level in both humans and animals. '

Art

[HekateMoon in reply to park_bear]

Thanks for the info, PB. Hope you get better soon...🙏

[Bolt_Upright]

Wow, so sorry to here this PB. Good luck and may God bless you.

[park_bear in reply to Bolt_Upright]

Thanks for your kind words! Much appreciated!

[Gcf51]

I take Alpha GPC + Uridine. Would that be safe?

[park_bear in reply to Gcf51]

Sorry I'm not able to say whether this applies to Alpha GPC. In the event that it does, the best course is to continue taking it without any changes.

[Gcf51]

Thanks

[Boscoejean]

ibs.it/novel-biochemical-ph...

[park_bear in reply to Boscoejean]

Thank you! We shall see if they are prepared to ship overseas.

[park_bear in reply to Boscoejean]

Unfortunately they were not willing to send to the us nor provide images of the relevant pages

[Boscoejean in reply to park_bear]

disappointing news

[JayPwP]

My pleasure park_bear 🙏🙏

[JCRO]

I have been thinking about adding this compound to my stack for about a year to try to reduce the C/L I take to give me some extra runway. It’s a cautionary tale about the risks we take as self-diagnosing Guinea pigs and citizen scientists - even the “proper” scientists are in the dark and at each other’s throats on supplementation. The thought of discontinuing a supplement and it doing significant damage is heartbreaking. Thank you PB for your candour and transparency. I hope that reintroducing reverses your progression and breakout symptoms.

[Kevin51]

Hi PB. I started citicoline at 250mg per day in early January. Initially tremor decreased with unchanged Sinemet but then this reversed and so I stopped after 12 days due to increased tremor and bradykinesia. Citicoline has a half life of around 2.5 days so it stacks (I calculate I was effectvely around 1gm/day after 10 days of taking 250mg daily, assuming exponential decay). Maybe that's why I experienced a turnaround. I haven't restarted as I wanted to pursue high DHA for my (diphasic) dyskinesia before doing that.

PS. I am not aware of anything changing dramatically recently. Could the 45 days refer to the timing of their follow-up assessment?

K

[park_bear in reply to Kevin51]

Probably was. I'm attempting to obtain a copy of the paper in order to assess such details.

My experience is that this issue has been coming on for a while and has now culminated to an intolerable level requiring changes in my medication regimen. I believe it is biological changes resulting from withdrawal of citicoline. Did not just appear all at once at 45 days.

[MarionP]

In that case I ran across these, might be interesting read (I thought they were):

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

and

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

[Dap1948]

If you take something like citocoline, which improves symptoms to such an extent that some people can reduce their levodopa dosage, then when you stop what was causing the improvement, you will of course feel a worsening of symptoms. The interesting thing is that the positive effect can last for 45 days before you miss citocoline’s help. The same would happen with the B1 therapy. If you stop taking it, you sale along quite well for a month or so, then your old symptoms would return. This is not a reason for not using these adjunct therapies to levodopa.

[park_bear in reply to Dap1948]

No, you are misunderstanding. What citicoline does is to improve the efficiency with which the brain converts levodopa into dopamine. It does not treat the underlying disease process. So I was able to reduce my levodopa dosage from baseline to something less. I did not take very much levodopa to begin with so that did not matter to me. Now, subsequent to quitting citicoline, it appears I'm needing about considerably more than the original baseline amount to have on time.

There was no "positive effect" lasting 45 days. What there was of a positive effect lasted for maybe about a week afterwards, then there was a gradual ongoing worsening. This treatment has nothing to do with B1 therapy.

[MarionP in reply to park_bear]

If I might ask, about how long roughly had you been taking citicholine in the first place? Months years etc.

[park_bear in reply to MarionP]

Only about 10 days!

[MarionP in reply to park_bear]

WTF?!

[park_bear in reply to MarionP]

Yeah this stuff is fast acting. Less than a week after re-starting at 500 mg daily I'm having to reduce my levodopa dosage, which is good. Also reducing my citicoline to 250 mg.

[MarionP in reply to park_bear]

Well worth taking note!

[JayPwP in reply to park_bear]

Which Citicoline are you taking?

[park_bear in reply to JayPwP]

amazon.com/gp/product/B004J...

[JayPwP in reply to park_bear]

Thank you 🙏

I have the same but haven't started yet.

[LAJ12345]

surely it means the citicoline has been keeping the symptoms at bay so when you stop it you you lose that benefit. Why does that make it a bad thing to take?

[park_bear in reply to LAJ12345]

It is Not keeping the symptoms at bay, other than to the extent it improves the efficiency of the brain's conversion of levodopa into dopamine.

The reason not to take it is gut bacteria can convert it into cardiotoxic TMA

[LAJ12345 in reply to park_bear]

I see

[Lolo2022]

hello  park_bear I did a copy past of the study 👇

Loeb et al [743] conducted a multicentre, double-blind study with citicoline for the treatment of parkinsonian patients. In this study, 65 patients were randomized to a group to which citicoline 1 g/day intravenous was added or to a placebo group. Treatment lasted 21 days. All patients continued their underlying treatment with levodopa plus mianserin or benserazide for at least eight weeks. Authors found significant differences between citicoline and placebo at the controls performed after 14 and 21 days of treatment in all parameters assessed by the Webster and Northwestern University disability scales. They also noted that patients treated with citicoline experienced a significant worsening 45 days after the medication was discontinued, thus showing the efficacy of citicoline as adjuvant treatment to levodopa in patients with Parkinson’s disease.

So we don’t have to be afraid…

[park_bear in reply to Lolo2022]

Your conclusion does not follow from the information given.

The text you have quoted is the review and not the study itself

[MarionP in reply to park_bear]

It is here, full text available, (all 87,000 blessed words of it) at

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

And here is the captioning:

Rev Neurol. 2022; 75(Supl 5): S1–S89.

Published online 2022 Dec 31. doi: 10.33588/rn.75S05.2022311

PMCID: PMC10548481

PMID: 36544369

Language: English | Spanish

Citicoline: pharmacological and clinical review, 2022 update

Julio J. Secades corresponding author and Pietro Gareri

[park_bear in reply to MarionP]

That is the review which I already have, and cited in my post. I'm looking for the study cited in the review, reference number 743.

[MarionP in reply to park_bear]

That's like 1985 inside some Elsevier book...Elsevier don't allow the public in without some good coin in their pocket for the article. Or someone friendly to us with some institutional access, usually research institution or university faculty account...everyone else has to pay the publisher a fee for access to the article...unless you happen to be near a medical school library, or sometimes a state library. I used to get mine from the latter but then the state closed it down and I retired anyway, Anybody know a college student? if you were friendly with a student or staff at a medical school or some allied health college/postgraduate program... But you know, maybe it's old anyway, 1985 was a while ago...

[park_bear in reply to MarionP]

The book seems to be pretty rare. Not available from university libraries in my area. I have sufficient clarity at this point so obtaining it is not a necessity.

[MarionP in reply to park_bear]

Maybe try Thriftbooks. Kind of old to be relying on though kind of old and obscure and who knows about what procedures they used or how reproducible the result could have been. I'd let it go and go have a pizza.

But that is a very interesting response you had and one would think there's definitely something going on. In your case 10 days man that is really short but again we know that happens with Zyrtec and other things that can do a severe rebound, like decongestants and eye drops, famous for it. For a perfectly applicable example, try doing it with heroin.

[Lolo2022 in reply to park_bear]

maybe but I don't think we need to worry

it's as if you wrote that your symptoms worsened 45 days after having stoped levodopa

Don’t you think ?

[MarionP in reply to Lolo2022]

10 days doesn't sound like a lot of time to develop relief and then upon withdrawal you get a nasty rebound, (although it is possible say with Zyrtec so it's definitely possible) such that Lovato is fat soluble and cumulative, or citicoline has some freaky Half-Life like 95 or 100 days... ( Or some other substance was messing up and interfering with metabolism such like what happens with grapefruit juice for example) or is fat soluble with an accumulative allergic effect that happens when the cells storing it or used up and start overflowing into his bloodstream and triggering antibodies. It just sounds odd. Definitely not impossible though so could be.

[MarionP in reply to Lolo2022]

Lolo: did symptoms change during any part of the 21 days; and did symptoms change after day 21?

And just to be sure, what is the reference of the study? Where can one read it?

[JayPwP]

"patients treated with citicoline experienced a significant worsening 45 days after the medication was discontinued"

This is a tricky statement. Significant worsening with patients returning to pre-citicoline state? Or significantly worse than pre-citicoline state?

[park_bear in reply to JayPwP]

I cannot speak for the researchers but in my case it is the latter.

[JayPwP in reply to park_bear]

But wherever I have searched, Citicoline is touted as being naturally produced in the body and therefore safe

healthline.com/health/citic...

[park_bear in reply to JayPwP]

Just because something is naturally produced in the body does not make it safe to consume in quantity. There are many substances produced in minute quantities by the human body that are poisonous in quantity, including formaldehyde. There are also a number of vitamins that are necessary for life yet adverse when consumed in excess.

[MarionP in reply to park_bear]

Absolutely correct!!!

[JayPwP in reply to park_bear]

Also someone needs to bring this TMA issue to Laurie's attention

😆😆

[Hope-full1970]

I'm sorry to hear this. I take 250 mg in the morning. I am not on any medication yet. I'm wondering if it would have the same effect if I stopped since I'm not on meds yet and if it would be wise to come off. I think it helps my memory.

[park_bear in reply to Hope-full1970]

Based on my understanding of what is going on, it would not have the same effect on someone not taking levodopa medication. However, there is no guarantee that my understanding is correct.

As to whether or not to continue, you will need to use your own judgment, based on this discussion, your experience, and any other information available to you.

[Hope-full1970 in reply to park_bear]

Good advice, thank you!

[Sydney75]

Dr Laurie Mischley approves of citocholine and that study quoted is almost 40 years old. Perhaps it slows progression. At lower levels 250mg it would be less toxic.

My HWP had two major surgeries in Dec due to fractured vertebrae had to stop almost all supplements for almost 2 months. Definite regression. Hard to determine cause, stress of surgery, pain etc? Adding back citocholine 250mg some B1 etc. as well as other supplements. Seeing some improvement. Accuncturist gave him a Chinese herbal formula tried 1/2 dose for 2 to 3 weeks initially ok then awful extreme fatigue. Stopped that symptoms abated. Can't mix prescription meds with too many herbs.

Tackling neuroinflamation is my goal.

-Syd

[park_bear in reply to Sydney75]

This all got started based on the recommendation by Dr. Laurie Mischley who recommended 1 g/day. It improves the efficiency by which the brain converts levodopa to dopamine. I'm not aware of any evidence that it slows progression.

Regarding the age of a study, old ≠ invalid.

[park_bear in reply to Sydney75]

Best wishes to you and to your husband for his recovery. After a recent X-ray of my lumbar spine, my doctor said my bones would be the envy of a younger person, and wanted to know what I was doing. The most important supplements for bone health are vitamin K as well as Vitamin D. Vitamin K is necessary for the body to get calcium out of the bloodstream into the bones. If it is deficient, a person is prone to suffer the double whammy of osteoporosis and hardening of the arteries. It is not clear which of vitamin K1 or K2 are essential so I supplement both.

My complete writings on supplements for bone health:

Vitamins and Minerals for Bone Health and Reduced Risk of Cancer tinyurl.com/hya5dwd

Vitamin K: Unsung and Essential tinyurl.com/yd9l4j3q

What You Need to Know to Reduce Risk of Hip Fracture and Cardiovascular Disease tinyurl.com/y8o9jy8u

[Sydney75 in reply to park_bear]

Thanks, I hoping we can get back to any real exercise as our movement specialist states that has been shown to slow progression. We take D3K2 liposomal, my husband's has long term back problems from genetic Spondylolisthesis and his PD has lowered his pain threshold.

I restarted his tea I make from steeped Schisandra berries and Hibiscus. I add 1 dropper of green tea, ginkgo, and rhodelia (herbal tinctures) I think it helps with cognition and energy a bit. I also think the Healus form butyrate is good for gut, berberine is a good addition to take, but in the past after about 2 months he had gastro issues. Might be something to take every other day.

Always looking for supplements that reduce neuroinflammation. I might have posted this article before.

Neuronutraceuticals Combating Neuroinflammaging: Molecular Insights and Translational Challenges—A Systematic Review

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

[park_bear in reply to Sydney75]

Cinnamon reduces neuroinflammation. My report, with references, here:

healthunlocked.com/cure-par...

[JayPwP]

PB,

Theoretically I could do a Citicoline flush every 2 or 3 months, for 15 - 30 days, and not experience any worsening.

Just a thought... 🙏

[park_bear in reply to JayPwP]

There would be some worsening over that period, just not as bad as at 45 days afterwards. I restarted at 500 mg daily instead of 1 G, which has been effective, and I've now cut that back to 250 mg daily. We shall see if that is good enough.

[JayPwP in reply to park_bear]

I am planning to start from 2nd April, 250mg in the morning for 15 days and then decide to titrate up or stay. Will assess every 15 days

[JayPwP in reply to park_bear]

I get Citicoline Sodium tablet 500mg, which are cheaper than the Jarrow's which I have currently. It's ok to use, right?

[park_bear in reply to JayPwP]

I'm not familiar with that version, but as long as it is from a reputable manufacturer should be okay.

[TL500]

so Dr Mischley’s hypothesis about high dose DHA and citicoline has bad side effects? Should we also not take high dose DHA suggested by her or is it ok as long as we don’t take citicoline? Thanks

[park_bear in reply to TL500]

Fish oil, including the high DHA version, has been very helpful for me. So for this I can give a thumbs up.

[TL500]

how much DHA are you taking ? And if stop it no side effects like citicoline? Thanks

[park_bear in reply to TL500]

My regular routine is either about a tablespoon of Arctic brand cod liver oil, which has about the same amount of DHA as the fish oil you're using depicted below, or a serving of salmon, daily. I did obtain a single 5 oz. bottle of Pharmax fish oils and consumed about a tablespoonful at a time. I did not notice any adverse effects from stopping.

[TL500 in reply to park_bear]

So you take about 4g DHA per day?

[park_bear in reply to TL500]

Nowhere near that. Maybe about 1 - 1.5 grams daily. If the Pharmax fish oil were actually available, I would consider using that in spite of the increased cost in order to get a higher dose, but every time I have looked recently it was not in stock anywhere.

[TL500]

I am taking 40ml of this . I think approximately 541mg x 8.

Melrose fish oil health & heart

[Squarepusher]

I'm taking 850mg/day divided into 3 doses, and I've never seen any effect on reducing C/L? Would I see a stronger effect if I took 850 mg in one dose?

[park_bear in reply to Squarepusher]

no

[Adam78]

Is see a PDF of the book is available for $199 at wonderclub.com/9780444009678?t

[park_bear in reply to Adam78]

Thanks for letting me know