Interesting Article: Promising new remedies for Parkinson's disease

[Bolt_Upright]

Update: I read and researched as I was posting this. I am happy they put NR and PEA in their article, but I think they got a little over their skis stating they had found a "A dynamic quartet"

Update Again! Please see Park Bear's Citicoline Warning healthunlocked.com/cure-par...

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Promising new remedies for Parkinson's disease Dec 2023 naturmedisinsentralen.no/Wo...

"Common treatment for Parkinson's today is to give l-DOPA, but its use has many side effects. L-Dopa does not inhibit the development of the disease.

Research has therefore been conducted on many forms of therapy against Parkinson's disease. Some have shown an effect.

NADH is now being researched in Norway. PEA has been shown to inhibit Parkinson's progression. And HXT is sought patented as a treatment for Parkinson's."

So...

NADH: This is the nicotinamide riboside in the NOPARK study. High school graduate that I am, I substitute nicotinic acid.

Palmitoylethanoalamide (PEA): I take 1200 mg a day.

"PEA is often given along with luteolin [13]. Luteolin is a powerful antioxidant and it is always advisable to take PEA along with an antioxidant.

However, there is a stronger and better antioxidant than luteolin.

It is Hydroxytyrosol (HXT). HXT also has a direct effect on the dopamine system [14].

The fact that HXT acts directly on the dopamine system means that there is reason to believe that HXT will have a better effect used together with PEA at Parkinson's."

Hydroxythyrosol (HXT /Htyr /HT): "Hydroxythyrosol (HXT), a substance found in olives, olive oil and wine. HXT has been shown to inhibit, among other things, many things that lead to neuro – degeneration [14]. HXT is therefore a promising drug for use against Parkinson's disease (PD). HXT inhibits several types of dopamine breakdown in the body. HXT also prevents dopaminergic cell death [15]."

Citicoline: Citicoline or CDP-choline is well studied in the treatment of Parkinson's disease. The results are only good [19,20,21,22,23,24].

"A dynamic quartet

Using PEA, HXT, Citicoline and NADH along with L-Dopa or other treatment therefore seems to be a promising way to go.

All three funds work fine together, they have no side effects – and can be used together with most medications.

The funds are also quite cost-effective and affordable in use. NADH in therapeutic doses becomes the most expensive part of treatment."

"This is not medical advice, but an overview of the doses used in the different studies. As mentioned, it may be wise to combine these funds.

600 – 1200 mg PEA per day.

500 – 1200 mg Citicoline per day.

500 – 2500 mg HXT per day.

25 – 40 mg NADH per day." : I think this is a typo. The NADPARK study was 1000 mg a day and the NOPARK study were give 1000 mg a day with a 1200 mg dose in the open label follow up study.

I will look into HXT and Citicoline.

[Bolt_Upright]

15. Karkovic Markovic, A., Toric, J., Barbaric, M., & Jakobusic Brala, C. (2019). Hydroxytyrosol, Tyrosol and Derivatives and Their Potential Effects on Human Health. Molecules (Basel, Switzerland), 24(10), 2001. doi.org/10.3390/molecules24...

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Update: I did not find the evidence these results are based on impressive. Mostly cell studies and preventive (prenatal I think) treatment. I will stick with my PEA with Luteolin.

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"3.3. Neuroprotective Effects

The neuroprotective effects of HTyr were studied in a great number of in vitro and ex vivo studies by different strategies, some of them employed chemically induced neurotoxicity or were based on the biochemical alterations that take place during the process of hypoxia-reoxygenation [10]. The brain accumulation of HTyr and HTyr-sulphate suggested their neuroprotective activity by the reduction of the oxidative stress at neuronal level [58]. One of the main age-associated neurodegenerative diseases is Alzheimer’s disease (AD), an amyloid disease characterized by the deposition of typically aggregated protein/peptides in tissues that are associated with brain degeneration and progressive cognitive impairment. HTyr has been studied in vitro in AD models. It protected neuronal cells against amyloid-β induced toxicity and prevented tau fibrillization [10]. HTyr was an effective inhibitor of hen egg white lysozyme aggregation, thus suggesting possible future applications of this natural compound for prevention or treatment of amyloid diseases [59].

HTyr is a promising compound for Parkinson’s disease (PD) medication, as it inhibits both enzymatic and spontaneous oxidation of endogenous dopamine, mitigates the increase in spontaneous oxidation during MAO inhibition, has a protective effect against dopamine and 6-hydroxydopamine (6-OHDA)-induced dopaminergic cell death and counteract α-synuclein-induced toxicity [60,61]. HTyr-butyrate also inhibits 6-OHDA-induced apoptosis through activation of the Nrf2/HO-1 (heme oxygenase 1) axis in neuronal cells [62].

In vivo studies have shown that HTyr attenuates the spatio-cognitive deficits, restores learning capacity and memory performance, and promotes cognitive function as well [63,64]. Also, the combination of HTyr and oleic acid was shown to inhibit cholesterol and fatty acid synthesis in C6 glioma cells [65]. HTyr may confer protection against ethanol-induced oxidative stress [66]."

[JackBruce2024 in reply to Bolt_Upright]

Interesting article! I haven't tried PEA with Luteolin yet. What brand do you use?

[Bolt_Upright in reply to JackBruce2024]

I have links to where I get all of my supplements here: rbd-pd-protocols.blogspot.c...

[EllCee in reply to Bolt_Upright]

Nice work Bolt_Upright. I totally agree with you on HXT vs Luteolin. "Lut" has such a robust body of evidence for its antioxidant properties that it shouldn't easily be dismissed. My partner with PD takes the same GoldHealth combo you take. I'm taking the more expensive Levagen+ form of PEA, along with the Algonot brand Neuroprotek luteolin - for osteoarthritis and general cellular health.

[Gioc in reply to Bolt_Upright]

Here you find Htyr

And also an interesting comment at the end.

Quote:

What is Oleuropein?

Oleuropein is a ‘phenylethanoid’ – a type of phenolic compound that is found in the leaf and the fruit of the olive. Phenolic compounds are produced by plants as a protective measure against different kinds of stress.

scienceofparkinsons.com/201...

Acacia on Como lake Italy

[Despe in reply to Gioc]

Gio,

Every meal we have is accompanied by Kalamata Olives. The best (no offense) .

[Gioc in reply to Despe]

True!🥇

[Bolt_Upright in reply to Gioc]

Beautiful photo!

[Gioc in reply to Bolt_Upright]

Thank you.

I ❤️ trees.

Do you know?🙂

Como lake . Mandello del Lario . Italy 🇮🇹

[Bolt_Upright]

Most of the studies on Citicolene are really old. This 2016 study is the newest:

24. Li, Z. & Wang, P. & Yu, Z. & Sun, H. & Zhang, J. & Cong, Y. & Sun and C. & Zhang, Y. & Ju, X.. (2016). Effect of citicoline adjuvant therapy on mild cognitive impairment in Parkinson's disease. 9. 4593-4598. ijcem.com/files/ijcem001792...

I did not find it convincing enough to add this to my stack.

[Boscoejean]

" Parkinson disease (PD) medications are not readily available in all countries. Citicoline increases dopamine synthesis and inhibits dopamine uptake. This systematic review aims to synthesize current existing evidence on the efficacy of citicoline adjunctive therapy in improving PD symptoms"

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

[EllCee in reply to Boscoejean]

This is a good article because it's a "systematic review" of all major studies of Citicoline through 2021. Thanks for posting it.

[Bolt_Upright in reply to Boscoejean]

Interesting! Thanks Boscoejean !

"Findings: 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."

Here is a link to the complete paper: sci-hub.ru/10.1016/j.clinth...

"CONCLUSIONS: Citicoline adjuvant therapy has positive effects on the improvement of motor function, delay of the progression of cognitive impairment, and reduction of bradykinesia, rigidity, and, to some extent, tremor in patients with PD. Citicoline also has a levodopasparing effect that allows the delay in initiation of and reduction of required dosage of levodopa therapy, thereby reducing the levodopa-associated adverse effects.

Furthermore, citicoline had negligible adverse effects. More well-designed, high-quality randomized clinical trials on the use of citicoline adjuvant therapy in patients with PD are warranted. Moreover, future studies are needed to establish the standard dose of citicoline that may be given to patients with PD.

Although available evidence is still limited, adjuvant citicoline in patients with PD may be considered."

Dosages: If you look at the table with the studies, 4 of the studies used IV or Intramuscular dosing of citicolene. One study used a combination of intramuscular and oral, and 2 studies used only oral citicolene:

400 mg 3 times a day, Eberhardt et al (1990), had a 550% Reduction in the dose of levodopa/DCI.

200 mg every 8 hours, Li et al (2016) , MoCA and SCOPACOG scores of the treatment group were significantly higher than those of the control group (P < 0.01); phospholipid levels in the treatment group were significantly lower than those in the control group (P < 0.001)

Based on this, 400 mg 3 times a day looks interesting.

[Boscoejean in reply to Bolt_Upright]

yes I did notice that some of the studies were using infusions followed by oral citicholine

[JCRO in reply to Bolt_Upright]

Impressive as ever Bolt. Any reason to avoid and any contraindications you’ve seen? I’m aware of your (non medical) HS degree and “caveat emptor” etc.

[ddartmouth in reply to Boscoejean]

This article seems to be behind a paywall. Did you need to purchase it?

[Boscoejean in reply to ddartmouth]

I didn't and I don't know why I did not have to purchase it. I just was able to find it on google so I can try to find a different source on that see if this works

clinicaltherapeutics.com/ar...

[ddartmouth in reply to Boscoejean]

Thanks. When I follow your suggested link however I get a page with the highlights and abstract (not the actual paper).

[Boscoejean in reply to ddartmouth]

ok I will see if I can find a better link a little later today

[Boscoejean in reply to ddartmouth]

does this work? sciencedirect.com/science/a...

[Bolt_Upright in reply to ddartmouth]

Which article are you referring to?

This one? naturmedisinsentralen.no/Wo...

Or this one: sci-hub.ru/10.1016/j.clinth...

[ddartmouth in reply to Bolt_Upright]

Thanks Bolt.

That wasn't the one I was looking for but it looks good (once I figured out how to view in in English instead of Norwegian!)

[ddartmouth in reply to ddartmouth]

I was too quick to reply ... the second link is the one I was looking for.

[Bolt_Upright in reply to ddartmouth]

Both links should work. There is no paywall. That second link may ask you to prove you are human.

[garygjs]

Re Citicoline.

If it works, it works fast.

And when it works, the results can be sensational. Overnight, my mum's gait was utterly transformed.

Which is to say, it's not the sort of thing you keep taking over months and years in the hope that it might be doing something.

Take it for a few days. If no improvement is noted, stop.

It has a fabulous side effect profile.

In trying it, the worst that would be a lost is a few dollars.

[EllCee in reply to garygjs]

I've read it can be stimulating and interfere with sleep unless taken in the morning. What's your experience? Thanks.

[garygjs in reply to EllCee]

Mum used to take 500mg at c. 6.30pm and it never caused a problem. Insomnia is not flagged as an issue in the literature. However, clearly it has a capacity to stimulate:

"Citicoline improves human psychomotor vigilance, arousal, and visual working memory with significant amelioration of oxidative stress compared with placebo."

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

So, I guess it might cause an issue. Experiment.

Worth noting: if you maintain your usual levodopa dose while taking citicoline, it may make dyskinesia worse...which wouldn't be great at bedtime. Many are able to drop their levodopa dose when taking citicoline.

[JackBruce2024 in reply to garygjs]

Hi, What brand and what daily dosage was your Mom taking? Thanks.

[garygjs in reply to JackBruce2024]

I use Cognizin Citicoline. It's a slightly fancy version that has been used in a few clinical trials. Best I can tell, there's no reason to believe that this is any better than the citicoline you can get from decent companies like Jarrow etc. A fool and his money are soon parted.

mindnutrition.com/nootropic...

She began taking 1000mg ( 4 caps) a day. She now takes 750 mg. (She spends more time snoozing during the day now, and my sense is that she requires a little less).

On starting the citicoline, it soon became clear that mum was in less need of exogenous dopamine...and I reduced her dose from 4 sinemet tabs to 3. This is a pretty common experience by the look of the literature.

[Bolt_Upright in reply to garygjs]

Sorry to bother again: 750 mg a day. 3 caps. All at once? Morning?

[garygjs in reply to Bolt_Upright]

At the moment: 500mg @ 10-11 am, 250mg @ 6-7pm (caps are mixed into a yogurt due to swallowing concerns)

When she started taking them (total 1000mg): 1 cap was taken 4 x a day, roughly spread across the day.

When dysphagia became an issue (early '23): 500mg @ 10-11am. 500mg @ 6-7pm (caps mixed into yog)

Dose changes didn't seem to have an impact on results.

[Bolt_Upright in reply to garygjs]

Thanks garygjs , so... overnight citicolene was sensational, but you would not want to keep taking it for months on end? Do the results diminish over time? Any insights would be appreciated.

[JackBruce2024 in reply to Bolt_Upright]

It sounds as if he's saying that if it doesn't work right away, discontinue. But if it does work, keep taking it indefinitely.

[Bolt_Upright in reply to JackBruce2024]

Good reading comprehension. Thanks!

[garygjs in reply to Bolt_Upright]

If it works, you certainly want to carry on taking it.

My mum started taking this during Oct or perhaps November '22. She still takes it today.

Overnight - literally overnight - her feeble Parkinson's shuffle became something of a purposeful walk. During her best hrs, her stride was long and strong...and looked nothing like the stride of a diseased octagenarian.

Diminishing results?

In August or Sept of '22 I bought a - very tasteful! - commode for the living room: it was becoming very clear that mum would not always be able to make it to the bathroom. It was called upon a number of times over a few weeks. I fully expected that, within months, it would be called upon most of the time.

Since beginning citicoline, that commode has not been used once....in fact, it now sits upstairs in a spare room, unneeded and gathering dust.

Her walk is stronger now than during the summer of '22 (pre-citicoline) but less strong than during those early weeks of citicoline's introduction (Nov/Dec '22).

My mum is 84, has a degenerating spine, vascular dementia, and, perforce, spends the vast bulk of her time seated...a degree of physical decline is pretty much inevitable, but I'm very sure we would be in a much worse place sans citicoline.

[Bolt_Upright in reply to garygjs]

Thank you so much! That's what I was looking for! Well done!

[JackBruce2024 in reply to garygjs]

That is a very moving testimonial. Thanks. I will pass this info onto a friend who has PD. I did a quick search on amazon and found the Jarrow and a few others:

-- Jarrow Formulas Citicoline CDP Choline 250 mg, Dietary Supplement

-- Swanson Cognizin Citicoline 1,000 Milligrams 60 Veg Capsules

-- Life Extension Citicoline (CDP-Choline) - Citicoline

The ingredients of each one seem to vary a bit.

[Getz]

Pity I can't understand the chemical language.

[Wildouiser10 in reply to Getz]

Same!!

[markland]

Hello

I am just wondering if this could help my husband who has Parkinsons and has been on Sinemet and gabapentin for a few months.

I have just started him on Vitamin B1 and was proposing to gradually increase that as per Dr. Santini protocol.

Can Citicoline be used in conjunction with B1?

[garygjs in reply to markland]

Not aware of a reason why you shouldn't. Alongside the citicoline my mum takes 500mg of B1.

[Gcf51]

Didn't mention Uridine. I have positive results with Alpha GPC Uridine. Not the same Citicoline either.

[emerald2393]

thank you for this information, it's very interesting. I will discuss with my naturopath. My husband's Neurologists just pushes pills which have lots of side effects.

[eschneid]

Thanks Dave,I need to go through it again, lot of info.

Eric

[Gcf51]

ar-Turmerone, Meriva® Turmeric Phytosome™, BCM-95

Meriva claims 19.5 fold better absorption, BCM-95 only claims 6.93; when I read about the better absorption of Meriva, I chose to stay with BCM-95 because I have not found any other capsules that contains Turmeric essential oil and I was after ar-Turmerone (I had read that ar-Turmerone reverses PD*). I question how much ar-Turmerone is in both?

*Best support I can find for that now ncbi.nlm.nih.gov/pmc/articl....

ar-Turmerone and Farnesol both I've read good things about and can't find good sources for neither.

[Bolt_Upright in reply to Gcf51]

Yes, I generally use Doctor's Best Meriva, but I have some BCM-95 I am using up.

I take a gram in the morning and another gram at night.

[Squarepusher]

Do you divide CDP Choline dosing into 2 or 3 doses per day or take it all in one shot?

[Gioc]

hi  Bolt_Upright ,

It appears that the oleuropein contained in olive leaf extract is a good and inexpensive source of HYT. * (I wanted to write HTyr = Hydroxytyrosol)

As you know, I am a fan of this supplement which, combined with niacin B3 and vitamin B1 HDT IM, is part of my stack. I have also tried PEA and CDP-Choline without success.

humanitas.it/enciclopedia/i...

Greetings from Italy

Prunus

[Bolt_Upright in reply to Gioc]

It must be Spring there!

[ghoegap in reply to Gioc]

Hi! What is HYT ?

[Gioc in reply to ghoegap]

I got the acronym wrong, sorry

I wanted to write HTyr = Hydroxytyrosol

🙏

Greetings from Italy

Margherita

[Gioc]

yup,  Bolt_Upright

Here is an Italian research on um-PEA (ultramicronized PEA) and PD.

You can write to her, I think..

researchgate.net/publicatio...

Notte

[Bolt_Upright in reply to Gioc]

I'm a believer: "For each item, the mean score difference between baseline and end of um-PEA treatment showed a significant reduction in most non-motor and motor symptoms. The number of patients with symptoms at basal was reduced after one year of um-PEA treatment. None of the participants reported side effects attributable to the addition of um-PEA. Conclusion: um-PEA slowed down disease progression and disability in PD patients, suggesting that um-PEA may be an efficacious adjuvant therapy for PD."