Dr Mischley also recommends citicoline. I strongly discourage anyone who is not already using citicoline from starting, because: "patients treated with citicoline experienced a significant worsening 45 days after the medication was discontinued". For further discussion see here: healthunlocked.com/cure-par...
Dr. Laurie suggests 4 grams per day of DHA from fish oil. A couple of people have inquired about safety. According to the study there was no adverse effect from 6 G daily of combined EPA and DHA: sciencedirect.com/science/a... From here: arthritis-research.biomedce... "A dose of 3 g/day EPA plus DHA has been assessed as safe for general consumption"
The Pharmax fish oils recommended by Dr. Laurie are available online at Amazon, and elsewhere, including sometimes at her affiliated pharmacy, simpharmacy.com/ Personal report: I have received the Pharmax DHA Finest fish oil and am using it. They have added a mild citrus flavor which seems to cover any fish taste or odor. I find it to be quite palatable on pasta or toasted English muffins.
Update - Citicoline Warning #2: Both citicoline and choline contain the trimethylamine structure which can be detached by gut bacteria into standalone trimethylamine. Trimethylamine is toxic. Excessive intake of choline results in a dramatic increase in the risk of cardiovascular disease. My writing on this subject here: tinyurl.com/2p8jjuf8
How about citicoline? According to this paper: ncbi.nlm.nih.gov/pmc/articl... "It is hypothesized that, compared to choline moiety in other dietary sources such as phosphatidylcholine, choline in citicoline is less prone to conversion to trimethylamine (TMA) " [Emphasis added] This is merely an hypothesis which has not been validated by laboratory testing.
On the other hand I've experienced a bit of numbness in my toes when I have ingested things that are detrimental to my circulation. After taking 1,000 mg of citicoline for about a week I began again experiencing that numbness, so I will stop taking it.
If you are already taking citicoline, based on my experience, stopping is unwise.
Partial transcript:
"There are a couple different ways to treat dyskinesia. If somebody comes to me and they are very dyskinetic the first thing I will do is a very high do fish oil a very specific type of fish oil. It has to be DHA fish oil... I have a product I use a lot it's a company called Pharmax they make a product called finest Pharmax High DHA oil. I like the liquid version and I learned this from a Canadian study. They took primates who they first gave them Parkinson's disease and then they administered such high doses of levadopa that the primates developed quite severe levadopa induced dyskinesia. What they did is they gave the primates 5 G per day of DHA fish oil which is a pretty hearty dose and after 30 days there was a 50% reduction in dyskinesia.
I wanted to see if that translated to humans and so I had two patients take four grams a day - one tablespoon of the oil I just described is the equivalent of about four grams a day. So I had people take 1 tablespoon a day for a month and one person had a 37% reduction in dyskinesia the other person had a 47 % reduction in dyskinesia. So it was not quite as robust as what they saw in the primate model but I didn't use that same high dose. So what i'll have people do is a tablespoon of this High DHA fish oil for two a month or two. It's a little pricey probably turns out to be about $40 a month $50 a month and it doesn't taste great. It tastes a little fishy. Some of the other fish oil I prescribe routinely tastes much better is less expensive. But when what we're trying to do is treat dyskinesia I will prescribe high does DHA fish oil and within a month or two we have an easy 50% reduction already in the dyskinesia.
And then what I will do after that is there's a supplement called citicoline or CDP choline and what it does we think that the mechanism is it makes you grow new dopamine receptors. So what I can do there is I will start somebody on this supplement of citicoline the best results come with two pills in the morning and two pills at night...x I believe the capsules are each 250 milligram so you have 500 milligrams in the morning 500 milligrams at night. And you start that and what happens is over the course of the month your levadopa starts working better and better and so what happens is at first you actually start to become more dyskinetic a week or two after starting this supplement called citicoline or CDP choline.You'll actually know it starting to work because you know a after the fish oil your dyskinesia started to improve now it's starting to get bad again that is a sign the citicoline is making your drugs more effective.
... So between by adding this CDP choline in you can make your eight pills work as well as 12 and that really also makes a huge difference in reducing the dyskinesia so kind of I have this two-part strategy and it takes a couple months and it requires a little coordination between the patient and the physician. It's not a Magic Bullet that kind of makes it all go away overnight but it very consistently works...
I test people's omega-3 fatty acids. I essentially test the fish oil in their blood. When we talk fish oil we're talking about these two fats EPA and DHA and as part of my baseline workup. I test all of my patients to see what their EPA and DHA levels are. People who are low get fish oil prescribed to them on day one as a supplement so that they're keeping their levels adequate. That's probably why I don't see many people develop dyskinesia. No study has shown us that the this is true or not but I've been in practice a long time and I just don't see patients going on to develop dyskinesia.... Before they even start medications I am making sure that they have as much omega-3 fatty acid as they need. So that I guess my hope is that it'll just prevent dyskinesia from ever starting.
The other reason I think people in our Clinic don't get much dyskinesia is we don't just target dopamine from the medication perspective. I think that when in the old days when a patient would go to the neurologist and complain of a new symptom when the only tool in the toolbox was levodopa it was really easy for the doc to just say take more take more take more. We would keep hitting this disease from the same direction and you burn that bridge. These days not only do we have the MAO-b inhibitors dopamine agonists all these other drugs. We have really come to appreciate that exercise makes dopamine that that good social connection makes dopamine. I think physicians really are getting better at what we call dopamine sparing strategies. There are things that you can do to boost dopamine that aren't dependent on levadopa. So if you can kind of hit your dopamine augmentation goals by things other than levodopa. I also think that that really helps not get as much dyskinesia as people used to get."
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"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."
That perhaps says something about the complexity of the thing...that Parkinson's may not a be discrete condition with an aetiology and disease process that all share.
My mum's transformation was swift and obvious. Others have said the same. I'm not sure I would persevere with it in the absence of clear benefits.
Thanks for posting this as I am also a big fan of Dr. Mishley. She spoke at the 1st Parky conference I went to 7or 8 years ago and i was fortunate enough to get to speak with her👍
I believe both are useful even if a person is not taking C/L. From the video:
"Before they even start medications I am making sure that they have as much omega-3 fatty acid as they need so that I guess my hope is that it'll just prevent dyskinesia from ever starting."
I just got my bottle of CDP Choline today. I have been on and off mucana. I will take them together and hopefully will have some improvement. This supplement looks very promising!
Regarding fish oil see transcript now posted above. Regarding Citicoline, at 3:15 in the video she recommends: "500 milligrams in the morning 500 milligrams at night"
Is it ok to say that all PWPs are not same and hence it may be worth starting low and titrate slowly upwards. We don't know what else these patients are taking, those who have benefitted from fish oil and citicoline.
Thanks for posting this park_bear I see her virtually and have done well under her care. Do you think we should take morning and evening doses if we don’t have dyskinesia’s? Mine is only 250 mg
I believe that she mentioned that it comes in 250 mg capsules. Based on the review cited above it seems to improve the underlying disease state. If that is the case it seems to me it would make sense to use her suggested dosage.
The science direct paper, referred to by garygjs above, mentions it can also be used to delay needing to take levodopa/carbidopa. I too am looking for recommendations on amount of Citicoline to take.
I have been taking Nordic Naturals DHA for over a year, not in the high amounts she mentions and it had no impact on my dyskinesia. I started the citicoline recently, just 300 mg in the morning and it had an immediate impact on all that has been reported it would have, rigidity, slowness of movement and reduction in dyskinesia. No reduction yet in Levodopa. If I take citicoline later in the day I will not sleep at night. I've tried to up it to 600 mg and I get too anxious, so I backed off to the 300 mg. I'm currently happy with the improvements on that dosage.
I just started the high-dose DHA on Dec. 15. Seems to be helping already. I didn't have time to post about it yet. My dyskinesia is relatively minor, but it was becoming a concern.
The Pharmax High DHA fish oil is not readily available in the UK. Is there a UK or European product which works in the same way and could be substituted? Many thanks.
"In the present study we also extended our recent observations regarding the effects of specific dietary interventions on a broad range of motor and non-motor symptoms in this mouse model of PD. It was previously shown that uridine and DHA were able to reduce circling behavior in the 6-OHDA animal model (Cansev et al., 2008) and we showed that uridine and DHA prevented the induction of motor deficits as well as the development of GI dysfunctions in rotenone models of PD (Perez-Pardo et al., 2017). Here, we show that the same diet (Diet1) given after the occurrence of motor problems, was able to reduce motor dysfunction, grip strength loss, cognitive deficits, delayed intestinal transit, colonic inflammation, and alpha-synuclein accumulation in the ENS.
This is the first study demonstrating a clear therapeutic effect of specific dietary interventions in a mouse model for PD.Dietary interventions were started after the motor symptoms had clearly developed. As a consequence, we see no effects of the diets on the number of dopaminergic cells in the SN, indicating that the diets did not reduce the loss of dopaminergic cells, i.e., they did not interfere with rotenone toxicity. The diets helped to improve the functioning of the remaining dopaminergic neurons, demonstrating that they have neurorestorative properties and therefore may have disease-modifying potential."
There was a comment on YouTube about blood thinning as a result of high quantities of fish oil, so I checked with my ND because I fall a lot and bleeding is a concern. She said that high DHA does not cause blood thinning; it is high EPA that causes it. She also said that she has had good results from her patients using the high DHA fish oil (although not necessarily for PD). I have tried citicoline several times and it definitely increased my dyskinesia so I stopped it. I’m not sure if I will try it again but I plan to pick up the high DHA fish oil this week. Fingers crossed that it reduces my dyskinesia.
Dr. Mischley says that citicoline increases dyskinesia because it grows new dopamine receptors. You then have to decrease your levodopa dose (which is great!) because you don't need as much. If it's giving you dyskinesia, I would think that means it's working.
Marti Masso JF, Urtasun M. Citicoline in the treatment of Parkinson's disease. Clin Ther. 1991;13:239-242.
Eberhardt R, Birbamer G, Rainer E, Traegner H. Citicoline in the treatment of Parkinson's disease. Clin Ther. 1990;12:489-495
Cubells JM, Hernando C. Clinical trial on the use of cytidine diphosphate choline in Parkinson's disease. Clin Ther. 1988;10:664-671.
Agnoli A, Ruggieri S, Denaro S, Bruno G. New strategies in the management of Parkinson's disease: a biological approach using a phospholipid precursor (CDP- Choline). Neuropsychobiology. 1982;8: 289-296. doi.org/10.1159/ 000117914.
Rainer J, Gerstenbrand F, Kozmab C, Hoppe HS. Clinical evaluation of CDP-choline in patients with Parkinson's disease. IPHAR-Report. 1977;76:112.
Li Z, Wang P, Yu Z, et al. Effect of citicoline adjuvant therapy on mild cognitive impairment in Parkinson's disease. Int J Clin Exp Med. 2016;9: 4593-4598.
Acosta J, Nombela M, Palao A, Pastor M, Recuero J. Multicenter trial: treatment of Parkinson's disease with CDP-choline (citicoline).
Park_bear, Promising, but research seems subpar…. The 7 studies are mentioned in the following meta-data analysis:
Citicoline as Adjuvant Therapy in Parkinson's Disease: A Systematic Review. Clinical Therapeutics/Volume 43, Number 1, 2021. Que, Diana-Lynn S. and Roland Dominic G. Jamora, 2021.
The Science News Working Group of the Dutch Parkinson's Association previously reported on as:
Misleading publication on the value of the dietary supplement citicoline as a Parkinson's medication. "The conclusion of the article is that adjunct citicoline therapy has a positive effect, but the evidence supporting this finding is still limited. Therefore, new, larger, and more meticulous studies are recommended. At the same time, the authors also believe that adjunct treatment with citicoline for Parkinson's patients is already worth considering.
The above conclusions are almost too good to be true. Unfortunately, it seems that is indeed the case because the underlying information has been treated with little critical analysis. Although the study is based on 7 investigations, only one of them is recent, from 2016. The others are old research from over 30 years ago. According to Günther Birbamer, an Austrian researcher involved at the time, it was not possible to draw firm conclusions back then. Apparently, the Filipino authors heavily rely on the recent research conducted in China. But there is something strange about it. The relevant publication is available on the internet but cannot be found in the usual scientific databases, and the research data is not accessible.
Professor Teus van Laar kindly examined the Chinese article critically. According to him, the research was primarily focused on cognitive improvement but does not establish that the drug has a protective effect, and that is even impossible with the chosen study design. In short, the article provides no evidence that the findings are clinically relevant. Therefore, we will have to wait and see what any new careful research will reveal. "
This is largely confirmed by a recent Systematic Review and a Meta-Analysis: Is Citicoline Effective in Preventing and Slowing Down Dementia? by Maria Bonvicini a.o. 2023
They came across the same 7 studies and reached the following conclusions:
"Our results confirm the positive effects of citicoline shown in other studies, but at the same time, they show that the available evidence is of poor quality and likely to be biased. Thus, well designed, high-quality randomized clinical trials are needed to qualify citicoline use for the prevention or treatment of cognitive decline. Meanwhile, citicoline should be used according to clinical judgement and taking into account the limitations of the available evidence. "
been taking CDP choline for years 250-300 mg. I increased to 1000 mg and noticed that my dose of 1.5 c/l as been more effective. Excellent Post. Thanks PB!
This is a great post! If it works for enough of us, it would be a huge relief in so many ways. Please let everyone know whatever your experiences and results turn out to be. I promise to do the same.
As for the price, the DHA that she suggests is a little more expensive than she said. I see Phamax DHA Ultra Pure in several online stores for $63.80, but that seems to be only enough for about 1200mg for 30 days. (Do I have that right?) So to get 4g you would need about 3 to 4 times as much. (Again, please check my math.)
With this, you would take 10 soft gels/day. There are 250 softgels, so this is enough for 25 days. Please double-check and let me know if any of this is incorrect or if you find a better deal.
This DHA comes from algae oil, not fish. It is identical to DHA from fish, but it has the benefit of not having any heavy metal contaminants, while DHA from fish has to be thoroughly filtered to make it "pure".
Someone pointed out to me that very large doses of EPA (another Omega-3) can cause blood to thin. DHA doesn't. The supplement I pointed to in my post above doesn't mention if the EPA has been removed or not,Yes
As for me, I'm ordering the Vegepower supplement. It's only DHA so no blood thinning worries from it. Each bottle costs about $22 for 90 softgels. Each softgel costs about $0.24. Each day of 10 softgels (4g) would cost $2,44 per day or about $73.20 per month.
As always, please let me know of any math errors or better deals.
Regarding dosage; the following breakdown is for the high DHA oil recommended by Dr. Mischley. Amounts given are for 1 teaspoon and 1/2 teaspoon (adult and child dose)
Fish oil (from sardine, anchovy and mackerel) 4,500 mg * 2,250 mg
Yielding
Docosahexaenoic acid (DHA) 2,075 mg * 1,037.5 mg
Eicosapentaenoic acid (EPA) 425 mg * 212.5 mg
Dr. M prescribes 1 tablespoon to those trying to treat dyskinesia. There are 2.5 teaspoons in a tablespoon, so the DHA dose actually appears to be close to 5,000 mg. I imagine this is why she uses liquid form, as getting this much DHA from capsules would be cost prohibitive, not to mention no fun to swallow.
EDIT Ok, figuring out dosage is turning out to be a dicey proposition, as Pharmax produces several fish oils. The one I posted numbers from above is their "Ultra DHA" formulation ultimatevitality.com/produc... and it has 2,075 mg DHA per teaspoon. So assuming 3 teaspoons per tablespoon, a tablespoon dose would provide 6,225 mg DHA.
Their "DHA Finest" formulation amazon.com/Pharmax-Supports... contains 1200 mg DHA per teaspoon, so a tablespoon dose would provide 3600 mg DHA.
They also produce a "Finest Pure Fish Oil" amazon.com/Pharmax-Essentia... which has 725 mg DHA in a teaspoon. It also has 950 mg EPA, so I doubt it's the one used by Dr. M, since it really doesn't qualify as "high DHA."
Maybe someone who has access to Dr. M can ask her which formulation she uses? I suspect it's probably the "DHA Finest," which begs the question of whether it or DHA Ultra would be the most cost effective to obtain 3600 mg DHA. Somebody with better math skills than me will have to work on that one!
Also, might not be a good idea to start fish oil and citicoline at the same time. Taken from Park Bear's notes at the top of this thread;
"But when what we're trying to do is treat dyskinesia I will prescribe high does DHA fish oil and within a month or two we have an easy 50% reduction already in the dyskinesia."
" And then what I will do after that is there's a supplement called citicoline or CDP choline and what it does we think that the mechanism is it makes you grow new dopamine receptors. And you start that and what happens is over the course of the month your levadopa starts working better and better and so what happens is at first you actually start to become more dyskinetic a week or two after starting this supplement called citicoline or CDP choline.You'll actually know it starting to work because you know a after the fish oil your dyskinesia started to improve now it's starting to get bad again that is a sign the citicoline is making your drugs more effective."
So it seems like it would be a good idea to follow Dr. M's protocol timing-wise, by starting the fish oil by itself first. Some people might get a good reduction in dyskinesia and decide never to add the citicoline. More importantly, if one gets an increase in dyskinesia after CDP it would reduce confusion about what's to blame, making it easier to decide how to go forward. Anybody know of a "patience pill?" 😜
For those who may not have noticed, I edited my post regarding dosage of fish oil. One really has to look closely at labels to see how much DHA is provided in a "serving" and to make sure EPA content is minimal. 🙄
After giving myself a headache doing this, one of the better options appears to me to be this; iherb.com/pr/now-foods-dha-...
Four softgels would provide the 4 grams of DHA suggested by Dr. M. I'll leave it to other, more math competent people to figure out the daily cost.
One capsule contains 1300 mg fish oil extract, and of that 1300, 1000 mg is DHA. So the most EPA a single capsule could contain is 300 mg. If you take 4 capsules, the most EPA you'd get would be 1200 mg. I suspect it would not be quite that much though, cause most fish oils contain some DPA (docosapentanoic acid) too.
Now is a reputable company and I would think they'd be glad to tell you exactly how much EPA is in each serving.
FYI The iherb NOW is $30.16. The same NOW product is on Amazon at $27.96 for 1x purchase. But, if you select subscribe and save, its $25.16. Both have free shipping.
Thanks. I posted the iherb one because I know some people don't trust Amazon since they've had problems with bootleg products. And I'm guessing very popular, high ticket items might be most susceptible.
Just to be sure I'm not steering anybody wrong, I messaged NOW, asking how much EPA is in their DHA 1000 product. Will report back when I hear from them.
In the meantime, for those wanting to stick with Pharmax fish oil, two teaspoons of their "Ultra DHA" contains 850mg EPA and 4150mg DHA. Three teaspoons of their "DHA Finest" contains 780mg EPA and 3600 mg DHA.
Just heard back from Nowfoods. Although they could not tell me precisely how much EPA is contained in their "DHA 1000" product, they did confirm that it can be no more than 300 mg. So it appears the EPA content is comparable to that of the Pharmax DHA formulations;
"Thank you for your inquiry.I’m sorry, we do not analyze for EPA or other fatty acids in this product. Our focus is the DHA content." Each softgel provides 1,300mg of total fish oil concentrate. Of that 1,300mg 1,000mg is DHA, so that leaves 300mg for other fatty acids naturally occurring in the fish oil concentrate."
Reading about the bleeding controversy has convinced me that the "risks" associated with fish oil use are largely a media concoction, and that fish oil use (especially EPA!) is actually associated with lowered incidence of cardiovascular events. Lots of studies out there, here's one fairly recent one; ncbi.nlm.nih.gov/pubmed/284...
"Results: In all the patients considered (over 600 subjects treated with the active product in total), with moderate to severe disease, with or without concomitant use of antithrombotic agents, at home or in an Intensive Care Unit (ICU), no evidence of increased risk of bleeding with use of n-3 LC-PUFAs was observed. Furthermore there were no statistically significant changes from baseline in measured coagulation parameters."
All that being said, I'm not a doctor, so please do your own research and consult with your physician if you have concerns about using fish oil.
Little Willow posted about another liquid fish oil option in a thread about DHA and sleep. Two teaspoons provides 4 grams (4,000 mg) od DHA. amazon.com/Genestra-Brands-...
Dr M suggests 4 G of day of DHA. Fish oil is not 100% DHA so the weight of the fish oil to attain this amount would be larger. That said, a tablespoon of her recommended fish oil would yield more than 4 grams of DHA. See detailed calculations by Rufous2 among these comments.
The fish oil did seem to improve my mild dyskinesia, and now that I have stopped it seems to be returning. Based on this, a maintenance dose of fish oil would be in order.
She does not address this, explicitly, as far as I know. What I found in the transcript that was relevant:
"as part of my baseline workup. I test all of my patients to see what their EPA and DHA levels are. People who are low get fish oil prescribed to them on day one as a supplement so that they're keeping their levels adequate...Before they even start medications I am making sure that they have as much omega-3 fatty acid as they need."
according to your comment:”If you are already taking citicoline, based on my experience, stopping is unwise.” that means one has to take citicoline for ever, just like c/l?
This is the danger. A work in progress - I'm experimenting with restarting citicoline and trying a slow taper. My advice; if you are not taking citicoline, don't start.
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