May be that you have problems with brain fog, mood, memory etc... I've been using it (250mg/day) since 6-7 months with excellent results. Not even every day, but only when need it.. works even better if combined with choline. Lots of info about brands, dosing and usage available in the Net, in case interested to try. Just be patient to find the dose you need. I started with 50mg/day, adding another 50mg every 3th day. At 250mg it kicked off. Highly recommend it..
Uridine - from my experience..: May be that... - Cure Parkinson's
Uridine - from my experience..
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dadcor
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How do you take it?
Gut-brain and brain-gut axis in Parkinson's disease models: Effects of a uridine and fish oil diet 2018 pubmed.ncbi.nlm.nih.gov/282...
" Abstract
Recent investigations have focused on the potential role of gastrointestinal (GI) abnormalities in the pathogenesis of Parkinson's disease (PD). The 'dual-hit' hypothesis of PD speculates that a putative pathogen enters the brain via two routes: the olfactory system and the GI system. Here, we investigated (1) whether local exposures of the neurotoxin rotenone in the gut or the brain of mice could induce PD-like neurological and GI phenotypes as well as a characteristic neuropathology in accordance with this 'dual-hit hypothesis' and (2) the effects of a diet containing uridine and fish oil providing docosahexaenoic acid (DHA), in both models. Mice were given rotenone either orally or by an injection in the striatum. Dietary interventions were started 1 week before rotenone exposures. We found that (1) both oral and intrastriatal administration of rotenone induced similar PD-like motor deficits, dopaminergic cell loss, delayed intestinal transit, inflammation, and alpha-synuclein accumulation in the colon; (2) the uridine and DHA containing diet prevented rotenone-induced motor and GI dysfunctions in both models. The models suggest possible bidirectional communication between the gut and the brain for the genesis of PD-like phenotype and pathology. The dietary intervention may provide benefits in the prevention of motor and non-motor symptoms in PD."
in reply to Bolt_Upright
By combining the uridine and the DHA, it is impossible to know if it was one or both making the positive effect. And inducing the “fake PD” AFTER starting the intervention leads to inaccurate outcome at best. But, as you know I think highly of uridine, as I recently posted about it as well. (Or I think I did. Don’t remember!) anyways….
I am tired of poorly done studies! (I’m learning PB!)
Promising Effects of Neurorestorative Diets on Motor, Cognitive, and Gastrointestinal Dysfunction after Symptom Development in a Mouse Model of Parkinson's Disease 2017 ncbi.nlm.nih.gov/labs/pmc/a...
"Abstract
Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic nigrostriatal neurons, with reductions in the function and amount of dopaminergic synapses. Therefore, synapse loss and membrane-related pathology provide relevant targets for interventions in PD. We previously showed the beneficial preventive effects of a dietary intervention containing uridine and DHA, two precursors for membrane synthesis, in the intrastriatal rotenone model for PD. Here, we examined the therapeutic potential of the same dietary intervention on motor, cognitive, and gastrointestinal symptoms. In addition, we tested the effects of an extended nutritional formula based on the same precursors plus other nutrients that increase membrane phospholipid synthesis as well as prebiotic fibers. C57BL/6J mice received a unilateral rotenone injection in the striatum. Dietary interventions started 28 days after surgery, when motor-symptoms had developed. Readout parameters included behavioral tasks measuring motor function and spatial memory as well as intestinal function and histological examination of brain and gut to assess PD-like pathology. Our results show that rotenone-induced motor and non-motor problems were partially alleviated by the therapeutic dietary interventions providing uridine and DHA. The extended nutritional intervention containing both precursors and other nutrients that increase phospholipid synthesis as well as prebiotic fibers was more effective in normalizing rotenone-induced motor and non-motor abnormalities. The latter diet also restored striatal DAT levels, indicating its neurorestorative properties. This is the first study demonstrating beneficial effects of specific dietary interventions, given after full development of symptoms, on a broad spectrum of motor and non-motor symptoms in a mouse model for PD."
Bolt,
This study is very interesting and I think, very important. This study addresses a PD model testing issue that park_bear recently brought up. In many studies, the tested substance is given before the PD model agent is given and this is not as accurate a response as giving the tested substance after the PD model agent has been applied to the test subject and PD symptoms have clearly developed.
In this study that you highlighted, the two test protocols were given after the model agent was applied and PD symptoms had already developed. The two tested formulations in this study were active against the developed symptoms, one protocol more so than the other protocol. This is a more accurate depiction of effectiveness of the tested formulations against this particular PD model. This is more inline with how these two tested formulations would actually be used in people with PD. They would be used in a person who already has PD and symptoms, not before. This important point is often overlooked.
We can only hope that this will become a continuing trend in PD and other studies where disease models are used.
Art
park_bear
Bolt_Upright
Taking citicoline raises the level of uridine. I just restarted taking citicoline on alternate days with Huperzine A but I'll switch to uridine next week which I bought a few years back to see how it compares.
healthunlocked.com/cure-par...
Uridine just arrived! Bottle doesn't have instructions of timing (before or after meal). He is on Liposomal Phosphatidycholine (BODYBIO) already, taking it with his 1/2 t Sinemet and 2 caps of NOW MP. He actually started this combo a few days ago and believe it works!
Please provide your expertise, Rescuema. 
I'm about to start uridine monophosphate sublingually (better absorption) which I bought 2 years ago. I'll start at 250mg daily tomorrow on its own for a week on alternate days since I'm on Hup-A today. I prefer to cycle as a precaution to avoid pushing neurotransmitters out of balance but stacking uridine with DHA/Omega3 and choline compounds such as Citicoline/Alpha-GPC may allow for an enhanced synergistic effect for others.
The general uridine dosage is 150-250mg twice a day along with food with your multivitamins. I've read it's best to take a few hours before bedtime for quality sleep, but in others, it can cause sleep problems so I'm personally going to err on caution and take it in the morning - I'll probably fall on the latter category based on experience with acetylcholine boosters.
Be sure to read the below articles for additional details and cautions to take into consideration. I don't feel comfortable with prolonged higher dosage used in some clinical trials up to 2g/day for long-term, and since it can't be patented, long term safety profile is lacking, which is why I haven't tried it yet. Try to shoot for minimal effective dose based on trial as in OP.
supplements.selfdecode.com/...
nootropicsexpert.com/uridin...
". . . but stacking uridine with DHA/Omega3 and choline compounds such as Citicoline/Alpha-GPC may allow for an enhanced synergistic effect for others."
That is the answer I was hoping for! Thank you.
Uridine, Jarrows Formula 250mg each cap is what I ordered.
I bought a powder form to avoid fillers and try sublingually because uridine may not absorb well through the stomach. You may be able to make liquid out of it.
This is the one I bought based on the reviews at the time.
amazon.com/Monophosphate-Di...
Great! I bought the Jarrows Formula as you and some other members think highly of this brand. I believe that, too. We are not too good with powders. . .
Jarrow is one of the better brands but they also tend to use fillers that some care about. I only mentioned the powder form (which may be dissolved) because I remember you telling me your husband tends to prefer liquid forms. We'll see how they work!
in reply to rescuema
Perhaps a dingy question but how do you use powder sublingually? I am going to buy the one you did. I don’t want fillers either.
rescuema in reply to
Measure it out using a mg scale and place it under the tongue until gone. I just opened the jar to check if it came with a scoop and it wasn't. I tasted the residue powder on my finger and it was mildly salty and not offputting. Definitely doable.
in reply to rescuema
Great! Will do!
rescuema in reply to
250mg is about 1/8 level tsp. Still, be sure to measure for accuracy. I used a small piece of parchment paper for tare to measure the powder weight and then used it to pour it under the tongue.
in reply to rescuema
For using a powder like uridine or others , I think getting a better scale is needed. I just have a kitchen scale from my baking days. What do you use?
rescuema in reply to
This cheap one works ok for me, but I recommend you get a better one with 0.001g scale for higher accuracy paying a bit more.
amazon.com/gp/product/B07DL...
Better options. Pick the one with 0.001g and better reviews.
amazon.com/s?k=0.001g+scale...
in reply to rescuema
Thank you to my PD Fairy Godmother who looks out for us and gives us the best advice! 💕🤓💕
rescuema in reply to
lol. anyhow I just ordered myself a new one because I often get frustrated measuring a minuscule smaller amount of powders. Hope it works better, and they all have their place in my arsenal. More precision and you're limited for heavier weight.
in reply to rescuema
I just quickly reread this. So I should take Citicoline OR uridine but both would be redundant? Maybe I shouldn’t do it than? I usually take Citicoline every other day. Maybe I should be taking it daily but when I eat eggs I don’t take it. And if I get the uridine maybe I shouldn’t take it at all?
☺️
rescuema in reply to
Choline sources and DHA will work together to augment the effect, so you can take it together. I'm trying it by itself (with food sources) for a while to see if I notice/feel anything, then I'll add other stacks as needed. Read the above articles to be fully informed.
"Choline sources. . ."
Reading about choline, it is a precursor for Phosphadylcholine which in trurn is a precursor for Acetylcholine.
Our Homeopathic doctor prescribed BODYBIO Complex of Phospholipids (Liposomal Phosphatidylcholine) rather that CitiCholine. Wouldn't that be the same as taking CitiCholine (Cognizin)?
Thank you, Rescuema (what would we have done without you and Art?)
It isn't the same since Citicholine (choline and cytidine) also contributes towards different metabolic pathways. edu.emersonecologics.com/20...
Thank you! Very interesting reading. He (hubby) had started with Cognizin, but later homeopathic doc started him on Phosphatidylcholine. So, back to Cognizin it is.
He also takes his Omega 3 after food, breakfast with lots of ghee, and second dose after supper.
I will order Huperzin A to take on alternate dates (your pass), twice a week.
Tina, I could only suggest you cautiously trial Hup A, alternate days or not, for less than 3 months for nootropic application, the extent to which it was found to be possibly safe thus far. I noticed that when I stacked Hup A/Uridine with DHA and Alpha GPC, I struggled with insomnia and loose stools (acetylcholine increases gut motility) and had to back off so I was clearly going over the balance even being careful. My heart rate also lowered, so if someone has a heart condition or BP instability, it should be used very carefully only after a thorough review of all its side effects and ideally after a discussion with your Dr. It has a clear effect on acetylcholine without a doubt so it may be beneficial for those who're deficient, but we should all be extremely careful about tweaking with neurotransmitters.
in reply to rescuema
So Citicoline is better than phosphatydlcholine? I recently read liposomal is best but I have not looked for it. I’m taking Citicoline for neuro protection, not for any symptom relief. Maybe then HupA would be too much for me? I bought uridine but have not tried it yet. I thought Alpha GPC is redundant with Citicoline. ?
rescuema in reply to
I tend to prefer citicoline or alpha-GPC and mentioned in the first place above because they tend to not promote TMAO as much (see my long reply to park_bear below). but it's not so simple to say what's superior because the benefits derived may depend on methylation needs and individual metabolic burden. For example, I certainly can't say taking any of these supplements is superior to eating eggs or other amazing natural choline sources such as the organic beef liver.
Thank you for sharing your experience with these Nootropics.
I would like to have him take Huperzin A twice a week. On these days, he will not have the rest of the stack. His BP is normal, however, I will observe very closely side effects.
You can combine with citicoline and DHA if deciding to trial. While monitoring closely, be sure to note his tremor doesn't worsen, have him report his bowel movements, and so on.
Thank you! Will do. He has been on Phosphatidylcholine + DHA + Uridine the last 2 days, and all is good so far. I haven't even ordered Hup yet, am about to.
Do you believe Phosphatidylcholine should be replaced with Cognizin? Phosphatidylcholine is expensive and I would hate to throw it away.
Use it up, and you can certainly alternate until gone. I think we already discussed this topic in the past, but unless you or he's noticing much better effect, it's probably not money well spent when $$$$$. Also question the homeopathic Dr for what specific purpose he wanted it used over citicoline to help with your decision.
Thanks, Rescuema! Next Ozone therapy is 3 months down the road. They won't discuss anything over the phone. However, I will try Cognizin, alternating with what I have. Makes sense to me.
Citicoline (stabilized CDP Choline) is a naturally occurring intermediate involved in the synthesis of phosphatidylcholine, a major constituent of brain tissue grey matter; Citicoline supplementation supports brain energy metabolism
Guess homeopathic doctor skipped the precursor (CDP Choline) of Phosphatidylcholine.
Would 50mcg Hup A be a good start? I can't find many brands of 50mg but there are plenty of 200mcg. Brand that you would recommend?
Thank you for all your help! Much appreciated.
Life Extension is currently running a huge sale, so get some now. I did. 200mcg should be ok.
lifeextension.com/vitamins-...
in reply to rescuema
I have read and heard from multiple sources that it is “protective.” I wonder if using it as a proactive protective measure would be a good idea? Evening walk was spent learning about AKG and more about Spermidine. Both look interesting.
rescuema in reply to
Marketing pitch. You should research everything thoroughly including all potential side effects and only supplement if it leans towards more benefit and makes sense for your symptoms.
in reply to rescuema
I don’t think it’s just a marketing pitch. It’s could be potentially helpful in reducing glutamate Excitotoxicity by being a NMDA receptor antagonist and it increases NGF (nerve growth factor) And, Citicoline is a Sirt 1 activator so I think Hup A would maybe be an even better Sirt 1 activator (but I have yet to seek that out.)
sciencedirect.com/topics/ch...
🤓
rescuema in reply to
Obviously I’m taking certain amount of risk by taking any compound that exerts changes in my brain function. This should never be taken lightly no matter how great the potential benefits may sound on literature. Anything can backfire and be toxic if out of balance, just as NGF can promote cancer.
One more question although I tried to find answers reading relevant posts. Uridine and Choline are water soluble, where Fish Oil (for DHA) is fat soluble. Do these three supplements have to be taken separately or altogether? Some people take them all together and some separately. What is your insight? Thank you!
in reply to rescuema
If one is taking lithium Orotate should they not take uridine? Lithium breaks down to uridine, I think? Do you think the general population of PWP can benefit from uridine? Wondering if I should add it. Likewise with Hyperzine A.
dadcor,
I will copy and paste your post into another post discussing this issue in our forum members where they are discussing what works for them. Hopefully this will give your post more exposure!
Art
A Nutrient Combination that Can Affect Synapse Formation 2014 ncbi.nlm.nih.gov/labs/pmc/a...
"Brain neurons form synapses throughout the life span. This process is initiated by neuronal depolarization, however the numbers of synapses thus formed depend on brain levels of three key nutrients—uridine, the omega-3 fatty acid DHA, and choline."
So to get...
Uridine: Looks like you need to get it from a supplement, from mothers milk, or from baby formula.
DHA: You can get this from canned sardines and herring.
Choline: You can get a supplement, but you can also create it in your body by taking B6, B12, and Folate. You can get folate from the foods in the picture.
Food High in Folate
Well this one has both Uridine and Choline: Alpha GPC Choline 600mg + Uridine Monophosphate 300mg-2-in-1 Nootropic Supplement. 2 month supply for $26: amazon.com/Monophosphate-No...
Lecithin is rich in choline. I dissolve it in MCT Oil and use that as as one would use butter.
healthunlocked.com/cure-par...
I prefer citicoline because it doesn't contribute to excess TMAO. Be careful of excessive lecithin use. pubmed.ncbi.nlm.nih.gov/313...
labs.selfdecode.com/blog/tmao/
Looks like acetyl l-carnitine is the one to watch out for.
Image from fulltext of this: sciencedirect.com/science/a...
"Conclusions Carnitine-related metabolites show associations with adverse outcomes in acute HF, in particular Lcarnitine and acetyl-L-carnitine for short-term outcomes, and TMAO for long-term outcomes"
Also, from here: thieme-connect.com/products...
"The multivariate linear regression analysis revealed that, in addition to L-carnitine as the strongest predictor of log transformed TMAO (p<0.001), the parameters of age, diabetes status and body mass index (BMI) were independently associated with increased log transformed TMAO levels (p<0.01)."
Worth a separate post at some point
Relative risk of death in heart failure patients versus methyl amine compounds
It's good to be aware of all choline sources that may contribute to excess TMAO, although the impact may vary dependent on microbiome compositions. Lecithin contains phosphatidylcholine, a precursor of choline. pubmed.ncbi.nlm.nih.gov/272...
You may possibly offset some of the ill effects by consuming diets rich in DMB (3,3-dimethyl-1-butanol) that interfere with bacterial choline metabolism. DMB is found in EVOO, balsamic vinegar, grapeseed oils, resveratrol, etc. often found in the Mediterranean diet.
clevelandheartlab.com/blog/...
in reply to rescuema
If the brain uses uridine to increase choline and choline increases TMAO then why/how then does that our way the benefits?
rescuema in reply to
Your body needs choline. TMAO is a gut microbe-dependent metabolite that becomes a problem when in excess. Again balance is of concern, so don't eat too many egg yolks or mounds of vegan butter made with lecithin.
in reply to rescuema
Balance is the goal but determine what enables balance is the challenge. I eat eggs 3 to 4 days a week and on those days I don’t take Citicoline. If that makes sense or not I’m not certain. And I rotate some antioxidants. Again not sure if this is helpful but it’s in an effort to strike a balance.
park_bear in reply to
See my writing here for the cardiovascular benefit of moderate egg consumption:
A Tale Of Two Studies Leads To A Deeper Understanding Of Cardiovascular Disease
From the table I posted above the hazard ratio associated with high choline levels was 1.07 which is clinically insignificant. The P value associated with this was .648 which was statistically insignificant. Do you have any data specifically showing a high level of cardiovascular hazard for elevated choline levels?
in reply to park_bear
No, I do not. I was only looking at it from a brain health perspective
The actual issue isn’t about elevated choline causal to cardiovascular health, but the downstream metabolite TMAO strongly associated with all-cause mortality depending on the gut microbiome. If you’re on an antibiotic, you can eat all the red meat and eggs and won’t produce TMAO. Vegans/vegetarians also produce limited TMAO due to different microbiota compositions. There’s no disputing that foods rich in TMA precursors, such as lecithin, choline, and L-carnitine, are the main sources of TMAO. Whether elevated TMAO level associated with various metabolic dysfunctions/diseases is a red herring or the eventual culprit hasn’t been fully elucidated yet.
Your posted study also states “TMAO is the final product of a complex metabolic 4 pathway (i.e. choline/carnitine)” and concluded TMAO is associated with long-term outcomes. Upon a casual glance, I suppose it’s possible to conclude that choline has no clinical significance for acute HF from looking at the data on the 30 days HR table. However, the data isn’t for direct TMA precursors and we have no info on the participants’ dietary intake near the time of the event. The study simply examined circulating plasma metabolites involved in the TMAO-choline/carnitine pathway from the “blood samples were obtained within the 24h period after admission to hospital with acute HF,, with a median age of 78 years, 95% patients with serious cardiac disease, many on drugs. In short, too many confounding factors, but I’d assume that any choline ingested, if at all, would’ve been used/absorbed by the intestine with any leftovers processed by microbiome to TMA, and FMO3 liver enzyme would’ve already converted to TMAO in over 24 hour from eating. While interesting to see the downstream carnitine-related metabolites in the plasma associated with acute HF, the study paints an incomplete picture and is not surprising to see the naturally formed derivative acetyl-l-carnitine (from carnitine made in the body, some from food, slower to convert than choline) that tends to be more abundant.
The selfdecode article I posted earlier with many study references should be more insightful, not just for acute HF of mostly ill elder, but for many associated diseases and major adverse cardiovascular events to be mindful of. I commented on lecithin use because I’ve noticed increased inflammation and other subtle ill effects upon use myself, and I stopped out of concern. Here’s a directly relevant article to consider.
Lecithin Supplements: Weighing Risks vs. Benefits
thedoctorweighsin.com/lecit...
If lecithin works for you, then great, we’re all different including our diet differences. It’d still be beneficial to be cautious and informed especially while most here are already more metabolically challenged than not. As with all things, essential nutrients in excess of contributory value may become hazardous in dose-dependent manners. The question is not whether you should eat egg yolks or other TMA precursors, but how much and what else are you eating for certain microbiome composition/dysbiosis that could possibly lead to ill consequences?
More related TMAO studies -
High TMAO plasma levels were associated with increased incidence of all-cause mortality [14 studies for 16 cohorts enrolling 15 662 subjects, hazard ratio (HR): 1.91; 95% confidence interval (CI): 1.40-2.61, P < 0.0001, I2 = 94%]
pubmed.ncbi.nlm.nih.gov/290...
Ten articles (12 studies) involving 13,425 participants from 2014 to 2021 were considered. Compared to low-level TMAO, elevated TMAO was correlated with MACEs and all-cause mortality in HF (RR: 1.28, 95% CI: 1.17, 1.39, P < 0.0001…Conclusion: Elevated TMAO may be an adverse prognostic indicator in patients with HF.
pubmed.ncbi.nlm.nih.gov/352...
In this large community‐based cohort of older US adults, serial measures of TMAO were associated with higher risk of incident ASCVD, with apparent modification by presence of impaired renal function and with higher risk of recurrent ASCVD.
ahajournals.org/doi/10.1161...
The present study validates TMAO as a pro-inflammatory factor that causes renal inflammatory injury and renal function impairment. Inhibition of TMAO synthesis or promoting its clearance may be a potential therapeutic approach of CKD in the future.
karger.com/Article/FullText...
In apparently healthy participants of the community-based middle-aged EPIC-Norfolk population, elevated plasma levels of the gut microbe-dependent metabolite TMAO, and its nutrient precursor choline, predict incident risk for CVD development independent of traditional risk factors.
pubmed.ncbi.nlm.nih.gov/336...
The ability of choline to produce TMAO was stronger than that of betaine and L-carnitine.
pubmed.ncbi.nlm.nih.gov/325...
TMA production from dietary precursors in an in-vitro model of the human colon, they found that the rate of TMA production from precursors is choline > L-carnitine > betaine > γ-butyrobetaine, and conversion of L-carnitine to TMA is slower than that of choline
pubmed.ncbi.nlm.nih.gov/339...
The gut microbiota-derived metabolite trimethylamine N-oxide is elevated in Alzheimer's disease
Question for dadcor You mentioned uridine helping for your non-motor symptoms, but have you noticed any effect or increase in your motor symptoms such as involuntary movements and tremors?
Pushing acetylcholine can result in muscle excitement worsening motor symptoms in some cases which is why some PWP are placed on anticholinergics, which often causes memory problems.
Hi thanks for questioning.. This is important to mention. Actually I tried to double the dose from 250 to 500 mg/day and my tremors worsened significantly. It took 3-4 days to normalize after that. Since than I keep it 250/day.
Yes, that makes sense. Thanks for the detail - I'm sure it'll help other PWP in their decision.
Yet another detail, I am using choline bitartrate (1000 mg/day) together with uridine.
It's probably even better to add some omega3 that’s good for just about everyone. You’ve stated you only use it when needed and not every day. How often do you use uridine? Did you notice it helps with your constipation? Increasing acetylcholine can help with intestinal motility, just as addressing thiamine deficiency can.
When identified the dose 250mg/day, I used it every day for 3 months and than reduced to every other day. Sometimes it happens that I miss two days or even three.. I just try to listen to my body and adapt.. Regarding the constipation you are right, the problem almost disappeared. I did not mention this fact, because I was not sure which was the decisive factor, either uridine or choline bitartrate.. I plan now to add to this protocol omega3 and also Magnolia.
I'd say both probably helped towards increasing acetylcholine including other brain phospholipids, and hopefully new synapses & new neurons through the activation of the P2Y2 receptor with NGF. It seems you have a pretty good strategy by listening and adapting to your body's needs.
👍
in reply to rescuema
Rescuema, are you an AI PD fairy godmother? Seriously, how do you know so much! So grateful!! 🌸. As might be evidenced in my researching and general spunkiness, I’m coming back to life!
KERRINGTON in reply to
Ditto 😃
I just made an order on this Uridine/DHA/Citicoline stack when I saw that this in combination with my Madopark can lead to (more) dyskinesia. Anyone have any reflections on this. Should one lower the madopark while trying this? Or should one not try at all? Hope someone has the time for a reply
Response under your new thread. healthunlocked.com/cure-par...
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