Curious. Who is taking NAC and mannitol? Anyone?
Just curious. Is anyone in the PD group taking these two supplements? If so I'd love to hear your experience.
N-Acetyl Cysteine May Support Dopamine Neurons in Parkinson's Disease: Preliminary Clinical and Cell Line Data
Have started NAC 600 MG twice daily since one week.
I took Mannitol for three months and after no effect discontinued it. Have resumed again after reading some users comments after a break of 2 months
Super! Thanks for sharing.
I'll offer some thoughts I am not in any way trying to suggest a thing just sharing some thoughts . . .
So this study showed that as little as 0.5% of mannitol molecules pass thru the stomach wall and make it into the blood stream:
Repeatability of the Sugar-Absorption Test, Using Lactulose and Mannitol, for Measuring Intestinal Permeability for Sugars
and this study in rabbits showed a high variability of BBB penetration amongst different animals:
Inconsistent blood brain barrier disruption by intraarterial mannitol in rabbits: implications for chemotherapy
Also, Mannitol is used in treating many illnesses and comes in different forms. One form used in CF is even inhaled.
I dissolve trehalose in water at a ratio of about 4 to 1 and put the solution in a nasal spray botttle. I'm thinking I might try the same with mannitol since the goal is not to get mannitol into your gut, but rather to get mannitol to your brain.
Anywasys, just thinking out loud
Instead of trying this which be dangerous, one can search for some substance which when mixed with mannitol make it more bioavailable ( like catalyst). Just like mixing black pepper with turmeric makes it more capable of crossing BBB
I like your idea regarding Mannitol delivery as a nasal spray. When you google mannitol you can see references that sugar alcohols may harm gut flora. I ordered mannitol and planning to try it. I have couple of cons though: 1) possibility of creating gut bacteria imbalance 2) I am starting a keto diet and adding sugars even with low net carb amounts is not good. Because you want your taste buds to forget this seductive taste.
So, I am actually quite excited to try this option. Though not sure how practical it to deliver 10-20 g through the nose. Perhaps it should be spited into few doses through the day?
Digested mannitol is just sucrose and would have no impact on PD. Most of the mannitol a person eats is excreted in undigested form. Complete mannitol molecules are what you want to get into your blood stream and the study below showed the mannitol molecules pass through human intestinal walls undigested at a rate of 0.5% to 2%:
What that means is that people who are eating 10 g a day are actually only getting about 1% or 0.1 g into their blood stream. A nasal spray can deliver something around 0.02 to 0.05 g of mannitol per squirt, but the nasal passage is an excellent conduit to the brain. Nicotine from a cigarette can hit the brain in 5 seconds when inhaled through the nose.
Also as to sugar alcohols from mannitol. Mannitol has a glycemic index of 0 because your body digests only a small portion. Presumably the impact on gut bacteria is equally small. Mannitol is a powerful diuretic and THAT should be kept in mind.
Lastly I would do more research on keto diets and neurological benefit. There is conflicting evidence and some studies show benefit while others show harm. A mostly vegetarian diet rich in cruciferous vegetables has been shown to be nothing but beneficial.
All the best,
Thanks for your mannitol comments. As for the diet, my hope is that keto may help with dystonia, which is my major PD problem. When I am in off state (mostly in the morning) I may have severe and very painful full body Dystonia. Keto diet is successfully used to treat epilepsy spasms. And I have similar experiences: when I pig out on sugar, next morning is a disaster. If I sustain or lower it significantly I can go few days without dystonia spasms. I may end up with a personal version of greens + protein + some fat and no grain or sugar. Will have to try and see.
If you have some thoughts or experience, will appreciate your input.
I've been on a pretty strict keto diet for about six months and I THINK it's made a pretty big difference--more than mannitol (yes I tried) and more even than azilect (which I am still on in case it is neuroprotective, but I have gone off, and on, just to see) I am not on anything else!
Obviously I can't discount placebo effect, but even my doctor was impressed. (I can finger tap again :o)
You can be a vegetarian if you want. It's just that much more restrictive. But it is NOT protein and some fat--it's the other way around. Lots of fat, some protein. I do eat lots of greens though! cooked in either olive or avocado oil.
So, here is another tip, I think, especially on keto, for those cramps: everyday make sure to eat two brazil nuts and a handful of pumpkin seeds. Hemp seeds are good too. That way you'll be sure to get minerals. Also, plenty of water and salt--bone broth is good.
Good stuff Amy! Thanks for sharing. You made me revisit the topic of a ketogenic diet this morning and I found some interesting material. I just wanted to reply directly to you so you would for sure see the reply to Lana below that has some info I hope you find interesting as well.
No matter what, please do keep us informed of how things go for you!
Thanks for sharing. Are you on Meds? Or just supplements?
How do you take your mannitol? Does it have to go w/ a caffeine Bev to cross BBB?
As for Keto diet, what protein do you take regularly? Eggs, Wild Salmon , lamb, chix breast ? Aside from bone broth.
Fats - avocado , nuts like walnut too? Coconut oil or milk? almond milk ?
Thanks again ..
I take Azilect, but I am unconvinced it does much of anything, for me. (I didn't notice a big difference when I started, and I've stopped here and there...no change.) I take it because my Dr. really believes it is neuroprotective. (yes, I know that's controversial)
I have not started any kind of dopamine replacement. I don't have anything against it, just don't need it yet.
When I took the mannitol I put a tablespoon in my morning coffee, yes, because I heard the same thing--that caffeine might help with absorption. But not the BBB, it's the gut that mannitol doesn't want to cross. I tried it for about 2 1/2 months and then kinda got sick of it. I didn't see any difference with that either...but it is entirely possible I didn't try long enough.
The thing is (I BELIEVE because of the keto) my symptoms are pretty mild, so it's hard to find big changes.
So, KETO: I use a lot of olive oil, avocado oil and, because my local store was having a huge sale, macadamia nut oil. I drink my coffee with heavy cream and unsweetened almond milk. I eat nuts, but avoid cashews (they're a little higher in carbs). I eat eggs and avocados, pretty much any meat or fish you will throw at me but I think liver's gross. :o) I make my own bread: almond butter, eggs. Scones: almond flour, eggs, sour cream, butter and stevia chocolate chips.
I do try to stick to about 80% of my calorie intake from fat, 15% from protein and 5% from carb--and most of that is green vegetable. (I mean, OK, cauliflower too)
But I don't weigh or measure. I don't need to anymore. So many recipes online! I really don't find it all that hard.
Thanks for sharing . You are lucky to have mild symptoms & do not need Meds.
Try diet...for a couple months! Just see, because what is the harm? You won't feel good for a week or so (keto "flu") so you gotta get past that.
BTW, I also use MCT oil, every day, a couple tbs. I will be happy to coach, share recipes...whatever. You can PM me. I am so curious to see whether ANYONE else gets the results I think I did!
Thanks Amy. Will try.
K. Please keep me updated. There's lots more I can share--I gave you the ten-second version!
Thanks. I'm also on gluten/soy/corn/dairy free diet. My starch intake is 20% -30% at times (quinoa/buckwheat/coconut wrap). Consume almonds/chia/walnuts & fruits /raw veg for snacks.
IMHO the more restrictive your diet, the harder (not impossible, of course not!) keto will be. Only because keto is so restrictive in itself. But the good new is that pretty much on keto you don't eat gluten anyway, or corn or soy. No buckwheat or quinoa :o( Chia and flax ok I think. Dairy would be hard for me to give up, since cheese and butter and heavy cream add a lot. You can't eat fruit...much, except the very occasional berry. For me, a great treat is a few raspberries or strawberries in heavy cream.
The main thing is to read labels. If you want to keep your carbs below 20-25g or so, you just have to figure out what's worth it! Of course you could have a spoon of quinoa, but you use up a lot of your allowance. BTW--my daily splurge tends to be tomato, fresh garlic, and onion. I cook with them, and they are on the high side, for veggies.
I'm reading more now on mannitol and gut bacteria. Looks like it's something called a FODMAP which makes it bad for people with IBD.
Thank you for researching. Do you mean that mannitol has a similar effect as lecithin in FODMAP group? Then again applying it through the nose should be way to go? A small amount of solution could be swallowed while you spray, but it should not be much.
The article I was reading did not mention lecithin so I can't really comment on that, but basically avoiding the stomach would be ideal, but kinda "out there" in terms of what most folks are willing to try, but I like being "out there"
As to the keto diet, Amy's comments made me revisit the topic this morning, and I found this article:
Ketone-Based Metabolic Therapy: Is Increased NAD+ a Primary Mechanism?
The full study is free to read, but essentially the researchers found evidence that the reason a ketone diet may help is because it increases production of NAD+. Now if you read any of my other posts on the ataxia forum and here, you will quickly learn that I am a HUGE fan of Niagen because Niagen is a new form of vitamin B3 that does not have the dangerous side effects that other forms of B3 have, and it's a proven booster of NAD+.
One of the major symptoms I used to have was stiffness in my legs. I have been a runner since age 14, but in the last couple of years I was running slower and slower and no matter how much I stretched my legs always felt heavy and stiff that was until I started taking 1000 mg a day of Niagen. I got banned from here last year because I came on a little too strong, but I can not say enough good things about Niagen. I REALLY wish everyone here would talk to their GP and then try 1000 mg a day for a month just to see for themselves. Niagen is a little expensive, but I believe it is the single best supplement to aide in neuroprotection. What's crazy though is that the role of NAD+ was first hinted at way back in 1993!
Nicotinamide adenine dinucleotide (NADH)--a new therapeutic approach to Parkinson's disease. Comparison of oral and parenteral application (the study from 1993)
Enhancing NAD+ salvage metabolism is neuroprotective in a PINK1 model of Parkinson's disease
Repeat dose NRPT (nicotinamide riboside and pterostilbene) increases NAD+ levels in humans safely and sustainably: a randomized, double-blind, placebo-controlled study
Nicotinamide riboside is uniquely and orally bioavailable in mice and humans
Whoa. Interesting. I SCOUR the web for articles, and you found a really good bunch!
BTW, the articles I have found on the keto diet (about PD, adult epilepsy, alzheimer's, etc) all say things like: well, it shows neuroprotective promise, but goodness, it's just far too difficult! No point in doing any research because we couldn't possibly expect people to stick to it! Everybody must have cake and cookies, after all!
And honestly? Why not let people with PD and adult epilepsy and alzheimer's decide for themselves?
I have found mannitol different taste to sugar luckily as i do not like sugar. Thought of tablespoon of sugar was awful but as said i find mannitol palatable. I take it as Syncolein.
Hi. Can you tell me where you get your NAC from? I may add to my mannitol. Ta
Bummer, looks like you can't take it orally and expect any result. The people in this trial took 6000 mg yes 6000 not 600 that the pill form has but 6000 with no effect. Bummer.
Repeated-Dose Oral N-Acetylcysteine in Parkinson's Disease: Pharmacokinetics and Effect on Brain Glutathione and Oxidative Stress
Is Trehalose similar to mannitol ? Which is more effective trehalose or mannitol?
Where can we purchase pqq, trehalose, niagen, benfotiamine, & what brand? Thanks.
My apologies. I think maybe you asked me some questions in a PM that I forgot to answer.
AGAIN - I AM NOT A DOCTOR. PLEASE TALK TO A DOCTOR ABOUT THESE IDEAS FIRST, and remember that 30 minutes a day of exercise at 80% max heart rate plus a healthy diet are more likely to be helpful than any of the supplements below.
Is trehalose similar to mannitol?
Yes, very similar, but based on the research I have read on mannitol, I believe it MAY be better than trehalose at removing toxins from the brain when taken orally, but the evidence to date is thin. However, mannitol is only 1.6 calories per gram and is a well known food additive so to me it seems silly not to eat 2 tsp a day of an undigestible sweetener if there is any chance at all it may be helping. Also - and I want to emphasize this - it is very likely that with either trehalose or mannitol people with PD will feel no different because the theory behind these two molecules is that they help clean out toxins thereby slowing or hopefully stopping damage. They will NOT make a person BETTER or repair damage. SO . . . IF your doctor says he or she thinks it's a good idea then I urge you to continue taking which ever one you choose FOREVER. Don't stop unless you have a negative reaction because even if you don't feel different it is distinctly possible mannitol is simply slowing the progression of your PD and there is really no way to test for that without studying hundreds of patients for many many years.
Now having said all that here are the supplements I am taking:
Finally I will add that of all the items listed I personally would talk first to my doctor about Niagen and mannitol. It is my belief based on all that I have read that those two supplements hold the greatest potential to actually be helpful. When you do talk to your doctor you should also make sure the doctor is familiar with Niagen. Niagen is nicotinamide RIBOSIDE. When you talk about vitamin B3 most doctors will be thinking of niacin or nicotinamide/niacinamide. They are VERY different from nicotinamide riboside.
Thank you for much Joe. I will inform MD.
I tried Mannitol too last year but had stopped it after 2 weeks bec I was on detoxed for 3 months. Now it's done I will resume & try mannitol again.
I am readearching on alpha spin by biophysics (EMF reduction) & alpha meta powder from Thailand.
My exercise right now is just walking w/ smovey ring on both hands. Stretching.
Researching on theracycle 200 if it's effective.
Good day Joe.
Hi--I have the theracycle and have found it to be very effective. I use it almost daily.
I do, Sunvox.
- Mannitol 9 g per day or 2x a day (depending on my mood) for nearly a year now
- N-AC since 8 month 3x 600mg a day (per os, far from meals)
It looks as if the disease had come to a halt - but that is very subjective.
Did you go on the CliniCrowd pages ?
No. I did send a message to Noy via email and got a voicemail, but I haven't called back yet. Is there some trick to making the website more responsive or is just slow?
Sorry to be answering so lately : I did not see your message.
Just to say their web pages do not work properly with Firefox. I have to use Internet Explorer.
If we all could laugh for five minutes a day, we would not have parkinsonism!
that's just an insult! for shame...it's a medical deficiency that laughter alone cannot solve!
Wish that were true. I laugh all day with my coworkers
I take 1200mg NAC, 3x day, and 1tbs mannnitol in my AM coffee. Along with a dozen other supplements, my good days are better and my bad days are not as bad compared to a year ago. I would take 2 tbs mannitol but my bowels cant tolerate it.
Thanks for that info! I'm reading positive comments from people that are actually taking NAC, and when you read the study closely it does say :
" peripheral antioxidant measures (catalase and GSH/GSSG) increased significantly relative to baseline . . "
Which says to me although it is not impacting oxidation immediately in as big a way who is to say that taking it daily for a lifetime isn't simply boosting your bodies anti-oxidant ability ever so slightly. Certainly the evidence is clear for the IV. It really is the same thing I am doing by taking trehalose. BioBlast showed the IV administered trehalose worked so I tried oral trehalose and against all scientific odds it appears to have helped.
So, I guess what I'm saying is I'll add this to my list.
Thanks for sharing everyone!
Remember, every case of PD is unique in what works, what doesnt, symptoms and causes. There are just so many anecdotal stories. Try anything that is safe until you find the magic bullet or combination. Just be careful. Here's what I tried and actually works for me:
a smoothie with Undenatured grass-fed Whey Protein Isolate, Creatine, yogurt, berries, milk and Kale
5-htp (with various co factors)
Organic diet high in green leafy vegetables such as kale, spinach, broccoli
Co Q10 with PQQ
lots of water
occasional strong cup of coffee
For some reason I thought you had read more of my stuff. It's evident to me now that just like others on this website you are not reading other people's posts sufficiently. I suggest you click on my name and read through some of my history. I am extremely well informed and not your average poster. In fact I am working with doctors at Harvard Med to develop a clinical trial of orally ingested trehalose for patients with ataxia. Also I do not have PD I have Spinocerebellar Ataxia Type 1. SCA1 is a polyglutamine disease and so shares many pathologies with PD, but it is faster progressing and always fatal.
What did I miss? In defense of me and others not reading everything on this site, it is exhausting as there is a lot of stuff! I'll try to do better, sorry.
currently, I have 7 tabs open on my browser and Im learning about L-Methionine. Any thoughts on that?
Yes, in terms of enzymes and cellular activity L-Methionine plays a much smaller role than NAD+ so before researching L-Meth why not focus on one of the fundamental building blocks of every cell in your body and figuring out what you can do to boost that.
I was actually looking into L methionine as an alternative to L cysteine or NAC as a source for sulphur replenishment. Just out of curiosity.
A good replacement for NAC is R-alpha lipoic acid. It is a glutathione precursor and it penetrates the blood brain barrier. When R-alpha lipoic acid is combined in a PD cellular trial,
"Most notably, we found that when combined, LA and ALC worked at 100–1000-fold lower concentrations than they did individually."
I have taken them both for years and they are best taken on an empty stomach between meals. Acetyl l carnitine has a stimulative effect so it should not be taken in the evening. R-alpha lipoic acid is best because it is the bioactive form of LA and most brands use a combination of R and S (synthetic) ALA. If you purchase ALA keep it in the refrigerator because ALA loses 25% potency when stored over 60 degrees.
Here is an overview of ALA.
Have you found cellular pathologies that differ between PD and SCA1? If so, do those differences alter supplement strategies?. Note that I am granting some similar pathways
(eg, reducing oxidative stress).
The reason to take methionine for PD is far different than taking a NAD-producing supplement. Methionine has actually been tested as a substitute amino acid for PD.
[L-Methionine treatment of Parkinson's disease: preliminary results].
Treatment of Parkinson's disease with L-methionine.
The second article is just a title so if you want to see the results of the experiment (I went ahead and paid for the article) I included it in the introductory video of my documentary:
What is not mentioned is, like levodopa, if you take methionine you need to be aware it raises homocysteine levels and you have to take cobalamin/B12, folate and depending on which type of levodopa you take, you may need P5P/pyridoxine (to lower homocysteine levels).
"Levodopa, the gold standard therapy for PD, causes an increase in homocysteine levels that induces neuronal death via N-methyl-D-aspartate (NMDA) receptor."
"Homocysteine is formed from methionine, and dietary manipulation of homocysteine in primates and humans with oral methionine is associated with endothelial dysfunction."
Those studies were done in the early 1980s. L-Methionine depletion is a result of the damage done to the cellular health of the brain. It is unlikely to be a solution other than a potential palliative.
NAD+ repletion has the potential to fix the problems that cause L-Meth depletion, and what's more Niagen is a proven and available NAD+ precursor that also enhances Sirtuins.
I would not write the epitaph for methionine yet. Quite recently,
Researchers Discover Why L-DOPA Stops Working in Parkinson’s, Seek Prolonged Treatment
"They discovered that L-DOPA triggered widespread changes in DNA methylation."
"The team also treated animals with a compound called RG-108, or with methionine supplementation, and saw that they could change the dyskinetic behavior of the animals. While these treatments are not suitable for humans, the experiments provide a proof-of-concept that by changing the methylation it is possible to harness the development of dyskinesia, and so, prolong the effectivity of L-DOPA."
The researchers obviously did not know that the 'not suitable' amino acid methionine was already tested with or without levodopa on PD patients in the 80's (and improved their conditions).
I am a believer that B3/niacin and it's many versions are great for PD and found that old fashioned niacin can be taken with Niagen. GPR109a is a source of inflammation in PD and only niacin - not nicotinamide, Niagen nor NADH affect Niacin Receptor 1:
"The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity
“The inability of NR to activate GPR109a illustrates how NR provides and alternative way to increase NAD+ and ameliorate metabolic homeostasis in the absense of the undesirable effects seen with NA. Since NR does not activate GPR109A, we speculate that NR reduces cholesterol levels through activation of SIRT1 in liver, which influences the activity of a number of transcription factors and cofactors linked to cholesterol homeostasis.”
Low-dose niacin supplementation modulates GPR109A, niacin index and ameliorates Parkinson's disease symptoms without side effects
As for NADH, it has had only 1 double blind study and though the sample size was small, NADH did absolutely nothing for PD patients. The other 3 studies were open label studies and the following doctor stated:
"At this time, the evidence for use of NADH for the treatment of Parkinson’s disease is marginal. The treatment appears to be safe for short-term use, but data on long-term safety are lacking. Patients who are interested in taking NADH should consider the enteric-coated formulation in a dosage of 5 mg/d, with monitoring of their symptoms. A four-week trial probably is sufficient to assess whether there is any benefit.”
I understand the relationship between resveratrol/pterostilbene and Sirt1 and I tried this supplement for 3 months (and it did absolutely nothing for me). iherb.com/pr/Life-Extension...
I have tried many herbs and had a better response from Olive leaf extract, Bacopa monnieri and, especially, Scutellaria baicalensis. S. baicalensis is the most flexible Chinese medicinal herb and has numerous applications in the human body including activating Sirt1 (and has been tested by Chinese scientists hundreds if not thousands of times):
"PGC-1α levels increased when cells were treated with flavonoids and extracts of S. baicalensis. In particular, the water extracts and baicalin at 50 μg/mL increased PGC-1α by 47.7 and 40%, respectively. SIRT1 intensity increased by 30% and 19% using more water and ethanol extracts of S. baicalensis at 50 μg/mL, respectively, compared with AMA cells."
But that is the whole point of this website. To discuss different (potential) neuroprotective supplements and whether they improve the condition of the person trying them. For you the herb Resveratrol/pterostilbene works and for me it is S. baicalensis.
Rich- Please, please forgive me because I am going to be very blunt. You are controlling your symptoms so keep doing what you are doing, BUT you are a landscaper. I am a Dartmouth grad with Magna Cume Laude honors. Every argument you make is not logical. GPR109A is a distant player in what I am arguing. NAD+ is at the forefront. The whole point of the study you quote is that NR is great and should be studied further which is the antithesis of what you are implying.
The second study you quote is old information and actually completely unrelated, and again you are looking at data that is 2 decades old, and what's more the study comes to the same conclusion that I have proposed on this site that NAD+ repletion is a potential therapy.
And, then you link a sales add???? Really??? Come on.
And, then extracts. Again, come on. It's a joke comparison. Really. Dude, recognize when something is a joke . . . please.
Read all of these studies front to back and report back to me with your thoughts and I will "Follow" you. Until then you are a Landscaper with Parkinson's. For the record I am back tracking and limiting my supps to trehalose, mannitol, niagen, and pterostilbene.
Lastly, I would point out that your list has B3 which I believe is the only supplement besides mannitol that is actually effective.
It's an established fact that the scientific studies are not the absolute conclusions. There are numerous studies which have proven wrong. Therefore I will prefer the experiencesof individuals rather than a half cooked scientific research
What’s NAC please
I have taken NAC for 2 years and mannitol for 3 months. I take a heaped tsp in my morning coffee. Reading your comments that isn't enough, yet my PD symptoms have improved particularly with regard to not feeling as mentally distant. My husband who didn't know I was trying anything new commented that I seemed much better, and my neuro last week said he thought no one would even know I had pd except a professional like him! I also didn't tell him as he's rather sceptical.
I also still take azilect and 150mg madapor. I've also reduced my protein intake as I think PD is something to do with ammonia due to the Rhesus negative thing (which I can't interest any researchs in!).
I'm 54 and been diagnosed 2 years.
Btw why are you asking about this combination?
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