Parkinson's Movement
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mannitol

clinicrowd.info/pd-registry/

Hi everybody, about 5 days ago I got my 5 kilos of mannitol and started taking it. If you want more information on it click on the link above. You can join their trial provide some of the information for their study. You can also look up #ranico posts.

I will keep everybody informed what is happening. I believe it takes at least 2 months to see any results. I have started on Zandopa again

Mannitol doesn't seem too bad, I do have some bloating and little bit of cramping. It is helping with constipation. I got the Mannitol on Amazon for a really good price. 5 kilos for about $70.

So I'm keeping my fingers crossed Mary

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I've started too (about 2 weeks ago). One level tablespoon of mannitol in my morning coffee.

Nothing to report yet.

Jeff

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Any update pls? Worth a try?

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At this stage (12 months) everything is still going really well. Everything I said in my previous updates at 8 months and 6 months (see below) is still valid.

I have recently become aware that there are probably very few of us left on the CliniCrowd trial who are still completing the survey every month. This will obviously impact the quality of the results of the trial.

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I'm very glad it's working out for you.

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Parkie13, What is the daily dose of mannitol you are taking? And how did you settle on this amount?

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I read 170lbs use tablespoon.

I'm 145 so I use a little bit less.

Can't find the article but it said if use too much it didn't work .

They experimented with different amounts

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Has it made a difference ?

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According to the CliniCrowd website, the recommended daily dose for a 70 kg person is 10 grams (1 tablespoon). For a 90 kg person, the recommended daily dose is approximately 15 grams.

Unfortunately, I think you have to complete an initial survey on the CliniCrowd website before you get to see the dosage information.

I'm 55 kg and I've opted for 1 level tablespoon per day, keeping in mind that mannitol is just a sugar and it is designated by the FDA as a food (GRAS - Generally Regarded As Safe).

Jeff

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that is right have no wifi for 2 more days

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Jeff and Parkie, Thank you much for the dose info.

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Jeff, any improvement?

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I've been taking mannitol for about 2 months. I think my tremor (my main symptom) has improved a little, and I think I'm sleeping a little better too.

The mannitol might also be slowing the progression of the disease, but that will only be evident after a much longer period of time.

I'm keen to carry on for many more months, and to continue being an active participant in the trial.

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That is really great.

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How are you doing? Any improvement with mannitol ?

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The only Improvement I have noticed is with constipation, it has gotten better. Otherwise I haven't seen any Improvement, I am still taking it.

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Any update on how mannitol is helping ?

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I've been taking mannitol for 6 months. I've also been taking N-Acetyl-Cysteine (NAC) for 3 months. I've also been doing 40 mins of high-cadence cycling every day for more than 12 months.

Things have been going really well for the past few months. How much of this can be attributed to mannitol, and how much to NAC (or the combination of both!), is not clear to me.

Mannitol might also be neuroprotective. This is something that is best measured over a period of years, rather than a period of months.

Putting a tablespoon of mannitol in my morning coffee each day is not very difficult, so I plan to keep going with the trial at least until my current stock of mannitol is used up (late next year).

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That's great . My mom is also taking NAC - and some other anti-oxidants . Given mannitol is a source of sugar - does it make people put on weight ? I am trying for mom to get her weight under control - I think its the immobility which is responsible for that - but wondering about mannitol.

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I don't know about other people, but in my case, mannitol has had no effect on my weight.

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I am taking mannitol with liposomal gluthione - I think you might need to take them both for the full impact. I agree that exercise is also very important.

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How is mannitol working for you at this time?

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I have stopped taking it, never saw anything positive except for better constipation relief

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At this time (in my 8th month), everything is going really well. However, I am not able to attribute this to any particular medication, supplement, or exercise (if you click on my name you can see all my medications, supplements, and exercises).

For me, the CliniCrowd mannitol trial is more about long-term disease progression, rather than short-term symptomatic relief. Hopefully, a few hundred PwPs around the world will stick with it for at least a year or two. Hopefully, that will generate some meaningful data.

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Yes, it is worthwhile to see.

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Since u are taking mannitol are you also taking sinemet. So you know whether or not the two are ok to take together?

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I have not taken any Mannitol in quite a while. Never noticed any difference. I was taking a small dosage of levodopa and Mannitol

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I received my mannitol order the day before Thanksgiving and started dosing Thanksgiving day Nov 24, 2016. For the first week I took one teaspoon once per day with coffee or tea. After a week I doubled the dose. Today, Dec 12, I took one teaspoon with morning tea and will have another teaspoon with afternoon tea. I've been having significant off time almost 50% of the time. After seeing my neuro, a movement disorders specialist, he put me on Amantadine. I started that on Nov 27. I took the 100 mg capsule once per day for a week, then went to two capsules per day o/a Dec 5. Amantadine enhances and extends the carb levo I've been on for 4+ years. My neuro also upped my carb levo dosage.

My dosing schedule was 3 oral dissolving tablets (ODT) at 5 am, 2 1/2 tablets at 9 am, 1 pm and 5 pm, 1-2 tablets at 8-9 pm, and one extended release tablet (50/200 mg) at bedtime. The ODTs are 25/100 mg carbadopa levodopa. My new schedule is 3 ODTs at 5 am, 11 am and 5 pm. 2 1/2 tabs ODTs at 8 am, 2 pm, 2 ODTs at 8-9 pm and one ER tab at bedtime.

So what's been going on?

Unbelievable results! I have zero off time and have cut back on my carb levo dosage too. Is this the result of the Amantadine or Mannitol or both! I do realize the placebo effect could muddy things. But to be almost symptom free? Also my sleep apnea, which has really been a killer, is much improved. This was starting to improve before my mannitol and Amantadine use. The ER tablet was a necessity at bedtime so I could sleep and get out of bed in the morning. The last week, at least three nights I haven't taken it. Something is working!

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It's great to hear about your tremendous improvement!

I don't think anyone could know at this stage whether it was the mannitol, amantadine, carb/levo increase, the placebo effect, or some combination of these.

If I was you I would probably just enjoy the tremendous improvement for a while before trying any more experiments. This would also test whether the improvement is persistent, which is an experiment in itself.

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I've had this persistent severe sleep apnea, which seems to be improving. The sleep improvement was underway before I started mannitol. I really really doubt, that all this improvement is due to one factor. You are right, let's see where I am a month or more down the road! I'll post periodically. I left out another med I'm on, selegiline 5 mg two times a day. No changes on that.

We are all on this journey together. I am always hopeful, and will fight this dreaded disease until there's a cure. Take care and keep moving!

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Has mannitol helped you ?

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Hi, I would say not except constipation is better. I am still taking it on and off.

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I stopped taking mannitol in January due to some fainting spells that just started up. Didn't know what was the cause. All my PD meds cause a drop in blood pressure. I think the Amantadine was responsible. After cardio did his thing EKG, stress tests all my Drs agreed it was the meds. I resumed mannitol in March. After a month, sadly I saw no improvement. Placebo effect highly possible. I don't know. I stopped all mannitol in early April.

Originally in November 2016 I was supposed to go on tasigna. This is the drug that the Georgetown U team has in a phase 2 study. I had a Dr who was going to prescribe it off label. No neurologist in the Albany NY area would follow me. I have a neuro now and expect to be on tasigna in a month. I'll post when that happens. There's initial and periodic blood work and EKGs required for tasigna use. That's being set up now.

Take care and keep moving.

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I'm taking Nilotinib too. I'm surprised a US doctor would prescribe it. Have you started? I'd like to compare notes with you. Have you read about it? It can be a dangerous drug if you're not careful.

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Yes, periodic ECGs and blood work is required. Only on it for three weeks. Way to early to say if it's working or not. I'm told not to expect results until after four months. I won't post until I see verifiable results. Yes I'm all for comparing notes with you.

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I saw a video 2 days ago where Dr. Moussa said they saw some results after 8 weeks. I'll look for the link for you. What is your dose?

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The following interview is about mannitol and PD:

Medical Food to Stop the Progression of Parkinson's Disease

blogtalkradio.com/parkinson...

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Hi, thank you for posting. It has been 2 weeks I have not noticed any changes. My intestinal discomfort is gone no more bloating or gas. Still keeping my fingers crossed. Mary

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Hi! I started on Mannitol 2 weeks ago, too. So far all I got is a lot of gas and the hershey squirts! Anxious to start seeing results!

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Hi any positive results I think we both started at the same time. Except for constipation is better but otherwise nothing to report

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What's the best place to buy Mannitol?

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You can try Amazon or go to bulksupplements.com

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Ive been on mannitol 9 months now. Cant say its doing a lot of good for me. Wondering if its worth the gas. Makes me wonder about the nature of Parkinson's and if that nature can vary from one person to the next. For example, do all pd patients actually have alpha synuclean plaques? Or are there other causes, that arent protein plaques, such as pesticide toxicity, crystal meth abuse or psychogenic causes from dissociative states? I learned that mannitol works by dissolving protein clumps. So technically it should work if protein clumps are your cause. Right? Most people on mannitol get their sense of smell back to some degree, ive heard reports of softening of the Parkinson's face mask. But thats about it. Never heard of any useful benefit. Except in fruit flies that climb up test tubes. It does taste good in coffee though.

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I started Mannitol about 3 weeks ago with some pretty good results! First of all, I have been able to leave my daily Mirilax dose in the cupboard. (After YEARS of taking it daily just to keep my gut moving. If it did nothing more than that, I would still be thrilled.) Next, I noticed that my energy is vastly improved. Don't seem so tired all the time. My cognition is a bit sharper. My voice is noticeably stronger and clearer. And my fine motor skills are improving. I'm still taking Sinemet but have been able to cut the dose in half. Still also taking Amantadine and Epsilon patch. My whole attitude is improving. I am taking one teaspoon daily. ( I weigh 140 pounds.) I did try various doses and discovered that too much actually had me more jumpy/tremmory. Hope that long term use brings even more improvements! Feel like there's hope for the first time in years!

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That's great!

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Any update pls Mary? Is it worth trying? Thanks

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Once in awhile you hear about good results that somebody had on this list. I have stopped it long time ago, I have not noticed any positive results myself when I was on it. I must be one of those fruit flies that does not climb up the test tube.

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Just so you know if you decide to try a Mannitol product, they are not all the same. I have tried two different versions. Several months ago I heard a guy on a radio show rave about a product called Syncolein. It contains Mannitol plus something called alpha galactosidase and maltodextrin. I was excited to try it as this guy had had great success with it. But for me, it didn't seem to do much of anything. I bought it through Amazon and spent $80 on it. Ended up throwing most of it away. My latest try came after reading some other success stories on Facebook and sticking with the pure mannitol. I also got it on Amazon for under $30, including shipping. It's called Pure Bulk Mannitol and only lists Mannitol under ingredients. I don't know if the ingredient difference was the deciding factor in my success versus failure. I'm just happy with the success I'm having with this one.

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I know what you mean, you always wonder is it the product, is something wrong with it should I try something different. I did just use Plain Mannitol and I did get it on Amazon too

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How long have you been using it and what results have you seen?

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Salad three and a half months, never saw any kind of a positive change so I just stopped using it. It made a positive difference with constipation.

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Parkie - I'm adding Mannitol to my list of supplements that I am taking. The thing about mannitol to keep in mind is that the theory behind the molecule is that it is "cleaning house" and not repairing damage so depending on how much damage a patient already has will most likely impact the results that are directly felt. The evidence, to me, seems fairly strong that mannitol is helping to clean out alpha- syn and very likely even if you felt no improvement it was slowing the damage caused by alpha-syn.

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People trying mannitol should not judge it based on months and a lack of improvement, but rather years and a slowness of the progression of their symptoms.

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10-15 g/day at 16 to 24 calories seems like a slam dunk easy supp to take for the rest of my life.

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Check out this guy:

outthinkingparkinsons.com/

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I might try it again. But I remember not all of the fruit flies in the experiment climbed up the test tube. I thought I was one of those fruit flies. Mary

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I think that some people taking mannitol for PD may think its only benefit for PD is the potential to reduce alpha synuclein aggregation, but it may offer other benefit in PD that has not been discerned yet even though there is probably enough information already out there for a good research team to put all of the available information together regarding butyrate and the brain to determine one way or the other. Then of course there is a problem of who would pay for that research for a non patentable molecule.

Mannitol is a polyol or sugar alcohol, but it is also a prebiotic. Not the same as a probiotic or synbiotic. Prebiotics are generally not digested as food but rather are broken down in the intestines through fermentation which I imagine accounts for some of the increased gas production that some users mention. This excess gas is the reason for the inclusion of Alpha-Galactosidase in the Syncolein product, to reduce gas output. Alpha-Galactosidase is the active ingredient in the otc anti gas product, Beano.

This bacterial action with mannitol produces short chain fatty acids (SCFAs) in the forms of propionate, acetate and butyrate. Of these three, butyrate is well noted for a couple of reasons. One is that it is a potent anti inflammatory in the gut, but can also have remote effects . The second important feature of butyrate is that it is a histone deacetylase inhibitor (HDACi), but that is a whole other story by itself.

ncbi.nlm.nih.gov/pubmed/283...

PD is known to have brain inflammation as a part of the disease process and butyrate is able to get to the brain and have effects there in terms acting in an anti inflammatory capacity and more.

Below is a very enlightening article that expands on some of the known effects of butyrate on the brain. Many of the things mentioned in this article are not usually mentioned in a discussion about mannitol and PD, but why not, if mannitol is a known butyrate agonist?

Here is an abstract of a PD mouse study using butyrate to good effect. It seems to me it was a non human study that first put the spotlight on mannitol!

ncbi.nlm.nih.gov/pubmed/289...

For that matter, most prebiotics are useful SCFAs producers, either directly or indirectly. These SCFAs have broad ranging effects in the body......including the brain, but the effects of butyrate are being increasingly researched and each new study seems to expose another facet of butyrate's abilities.

sciencedirect.com/science/a...

After reading this article and absorbing the implications of it, you have to ask yourself, how can the research into mannitol and PD not even consider what is obviously a very important aspect, its ability to produce butyrate and act as an HDACi ???

Butyrate itself can be taken as a supplement, but prebiotics seem like a more natural way for the body to make its own. Did I mention I am a huge fan of some prebiotics and different prebiotics produce SCFAs in different proportions.

This very brief abstract gives a clue about how gut inflammation can have an affect on the brain.

ncbi.nlm.nih.gov/pubmed/282...

After reading that abstract, it makes me wonder if the reason that some people respond fairly well to mannitol and others don't is because the non responders do not get the butyrate effect because their gut has insufficient amounts of the bacteria needed for the mannitol to interact with and produce butyrate while the responders may have just enough of those butyrate producing bacteria for the mannitol to make enough? Perhaps the answer lies in synbiotics (prebiotic + probiotic)? Give the gut the appropriate probiotics for butyrate production and give the prebiotic mannitol with it. Butyrate seems to be a very potent and active SCFA that should not be minimalized in any way whatsoever!

Just some food for thought!

Art

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Very interesting, thank you for posting. Mary

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Art,

thanks this is the maximum.

Very beautiful and above all aplicable and functional.

The difference in people like you Art and others, is definitely in the intelligent assessment of what is important and what is not, in a sea where every drop is equal to another , only those who are driven by a strong intention to help make the difference because they are on the field in the front line, with the people who suffer. and there moved by his willingness to help develop the sense of duty which is the highest motivation of the human spirit.

When I see these noble persons I recognize them immediately from their competence. Thanks Art, you are one of them.:-)

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Wow, Gio, that was very nice of you to say! Thank you!

Art

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Art n.1

keep it up

Ciao :-)

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Here is further support to add confirmation to the idea that PWP's are likely to have significantly less butyrate producing bacteria in their gut. Under those conditions, mannitol alone may not be enough to get butyrate production up regulated. It takes two (mannitol + butyrate producing bacteria) to make enough butyrate.

ncbi.nlm.nih.gov/pubmed/261...

Art

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The following study shows that mannitol can aid the absorption of magnesium in the body.

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

Art

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And further confirmation on the effects of butyrate in a PD rat model.

Art

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Behav Brain Res. 2015 Sep 15;291:306-14. doi: 10.1016/j.bbr.2015.05.052. Epub 2015 Jun 3.

Beneficial effects of sodium butyrate in 6-OHDA induced neurotoxicity and behavioral abnormalities: Modulation of histone deacetylase activity.

Sharma S1, Taliyan R2, Singh S1.

Author information

Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disorder. Recent studies have investigated the involvement of epigenetic modifications in PD. Histone deacetylase (HDAC) inhibitors have been reported to be beneficial in cognitive and motor deficit states. The present study was designed to investigate the effect of sodium butyrate, a HDAC inhibitor in 6-hydroxydopamine (6-OHDA) - induced experimental PD like symptoms in rats. To produce motor deficit, 6-OHDA was administered unilaterally in the right medial forebrain bundle. Three weeks after 6-OHDA administration, the rats were challenged with apomorphine. Following this, the animals were treated with sodium butyrate (150 and 300 mg/kg i.p.) once daily for 14 days. Movement abnormalities were assessed by battery of behavioral tests. Biochemically, oxidative stress markers, neuroinflammation and dopamine were measured in striatal brain homogenate. Further, to explore the molecular mechanism(s), we measured the level of global H3 histone acetylation and brain derived neurotrophic factor (BDNF). 6-OHDA administration results in significant motor deficit along with reduction in striatal dopamine level. 6-OHDA treated rats showed elevated oxidative stress and neuroinflammatory markers. Treatment with sodium butyrate results in significant attenuation of motor deficits and increased striatal dopamine level. Moreover, sodium butyrate treatment attenuated the oxidative stress and neuroinflammatory markers. These effects occur concurrently with increased global H3 histone acetylation and BDNF levels. Thus, the observed results of the present study are indicative for the therapeutic potential of HDAC inhibitors in PD.

KEYWORDS:

6-OHDA; HDAC inhibitors; Histone acetylation; Histone deacetylases; Parkinson’s disease; Sodium butyrate

PMID: 26048426 DOI: 10.1016/j.bbr.2015.05.052

[Indexed for MEDLINE]

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And another study adding confirmation.

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Neuropharmacology. 2012 Jun;62(7):2409-12. doi: 10.1016/j.neuropharm.2012.01.026. Epub 2012 Feb 13.

The histone deacetylase inhibitor, sodium butyrate, alleviates cognitive deficits in pre-motor stage PD.

Rane P1, Shields J, Heffernan M, Guo Y, Akbarian S, King JA.

Author information

Abstract

Parkinson's disease (PD) patients often times experience impairment in their cognitive abilities early on in the progression of the disease. The reported deficits appear to mainly involve functions that are associated with frontal lobe and frontal-striatal pathways subserving attentional set-shifting, working memory and executive function. The current study explored executive function deficits in a rat model of PD in the pre-motor deficit stage. The rats were lesioned with 12 μg of 6-hydroxydonpamine (6-OHDA) in the striatum in a two step process (10 μg/μl followed by 2 μg/μl) 48 hours apart. Executive function was tested at 3 weeks post-surgery using a rat analogue of Wisconsin card sorting test called the Extra Dimensional/Intra Dimensional (ED/ID) set-shifting task. The results demonstrated that performance by the pre-motor rat model of PD was equivalent to that of the control groups in the simple and the compound discriminations as well as the intra-dimensional set-shifting. However the PD group exhibited attentional set-shifting deficits similar to those observed in PD patients. Additionally, sodium butyrate, a short chain fatty acid derivative and inhibitor of class I and II histone deacetylase (HDACi), was tested as a potential therapeutic agent to mitigate the pre-motor cognitive deficits in PD. The results indicated that the sodium butyrate treatment not only effectively alleviated the set-shifting deficits, but also improved the attentional set formation in the treated rats.

PMID: 22353286 DOI: 10.1016/j.neuropharm.2012.01.026

[Indexed for MEDLINE]

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If the idea of mannitol and butyrate is to improve the gut microflora and reduce gut inflammation to ultimately repair some of the brain damage associated with PD, then it seems the fastest way to test that idea might be with a fecal transplant from a healthy non PD test subject .

The following study tests that theory in a PD mouse model........effectively!

Art

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Send to

Brain Behav Immun. 2018 Feb 20. pii: S0889-1591(18)30017-5. doi: 10.1016/j.bbi.2018.02.005. [Epub ahead of print]

Neuroprotective effects of fecal microbiota transplantation on MPTP-induced Parkinson's disease mice: Gut microbiota, glial reaction and TLR4/TNF-α signaling pathway.

Sun MF1, Zhu YL1, Zhou ZL1, Jia XB1, Xu YD1, Yang Q1, Cui C1, Shen YQ2.

Author information

Abstract

Parkinson's disease (PD) patients display alterations in gut microbiota composition. However, mechanism between gut microbial dysbiosis and pathogenesis of PD remains unexplored, and no recognized therapies are available to halt or slow progression of PD. Here we identified that gut microbiota from PD mice induced motor impairment and striatal neurotransmitter decrease on normal mice. Sequencing of 16S rRNA revealed that phylum Firmicutes and order Clostridiales decreased, while phylum Proteobacteria, order Turicibacterales and Enterobacteriales increased in fecal samples of PD mice, along with increased fecal short-chain fatty acids (SCFAs). Remarkably, fecal microbiota transplantation (FMT) reduced gut microbial dysbiosis, decreased fecal SCFAs, alleviated physical impairment, and increased striatal DA and 5-HT content of PD mice. Further, FMT reduced the activation of microglia and astrocytes in the substantia nigra, and reduced expression of TLR4/TNF-α signaling pathway components in gut and brain. Our study demonstrates that gut microbial dysbiosis is involved in PD pathogenesis, and FMT can protect PD mice by suppressing neuroinflammation and reducing TLR4/TNF-α signaling.

KEYWORDS:

Glia; Gut-brain axis; Microbial dysbiosis; Neuroinflammation; Neurotransmitter; Parkinson’s disease; Short-chain fatty acids; TLR4/TNF-α signaling

PMID: 29471030 DOI: 10.1016/j.bbi.2018.02.005

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Art,

This is a beautiful job. I'm reading and rereading. And looking for a practical implication even for those who respond less or increase the effect in order to put this foundation to the test.

thank you very much!

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Gio,

Failing to locate the proper bacteria in a commercially available probiotic, there is commercially available butyrate supplements, but I am doubtful that they would have the desired effects because butyrate as an oral supplement does not have the same gut protective effects as butyrate produced in the gut according to available studies.

My thinking is that many of the benefits of butyrate originate in the gut and have global effects throughout the body.

How hard can it be for scientists to isolate the missing bacteria and experiment with them since these bacteria are normally occuring in the normal gut flora?

Art

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Art,

I understand, but if your idea is correct, I do not think technology is lacking to verify it.

thank vou!

Gio

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I couldn't agree more, Gio!

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Hi Parkie13 >>> just read your post about Mannitol a year ago.....how are you doing now

with that ?? You have stopped for a while and than start again ? I'm a bit skeptical, but not so much anymore because the good post of MBAnderson convinced me again a bit more...

There was a post here of somebody that purchased Mannitol who doesn't cause gas.........do you where and who that was ??

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I did not notice any positive change. So I did stop and have not started it again. When they quoted the study they said some of the fruit flies never climbed up the walls of the test tube. I feel I'm one of those fruit flies. There must be something too it, there are many good reports from people taking it.

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