Parkinson's Movement
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Mannitol and why some may not respond

I posted the following in another thread, but thought it might be found easier on its own.

Art

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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 mannitol, 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 of 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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Interesting post...

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Here is further support to add confirmation to the idea that PWPs 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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Recently I posted studies about butyric acid, sodium butyrate and phenylbutyrate:

healthunlocked.com/parkinso...

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Thanks again. Keep them coming.

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Art, have you read this

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

?

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Xenos,

Yes, I believe that is the study that got the interest in mannitol started. As you can see, they concentrated on the ability of mannitol to ameliorate alpha synuclein aggregation, but they did not go into the ability of mannitol to act as a butyrate agonist, which is also very important for PWPs. It's like the mannitol works on the brain irregularities of PD and butyrate can help repair gut issues and work remotely from the gut through multiple pathways to work against PD symptoms.

That was almost 5 years ago. Given the the known safety profile of mannitol in humans, it sure would be nice to see a human PD study using mannitol for PWPs!

Art

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Art, is there any supplement to your knowledge that would give us enough butyrate to balance the adverse effect you mention ?

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Xenos,

The problem is that the butyrate producing bacteria are low in PWPs and it takes mannitol plus the proper bacteria to produce butyrate. Butyrate can be taken as a supplement, but I am doubtful it would be effective because studies show that butyrate taken orally is not as effective at improving the status of the gut in terms of different gut issues and gut issues are a significant problem in PD.

There are certain gut bacteria that are known to work with prebiotics to effectively produce butyrate. Here are a few.

Roseburia

Anaerostipes

Faecalibacterium prausnitzii

Prevotellaceae............this bacteria family is known to be deficient in PD

Eubacterium

Fusobacterium

Blautia

Coprococcus

I have not seen any of these bacteria species in probiotics before and it is sad considering the known value of butyrate in many aspects of human health.

Another consideration would be a fecal transplant, but that would require a doctor versed in fecal transplant and a very healthy donor. I have heard mention of these for PD in the literature, but I have not found a case study for that yet.

I plan to research this further, but I am a little pressed for time right now.

Art

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I was just reading a study discussing gut issues in PWPs. Here are two quotes from the study. Notice in the first quote they are discussing diminished levels of thiamine. I wonder if that could be another reason why some people respond to Dr. Costantini's thiamine/B-1 protocol very well and others not so much?

1.

The under-representation of Prevotellaceae diminishes the levels of health-promoting neuroactive short chain fatty acids (SCFA) and the capacity for biosynthesis of thiamine and folate (Arumugam et al., 2011), which is in line with decreased levels of these vitamins in PD patients (dos Santos et al., 2009; Luong and Nguyễn, 2013).

2.

The study showed a lower abundance of bacteria associated with anti-inflammatory properties such as of SCFA butyrate-producing bacteria from the genera Blautia, Coprococcus, and Roseburia in PD fecal samples, thereby concluding that a reduction in SCFA might contribute to gut leakiness.

Here is a link to the full study:

sciencedirect.com/science/a...

Art

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It appears that the probiotic Clostridium Butyricum may be a butyrate producing bacteria in conjunction with a prebiotic.

Here is a link to the full study.

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

Art

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It would seem we can also buy on the web!

Today you have done a great job of competent research for us PWPs.Now we will have to submit it to the test of facts, but thanks to your work we have a map that we can follow. Let's hope!

thank very much Art! :-)

Gio

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You're welcome, Gio!

Maybe I'm looking at this in too simplistic of a way, but it seems that if scientists already know that PWPs have a gut that is very low in prevotella bacteria and they also know that many symptoms may be related to the lack of prevotella bacteria, then why don't they make a synbiotic that has the prevotella and other deficient gut bacteria to try it in studies. Healthy people already have these bacteria in their guts and it helps to keep them healthy, so it seems like a fairly safe and straight forward way to find out if replacing the deficient bacteria will help or not! The other thought is just to go ahead with a fecal transplant. I think there are probably a few PWPs who might be willing to try a fecal transplant of the deficient bacteria.

ncbi.nlm.nih.gov/pubmed/294...

Art

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Of course, we have a logical basis that we must verify, it will not be short or easy or maybe yes, but never in the history of the discoveries it was. Here in Italy we have had governments saying that it is the sun that goes around the earth, etc., but it was not true. Times have changed, but the logic of power is not much.Often we have these big multinational companies that have to make profits otherwise they will make Kaput (the German word non-randomly), and marketing is their job: is create a demand and satisfy it ; is easy in health. How to blame them? you do not want to increase unemployment? :-).

In other words, they will never do it. (I intend a search on the supplements).

Simplicity?

You would also tell him about the pennicilina and yet if we are all alive after the influence, we should give it a mold also found on a melon, but above all to A. Fleming that with his intention and observation gave us the antibiotic; he was looking for it ,was not all a case , believe me.

The point of view is whether it works is true or as the doctors say a criterion "ex juvantibus" : the applied treatment has worked.

Definition:

Ex juvantibus or ex adiuvantibus is a Latin phrase that literally translates as "from the joys". In medicine we talk about "criterion ex juvantibus" to indicate a diagnosis supported by a time of remission of the pathology following a given treatment.

Conclusion: I can verify it, it is not difficult, you gave me the map, there are indicators that they will tell us if we are on the right path, we will reach the goal, I do not know, but the foundation on which it is based is promising.

Art thank you for the help you are giving us. :-)

Gio

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Ah i almost forgot!

Now I'll tell you something a little mystical: if in point of the earth at random let's say in Tokyo, a man has an idea and is about to make a discovery, it is easy that another man on the other side of the earth we say to New York will have the same idea.

I'm joking, I do not know if it's true, but I'm expecting some scientists to soon work on this thing here and there on earth, we would need it so much.Let’s hope.:-)

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The only problem with such studies is the facts can be possibly misleading. A chicken before egg dilemma - Is the slowing down in peristaltic movement causing the imbalance and population differences of bacteria type - Or are the imbalances in bacteria numbers causing the peristaltic motions to slow down?

Treatment through taking in more live bacteria food (or fecal capsules) is unlikely to work or last for long; until the Environment of the gut has changed and sustains a good balance in more speedy/relevant movement in peristaltic motion subject to the functions of each part of the digestive system.

I do wonder whether the use of Mannitol over a long period in time may induce damage in the gut tissues in some way ?

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Hi Beauxreflets,

Your thought here is true, but I am for simple and practical things.

I think the important thing is to remedy the shortcomings of any kind that then give a malfunction that becomes serious, it becomes disease.

This is why it is essential that the intestine must function properly to assimilate everything else and so be treated anyway ... Maybe.:-)

GioCas

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If Mannitol rebalances the gut one would hope weaning off it would follow once the correct balance in bacteria has settled in.

I have not tried it as yet, because at present I keep regular (and my leaky gut repaired last November) to the extent of being able to now eat any food types without getting any constipation (hope I have not spoken too soon ;) ) :)

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Do not worry, for my experience eventually thiamina HCL will fix everything :-)

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I eat quite a lot of veggies etc., and hopefully get enough VitaminB1 :)

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I think that replacing what bacteria is deficient is needed in order to instigate a workable treatment because the deficient bacteria are known to increase butyrate as well as help replenish the insufficient B-vitamins through normal bacterial interactions in the gut. Replenishing the deficient bacteria will result in increased butyrate production which is known to be lacking in PWPs and will also re-establish normal production of hydrogen sulfide H2S, which is decreased in PWPs, and in turn can help to repair the gut mucosa to help eliminate leaky gut and afford timely fecal transport. Since it is known that the gut microbiome is disturbed in PWPs as well as other disease states, trying to bring the gut microbiome back to, or close to, what is known to be a healthy bacterial balance as seen in healthy people, seems like a needed step toward reversing the disease process. Both butyrate and H2S are known to have neuroprotective effects, something that is definitely needed in PWPs.

It is already thought that the perturbed gut bacteria in PWPs contributes to the progression of the disease process and may actually start there and contribute to the misappropriation and adulteration of alpha synuclein.

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

An unbalanced gut microbiome always seems to have an unhappy ending for the person who owns it, no matter what the disease is!

Art

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Thanks for sharing the link. I tend to agree with you, and I certainly think that getting the mucosal properties in the gut and airways 'lines of defence' into tip top shape, is vital in the fight against PD and as they say 'Every little helps' :)

I wonder whether mice have the same bacteria in their gut as humans do, as I suspect there is a lot more work to be done in pinning things down so that misfolded alpha synuclein end up where they ought to be!

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Apparently whatever bacteria balance confers PD symptoms in mice, transferring those microbes to non PD symptom mice will bring on the PD symptoms in the formerly symptomless mice.

I feel that scientists are relatively close to unraveling that puzzle, but the funding for those needed studies may be far from adequate. I think that fecal transplants may be the most practical way to find out while using the least amount of available funding.

Scientists know what a healthy microbiome should look like, so it shouldn't be too hard to determine a good donor from a not so good donor.

Figuring this out in terms of PD, will go a long way in the research of other major diseases so I can see where there will likely be resistance to the idea.

It's looking more and more like the gut is determining a lot of what happens in the brain than was previously thought.

When they take the gut bacteria from PWPs and transplant it in germ free mice, the mice develop PD symptoms whereas when they take the bacteria from healthy people and transplant it to those same mice, they do not get PD symptoms!

neurodegenerationresearch.e...

Art

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Yes!!!

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Butter apparently.

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FYI !!!

Clostridium butyricum: from beneficial to a new emerging pathogen: sciencedirect.com/science/a...

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dadcor,

Here is a quote from that study:

Whereas non-toxigenic strains are currently used as probiotics in Asia, other strains have been implicated in pathological conditions, such as botulism in infants or necrotizing enterocolitis in preterm neonates.

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Yes, I think most people are going to want the "non-toxigenic" strains as would be found in commercially available probiotics. Many gut bacteria families have good players and not so good players from the same family of bacteria........hmmm, sounds just like people!

Art

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So this deficiency of Prevotallaceae bacteria seems to have multiple negative effects on PWP's. It reduces production of thiamine. It reduces production of small chain fatty acids of which butyrate is one! It reduces production of hydrogen sulfide, a neurotransmitter gas in the human body that has shown to have many positive effects in more recent studies. In high doses it can be fatal, but in very low doses as produced in the body, it is a potent antiinflammatory and neuro protectant as in it can help protect dopaminergic neurons. There have been recent papers and studies suggesting that H2S may be very beneficial for PWPs. The fact that the deficiency of the prevotella bacteria equals decreased production of H2S seems like a clue!

Deficiency of prevotella does not stop there though, because it also means decreased vitamin production in the gut such as some of the B vitamins other than thiamine/B1. It also means that the decreased H2S results in constipation and increased gut permeability which is common in PWPs. The increased gut permeability/leaky gut in turn leads to toxins and bad bacteria going to places in the body where they shouldn't be......that can't have a good outcome!

A quick search of PubMed for "hydrogen sulfide Parkinson's disease", retrieves 121 results. Without going into a bunch of quotes and links, suffice it to say that not enough H2S is very detrimental to PWPs and sufficient H2S is healing! The effects in the human body are nothing short of amazing! Here is a link to the 121 results, you be the judge!

ncbi.nlm.nih.gov/pubmed/?te...

Since H2S is a gas, and a stinky one at that because it smells like rotten eggs, some studies have used test animals to inhale so many parts per million or billion per day. I imagine that may be an easy way to target the brain. Here is a brief abstract that discusses some of the actions of H2S:

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Mol Neurobiol. 2017 May 23. doi: 10.1007/s12035-017-0617-0. [Epub ahead of print]

A New Hope for a Devastating Disease: Hydrogen Sulfide in Parkinson's Disease.

Cao X1, Cao L1, Ding L1, Bian JS2,3.

Author information

Abstract

Hydrogen sulfide (H2S) has been regarded as the third gaseous transmitter alongside nitric oxide (NO) and carbon monoxide (CO). In mammalian brain, H2S is produced redundantly by four enzymatic pathways, implying its abundance in the organ. In physiological conditions, H2S has been found to induce the formation of long-term potential in neuronal cells by augmenting the activity of N-methyl-D-aspartate (NMDA) receptor. Likewise, it also actively takes part in the regulation of intracellular Ca2+ and pH homeostasis in both neuronal cells and glia cells. Intriguingly, emerging evidence indicates a connection of H2S with Parkinson's disease. Specifically, the endogenous H2S level in the substantia nigra (SN) is significantly reduced along with 6-hydroxydopamine (6-OHDA) treatment in rats, while supplementation of H2S not only reverses 6-OHDA-induced neuronal loss but also attenuates the following disorders of movement, suggesting a protective effect of H2S in Parkinson's disease (PD). Remarkably, the protective effect has been extensively demonstrated with various in vitro and in vivo PD models. These suggest that H2S may be a new hope for the treatment of PD. Further studies have shown that the protective effects can be ascribed to H2S-mediated anti-oxidation, anti-inflammation, anti-apoptosis, and pro-survival activity, which are also summarized in the review. Moreover, the progresses on the development of H2S donors are also conveyed with an emphasis on the treatment of PD. Nevertheless, one should bear in mind that the precise role of H2S in the pathogenesis of PD remains largely elusive. Therefore, more studies are warranted before turning the hope into a real therapy for PD.

KEYWORDS:

Anti-oxidation; Brain modulation; H2S donors; Hydrogen sulfide; Parkinson’s disease; Protective effect

PMID: 28536975 DOI: 10.1007/s12035-017-0617-0

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As you can see H2S is a very potent gas signaling neurotransmitter and while it does look likely that it would be very beneficial for PWPs, human studies for H2S and PD are still lacking. Plenty of rodent studies though. There are ways to help your body produce it naturally such as a more vegan type diet, but let's not forget how we got here from starting out talking about mannitol. All these supplement shortcomings in PWPs seem to point directly at a lack of Prevotellaceae bacteria. Rather than trying to replace each of these missing or deficient supplements, wouldn't it be more useful and effective to see if replacing the prevotella bacteria can resolve some of these issues? Failing that, a fecal transplant from an ultra healthy donor?

One problem with H2S is that it would be very difficult to try to deliver to the body in the right amount at the right time and in the right place. When it is made in the gut by the proper bacteria, those three problems go away. It takes such small amounts of the rotten egg gas, H2S, for it to do its jobs, it would be very hard to try and replicate what the body does to deliver and control H2S, so I feel that it may be more beneficial and realistic to try and replace the proper bacteria in the gut along with a prebiotic like mannitol.

Art

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Here are a couple of studies and an article that are helpful as regards H2S and PD. In the first study, H2S was delivered to the mice through inhalation of the gas, but that could be problematic for human delivery to control the delivery amount and rate to an optimal level without delivering too much. It is a dangerous gas if the levels become too elevated. Again pointing toward attempting to replace the deficient H2S producing bacteria as a more realistic approach.

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

This second study looks at the potential of H2S releasing L-dopa derivatives. Given the length of time that they have been trying to develop H2S releasing NSAIDS for market, this one seems like a long shot at best.

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

This last study looks at the effects of long term inhalation of very low dose H2S by humans in an area with H2S naturally occurring in the air due to previous volcanic activity. While likely to be helpful for PWPs, not very practical as a large scale treatment for PWPs.

scienceofparkinsons.com/tag...

Art

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In this study, scientists took mice that over produce apha synuclein and gave them bacteria orally from PWPs which worsened the physical impairments of the mice compared to bacteria from non PD people which did not.

cell.com/cell/fulltext/S009...

Art

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In this case , scientists are very close to a conclusion. Why their pace so slow? Big Pharma Conspiracy theory? Donot think so.

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I imagine it is a big jump to go from mouse to human studies and of course there are probably many more regulations and standards for the human studies. Just the design of the study can probably be quite intensive, but it sure seems like there are plenty of clues about what those studies are likely to show if/when they are ever done. I'm thinking there will be many companies generally inside the medical community that would be very resistant to those human studies and would be quite happy if they never occur.

Art

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hi Kia

not necessarily, but bigfarma works to get profits and marketing is the way they do it. Marketing is "creating or discovering a demand and satisfying it". They are already in possession of parkinson's drugs with which they make profits. Why push something else that does not give the same certainty. No manager will ever risk his place.:-)

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In a study I was reading yesterday that was talking about gut health, they mentioned the often quoted fact that PWPs have a gut that is low on the bacteria Prevotellaceae and discussed the implications of this defiency.

Here is a quote from that study:

The under-representation of Prevotellaceae diminishes the levels of health-promoting neuroactive short chain fatty acids (SCFA) and the capacity for biosynthesis of thiamine and folate (Arumugam et al., 2011), which is in line with decreased levels of these vitamins in PD patients (dos Santos et al., 2009; Luong and Nguyễn, 2013).

Here is a link to the full study:

sciencedirect.com/science/a...

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It made me wonder if this lack of Prevotellaceae gut bacteria and its effects on thiamine

might be a factor in different responses to Dr. Costantini's thiamine protocol?

Art

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As far as I could understand from what Costantini says in his second part interview on you tube, thiamine acts on multiple organs, at different levels (both energetic and in strii ways) for various neuro-degenerative diseases, maybe even these intestinal mechanisms are interested, but I think this vitamin b1 has more features.

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He told me that it (thiamine) will often be very helpful for diseases that have fatigue as a major symptom........well at least as far as relieving fatigue goes.

Art

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More than a symptom, as a common denominator of neurodegenerative diseases that may have something to do with b1

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perhaps in theory, but here are several success stories that make the difference between the b1 and the rest. Sorry

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Oh definitely, Dr. Costantini has proven B-1 as beneficial by giving to hundreds of PWPs.

Art

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One question about Prevotellaceae and similar. is it possible, according to you, to restore these microorganisms in the human intestine with a special diet and the use of specific probiotics? it would be an easy way to do it, if you ... what would the indicators be working? (type of intestinal gas increase, or other)?

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I haven't seen any human research where this has been attempted.

Art

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Art,

Thank you, I will be a pioneer :-(

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Let us know how you do!

Art

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I bought this will arrive late April:

iherb.com/pr/Advanced-Ortho...

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I've seen that one before and it is a popular one. That seems like a very long time to get your order! The drawback to ordering probiotics on line or even from the store is that once the weather warms up the bacteria in the capsules can be exposed to very high temperatures inside the truck during shipping. These are live bacteria and excessive heat can kill them!

Art

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😂😂😂 it's spring, if it saves a couple then they'll have children :-)

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thank I have also the plan B, after i explain you , now i am to close shop

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Plan B is to change the diet so that it is very favorable to the development of these bacteria that you indicated in the previous posts, so I needed to know what were the indicators of the body that say we are on a good road. I'm studying the diet.

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Hi Gio Cas. Any improvement with the ''Advanced Orthomolecular Research AOR, Probiotic-3s'' above? Thanks

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The difficulty lies in attributing the right cause to an effect, having the parkinson among the no motor symptoms I had major intestinal problems up to vomit.The 90% of these intestinal problems have been solved by thiamina hcl but there were still some episodes of constipation for changes in temperature at work (cold room for flowers) that has been brought to zero episodes in the last two months used this probiotic I use probiotic-3 etc .. because I've put the post of Art and much better than other common lactic ferments that you find in the pharmacy, but there are other good ones, ask to Art. Gio

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Well if you are able to get butyrate and H2S production back on track with the right bacteria assortment and prebiotic, these are both highly potent antiinflammatories and should start to reverse the disease process, which should be quite noticeable!

Art

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Here is something interesting to the Gestalt comment below.

you should read the Gestalt comment below in this post to understand what I intend to do

forums.phoenixrising.me/ind...

I will go to use this in the manner described above by Gestalt

La Migliore Farina Di Banana Senza Glutine (454g) amazon.it/dp/B0781SVDV7/ref...

very easy do you think?

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Okay, I experimented with resistant starch many years ago when it was all the rage. I was never able to notice any change from it except for the gas, which was through the roof! It was so much gas that it was just ridiculous! I couldn't go out in public it was so bad and it had a mind of its own not too mention the smell! Definitely made me think that fecal transplant might be a good way to go, but even those are noted for initial gastrointestinal distress!

I think what he is describing is correct in that taking it earlier is also likely to mean that you will have more butyrate available by the time you go to bed, assuming that you have enough of the appropriate bacteria present to interact with the resistant starch. I think resistant starch just sitting in the gut while sleeping might be less effective as he seemed to say.

Art

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eh yep yep yep, if you do not have a destination, what do you do with a map. That of arranging the intestine and only the first part of the plan B. It is obvious that if the intestine is not in place it does not assimilate correctly and will cause deficiencies. So any supplement to give results needs a healthy gut, with all the microbial flora in place or not?

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An easy to read article discussing the gut microbiome of PWPs and some missing and over abundant bacteria issues common to PWPs and how they impact on disease activity.

realnatural.org/parkinsons-...

Art

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Of course, if I could find a probiotic on the market with a prevotellace bee inside it would be easier for all.But I dont find it.

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Look at this list of bacteria that are either over abundant or deficient in PWPs.

ncbi.nlm.nih.gov/pubmed/284...

Prevotella is a big one, but not the only one!

Art

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ah! good.

thank you Art!

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After reading the very brief article link below where scientists were able to improve Alzheimer's patients test scores on the MMSE questionnaire in just 12 weeks through the administration of very common probiotics, which is unheard of for AD, it does not seem like much of a stretch to think that probiotics or fecal transplants may be quite useful for PD also!

sciencedaily.com/releases/2...

ncbi.nlm.nih.gov/pubmed/297...

Art

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I wonder if soy lecithin plays a practical role with fatty acids. What do you think about it?

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I think soy lecithin has health value......well at least the granular type as opposed to the soft gel caps and definitely Non-GMO!

I have used lecithin as an effective means to lower cholesterol.

I think lecithin can aid in the repair of damaged myelin sheathing, which could likely be useful in neurodegenerative diseases and MS.

Art

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eh! but if I have not misunderstood soy lecithin has the ability to make water-soluble fats, can it be useful?

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I'm not sure I am understanding your question? Lecithin can act as an emulsifier so it can potentially solubilize fats, yes.

Art

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yes

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Soy lecticitin, could it improve the availability of SCFA in the intestine?

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I'm thinking that lecithin may have an impact on the intestinal biome, but possibly with medium chain fatty acids. As far as interaction with SCFAs, I would have to read about it.

Art

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Good post, thank you! Butyrate can be synthesized by the right gut bacteria, but there is a novel supplemental source i saw recently by a company called Tessmed. The butyrate is encapsulated for organoleptic reasons (it smells and is bitter). I just purchased a bottle. Too soon to note anything yet.

Also a very well studied prebiotic is Orafti Inulin. Some good human and animal studies showing reduced inflammation at 10 grams per day. Looking at USA fiber intake, we consume ~11-13 grams daily with an RDA of 35 grams. Early man consumed upwards of 100 grams daily from plant (not grain) fibers which would make for an amazing microbiome. However, I wouldn't suggest increasing intake to that level of consumption abruptly. In addition to that level of fiber, the plants also contain an abundance of antiinflammatory phytonutrients.

Another potential use for mannitol is that it transiently increases the permeability of the blood brain barrier which can be a double edged sword depending on what's in your blood. Some physicians administer it with stem cell treatments.

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Jandeb,

Thank you for saying so!

Yes, some fiber, like resisitant potato starch and prebiotics like mannitol and xylitol are well noted for their gas producing effects. This is why the guy who developed the Syncolein mannitol product added the alphagalactosidase (Beano) to it to try and calm that effect. Xylitol is noted for being one of the better butyrate producing prebiotics, more so so than the more common prebiotics, FOS and GOS.

' 100 grams daily ', wow, that's a lot!

Please keep us posted on your results!

GioCas did well with his butyrate producing bacteria probiotic/mannitol combo!

Art

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I always try something that increases organ function from a practical point of view, this probiotic added to prebiotics as mannitol xylitolo increases a lot of intestinal activity.Restoring intestinal function is the basis of a proper assimilation of each subsequent supplement. it's worth it.

Thank Art for this map about probiotics and prebiotics. GioCas

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Hi Art

I have been using Mannitol for around 4 months. I want to take some probiotics as well which has Butyrate and in general those good for PWPD.

Please can you send me links where I can get some.

Many thanks

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This is the one that Gio used to good effect:

amazon.com/Advanced-Orthomo...

It has the clostridium butyricum in it which is said to interact with prebiotics like mannitol or xylitol to create butyrate.

Art

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Thank you

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Art

Dose the Butyrate produced as a result of clostridium butyricum have the same effect as β-hydroxybutyrate that is a metabolic constitutes of ketone bodies produced during ketosis?

Thanks

Kia

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Kia, they are different from each other, but apparently they may have synergy together according to this recent review:

hindawi.com/journals/jnme/2...

Art

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Thank you Art

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In my opinion, in this type of research it is better to point to something that restores the function of cellular life or of an organ like the intestine that does not repair a structure or add to the body a substance or final product. The restored function will produce everything necessary for life. Behind the Life we ​​see there are millions of years of evolution and millions of "experiments" already made, a great deal of knowledge.

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I was given Mutaflor by my integrative GP straight away. Quite expensive though.

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Kia,

Were you able to get the AOR probiotic and if so, have you been able to test it yet?

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Hi Art

I have tried AOR probiotics and it works amazing . Started around 10 days ago seeing its benefits from early days.

Thanks very much to you and Gio

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Hi Kia,

GioCas mentioned that it worked very well for him and you say, "it works amazing". Can you explain what you think it does for you?

Thank you!

Art

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Hi Art

As I was guessing and according to the study you sent me earlier the AOR probiotics 3 TRULY has a synergy with BHB that I have been taking during intermittent fasting from pure C8 MCT oil and organic butter and Ghee butter as well as taking good prebiotics ( Mannitol and Green vegetables) . They all help me with improvements in my non- motor symptoms including feeling better in general , more energetic, better sense of smell, Much Better mental and physical performances. However it has created some constipation in comparison with days before I started the probiotics ,but I can deal with the constipation with taking more fluids and magnesium.

In general I am quite happy so far. I will update again in a week time.

Thanks again

Kia

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Thanks for that , Kia!

I am glad that it is working well for you and perhaps the additional magnesium will be additive!

I look forward to your update!

Btw, Dr. Costantini answered your question regarding thiamine intramuscular or oral dosing and it now appears as question and answer #42 on the thiamine FAQ page!

Art

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This fairly recent mouse study suggests that xylitol may help increase the Prevotella bacteria in the gut. Perhaps xylitol may be a better prebiotic for this purpose than mannitol which has not been shown to increase Prevotella bacteria....at least not yet?

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

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Art, I will soon make an update on the use of probiotics and prebiotics but I can already say that they work very well and even in the absence of PD. Much more than I expected. I changed the mannitol with xylitol because the manitol does not seem a good thing, sorry if I say, others will benefit but I do without it. I think mannitol is to much strong for my cellular life and so I replace with Xylitolo.Another piece of knowledge about human health completely neglected by traditional medicine.

bah! an old story.

Thank you Art for bringing this knowledge to PwPs here on HU.

Gio

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Gio,

I anxiously await your probiotic / prebiotic update!

Art

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I wil do soon :-)

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In PD mice, it appears that fecal microbiota transplantation is a viable option to help rebalance the perturbed gut biome , protect them and reduce symptoms according to this PubMed abstract:

Brain Behav Immun. 2018 May;70:48-60. doi: 10.1016/j.bbi.2018.02.005. Epub 2018 Feb 20.

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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I've recently changed mannitol with xylitol and it's better for me. But one thing that helps a lot of intestinal function is cold rice three times a week plus probiotics.

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