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.
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!
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.
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.
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!
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.
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!
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
• in reply to
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.
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!
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.
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.
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.
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 ?
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 )
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.
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!
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!
1) These are mice engineered to be predisposed to get PD: they overproduce alpha-synuclein.
2) Did you see THIS? It's from the article you cited. It seems to contradict your idea that short-chain fatty acid (SCFA) supplementation is good for people predisposed to PD.
"Indeed, when germ-free mice were fed SCFAs, cells called microglia–which are immune cells residing in the brain–became activated. Such inflammatory processes can cause neurons to malfunction or even die. In fact, germ-free mice fed SCFAs now showed motor disabilities and αSyn aggregation in regions of the brain linked to PD."
3) Still, this is astonishing:
"In a final set of experiments, the researchers obtained fecal samples from patients with PD and from healthy controls. The human microbiome samples were transplanted into germ-free mice, which then remarkably began to exhibit symptoms of PD. These mice also showed higher levels of SCFAs in their feces. Transplanted fecal samples from healthy individuals, in contrast, did not trigger PD symptoms, unlike mice harboring gut bacteria from PD patients."
Yes, It is a mouse study , but in humans butyrate has shown the ability to help repair a damaged gut and act in an anti inflammatory manner, both important characteristics for humans with a damaged gut biome which is very common in PWPs.
Very interesting! I'm considering trying mannitol for tremors. How do you know how much to take and how do you counter the excess gas it causes? Thanks
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.
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
• in reply to
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!
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:
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.
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
• in reply to
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.
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.
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.
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.
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.
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.
• in reply to
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).
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.
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.
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)?
I haven't seen any human research where this has been attempted.
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!
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.
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
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!
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.
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?
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.
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!
Soy lecticitin, could it improve the availability of SCFA in the intestine?
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.
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.
Jandeb,
Thank you for saying so!
Yes, some fiber, like resistant 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 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!
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
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?
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.
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.
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
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?
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
Gio,
I anxiously await your probiotic / prebiotic update!
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:
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.
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.
The cold rice is a resistant starch which is generally considered quite healthful.
Art
So it is already known that mannitol and xylitol among many others are able to improve butyrate levels which is good for PWPs for multiple reasons such as its anti-inflammatory effects in the body, neuroprotective effects, the ability to act as a histone deacetylase inhibitor and its gut healing effects as a partial list of some important effects of butyrate.
In a study I was reading it was pointed out that butyrate is also a GDNF/BDNF/NGF agonist and there have already been plenty of posts on this forum discussing the value of GDNF as it relates to PD! Butyrate, unfortunately is generally diminished in PD so you can see why mannitol and xylitol may be useful supplements, especially when combined with bacteria that is known to help increase production of butyrate and other short chain fatty acids. This just adds one more health benefit to the growing list associated with improved butyrate status in the gut of PWPs!
Yes, Unfortunately the prevotella bacteria family have not been found in any probiotic so far, but it appears from at least one study that the prebiotic xylitol may help to induce production.
According to some studies, mannitol may not be digested easily and might cause gastrointestinal issues lower down in the colon. You have mentioned this and suggested ways around it, but a much better way to reduce inflammation - both in the body and the brain - might be cutting back on omega-6 and increasing omega-3. The ratio of these has gone completely bonkers in the modern diet, and this is probably the first thing to do.
Taking one or more antioxidants capable of traversing the blood-brain barrier, such as fisetin, is also a good idea. Eating a cup of blueberries every day is also a fantastic idea.
You mention a second advantage of mannitol is an increase in butyrate. It might be better to increase butyrate the natural way by increasing your fiber, preferably with a whole-food plant based diet full of veggies, fruit, nuts, and other foods that are no more than lightly processed. If you do this, you are likely to develop a healthy biome, heal any "leaks" in your gut wall by naturally cultivating bacteria that will generate butyrate, etc.
Probiotics may help some people who have messed up gut biomes, but there is a down-side to them and I think they shouldn't be taken long-term. For example, if you're coming off of antibiotics, it might be useful short-term until you've built your biome back up. As you've mentioned, there are probiotics that include bacteria that produce butyrate etc. and that might be good in these cases, but only short-term.
But if you've been eating as I described above and you've developed a diverse gut biome, you probably shouldn't be taking any probiotics, because you're probably giving your gut repeated mega-doses of different bacteria than what is it has naturally developed. In other words, if it ain't broke, don't fix it. And if it is broke, a better way to fix it might be the natural way as I've already described.
Probiotics have a reputation for not causing harm and being safe. But, as I say, there is a downside and a bit of a risk that everyone thinking of taking probiotics long-term should be aware of. nutritionfacts.org/video/cu...
JerMan22,
Mannitol is a prebiotic and is digested by fermentation resulting in increased butyrate.
You are correct in the general population, however on this forum and other similar forums, we are specifically dealing with a group with damaged guts as the norm and in this post, specifically with the use of mannitol by quite a few members and non members. I posted this specifically to try and shed light on why there seems to be such variation in the results that PWPs are getting with mannitol, hence the title of the post. I am a firm believer in the use of prebiotics, probiotics, synbiotics, fermented foods and similar food items with useful bacteria. I also believe there is tremendous potential in fecal transplants. All of this based on current knowledge from available studies which continue to grow on a daily basis as you can see from the multitude of links above.
I understand, and I appreciate everything you're doing for PwP. My dx was 2010, so I've been living with PD for 8 years. In addition to many other PD symptoms, I had constipation for the first 3 years. I became vegetarian (nearly vegan/WFPB) and it went away never to be experienced again - I hope. I've been looking into gut biome issues ever since.
My point is that, at least for me, WFPB works. My digestion is great. I enjoy a diverse variety of super-nutritious foods, and I encourage others to try it. Some might not be able to. Those who can do it might find a solution to some of their symptoms.
I wonder if the messed up gut biome comes from having PD, or if having a damaged gut biome contributes to getting PD. I suspect that the gut issues pre-date and contributed to contracting PD, so I consider healing my biome to be an important step towards healing my PD.
Based on my experience, it is possible to repair the gut biome after getting PD and I hope that others will try.
I often wonder about that also. I think people assume that the gut is first because they may experience issues like constipation for many years before what they later learn were early symptoms of PD. It seems like it would be difficult to study it though.
My gut must respond to butyrate as it creates gas enough to fuel an engine! My daughter refers to my swollen belly as “the baby”. I’m past child rearing!
The mannitol is well noted for that "special effect"! Have you tried the alpha-galactosidase to help offset this issue? It is what they add to the mannitol based Syncolein product and also the active component in Beano. The best deal I have been able to find for it is the Walmart house brand that is half the cost of Beano and twice as concentrated.
Another possible way to deal with the gas is by mixing your mannitol in a 500 ml bottle of water and sip throughout the day to give a slower release and reduce times of high concentration.
Having the h2s and the butyrate together is a good thing and they are both naturally occurring in a healthy gut environment. The h2s has potent anti inflammatory effects as does the butyrate and the butyrate has the potential to help heal a leaky gut and together they can help to protect the brain as well as lower the total inflammatory load and consequently reduce excess oxidatative stress, all important things in many disease states.
It's true that h2s is generally anti-inflammatory, but the video quotes the report:
"The toxic effects of sulfur reducing compounds, particularly hydrogen sulfide, at concentrations commonly found in the lumen of the human colon appear to be mediated through impaired utilization of butyrate by colonocytes."
The video is saying that levels of h2s in the "lumen of the human colon" is "commonly found to be" too high and it may "play a role in inflammatory bowel diseases" and "impaired utilization of butyrate". Reducing the amount of Methionine in our diet should help this imbalance.
Amazing information - thanks for sharing your knowledge. It's a bit over my head, I confess, so I will ask my simple question for your advice....I have before me an unopened container of mannitol I ordered through Amazon, which came all the way from Israel. I gather that it MIGHT help me, but only if I have the right kind of bacteria in my gut. Should I give it a go? I do eat kimchi and yogurt along with my fairly decent diet of lots of veggies, and wholegrains, fish, meat, and cheese. Where I tend to fall down is with my addiction cookies, cakes and pastries, espcially if they involve chocolate.
Given the results that some people have gotten from taking mannitol and a relatively good safety profile, if it were for myself, I would try it to find out if I was one of the fortunate ones who respond well to mannitol.
The reason I wrote much of the above was just to offer a possible reason why not everyone seems to have a positive response to mannitol. By testing the mannitol, what do I stand to lose compared to what do I stand to gain?
Hi Art, I was reading your posts which detailed the benefits of clostridium butyricum. I also read that probiotic strains in Asia have this strain and that it has been approved for use by the ministry of Health, Japan and hence quite readily available. Failing to find anything other AOR probiotic 3, I found a Japanese brand on eBay- miyarisan strong tablets of clostridium butyricum. Has anyone tried?
Since they are the originators of the product I reckon they hv more experience and knowledge. What do you think?
I have been giving my husband a generic probiotic and now have zeroed in on this specific one after reading yr posts.
Thanks for all the work you hv done keeping all of us informed.
Millbrook,
Gio is the one who actually tried it and he seemed to feel it helped him significantly. I believe Kia17 may have also tried it, so they may be better able to give you information on it.
It would be nice if the Japanese manufacturer would share information in the way of studies and patient results. I am of the mind that Fecal Microbiome Transplants (FMT) are actually the cheapest and fastest way to find out exactly what altering the gut microbiome can do for PWPs and apparently there may be a study or two in the works, but nothing definitive yet.
Part of the problem is that probiotics only contain milligrams of living bacteria whereas our gut biome bacteria are measured in pounds or kilos. At the cost of some of these more expensive exotic synbiotics it would be cost prohibitive to take in quantities that might effectively alter the gut biome enough to alter the course of a disease in a meaningful way. I feel the probiotics are not able to provide the bacterial diversity or quantity that is truly needed in order to normalize out of balance microbiomes whereas FMT potentially has it all, the right quantity and diversity and if it works, it usually works very quickly. I do believe that probiotics in the right amount and the correct diversity could do a lot to improve the gut biome, but not as easily or as fast as FMT. So I continue to look and hope for those FMT for PD studies to move forward and answer these burning questions!
Here is a link to a probiotic / Alzheimer's disease article about a study that showed positive results in just 12 weeks in AD patients. Note in the article that they only used 4 very common bacterial strains, but to me what is really interesting about this study is the amount of probiotics (1.6 trillion per day) that were used and I believe this to be a very good clue about the quantity of bacteria that are minimally needed in order to effect a significant change for the better in our gut biomes. Also interesting in this study was the other positive health effects offered by this probiotic combination!
Sadly, Art has left the forum. He put up a farewell post under the name Safetyfirst. That post still exists but it now shows the name as "hidden" just like this post which is what happens when a member deletes their profile. Here is the link to the post.
OMG! Where have I been under a rock! I started a new job and lost touch. I am so saddened to see him go and everything that I have read. Thank you so much for letting me know. He will be missed!!!
It's been a few years, so I thought it might be time to update this post on Mannitol which was discussed extensively in the original post at the top of this thread and in the thread itself.
The following Psychology Today article linked to below is not specifically about Mannitol or PD, but it does seem to further explain how mannitol, a prebiotic can be of use in PD in an indirect way. The gut microbiome in PwP is frequently imbalanced toward pathogenic bacteria and mannitol is known to act as a prebiotic that can help alter the gut microbiome toward less pathogenic bacteria and a more diverse microbiome that can be more conducive toward butyrate and hydrogen sulfide production, two very useful and healthful molecules that are insufficient or deficient in PwP.
In that same line of thought, melatonin is also shown to increase the microbiome diversity which would be very useful in PwP who are known to have diminished gut microbiome diversity. Melatonin has also shown benefit in terms of having gut protective and gut antiinflammatory activity. These combination of effects by mannitol and melatonin (m&m) as well as their downstream indirect effects would seem highly likely to be useful for PwP. This combination of events is also likely to improve sleep and improved sleep is also thought to have a positive effect on gut microbiome diversity that is less pathogenic in nature, which again would be considered useful for PwP.
Based on this article and other studies, m&m seems likely to be beneficial for PwP overall and likely to improve the gut microbiome in ways that could have far reaching unsuspected health effects.
To me this seems like two major pieces of a puzzle that offer significant potential for improvement of the underlying pathology via increased butyrate production, increased production of H2S, inhibition of Histone Deacetylase (HDAC i), reduction of gut and cerebral inflammation as well as significantly increased antioxidant and radical scavenging activity body wide and these known benefits of m&m are showing very substantial health benefits in combination against PD! Here is a link to the PT article :
The following two links discuss why HDAC inhibition is important for PwP, a subject that is rarely discussed, yet is likely another major piece of the puzzle that gets little, if any attention :
I forgot to mention that all of these PwP benefits are in addition to what is already considered to be the standard benefits of Mannitol and Melatonin for PwP.
Yes I do. The melatonin helps me sleep longer. Mannitol in the morning , B1 in the afternoon and Melatonin at night are my 3 consistent go to's. Also taking a quarter of a teaspoon of mucuna during the evening.
Now that this Fecal Microbiome Transplant study is done in PwP, I am adding the link to this thread because it tends to confirm much of what has been discussed throughout this thread and adds further confirmation to the idea that PD is very strongly affected by the gut bacterial balance which can either exacerbate or improve PD.
This is a copy of a reply I made to forum member Rebtar, but is very relevant to this thread and gives further reasoning on why mannitol may not work for all PwP and the main reason still looks like lack of butyrate production and the following explains why and is also an explanation for why it works at all. Mannitol is thought to reduce clumping of alpha synuclein in the brain and is the usual reason suggested for its use in PwP, but this seems more like a longer term effect that might not be so readily apparent in early use.
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There is concern about the idea that mannitol can increase the blood brain barrier (BBB) permeability but this effect of increasing permeability of the BBB by mannitol is short lived as in 10 minutes or less.
Such a short window of opportunity makes me think that the actual benefit of mannitol is due to increased butyrate production and other Short Chain Fatty Acids (SCFAs) leading to reduced inflammation of the gut microbiome and a possible reason that mannitol does not help all PwP is because some PwP no longer have enough of the specific gut bacteria that mannitol interacts with to increase production of butyrate, hence no increased butyrate production and no benefit in terms of symptom relief.
Butyrate has also shown to decrease intestinal permeability, which is increased in PwP.
Previously in this thread I mentioned that some PwP may not respond positively to mannitol because they have insufficient amounts of the bacteria that can react with mannitol to produce the short chain fatty acid, butyrate. PwP are known to be deficient in these butyrate producing bacteria.
In my search to find foods that are high in fiber and that I actually like the taste of and could potentially eat for the rest of my life, I found pistachios to meet these requirements. Sure, there are plenty of high fiber foods that you can eat, but if the taste is horrible to you, are you very likely to eat it for the rest of your life? Just trying to be real here.
In reading about pistachios, I came across the following study that shows that aside from pistachios being a high fiber food which can be beneficial for human health, pistachios also increase gut bacteria capable of producing butyrate and can modify the gut biome in beneficial ways! I really like pistachios and can see myself eating them everyday! Win, Win, Win, Win!!! Here is a link to that study:
When you combine the information from this study with the fact that PwP are low in butyrate as well as butyrate producing bacteria in their gut, you can see that pistachios may be a seed/nut that PwP can use as a health promoting snack that is likely to go very well with mannitol usage because mannitol works with butyrate producing bacteria in your gut to produce more butyrate and possibly correct this very important deficiency in PwP !
Butyrate is a predominant short chain fatty acid (SCFA) and two other predominant SCFAs are acetate and propionate. The following study illustrates how pistachios increase SCFAs by 1.9 to 2.8 fold higher. Here is a link to that study :
>>> ' Fermentation of nuts resulted in 1.9- to 2.8-fold higher concentrations of SCFA compared to the control and a shift of molar ratios toward butyrate production. ' <<<
Acetate and propionate also are active SCFAs and propionate is known to be the lowest of these 3 SCFAs in PwP, but these 3 SCFAs are all lower in PwP, so it is important to fortify production of all three, not just butyrate. This is why supplementing butyrate is not likely to be as effective as increasing all 3 of these specific SCFAs in the gut. Pistachios seem likely to be beneficial toward health in general and PwP in particular due to pistachios ability to increase SCFAs as well as the bacteria that produce them.
Lastly and of significant importance, pistachios contain high amounts of melatonin compared to other food sources and this can potentially be a way for people to get larger and useful amounts of melatonin and avoid "the melatonin hangover" and get the benefits associated with higher dose melatonin. If you can take large healthful quantities of pistachios without issue, then you can get melatonin at higher more healthful doses and avoid next day drowsiness.
I just wanted to mention how I take my xylitol and this may apply to mannitol also. Each morning I take a 500 ml bottle of water and drink one third of the bottle. Then I put my 16 to 17 grams of xylitol granules in the bottle, replace the cap and shake the bottle until the xylitol is fully dissolved. Then I top off the bottle with either orange juice or Gatorade. The xylitol or mannitol sweetens the mix to just about make it taste like orange juice or Gatorade again. I sip this bottle throughout the day.
The reason I do it this way is because this is essentially making the xylitol or mannitol as an all day time release formulation and I think this can do two things. It is likely to help reduce any gas issues and I don't think the body really handles so much xylitol or mannitol very well all at once. I think you are likely to get a better effect from either one this way and it is easy to do. It doesn't seem likely that either one is going to stay around all day in your system at useful levels if you drink your entire daily dose all at once in a morning cup of coffee, yet having it stay around all day seems like it would maximize the benefit of your daily dose of either one. I notice if I take my full dose of xylitol all at once in the morning, I can get significant gas, but when I do it this way, there is never any gas!
As a basic comparison, think what would happen if you take your entire C/L daily dose all in one dose per day. Spreading it out as evenly as possible throughout the day seems like it would be the much more effective approach. It seems like they could formulate the liquid C/L in a watered down version that could be sipped throughout the day to get a more balanced release of C/L that might offer increased on time and a reduced chance for dyskinesia???
If you want to try to be a little healthier, you can probably substitute real lemon juice for the orange juice or Gatorade.
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