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!
Just some food for thought!