Could Butyrate Be Bad for PWP? (MIT Study)

[Madame-Mango]

Earlier this year (2021), I learned about the benefits of butyrate from different sources and studies, then started dietary measures to boost its production in my gut.

Shortly after, I came across a January 2021 report out of MIT that said the benefits of SCFA (including butyrate) have “opposite effects” (that is, negative) for people with Parkinson’s. Yikes!

So I was confused and conflicted about my course of action.

Art @chartist and others, you seem to have a keen grasp of the science and biology behind the mechanisms involved (which are above my pay grade). I’d be interested in your comments about the report. (I want MIT to be wrong : / )

EXCERPT from MIT News: To help researchers better understand the gut-brain axis, MIT researchers have developed an “organs-on-a-chip” system that replicates interactions between the brain, liver, and colon.

Using that system, the researchers were able to model the influence that microbes living in the gut have on both healthy brain tissue and tissue samples derived from patients with Parkinson’s disease. They found that short-chain fatty acids [SCFA], which are produced by microbes in the gut and are transported to the brain, can have very different effects on healthy and diseased brain cells.

“While short-chain fatty acids are largely beneficial to human health, we observed that under certain conditions they can further exacerbate certain brain pathologies, such as protein misfolding and neuronal death, related to Parkinson’s disease,” says Martin Trapecar, an MIT postdoc and the lead author of the study...

They found that for healthy brain cells, being exposed to SCFAs is beneficial, and helps them to mature. However, when brain cells derived from Parkinson’s patients were exposed to SCFAs, the beneficial effects disappeared. Instead, the cells experienced higher levels of protein misfolding and cell death.

Reported from news.mit.edu/2021/gut-brain...

(I couldn’t find a link to the source study in their report.)

[chartist]

M-M,

Good question! It is difficult if not impossible to create a simulator that can accurately replicate something as ultra complex as the human body and its multitude of functions and that includes just about any part of the body. In the case of that study, they are trying to replicate brain, liver and colon activity as well as the interplay between them. I'm not even sure that is even possible since we don't even fully understand any of those 3 components. Their idea is a lofty goal, but I am highly doubtful that they can replicate the activity of 3 major components of the human body as well as the interaction of those three in a simulator.

Just considering the gut microbiome in the colon, much knowledge has been gained in the last 15 years about what is going on in there and what that knowledge has shown us is that in truth, we still are not close to fully understanding the gut microbiome nor do we know all that much about the gut brain axis and the communication process between them. I won't even go into the idea that anyone really knows enough about the brain to accurately build such a device.

Here is a very basic example of why I think they may not have allowed for all variables when it comes to their simulator. If you have been reading much here on the forum of late, you are aware of FMT and the results of FMT in PwP, which were impressive. FMT tends to bring the gut biome back towards that of a healthy person with a healthy gut microbiota. Such a gut microbiome has very increased SCFAs which includes significantly increased Butyric Acid as outlined here :

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

Now keep that thought in mind and then look at the results of the 2021 FMT/PwP study as shown here :

healthunlocked.com/cure-par...

So what we see from these two studies in real people is that FMT increases butyric acid significantly in recipients of the FMT. In PwP who receive FMT they get better in terms of multiple test scores that are measuring non motor and motor symptoms in PwP with a 50% or more improvement in motor and non motor symptoms, as they have to in order for the test scores to improve, SIBO is significantly reduced as is constipation which both steadily improved right up to the end of the 12 week study.

If you know of any other adjunctive treatment that has done this much for PwP, please share what that is with us. The point of all of this is to show that FMT elevates butyric acid levels significantly and instead of causing damage in real people with real PD, it makes them better. Now based on these real results in real people with real Parkinson's disease who have a real liver, a real brain and a real colon, are you going to believe these real results in real PwP or are you going to believe the MIT team with impressive credentials and an impressive simulator that probably cost an obscene amount of money to design and build???

Let me think about that for a moment or two......

Art

[Madame-Mango in reply to chartist]

That's just the cogent argument I needed to carry on with my original plan. From what you laid out, it appears the MIT team IS wrong. (Yea!) Thanks, Art. Brilliant.

PS: I'm relatively new to the forum (starting in May 2021 = two months at this writing) and I'm blown away at the breadth and depth of knowledge among members. Learning lots. Thanks again.

[chartist in reply to Madame-Mango]

M-M,

Glad to hear that you like it here and belated welcome to the forum!

Art

[Bolt_Upright in reply to chartist]

Thanks Art. I'm not ready to stop my Niacin and Butyrate cocktail yet!

[Millbrook in reply to Bolt_Upright]

Bolt, the butyrate you mentioned -6 x2 =12 capsules- my only apprehension is the amount of calcium you get from the supplement -worried about calcification in soft tissues or bones.Incidentally the forum phoenixrising has got 65 pages on clostridium butyricum.

I have ordered butyrex. I will probably try 6 capsules first and 250 mg flushing niacin.

[Bolt_Upright in reply to Millbrook]

I need to go back and edit or delete my post. That guy doing butyrate 6 x 2 is self diagnosed. That is a very unreliable source and I'm sorry I shared it.

I am not following his recommendation anyway. I went with 2 pills 3 times a day.

I wonder about all the calcium also. And the magnesium. Not sure if I should keep taking my L-threonate magnesium.

And wonder if his brand was a good suggestion.

I'm really wondering if Butyrate is even a good idea after reading that our plasma level of butyrate is not low after all.

[Millbrook in reply to Bolt_Upright]

Hi Bolt,

Please do not delete that post. The article on the work done by Wakade and Chong on butyrate and niacin was very interesting. Even if that person who shared that post on what he took is self diagnosed it does not disqualify his experience. My husband has not been diagnosed but after 2 years on this forum I am sure he has it. He lost his sense of smell at least 10 years ago and he also has active dreams boxing in his sleep. Whilst B1 has helped some aspects I realised that he has slowed down quite a bit and he was prone to falls. Probiotic PS 128 brought about a great change- he can drive normally, more alert, reflexes faster and balance improved- which is really a blessing. Who would have known? Similarly for B1. So, yes I would try.

He is also using the coronet but red light takes some time before the benefits show and he has been on it almost 2 months now.

I have increased his B1 to 200 mg daily and niacin 250 mg. Also increased his Miyarisan to 5 tabs 3x a day. Ubiquinol 400 mg 2x with fish oil

PS 128 at bedtime 2 sachets

[Bolt_Upright in reply to Millbrook]

Thanks. You know I corresponded with Professor Chong and he told me his next trial will be to compare niacin versus niacinamide @ 100 mg twice daily (for a total of 200 mg / day). B3 is water-soluble, so they want to see if boosting B3 levels all day long may be of benefit. (I think his point is that B3 being water soluble does not stay in the body, so spreading it out should keep more available).

[Millbrook in reply to Bolt_Upright]

Thanks. I will spread out his B1 and niacin between breakfast and lunch.

[Hidden in reply to chartist]

TUDCA Phenyl Butyrate was combined for ALS with success. Dr. Rudolph Tanzi has spoken about this at length and in an interview mentioned it should be trialed for PD. I’m so confused and worried about the MIT study above. I take Butyrate and eat a diet to maximize it.

[chartist in reply to Hidden]

matcharoe,

The human body produces SCFAs, including butyrate with proven healthful effects. Like melatonin and vitamin D, SCFAs, including butyrate decline with age. With that age related decline, the onset of age related diseases, of which PD is one, take hold and gain momentum in terms of progression. The intimate interplay between melatonin and SCFAs also declines, increasing gut permeability, dysbiosis, inflammation and oxidative stress. PD progression is driven by oxidative stress and inflammation. The dysbiosis or imbalance of the gut microbiome is a definite problem in PD. In PD, the increased SCFAs in the blood is problematic. SCFAs do their good work in the gut through multiple means including interacting with melatonin to increase melatonin as well as melatonin receptors in the gut which melatonin, in return increases SCFAs in the gut. this is what is wanted and needed. Melatonin in conjunction with SCFAs help repair the mucosal gut barrier as well as improve the epithelial function, tight joint function and reduce inflammation and oxidatative stress in the gut.

These are processes that happen with Fecal Microbiota Transplants (FMT) and the result is decreased motor and non-motor symptoms as seen in initial trials in PwP.

I have always felt that supplementing butyrate in PD is not an optimal way to increase butyrate, because some of that butyrate is likely to end up in the blood, which apparently is not helpful in PD sometimes, based on multiple conflicting studies. Helpful in healthy people, but not fully determined in PD. I think it is better to try and stimulate SCFA production, including butyrate, in the gut of PwP. This is the way the body would normally do it, but in PD, SCFA producing bacteria are diminished and steps to increase natural SCFA producing bacteria are likely to be more useful than actually supplementing with butyrate. I think this is why it has been reported that butyrate supplementing in PwP, often shows little to no benefit, even at high dose, but increasing SCFA production, including butyrate, in the gut, has shown benefit as illustrated by the use of probiotic PS128 and one other probiotic that has been discussed on this forum. Unfortunately that is an expensive way to go.

I also believe the semi natural restoration of SCFAs and melatonin by FMT is a major reason for its effectiveness in two preliminary studies in PwP. For people who still have enough SCFA producing bacteria in their gut, increasing fiber and prebiotic intake may be enough to stimulate SCFA production.

You may find some useful information in this post :

pubmed.ncbi.nlm.nih.gov/216...

Art

[Bolt_Upright]

This is not a point or a counterpoint. Just something I was looking at when you posted Madame.

Plasma Short-Chain Fatty Acids in Patients With Parkinson's Disease

pubmed.ncbi.nlm.nih.gov/321...

[Madame-Mango in reply to Bolt_Upright]

Reading the studies is always interesting, if not confounding...🤔

[Bolt_Upright in reply to Madame-Mango]

Sad to say, but I get confused when they say X is inversely related to PD severity. Is that good?

[MBAnderson in reply to Bolt_Upright]

maybe - if controlling for X is possible. (It means the more X, the less PD.)

[MBAnderson in reply to Bolt_Upright]

"Conclusions: Plasma short-chain fatty acids were paradoxically increased in PD and were associated with disease severity and antiparkinsonian medications." Could be another meaningless conclusion because it isn't clear. Isn't disease severity always associated with anti-PD medications, i.e., the longer the progression, the more severe the disease, the more drugs (higher dosing) that are administered?

[MBAnderson in reply to MBAnderson]

PS. Yet another MBA adage; Studies which end up proving nothing are often written by people clever enough to mostly conceal that in their write up of findings.

[MarionP in reply to MBAnderson]

Ha.

[Rhyothemis in reply to MBAnderson]

Unfortunately the article is paywalled, but the results section of the abstract indicates it was only acetic acid that was increased in plasma. Butyrate was correlated with MOA & and anticholinergic use - these drugs may have effects on the gut microbiome (pretty much everything we ingest seems to affect the gut microbiome).

[MBAnderson]

"...we observed that under certain conditions they can further exacerbate certain brain pathologies, such as protein misfolding and neuronal death, related to Parkinson’s disease,” says Martin Trapecar, an MIT postdoc and the lead author of the study."

Apparently, those "...certain conditions..." aren't important enough to tell the reader what they are or else doing so renders the article pointless.

It's an article written by an MIT employee whose job it is to highlight MIT accomplishments and while whatever it is that they've done (which, again, isn't explained here,) might be an accomplishment (or it might be professors playing with computers,) I'm going with ART on this one - 'nothing to see here folks, move along.'

[MBAnderson in reply to MBAnderson]

PS. MBA's rule of thumb - if it's an article, it starts out with a 50% credibility deficit.

[MarionP in reply to MBAnderson]

Double ha. What conditions? Since they are certain, then they can be listed. If they can be listed, then they should be.

Scientists are as careful and serious about their language and terminology as lawyers are, intentionally...the idea is to be as nearly perfectly autistically exact with their word choice as possible, or the science does not work...thus, they positively intend that their wording be taken just as literally and exactly...in scientific writing, there are supposed to be no synonyms.

So then, ok, words taken seriously as intended, thus what are the certain conditions? Not listing them implies the author/editor wants to not do so, i.e., has a reason to not attract inquiry. Well, that needs to be explained...omission is considered to be as intentional as commission, but noticing that is beyond casual reading and is a subtle way of glossing or "please don't notice this."

[MBAnderson in reply to MarionP]

Explained oh so well.

[Madame-Mango]

Thanks to those who responded. I appreciate your input and perspectives. I'm resuming my butyrate booster tactics as a result.

[Despe in reply to Madame-Mango]

Try ghee, if you want to stop your butyrate supplement. Hubby spreads ghee on a piece of sour dough bread and takes butyrate as well.

lifeirl.com/products/healus...

[Rhyothemis]

Interesting study, thanks for posting.

Note that the donor cells were all from people with a particular mutation, A53T.

There was no simulation of the BBB in this set up and the authors suggest this as a future improvement to the model (though it would be very difficult to simulate the BBB)

Tissue transglutaminase 2 was upregulated (but not statistically significant) (TTG2 is the enzyme that pw Celiac have autoantibodies to).

Cerruloplasm (involved in iron regulation) was repressed.

UCHL1 and DJ-1 went down also.

Original research article:

advances.sciencemag.org/con...

~

What I would really like is to be able to get neurofilament light chain testing on a regular basis (affordable, direct-to-consumer) so I can assess what effect interventions (diet, exercise, supplements, photobiomodulation, etc.) are actually having on neurodegeneration. I emailed Life Extension Foundation about it a while back, they said they would look into it. Perhaps they would 'look into it' a littler faster if more people did the same?

Here's their contact page:

lifeextension.com/quest-com

[Rhyothemis]

A news article about a study that might be relevant - maybe - I am not able to digest all this right now due to headache (pun intended).

sciencedaily.com/releases/2...

The mevalonate pathway was implicated in the MIT study; CoQ10 is a product of the mevalonate pathway. The MIT study gut organoid model did not have a microbiome, of course, and did not include interaction with hydrogen sulfide. Not sure if there's any relevance, but I wanted to post before I forgot everything.

~

I should also mention that H2S is not just produced by gut bacteria but also by our own cells in small amounts; it is used as signalling molecule - a gasotransmitter, like NO and CO (yes, carbon monoxide is made inside of us and has important functions).

[Hidden in reply to Rhyothemis]

Are you familiar with the TUDCA butyrate combo that proved helpful for ALS? Many months ago I sought more info on this and read and listened to Dr. Rudolph Tanzi discuss it. He mentioned it would be good to trial it for PD.

[Rhyothemis in reply to Hidden]

Not familiar with combining TUDCA & butyrate, thanks for the info.I had heard of Dr Tanzi from the interview series by Modern Healthspan - mostly about Alzheimer's -

youtu.be/gcdFU7JXg4g(Not working as expected?)

[Hidden in reply to Rhyothemis]

I like modern Healthspan. UDCA the prescription version of TUDCA is being trialed for pd in the UK