Part 1 : Melatonin, PPAR- gamma and SCFAS... - Cure Parkinson's

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Part 1 : Melatonin, PPAR- gamma and SCFAS Including Butyrate and Do They Have Synergy Toward Gut Microbiota Repair of Gut Dysbiosis?

chartist profile image
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While I normally attach study links to my posts with a basic explanation and possibly a quote or two from the study, I have made a decision not to do that in this particular post in order to try and make the post a bit shorter, in the hope that more members will read it as I feel this is potentially an important message which I want as many members as possible to be aware of for its potential to fix the broken gut microbiota without FMT.

I've discussed melatonin at length on this forum as well as Short Chain Fatty Acids(SCFAs) including butyrate, but I have not previously discussed Peroxisome proliferator-activated receptor gamma or PPAR-y (PP-y). In a video that Bolt_Upright was kind enough to post (thank you!) on Saturday (07-10-2021), Lucy Mailing, PhD, discussed PP-y and described it as a "master switch" to initiate repair of the gut microbiome and went on to describe a dozen or so methods of increasing PP-y using supplements, herbs, CBD etc. Her suggestion was to consider these known increasers/agonists of PP-y either alone or in combination to try and increase PP-y enough to have that effect of increasing PP-y. I had not previously heard of PP-y as useful in terms of gut repair, but she was certain about its effects. So it made me do a little digging since I have always been interested in the gut microbiome and that interest has increased exponentially with the results of the FMT/PD studies from 2020 and 2021 which saw significant improvement in multiple PD test scores as well as motor and non-motor symptoms in PwP. What these studies suggested is that gut dysbiosis is a major contributing cause to PD symptoms. Here is a link to her video as it is the basis for this post.

youtu.be/s2LIHwicPQk

The thing I was wondering about from her video is that Dr. Mailing chose to use substances that are not native to the body to try and increase PP-y. My thinking is that it might be another option to consider a molecule that is not only native to humans and animals, but plant life also and is known to be healthful in all three instances of application. Dr. Mailing also discussed the important role of inflammation and oxidative stress in fueling the fires of gut dysbiosis, but her focus was directed more at the inflammatory aspect of gut dysbiosis. So it would be quite useful if this same molecule could also have potent antiinflammatory and antioxidative stress effects in the gut, and fortunately this molecule does exactly that. Another issue that Dr. Mailing noted as a result of dysbiosis is excessive mitochondrial stress that she said would also need to be addressed and again this molecule is very protective of the mitochondria and in fact is produced in the mitochondria.

To be clear, the molecule I am describing is Melatonin and what her video did was to motivate me to look even closer at melatonin to see if it is likely to have even more benefits for PwP than I have mentioned in my many previous posts on this forum about melatonin and its many healthful benefits. I decided to make a list of some of the benefits of melatonin that I have not previously mentioned. Here are the important items that I found that can be added to that list of potential melatonin health benefits.

1. Melatonin increases PP-y at the gene level and according to Dr. Mailing, this is a very important step in initiating repair of the gut microbiota.

2. Previously I have mentioned that butyrate can increase melatonin production in the gut, but I only recently found out that melatonin can not only increase Short Chain Fatty Acids (SCFAs) including butyrate, but it can also increase butyrate producing bacteria in the gut microbiota and this is very important because PwP are low in the 3 dominant SCFAs as well as the bacteria needed to increase SCFA production and butyrate in particular. The other two dominant SCFAs are Acetate and Propionate. Of these three, propionate is the lowest in PwP. This is only a recent PD mouse model study, but in it, it was shown that increasing the propionate level could also improve motor symptoms in these mice.

3.Another point that Dr. Mailing said needed to be dealt with in order to functionalize gut repair was to reduce Proteobacteria in the gut and again melatonin has shown the ability to modestly reduce this bacteria.

4. I have often wondered about the role that SCFAs, Acetate and Propionate play in the gut microbiota and interestingly, they have shown the ability to increase melatonin receptors in the gut and in conjunction with the fact that butyrate increases melatonin production in the gut seems to add further credence to the importance of melatonin in the gut microbiota. Also keeping in mind that production of melatonin in studies was shown to be anywhere from 400 to 1000 times as high as what is produced by the pineal gland which seems to further highlight the importance of melatonin in the gut. Add in the potent antioxidative stress and antiinflammatory effects that melatonin has shown in many studies and a clearer picture of the importance of melatonin in the gut microbiota is starting to emerge. It is also important to remember that melatonin declines with age, conversely to how age related diseases increase with age. PD is an age related disease and advancing age is the number one risk factor for getting PD. PD and its symptoms are enhanced and advanced by excess oxidative stress and inflammation and returning these two features to normal levels, imo is like starving the disease. This is essentially what FMT does, returns the gut microbiota to a more normal state where oxidative stress and inflammation are very well controlled and clearly was beneficial for PwP in the FMT studies.

5. Both melatonin and butyrate repair the gut mucosal barrier function as well as protect the epithelial cells against inflammation which is very important for the purpose of reducing or preventing leaky gut and improving gut barrier function as a means to reduce inflammation and oxidative stress associated with gut permeability. Together they have synergy and health promoting effects as the gut microbiota seems to be an important determining factor in whether we are healthy or not.

6. Another issue that Dr. Mailing said that needed to be addressed in terms of gut repair was Mitochondrial oxidative stress. Interestingly melatonin is produced in the mitochondria and can apply its potent antioxidative stress and antiinflammatory qualities in a timely manner to neutralize oxidative stress almost instantly and mitochondria can also draw melatonin into the mitochondria if there is ample melatonin available around the mitochondria, but if butyrate increases melatonin production and butyrate is very low, melatonin levels in the gut may decline to levels that are insufficient for melatonin to be able to apply all of its protective effects in the gut microbiota and mitochondria. I believe melatonin is one of the main reasons that PD can take one or two decades to show symptoms enough to actually have a diagnosis because melatonin is doing such a good job of controlling inflammation and oxidative stress while protecting dopaminergic neurons and mitochondria in the brain. With the age related decline of melatonin, PD and its accompanying chronic inflammation and oxidative stress, melatonin and SCFAs eventually begin to lose their ability to protect the gut microbiota. Possibly, repairing the gut biome via increased melatonin and SCFA may improve disease symptoms significantly as illustrated by the FMT / PwP studies that repair and rebalance the gut flora back to levels of healthier bacterial balance between pathogenic bacteria and health promoting bacteria.

7. This one is going to be a leap of faith and is pure speculation on my part. I was not previously aware that melatonin increases butyrate and butyrate increases melatonin. We are all mostly aware that inflammation creates oxidative stress and in turn oxidative stress creates more inflammation in a repetitive negative cycle that tends to destroy health and create health issues of all types as well as fuel many disease states such as PD,AD and MS to name only a few. Have you ever wondered if there is a similar effect that is "pro-health" instead of "anti-health"? I have! I'm trying to understand this intimate relationship between these three dominant SCFAs and melatonin and if I am seeing this correctly it is the closest thing I have seen to a health promoting positive repetitive cycle. Butyrate as well as acetate and propionate have multiple health promoting effects in the gut and the butyrate increases melatonin. Melatonin has health promoting effects throughout the body and specifically in the gut and it increases butyrate. Acetate and Propionate increase melatonin receptors in the gut. As SCFAs and melatonin increase in this repetitive cycle, theoretical repair of the gut biome would be expected based on the available science and based on these known activities, this cycle should continue until the gut biome is returned to homeostasis and from there overall health body wide should follow. Pretty much the reverse of what is seen once excess oxidative stress and inflammation are allowed to advance unabated, the gut biome goes into a state of dysbiosis followed by a general decline in health followed by disease, general ill health and ultimately a potentially premature death. So this idea of a potential healthful cycle is new to me and I have not previously thought that there was a healthful cycle that could be the healthful version of the unhealthful oxidative stress/inflammation cycle, but melatonin and SCFAs could very well be it! In PD, SCFAs as well as SCFA producing bacteria are depleted as well as melatonin in the gut and brain, so this gives an idea of how this positive health cycle could be quite beneficial in PwP.

So in my opinion, the molecule she failed to include in repairing the gut microbiota is melatonin, because it simply checks most of the boxes that she said needed to be checked in order to repair the gut microbiota and it is naturally occurring in the body and gut in particular in large amounts and has protective effects throughout the body. It also seems to have synergy with SCFAs and butyrate in particular and may be of very significant importance in promoting a positive health cycle where SCFAs feed off of melatonin and melatonin feeds off of SCFA to continuously promote repair of the gut microbiota and the body as a whole.

I am putting this theory out there for your consideration because it is the best understanding I have been able to determine from what I know about melatonin and SCFAs so far. If the theory is correct, then it should be able to essentially replicate what FMT has shown to do in PwP. While FMT is currently available for a handful of health issues, it is not yet available for PD. As such, this healthful cycle theory may be an available option worth considering now for having a potentially similar impact as FMT. An important point to keep in mind is that I have not seen any other adjunctive treatment that can improve PD symptoms and test scores anywhere close to what FMT does and it is likely to improve overall health.

Art

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wriga profile image
wriga

Hi Art,

As usual we see similar processes that have turned into vicious circles and that with a little help can become virtuous circles. I don't think it requires a leap of faith to visualise the possibilities that you suggest. To me it is obvious that if you give the microbiobiot the right food, the good bugs will thrive. The microbiot profile disorder is obviously reversible.

Afterwards, just how this redistribution manages to produce enough SCFAs and melatonin to reset oxidative stress and mitochondrial dysfunction is less easy to follow, but I would be happy to be convinced.

I know you said that melatonin upregulates Nrf2 so that would be a parallel pathway to that of sulforaphane which is my favourite solution and one that I'm still making headway with. The combination of sulforaphane and melatonin could be worth trying.

I think we are making serious progress this year on understanding the mechanisms that lead to PD. This does not mean to say that the medical profession will embrace this progress.

The well-established myth that "The cause of PD is unknown" suits everyone except the patients. It's a one-line false-truth that is easy to promote and make patients believe. They, and many doctors are not inclined or incapable of understanding the complex scientific arguments that prove the opposite. This is what makes these false-truths so popular.

The problem also remains that this progress is being made on non-patentable products that will never get to see phase 3 trials because there's no money to be made from them.

wriga

chartist profile image
chartist in reply to wriga

Hi Albert!

You said:

>>> ' I think we are making serious progress this year on understanding the mechanisms that lead to PD. This does not mean to say that the medical profession will embrace this progress. ' <<<

I can't agree with you more! It is unfortunate given the safety profiles of what we are talking about here.

I agree that the combination of melatonin and sulforaphane are likely to have a certain synergy together and I am glad you are continuing on with sulforaphane and its practical application! Sulforaphane helps maintain gut barrier function and the combination of sulforaphane, melatonin and butyrate will all be working to repair and enhance the gut barrier function thereby eliminating that major single cause of inflammation in the gut and ultimately in the body as a whole has to be beneficial for human health! Melatonin and sulforaphane are Histone Deacetylase inhibitors (HDACi) and that is definitely good for PwP. They are not the same by any means, but seem very likely to work well together.

The glacial speed at which the scientific communities move with research into PD and other major diseases and their resistance to accept what the science has been showing for years is beyond frustrating!

Art

Bolt_Upright profile image
Bolt_Upright in reply to wriga

Hello wriga! Thank you for sharing your wisdom.

I am intrigued by sulforaphane. First by your posts on the topic, and then it made Dr Mailing's presentation as a tool to fix dysbiosis.

I'm not a boil seeds at the stove with a thermometer type of person. In fact, I only eat foods that have single ingredients.

So... do you have a recommendation for store bought sulforaphane supplements?

I'm thinking this would fit into a:

- SCD

- Niacin

- Butyrate

- Melatonin

- Sulforaphane

protocol.

Maybe this would be the "fix the microbiome" arm of a larger protocol.

Suggestions please?

Thanks,

Bolt

JBOVERT profile image
JBOVERT in reply to wriga

WRIGA,Hi Ive found broccoli seed sprouts for sale in one of our local stores and so I purchased them for the sake of sulforaphane and because sprouting seems to be impossible for me.. what s the chances of me using these sprouts to get that end result?

wriga profile image
wriga in reply to JBOVERT

Hi JBovert,It all depends on the seeds. Sometimes "Broccoli " seeds sold for growing sprouts aren't broccoli at all, but a cousin of broccoli. That was my first mistake in this story. Broccoli is Brassica oleracea var. Italica. Seeds sold for growing so-called broccoli sprouts can also be Brassica rapa cymosa and you cannot tell the difference, but they don't have the molecule from which you can extract sulforaphane.

If they are true broccoli try to find the name of the cultivar for more precision.

I'm working on a new extraction process. If you want to know more, email or message me with your email address.

JBOVERT profile image
JBOVERT in reply to wriga

HI WRIGA WELL I CHECKED THE LABEL ON THE BOX THEY CAME IN AND IT SAYS THEY ARE "BROCCOLI SEEDS" IT ALSO SPOKE OF HOW THEY WERE Q grown in the organic sensei would send you a pic but I do not know how to send them on this platform and I dont have any other way of contacting you

JBOVERT profile image
JBOVERT in reply to JBOVERT

Wriga other thing is that ai cannoy=t seem to sprout them myself snd do not know why they just wind up smelling like horrible and the idea of doing that makes alit of sense to me but for the time being it going to have to be a step by step instruction from maybe you or I could contact Rhonda Patrick and see what she has to say...

Bolt_Upright profile image
Bolt_Upright

Well written as always Art!

I was thinking you were going to propose supplementing with acetate and propionate also, but I tried to find these supplements and could not.

I think you are mostly correct that we can replicate the success of FMT without FMT. This is what I am trying to do with the Specific Carbohydrate Diet. The key, I think (and based on that report on the SCD normalizing the microbiome) is that your gut has to still include all the needed flora. But I would wholeheartedly endorse going the microbiome reconstruction method before adding FMT (who am I kidding, put a bowl of frozen crapsules in front of me right now and I am popping those in like M&Ms!). I would also mandate this microbiome reconstruction protocol (once worked out) before FMT, during FMT, after FMT, and forever (to some degree).

I was going to ask you what your recommended protocol would be now. I see you've laid out some of it with wriga: Sulforaphane, Melatonin and Butyrate.

I would suggest adding Niacin and Curcuminoids to the protocol.

How much of what and when? For how long? Diet modifications in the protocol? Do we keep HDT? Does Mannitol work for us or against us in this protocol?

Much to think about. Good stuff. Thanks!

Bolt

chartist profile image
chartist in reply to Bolt_Upright

Bolt,

After reading the FMT studies it altered my concept of how to work against PD because FMT appeared to be more potent than even I, was anticipating. When I watched Dr. Mailing's video, it made me think more and that is why I wrote the post above. I hadn't considered that there could be a positive health repetitive cycle because I had never seen or heard of it before, but as I wrote and started looking at the interaction of SCFAs and melatonin, that is the idea I arrived at. Finally, a relatively simple way to counter the excess oxidative stress(OS) and inflammation vicious cycle that drives PD and many other disease states. I had always wondered why there was no positive counterpart for the negative OS/inflammation cycle, but that is as far as I ever took that line of thinking, but perhaps SCFAs/melatonin might be such a positive health cycle.

So if this theory turns out to be correct, increasing melatonin should increase SCFA producing bacteria which is lacking in PD and the melatonin should also potently inhibit oxidative stress and inflammation in the gut . This should increase acetate and propionate which will increase melatonin receptors in the gut which are also lacking in the gut and brain of PwP. Butyrate will also be produced with acetate and propionate. The butyrate will increase melatonin further and melatonin will increase propionate, butyrate and acetate and this cycle should continue to restore the gut microbiota to homeostasis for each individual. This cycle, over time should be able to replicate what was seen in the FMT studies over a 3 month period. Of course altering the diet away from foods that feed pathogenic bacteria and taking in foods and fiber that feed health promoting bacteria should speed this process up and sulforaphane should also speed the process up considerably. This will repair and fortify the mucosal lining in the gut, protect the epithelial cells and stop the significant inflammation caused by gut permeability and reduce oxidative stress back to homeostasis or levels seen in healthy people. Supplementing with melatonin and more things that can increase SCFA producing bacteria for an initial period of time should further speed the process along and can be reduced or dropped at a later time when symptoms are significantly reduced.

Well, that is the theory and it needs to be tested.

Art

JBOVERT profile image
JBOVERT in reply to chartist

ART, I am thinking that the colonoscopic approach after all the back and forth speaking about the butyrate and mannitol. What are your thoughts on this rather than waiting to hit and miss while trying to replicate the gut biome through building it from the ground up why not just get the elevator off the ground floor and take it up to the 50th floor and then get on?...Is there any negative potential to trying this? because I am thinking that this gut issue is the reason why I am sick and I want off this merry go round. what are your thoughts? Jim

Bolt_Upright profile image
Bolt_Upright in reply to JBOVERT

There are at least 3 really good FMT groups over on FB. You should join a couple maybe. It's not hard to find stories of people who have made things worse with FMT. Even people who have made their kids with Autism worse.

Don't get me wrong. If you put poop pills in front of me, I am eating them.

chartist profile image
chartist in reply to JBOVERT

Jim,

I'm not sure if you are talking about delivery of FMT via colonoscopy or delivery of SCFA and melatonin in that way. I think either way could potentially work, but that second option is not going to happen at this time for lack of testing in studies and trials.

I think delivery of FMT via colonoscopy is the most effective delivery method and is just a one time dose to see positive effects for a minimum of 12 weeks or more. Of course altering the dietary intake in a way that will support the FMT may extend the effects, but that would require further testing. The wrench in the works is that PD is not yet on the list of approved diseases for treatment and there are only a handful of health issues that it is currently being used for. It may be possible to have it done "elsewhere", but that would take some searching to see if you can find a reputable place that does it. It seems the downside from FMT is mainly making sure the transplant and donor have been well screened and effective screening entails a price premium. The nasal tube delivery is a poor option based on two studies where it showed inferior benefit when compared to colonoscopy delivery. The enema delivery route does not seem to be as efficient as the colonoscopy delivery as the enema kit I saw looked like it had about 6 frozen enema bottles in it and is a bit pricey when you consider it is essentially fertilizer, but "prime fertilizer" to be sure.

"Poop pills" looks like it may take quite a few pills for effective treatment, but is much less invasive than colonoscopy delivery and probably the simplest delivery method that does not require any type of equipment for delivery. I have seen dogs eat other animals feces and I wonder if they innately understand more about that than we do with all of our science and research? Dogs seem to naturally have a strong desire to sniff other dog's rear ends. Are they actually searching for a healthy mate? For the masses poop pills seem like a doable approach, but I have not yet seen how the two compare in terms of overall benefit. This science is in its infancy for some reason even though studies date back about 15 years. I wonder why that is? Another puzzling question to me is why is Asia leading in this area of science that could have such profound health benefits for those who really need it?

No matter the choice, it seems like change of diet or addition of SCFA+ Melatonin or both is likely to at least help maintain the FMT effects and possibly improve on them?

Jim, I should add that SCFA + Melatonin appears to be the natural pro-health cycle that the body uses to maintain homeostasis of the gut microbiome.

Art

Resano profile image
Resano in reply to chartist

Why is Asia leading ? Perhaps because of its Ayurvedic medicine involving a pre-diagnosis based on the analysis of imbalances of the Dosha, Pitta and Vata factors and the fundamental "relationship between stool and mind" (sic):

easyayurveda.com/2018/09/18...

See also:

sciencedirect.com/science/a...!

JBOVERT profile image
JBOVERT in reply to chartist

HI Art, Ok I'm going to wait for now at least and do the following for next few weeksuntil I get the Viome test results back: intermittent fasting - intermittent fasting - intermittent fasting. I have lost 15 lbs since July 18th and I wasn't even seriously fasting like I am right now; so I will see where that leads me first but I have to say that right now I'm feeling pretty good...I just need some relief in my ability to swallow and

I cant seem to get control of the amount of saliva and mucus that I am producing! Its like waking up and start being waterboarded ok I am not complaining thats just how it is rolling for me these days..I am sure that l will get some relief somewhere down this

rocky road...anyway I just want you to know how much I appreciate everything you are saying to me and I will continue to do my red light twice per day and continue to eat my cinnamon 5 grams daily. and if my piling machine ever arrives I will start the HDT therapy and that's about it for now --just have to figure out why everything is going underlined :) Jim

chartist profile image
chartist in reply to JBOVERT

Hi Jim,

I am glad to hear you are doing fairly well and your regimen sounds very good as does your plan moving forward. In your intermittent fasting , are you using an 8 hour window of eating or something else. Your weight loss results are very good. A friend of mine eats only one meal a day in the late afternoon and has remained slim and trim to his current age which is about 75. His health has always been good also. Please keep us updated on how everything is working out for you. Sharing is caring!

Do you feel you are getting benefit from the red light therapy yet? Reported benefits seem to be slow and steady over a period of months with regular daily use, in the reports so far.

You must have accidentally hit the underline tab when you were typing your message.

Art

JBOVERT profile image
JBOVERT in reply to chartist

Art right now I am only eating between the hours of 2:00pm -4:00pm and this something I just started yesterday so I will see how this works and let you know.as for the red light im not at the stage where I can discern any noticeable differences..

I will keep you advised though and hope that everything I am doing will add up to a better daily existence..I am also planning to pick up on the niacin therapy as well just as soon as I can get over to the next island and pick some up, ok thats it for now Jim

JAS9 profile image
JAS9 in reply to JBOVERT

JB, I've also gone through the "waterboarding" experience several times. It has to be said: it was SCARY! I learned a long time ago not to mess with the strength of stomach acid; it's a balancing act that I don't feel I have the tools to address. Instead, I looked at what stops the acid from coming back up. Here's a link to a page that explains a lot, although in the end, it wasn't quite enough info for me to resolve my problem. I think you should read this article over and make sure you've considered the standard medical info, then read the rest of this post where I tell you what eventually helped me. (Note that on this website, they suggest using proton pump inhibitors; something that I personally think is a very bad idea.) asge.org/home/for-patients/...

OK, so this is what I learned after looking at all the "mainstream" info. In the wake of Dr Constantin's and Dr Lonsdale's work, others have started using HDT therapy. One such person is Elliot Overton, a certified functional medicine practitioner & naturopathic nutritional therapist who practices in the UK. For years now, he's used HDT therapy to treat several different conditions (although he uses Thiamine TTFD, not HCL). He points out that when we increase one thing (thiamine) we have to be careful not to cause a new imbalance. He's discovered that HDT can cause side effects (especially TTFD but also HCL). The two things that he's found most useful to supplement are magnesium and potassium. Both of these can be depleted by increasing thiamine, especially to the levels we're talking about. Here's a link to that video. You may want to watch his other videos on youtube. Personally, since I've started supplementing these two things, my "waterboarding" has stopped completely. This happens when the valve between the stomach and the esophagus, known as the lower esophageal sphincter, does not close properly. It (as well as other muscles in our body) needs magnesium to function as designed. Potassium has also helped with my headaches. Good luck!

youtu.be/-DxvSUEVT_4

chartist profile image
chartist in reply to JBOVERT

Jim,

I forgot to mention about the waterboarding/choking effect you described, it can possibly be from PD, but sometimes is caused by too little stomach acid. You can try Betaine HCI with pepsin to see if it helps, but it may be a problem with narrowing your eating window to only 2 hours a day because it has to be taken with food, otherwise the increased acid can cause damage. You should know if it is the cause by the end of one bottle. If it causes heat or heartburn, it can be neutralized quickly with a half teaspoon of baking soda in water. I wrote about GERD and PD as it is 4 times more likely to occur in PwP. Here is a link to that post :

healthunlocked.com/cure-par...

Art

Bolt_Upright profile image
Bolt_Upright in reply to chartist

Stumbled across this Art,

Even though acetate, propionate, and butyrate are reduced in feces of patients with Parkinson's disease, concentrations of acetate, propionate, and butyrate in blood plasma did not differ between patients with PD and controls.

After correction of covariates, acetic acid concentration was higher in patients with PD than in controls (116.47 ± 16.83 vs 108.20 ± 18.37 μmol/L; P = 0.010). In correlation analyses, acetic acid concentration was positively correlated (R = 0.374, P = 0.021) with age, propionic acid concentration was negatively correlated with UPDRS part III score (R = -0.376, P = 0.020) and use of entacapone (R = -0.325, P = 0.047), and butyric acid concentration was correlated with monoamine oxidase inhibitor use (R = 0.382, P = 0.018) and anticholinergic use (R = -0.385, P = 0.024).

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

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

Conclusions: Plasma short-chain fatty acids were paradoxically increased in PD and were associated with disease severity and antiparkinsonian medications. Further studies are warranted to elucidate the relationships of gut dysbiosis and inflammation with plasma short-chain fatty acids.

What does it mean?

Bolt

chartist profile image
chartist in reply to Bolt_Upright

Bolt,

Look at the very first sentence that you pasted. SCFAs are produced in the gut for the health of the gut microbiome but are reduced in PD. The low fecal content suggests low colon content and that generally is associated with dysbiosis of the gut microbiota as seen in PD. What is in the plasma was at normal levels as seen in the controls, but the damage to the gut microbiome is going all the while and that has been what we have been talking about for quite awhile now. FMT improves gut dysbiosis and increases the SCFA butyrate and people improve.

Art

Bolt_Upright profile image
Bolt_Upright in reply to chartist

Yikes! Check out the new post "Could Butyrate Be Bad for PWP? (MIT Study)"

chartist profile image
chartist in reply to Bolt_Upright

Bolt,

I answered that already.

Art

Bolt_Upright profile image
Bolt_Upright in reply to Bolt_Upright

This really caught my eye: Plasma short-chain fatty acids were paradoxically increased in PD and were associated with disease severity and antiparkinsonian medications.

Resano profile image
Resano in reply to Bolt_Upright

It appears that blood concentrations often poorly reflect the complex reality at the cell level as in the case of thiamine, potassium, etc.

"concentrations of acetate, propionate, and butyrate in blood plasma did not differ between patients with PD and controls."

gwendolinej profile image
gwendolinej in reply to chartist

Hi Art, I’d love to be able to be involved in these conversations…yeh right😂. Love to read them though and really appreciate the time you all are prepared to put in.

Bottom line is ..can you recommend dosages of these:

Butyrate (and which one)

Sulforaphane

Melatonin

Niacin?

Gwendoline

Resano profile image
Resano in reply to chartist

The Thiamine way in the gut ? Garlic increases the bacterial synthesis of thiamine in the gut (Matsukawa & Sato 1951). If the latter is enough alkaline, then Allithiamine appears. Allithiamine, generated this natural way or supplemented, is excellent for those who suffer from gut dysbiosis.

____

A repetitive cycle: “The butyrate will increase melatonin further and melatonin will increase propionate, butyrate and acetate"

jrg54321 profile image
jrg54321 in reply to Bolt_Upright

Doesn't mannitol produce butyrate in the gut? I read that on this forum, not in a peer-reviewed journal.

Bolt_Upright profile image
Bolt_Upright in reply to jrg54321

From my post on Mannitol:

"In addition, moderate doses of polyols increase the number of bifidobacteria in the microbiomes of healthy individuals and may therefore be beneficial as a prebiotic"

Bifidobacteria help modulate the gut microbiota, prevent inflammation and protect from many diseases, including colorectal cancer, enteric infections (of the intestines) and diarrhoea, inflammatory bowel diseases (Crohn's, ulcerative colitis), and even depression.

PS: I'm not saying it does not produce butyrate. This is just all I have on it.

LAJ12345 profile image
LAJ12345

Can one take melatonin during the day to split a dose and to keep levels up without feeling sleepy all day? It seems it might work best if the dose is constant but is it practical? Or do you think large daily doses before bed would do the same thing?

Do large doses affect gut bacteria? Don’t want to kill them!

chartist profile image
chartist in reply to LAJ12345

Large doses are beneficial for multiple health issues, but taking melatonin orally during the day is not a good idea except in certain instances such as Covid-19 and rapidly advancing health issues such as cancer and ALS. I think if you are taking melatonin for gut repair, suppository melatonin available online might be one way to be able to take it during the day. Suppository melatonin in studies is reported not to cause next day drowsiness or daytime drowsiness. Melatonin produced in the gut does not cause drowsiness the way that oral melatonin does. Increasing SCFAs increases gut melatonin production and then melatonin increases SCFAs producing bacteria in the gut which produces more SCFAs which produces more melatonin in the gut. This is a positive repetitive health cycle with melatonin increasing SCFAs and SCFAs producing more melatonin in an effort to repair the gut, but PwP need the bacteria that are capable of producing SCFAs and melatonin is one way to get those bacteria and probiotics containing the bacteria Clostridium Butyricum can also increase SCFAs. Pistachios would be another source. Taking butyrate itself may not give you acetate and or propionate.

Melatonin will benefit the gut microbiome, not hurt it. That is explained in the original post to this thread. It will benefit the gut in multiple ways and will help increase SCFAs, which is very important.

I take a total of 106 mg or more of melatonin every evening, but this is mostly gone by late morning the next day.

Art

sharoncrayn profile image
sharoncrayn

chartist wrote:

"results of the FMT/PD studies from 2020 and 2021 which saw significant improvement in multiple PD test scores as well as motor and non-motor symptoms in PwP. "

from a study where n = 11 ? in Evaluation of fecal microbiota transplantation in Parkinson's disease patients with constipation...2021.

Besides, UPDRS score improvements were from part II, and conveniently did not include part III.

sharon

chartist profile image
chartist in reply to sharoncrayn

That's all the PD/FMT studies there are, Sharon. The 2020 study saw similar results but these initial studies are small. Do we just ignore them ?

Art

chartist profile image
chartist

This mouse study came out today and gives a potential idea of what melatonin is doing in the gut and it sounds familiar :

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

Here is a quote from the study :

>>> ' Further, we demonstrated melatonin-mediated MT2 weakened GR feedback, suppressed oxidative stress, restored the intestinal microbiota and its metabolites homeostasis, and inactivated the STAT3/AP-1/NF-κB pathway-induced inflammatory response in vivo and in vitro. ' <<<

It is only a mouse study, but it may give clues about what melatonin might do in the gut of humans.

1. It suppressed oxidative stress

2. It restored the intestinal microbiota and its metabolites homeostasis

3. Inactivated STAT3/AP-1/NF-kB pathway-induced inflammatory response in vivo and in vitro

These sound like things we could all use if we have gut dysbiosis.

Art