Part 2 : Melatonin, PPAR- gamma and SCFAs... - Cure Parkinson's

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Part 2 : 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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In case you missed it, Part 1 of this post where I laid the foundation for the idea and reason for my current regimen is here :

healthunlocked.com/cure-par...

When I wrote that post 3 weeks ago, I had already started a self experiment to try and test whether this theory had any merit. If this theory is correct it should have benefit for a multitude of diseases not just PD, similarly to Fecal Microbiota Transplantation( FMT ) with positive health effects in many diseases. I had decided that I would test this theory for 12 weeks to try and replicate the length of the 2021 FMT Study.

As some of you may be aware, I have severe psoriasis in multiple forms, two of which almost killed me and landed me in the hospital with about 95% body coverage. I have battled with psoriasis for decades and though in recent years I have been able to manage it fairly well using an assortment of natural products that have produced mixed results of varying degrees. Despite my many efforts my previous best response was as high as 95% clear skin, but that turned out to be short lived and I have since been bouncing around between 70% clear to 90% clear, but I have never made it back to 95% clear again and it seems that each attempt to recover from a disease exacerbation was met with greater resistance and length of time to recovery in an age dependent manner. To say that a little differently, the older I get, the harder it is to recover from any disease exacerbation and the longer it takes me to start to see any benefit. I was about 80% clear when I started this regimen.

I have been testing my current regimen for about a month now in an attempt to see if I could potentially replicate FMT effects as observed in the study over the 12 week study period without actually using FMT. Now you may say that psoriasis is not PD and you are exactly right, but the benefit in the study was seen in PwP not people with psoriasis. The interesting thing with FMT is that it appears to benefit many different health issues and psoriasis is supposed to be one of those issues, so if it works for PD, there is a good chance it will work for psoriasis, even severe psoriasis.

At about 5 weeks in to using this regimen, I would like to discuss my results so far. At about a bit over one week in, I had the impression that my current exacerbation was no longer worsening. At about 2 weeks in, it seemed like I might be seeing actual improvement. At about three weeks in, improvement seemed to be continuing at a rate where I could actually see small visual improvements day to day or every other day.

I am now about 5 weeks into this regimen and what I see is that I am still seeing daily to every other day small improvements in my skin coverage area, but very importantly, it appears that I am now at least 95% clear again and so far the trend is continuing! I am very happy and excited with these results! Also important and worth mentioning is that during this time I have also been dealing with a very stressful personal situation in my life that would have surely exacerbated my psoriasis quickly and relentlessly, but that has not been the case this time.

One interesting point about psoriasis and the only interesting one that I am aware of, is that because its effects appear on the surface of the skin, it makes me a guinea pig of sorts as I can fairly quickly see how the skin reacts to changes in my supplement regimen and this is what allowed me to see how quickly this regimen is working in me! Well at least I found one good use for this horrible disease! What is that well known saying, "when life gives you lemons, make lemonade"?

So what regimen am I doing to achieve these results which to me are very impressive? It is very simple and I have mentioned them on the forum at various times. Some of you on the forum are aware that I am taking 106 + mg of melatonin every night and I believe that has kept me from a severe exacerbation as I have had many times before, but not since the addition of 106 mg+ of melatonin now in the beginning of my 11th month at this dose.

One major finding about FMT is that it increases gut melatonin levels so this is something I want to include with this regimen. Melatonin production declines with age and even more so with PD, so this seems like an important step in trying to replicate FMT, but I think melatonin supplementing is only needed temporarily in this process until higher gut melatonin production is restored through increased SCFA levels and it may potentially speed the process up. According to Dr. Mailing in her video in part one, it is very important to activate PPAR-y and melatonin does this at the gene level! She says activating PPAR-y is like throwing a switch that promotes repair of the gut microbiota to get rid of gut dysbiosis

What I added was high dose thiamine microlingual at 400 ~ 600 mg/day. The reason for this is that thiamine is produced in the gut. PD is known to have gut dysbiosis and psoriasis is too. Gut dysbiosis is known to disturb this natural production of thiamine and I wanted to be sure I have plenty of thiamine to cover what I may be losing from gut dysbiosis.

In a recent post, I discussed how one of the important effects of thiamine in the body was helping to control the production of the inflammatory cytokine IL-17. In healthy controls IL-17 is generally undetectable or very low, but in PD and psoriasis, IL-17 is activated and promoting the inflammatory cascade. I discussed this here:

healthunlocked.com/cure-par...

Keep in mind that FMT appears to restore normal gut health and one of those things that are restored would be natural production of thiamine in the gut, so I felt it was an important aspect of how FMT is working as well as it does and since I am trying to replicate some of the major features of FMT, thiamine had to be included.

The next item of this regimen is pistachios in three servings per day which is my snack food in place of any junk snacks. Why pistachios you may ask? A few reasons actually. Pistachios are reported to increase bacteria in the gut that can create Short Chain Fatty Acids (SCFAs) when they are delivered with prebiotics or fermentable fiber. Pistachios also happen to contain fiber! Pistachios taste good (to me) and are very healthful. Pistachios also have one of the highest contents of melatonin in any type of food. I use a container such as the size they give you salad dressing or ketchup in at a restaurant. My container holds exactly 4 ounces of water when filled to the brim. I use this container to scoop pistachios out of my big bag and fill the container to overflowing with pistachios and I eat three of these spread out through the day.

In "part one" of this post, I discussed a potential synergy between melatonin and Short Chain Fatty Acids (SCFAs) where they feed off of each other to promote production of more SCFAs, melatonin and melatonin receptors, which I theorize all work together to promote healthful bacteria, repair of the gut mucosal barrier, protection of the epithelial cells, reversal of gut inflammation, decrease gut oxidative stress, repair gut dysbiosis, shift the gut microbiota toward health promoting bacteria and away from pathogenic bacteria to ultimately reduce disease symptoms significantly. Together they do much more, but these are the basics of what I describe as a "pro-health repetitive cycle".

The other thing I am doing is walking 2 miles a day at a brisk pace. Exercise has shown in studies to increase gut content of SCFAs and we need those SCFAs to stimulate this process.

One thing I have not introduced that I had planned to was fasting because this too increases SCFA promoting bacteria or SCFAs, but I will keep this option on the back burner in case I need extra help as I have had good results with intermittent fasting in the past and I trimmed down with it and just seemed to feel better. For now, I have not needed to add it as the basic regimen is working very well.

So although I have psoriasis and not PD, I seem to be responding similarly to how those PwP did with FMT and I hope that this regimen can work similarly in PD as it is with my psoriasis. Twelve weeks is about 7 weeks away for me at this time.

Well that is my complicated regimen that I wanted to share with all of you and my intent is to eventually reduce or stop my melatonin supplementation and count more on the gut produced melatonin, but the condition of my skin going forward will probably help determine what I do and when. On a related note, it is possible that I continue high dose melatonin due to Covid-19 as FMT has also shown benefit in Covid-19, but right now, I just want to enjoy my current very improved skin condition! It is wonderful!!!

Art

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Querkle profile image
Querkle

Thanks for posting such a positive outcome, I hope it lasts and great that you feel so good.Maureen

chartist profile image
chartist in reply toQuerkle

Thank you Maureen!

My hope is that it also works for PD in a similar fashion to how FMT has worked in PwP! That is the reason I am describing my response to it. I don't have to wait for FDA approval or lengthy RCTs in order to test a small combination of products that are already known to be safe, I can just do it and quickly report my results here!

Art

Congratulations! That is very encouraging, especially since you have tangible results so quickly.

chartist profile image
chartist in reply to

crimsonclover,

Thank you for saying so! It is a very good feeling to be almost back to normal! Hopefully it will have positive effects in PwP also!

Art

bpoe profile image
bpoe

Hi Art...just a request before I read the entire post....please define FMT...this is not directed particularly at you, but I would like to put out there it is important to define acronyms....there are what seems like millions out there..I see this regularly with contributors here, it can be very frustrating...Looking forward to reading your post!

chartist profile image
chartist in reply tobpoe

bpoe,

I'm sorry for not including that info. It has been talked about so much on this forum, I thought everyone would be familiar with it, but that is a mistake on my part.

FMT = Fecal Microbiota Transplantation

This is where poop from a healthy person is transplanted into a person with a health issue such as PD. There are two completed FMT studies that used FMT in people with PD. The results were a greater than 50% improvement in motor and non-motor symptoms with corresponding reductions in test scores for people with PD.

Art

glenandgerry profile image
glenandgerry

Once again Art, you have worked tirelessly for PWP on this forum for which, I for one, would like to thank you. The fact that you have had such tangible and encouraging results for your own condition is absolutely brilliant, I'm so thrilled for you Art. Thanks for being our guinea pig!Gerry

chartist profile image
chartist in reply toglenandgerry

Hi Gerry,

Thank you Gerry, it seems like it has been a long time coming and I so needed to make some progress with this disease. I think we can all appreciate some relief and I hope this turns out to be something that can offer that relief to others.

Art

park_bear profile image
park_bear

Pistachios good

😀

chartist profile image
chartist in reply topark_bear

Hah! Pistachios good, good, good!I love it when a food that is very good for us can taste good too!

Art

kgold profile image
kgold in reply tochartist

Unsalted, in shell? Glad this approach is yielding results!

chartist profile image
chartist in reply tokgold

kgold,

I am eating sea salted pistachios in shell.

Art

Annieartist profile image
Annieartist

Fantastic - inspiring- and any excuse to eat pistachios

chartist profile image
chartist in reply toAnnieartist

I thought that when I started eating so many pistachios everyday, that I would soon get tired of them, but I still love pistachios and can feel good about eating them too since they are so healthy for us! I hope this helps others!

Art

LAJ12345 profile image
LAJ12345 in reply tochartist

Buying pistachios tomorrow😊

chartist profile image
chartist in reply toLAJ12345

LAJ,

I figured I would give it 12 weeks to see what they could do since the FMT/PD studies showed steady improvement right up to the end of 12 weeks and those study participants received less than 2 ounces of fecal transplant only once, at the beginning of the study. This to me suggests that FMT activates or stimulates a pro-health repetitive cycle in the gut microbiota, otherwise you would have expected any benefit to be lost in the first several days? The fact that the 2020 study had follow up for 24 months and saw the majority of participants improvements decline over that period with only two participants maintaining their benefit for the 24 months suggest that the FMT only stimulated the the theorized pro-health cycle and those two participants possibly took steps on their own to maintain it.

Art

rebtar profile image
rebtar in reply tochartist

If I'm not careful, I can go through a LOT of pistachios in one sitting! YUM YUM.

chartist profile image
chartist in reply torebtar

Too much though and you can get gas and I speak from experience! 😷😷😷

Art

rebtar profile image
rebtar in reply tochartist

Not me...but I find it hard to stop once I start...

Do you take a butyrate supplement?

chartist profile image
chartist in reply torebtar

I don't supplement with butyrate because the acetate and propionate also play a part in this cycle of at a minimum, producing more melatonin receptors in the gut, which are low in PD. Of these 3 predominant SCFAs, propionate is the lowest in PwP. In a mouse PD model study, the addition of propionate caused the mice to improve their motor symptoms.

Art

rebtar profile image
rebtar in reply tochartist

So fermented foods?

chartist profile image
chartist in reply torebtar

No fermented foods.

Art

rebtar profile image
rebtar in reply tochartist

Could you post the link for low propionate in PD?

chartist profile image
chartist in reply torebtar

rebtar,

Here is a link to one recent study (2021) describing the motor symptom improvement that I mentioned in mice from propionate. Mice effectiveness does not mean it will be the same in humans, but I think it illustrates that it would be foolish to think that propionate and acetate are just along for the ride with butyrate, they play a part and that is why I am looking at all three predominant SCFAs as a major part of the gut microbiome repair process with gut produced melatonin being the other half of this pro-health repetitive cycle.

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

Here is a relevant quote from the study :

>>> ' Two months of orally administered propionate successfully rescued motor deficits and dopaminergic neuronal loss in PD mice. ' <<<

A healthy balanced microbiota confers significantly improved health. I am attempting to test ways to get there other than FMT.

I'm not sure why, but several links I have put up lately do not copy properly and are dead. I hope I fixed this one as it did not work initially.

Art

chartist profile image
chartist in reply torebtar

rebtar,

I forgot to include the link you asked for that showed that Propionate was the most reduced of the 3 predominant SCFAs in PwP. Those three are acetate, propionate and butyrate . Here is the link you asked for :

pubmed.ncbi.nlm.nih.gov/334...

Here is a quote from the study :

>>> ' The concentrations of SCFAs, including acetate, butyrate and propionate, were significantly downregulated in the fecal samples of Parkinson's disease patients, and among the SCFAs, propionate decreased the most. ' <<<

Art

chartist profile image
chartist in reply tochartist

Given that propionate is the most depleted of the 3 predominant SCFAs in PwP, it is worth mentioning that Xylitol increases propionate more than acetate or butyrate, but it does increase all 3 predominant SCFAs according to the following study with butyrate acting to improve the mucosal barrier. Propionate also lowered the gut pH to the detriment of pathogenic bacteria such as Escherichia and Staphylococcus.

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

Art

aek222 profile image
aek222

Hi Art:Congrats on your progress and thanks for keeping us updated.

As food for thought, this paper treated PwP by dietary intervention and lower bowel cleansing (i.e. daily enemas) with outcome comparable to FMT with respect to improvement of gut microbiome. I am considering trying this, though I need to do more research about risk vs benefit.

doi: 10.3390/cells9020376

Interventional Influence of the Intestinal Microbiome Through Dietary Intervention and Bowel Cleansing Might Improve Motor Symptoms in Parkinson's Disease, Cells 2020 Feb 6, 9;376

chartist profile image
chartist in reply toaek222

aek222,

Thank you for the link to this study abstract which I had not previously seen. Here is a link to the full study :

mdpi.com/2073-4409/9/2/376/htm

To me this is important reading for all PwP to further establish the true health value of FMT and gut microbiome manipulation in general. Because most of these studies are small, more of them that show positive effects in PwP are very important toward potentially generating more interest in FMT and microbiota manipulation and possibly larger controlled trials.

In the meantime I am trying to take the information gleaned from these studies to try and manipulate the gut microbiota in a similar way to FMT, but via simpler and safer methods that can be done by individuals without having to resort to FMT in its different forms which has shown its detractions at times. The colonoscopy delivery method seems quite effective, but colonoscopy to me, seems somewhat invasive and has been known to cause tears in the colon or inflame an unknown or existing case of diverticulitis. For this reason, I would tend to lean toward the "crapsules" or "enema" versions of FMT if I intended to use FMT with crapsules being my first choice over enema, but hopefully what I am reporting here might offer another alternative to FMT. The nasal gastro delivery seems to possibly be inferior in terms of positive health effects when compared to the other 3 forms of FMT.

Your study link used the enema and nutrition change to significant effect in PwP and this adds further confirmation to the two FMT/PwP studies I discussed here :

healthunlocked.com/cure-par...

The sum total of these studies will hopefully drive the desire for larger randomized controlled trials (RCTs).

Art

Bolt_Upright profile image
Bolt_Upright

I'm so happy for you Art! Thanks for sharing. It is amazing how similar the strategies needed between the 2 diseases seem to be.

So you are on High Dose Thiamine! Could you please share your brand of choice for high dose thiamine microlinguals?

Good job on the 2 miles of brisk walking a day. I need to add that.

Thanks!

chartist profile image
chartist

Thanks Bolt!

Here is a link to the ones I am currently using as suggested to me by forum member "Dap".

pureformulas.com/no-shot-b-...

I also will be switching to 100 mg thiamine HCI capsules when I run out of these to see if there is any difference that I can tell between them, but I still have two bottles of these ones to go through first. These don't taste good at all, but as Dap told me, you almost get used to them. Compared to the very bitter thiamine bulk powder, these are like dessert! I do 4 to 6 of these tabs per day and preferably earlier in the day.

Art

LAJ12345 profile image
LAJ12345

That is exciting. I have wondered what your condition is. I haven’t seen you mention it before. I truly believe most chronic conditions could be helped by exactly the same treatments (not drugs!) so I am not surprised.Can I ask if you have tried pantethine, digestive enzymes, berberine and allimed? They cleared up hubby’s rosacea and got rid of PD smell (at least I think it was them) so I wonder if they could help your issue too being a skin issue?

chartist profile image
chartist in reply toLAJ12345

Yes, I have tried Pantethine, digestive enzymes, berberine and I have not tried Allimed. At the time that I tested them, I did not notice a difference. As of today, I have reached about 96% clear skin!

Art

LAJ12345 profile image
LAJ12345

Are you gluten free?

chartist profile image
chartist in reply toLAJ12345

No, I am not gluten free.

Art

LAJ12345 profile image
LAJ12345

So to summarise:106+ mg melatonin at night

400-600mg sublingual thiamine hcl

A handful of pistachios eaten over the day

Exercise walking.

Is this correct?

chartist profile image
chartist in reply toLAJ12345

Yes, that is my regimen.

Art

LAJ12345 profile image
LAJ12345 in reply tochartist

Ok I have bought bag of pistachios so will start adding this to diet every day. He is already taking B1. I will try and get strong melatonin.

By the way is there a substitute for pistachios or is it the only thing that will work? They are so expensive and salty.

chartist profile image
chartist in reply toLAJ12345

LAJ,

They do have unsalted pistachios, but as far as a substitute, melatonin, exercise and fasting are what I have found so far, but I will continue searching for other potential options. I'm so new into this LAJ and am trying to just see if it will work before I put more research into it, but I will keep looking for other ways of getting SCFA producing bacteria. Adding a good prebiotic or fermentable fiber will make the most of the SCFA producing bacteria in your system already plus what you add.

I was moving forward on the basis that my SCFA producing bacteria are very low since I have had this disease for the entirety of my adult life. So I wasn't necessarily trying to increase my prebiotic or fermented fiber content a tremendous amount as I was trying to increase the SCFA producing bacteria and then counting on the fiber content of the pistachios since I am eating so much of them. If I find others, I will definitely post them as an addition to this thread.

Art

LAJ12345 profile image
LAJ12345 in reply tochartist

Thanks. I will be interested.

LAJ12345 profile image
LAJ12345 in reply tochartist

Your scoop of pistachios, are they in their shells or have they been shelled?

chartist profile image
chartist in reply toLAJ12345

They are in the shell and sea salted, but are also available unsalted . I recently found out that the hulls have very significant nutritional content also and am wondering if they can be used to make tea out of, in order to try and get some of that nutritional benefit also? "Pistachio Tea", at least sounds interesting.😋😋😋 I like pistachio ice cream!

Art

LAJ12345 profile image
LAJ12345 in reply tochartist

Or roast and grind into coffee? They are very hard though. I wonder if the tannins in them are ok?

chartist profile image
chartist in reply toLAJ12345

Pistachios do contain tannins, but tannins can be healthful too and probably showing more health benefits that anti-health issues for the amount of pistachios I am currently taking, plus I hope in time to be able to cut back on my pistachio intake, if there really is a pro-health repetitive cycle as suggested by continued improvement in the FMT/PwP studies well beyond the end of the 12 week study period.

Possibly stimulating this cycle on a regular basis rather than continuously is sufficient to maintain health benefits derived from SCFAs and SCFA producing bacteria stimulation.

Art

LAJ12345 profile image
LAJ12345

Sorry, more questions. How fast did you increase your melatonin dose and what is the largest dose capsule you’ve been able to find? Ie the brand and supplier? We have 3 mg and 5 mg so they are a bit low.

chartist profile image
chartist in reply toLAJ12345

I have been taking high dose melatonin for years, but 11 months ago I stepped it up to 106 mg+ per night. My intent is to eventually rely on the increased melatonin production in the gut rather than supplementing and the only thing that might prevent me from doing that is Covid-19, because the Cleveland Clinic study suggested that melatonin may act as a prophylactic to Covid-19 and never getting Covid is a very nice idea to me!

Art

LAJ12345 profile image
LAJ12345 in reply tochartist

Seems a sound theory. How do you get such a high dose of melatonin? Is it prescribed? That would be21 of the ones we have!

chartist profile image
chartist in reply toLAJ12345

In the US, melatonin is as common at the local drug store, as cough syrup, but I usually order it online as it can be found at less expense. If this theory works as expected, it may not be necessary to supplement melatonin if the SCFAs actually do buildup melatonin and its receptors as shown in multiple studies. The highest available single dose I have seen is 400mg in a suppository delivery dose. Things may just happen slower than with melatonin supplementing as I am doing, but I know for a fact, that melatonin alone at the dose I am taking was only able to prevent severe exacerbations of my psoriasis and not get me anywhere near 96% clear, as I am today! I have 7 weeks to lose those last 4%.

Art

LAJ12345 profile image
LAJ12345 in reply tochartist

That’s pretty exciting!

I have just gone back to my go to place for melatonin and they have put a stop to ordering it without a prescription. Really I am sick of all this interfering in our ability to buy things. Grumpy now. 😖

chartist profile image
chartist in reply toLAJ12345

Well look, LAJ,

The pistachios are one of the foods with the highest content of melatonin and I guess that makes it just that much more ideal for this specific purpose of trying to increase SCFAs and melatonin in the gut and maybe that means you can get by without using it as a supplement. That is the goal in the long run anyway! In any case, I will continue searching for other SCFA Producing bacteria options.

Art

chartist profile image
chartist in reply toLAJ12345

LAJ,

There is another idea to pursue along this course and that is to attempt to starve the pathogenic gut bacteria while feeding the health promoting bacteria. That would entail cutting back on sugar and the type of carbs that can feed pathogenic bacteria. Making the pathogenic bacteria weak will make it easier for health promoting bacteria to regain control and build momentum toward promotion of health. Just a thought for you to consider.

If you think about it, the body may be craving what the dominant bacteria want. It may be that these bacteria send chemical signals to the brain and the brain relays these message signals that ultimately give us cravings for certain foods. One thing I've noticed is that my usual cravings for sweets, candy, ice cream and desserts have dropped off very significantly in the past few weeks. I still get them, but not like before.

Art

LAJ12345 profile image
LAJ12345 in reply tochartist

Hi, yes that is what we did right at the beginning so we don’t eat sugar or gluten or as many carbs for the last 2 1/2 years. And then the berberine and allimed kill the bacteria as well. That did take well over a year though so not quick. If I try something sweet now it tastes unpleasant and I vegetables taste very sweet now.

That’s why I wondered if you have tried gluten free. It might give you an extra boost. Less carbs for one. Also a friend of mine has been dairy intolerant and has had bad eczema her whole life. She got also a diagnosis of crohns a year ago. She has gone gluten free about a year ago, she started replicating our high vege diet, and she said she can now eat dairy again and her eczema is gone and her digestion seems back to normal!

Giovi1960 profile image
Giovi1960

So happy for you! Hope the improvement continues. All the best.

chartist profile image
chartist in reply toGiovi1960

Thank you, Giovi!

Yes, I definitely hope it continues! This is the first time I ever specifically tried to manipulate the gut microbiome and the only reason I did it was because of the exceptional results obtained in the FMT/PD studies!

Art

Giovi1960 profile image
Giovi1960

I'm thinking of giving it a try. I tried the intermittent diet once but it made me awfully constipated. So not doing it again. Could you tell me where do you buy the 106 mg melatonin? Do you know if it would be the same for a woman of 61 y.o. and 113 pounds? Sorry to bombard you with so many questions, but I have read your posts before and I think you're a very well informed person. Someone I can trust, sort of lol.I'm going to read your previous posts too.

Have a great day.

chartist profile image
chartist in reply toGiovi1960

Giovi,

My thinking is that the melatonin supplementation may not even be needed, as, if the science is correct, the SCFAs should slowly build the level of melatonin in the gut back up to being similar to what you were when you were healthy. For me, I'm thinking that supplementing with melatonin at high dose may speed the process up and I am also interested in getting the other health benefits associated with melatonin including for use against Covid-19.

Art

Giovi1960 profile image
Giovi1960

Hi Art, Thanks for writing back. I see what you mean. I'm taking 10 mg at night to help with my sleeping problems. So I will stick to that amount (for the time being anyway).

Keep safe and regards.

Gio

LauraYu profile image
LauraYu

Hi Art, thank you for sharing your knowledge and experience, greatly appreciate it!

In terms of melatonin supplements, is it interacting with Sinemet? I take Sinemet right before bedtime, is it ok to take melatonin right after? Many thanks, Laura

chartist profile image
chartist in reply toLauraYu

Hi LauraYu,

These two links should answer your question :

drugs.com/interactions-chec...

drugs.com/drug-interactions...

Art

LauraYu profile image
LauraYu in reply tochartist

Thank you!

MarionP profile image
MarionP

Like your approach here very much, and especially demonstrating at least in your case usefulness and at least the apparently non-adverse situation with high dose melatonin, which more than a few should be interested in, as well as general HDT, very nice indeed... Very good.

chartist profile image
chartist in reply toMarionP

Thank you, MP!

Now I am going to look for other ways to try and get the bacteria that produce SCFAs.

What seems really odd to me is that science now knows exactly which specific bacteria will interact with prebiotics and fermentable fiber to create SCFAs which are known to be low in PD, psoriasis and other disease states, but there appears to be no effort to create a synbiotic to test and ultimately make available to the public? This is such a noninvasive approach, why wouldn't it be tested already?

Art

MarionP profile image
MarionP in reply tochartist

Maybe nobody thought of it til now!

chartist profile image
chartist

Apparently, some diets are not SCFA friendly, according to this article which says that low carb /high fat and high protein diets may be counter productive for SCFAs.

atlasbiomed.com/blog/butyra...

Art

faridaro profile image
faridaro

Another brilliant approach Art - glad it's working for you and thank you for sharing!Have you ever thought of writing a book?

chartist profile image
chartist in reply tofaridaro

Thank you faridaro!

Have never considered it, but the sum total of what I have written on this forum is probably close to a book.

Art

chartist profile image
chartist

I am posting a link to this study that forum member Bolt_Upright (thank you, Bolt!) sent me regarding boosting butyrate in the gut via application of resistant starch. Resistant starch (RS) has effects in the gut that are somewhat similar to prebiotics and fermentable fiber and can act as food for short chain fatty acid producing bacteria to interact with and create short chain fatty acids (SCFAs).

medrxiv.org/content/10.1101...

In order to get the maximum benefit from RS, your gut has to have enough SCFA producing bacteria available and if there is insufficient type and number of these bacteria present, the benefit will very likely be less than FMT. This study tends to confirm this idea because RS was only able to ramp up production of Butyrate enough to reach statistical significance, but could not do the same for Acetate and Propionate, the other two dominant SCFAs.

The end result was measureable improvement, but not in the same range of improvement as FMT showed in the FMT/PwP studies. This to me is somewhat similar to what we see with mannitol which is a known butyrate agonist in the gut, but not so much for acetate and propionate. I think it will take stimulation of all three predominant SCFAs in order to come closer to the FMT results in PwP.

Art

Ghmac profile image
Ghmac

Roasted or raw Pistachios?

chartist profile image
chartist

I am using roasted, sea salted and shell on pistachios. Any way you slice it, pistachios are a very healthy food and not just as I have mentioned in the original post above, but also as discussed here :

youtu.be/wQXsfPskVQY

What's not too like about pistachios and they taste good too!

Art

chartist profile image
chartist

Just an update as of today, Monday (08/16/2021).

In the 2021 FMT/ PwP study, they mentioned the FMT side effects encountered by participants as :

1. Flatulence

2. Diarrhea

3. Abdominal Pain

Since I am trying to replicate the effects of FMT, it seems likely that I might get one or two of these side effects, and I am. I have gotten flatulence and abdominal pain, but no diarrhea. The flatulence is mild to moderate and nowhere near as much as I got from my Potato Resistant Starch experiment I did years ago. The abdominal pain seems like it is caused by the flatulence.

I am now about 97% clear. Daily improvements have slowed to every three days to see very small improvements. This too seems in line with the FMT studies with improvement increasing right up to the end of the 12 week trial period. So I am currently in the 7 to 8 week range. I can't remember the last time I was this clear, but it was years ago. I am finally able to wear shorts again!

Art

chartist profile image
chartist

This new study (August 2021) details how Short Chain Fatty Acids in PwP are lower than healthy controls and even with the addition of SCFA promoting fiber in both fecal fermentation tests from each group, the SCFA levels remained lower in PwP samples. The study doesn't say, but again this is likely due to the fact that PwP have less SCFA producing bacteria than healthy controls in their gut microbiome.

nature.com/articles/s41531-...

Interestingly in these fermentation tests, inulin appeared to be the better tested fiber for increasing SCFAs. Inulins > Oligosacharides > Resistant Starch > Pectins.

This adds further confirmation to the idea that increasing fiber and prebiotics is not enough to normalize the PD gut, you have to also increase the SCFA producing bacteria levels.

Art

chartist profile image
chartist

This new animal study abstract (9/2021) gives a major clue about what happens when melatonin is plentiful in the gut and serum.

pubmed.ncbi.nlm.nih.gov/344...

Melatonin seems like it should be called a "smart molecule"!

Art

chartist profile image
chartist

I said I would report any beneficial substances that are likely to either supply short chain fatty acid (SCFA) producing bacteria or increase SCFAs themselves and this recent study (July 2021) shows that Lactulose, which is commonly given for constipation as well as for hepatic encephalopathy can increase SCFAS as well as other gut health promoting activities.

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

Here is a quote from the study :

>>> ' a wealth of evidence demonstrates that, at low doses, lactulose can also be used as a prebiotic to stimulate the growth of health-promoting bacteria in the gastrointestinal tract. Indeed, multiple preclinical and clinical studies have shown that low doses of lactulose enhance the proliferation of health-promoting gut bacteria (e.g., Bifidobacterium and Lactobacillus spp.) and increase the production of beneficial metabolites [e.g., short-chain fatty acids (SCFAs)], while inhibiting the growth of potentially pathogenic bacteria (e.g., certain clostridia). SCFAs produced upon microbial fermentation of lactulose, the most abundant of which is acetate, are likely to contribute to immune regulation, which is important not only within the gut itself, but also systemically and for bone health. Low-dose lactulose has also been shown to enhance the absorption of minerals such as calcium and magnesium from the gut, an effect which may have important implications for bone health. ' <<<

These are many of the things we would be looking for in order to try and reverse gut dysbiosis!

The downside here is that lactulose is a prescription medication and may not be easy to talk your doctor into writing a prescription for it unless you are constipated.

Art

chartist profile image
chartist

I was just reading this Australian study that seems interesting in terms of gut repair. In the study they used a formulation of ingredients that are thought to improve gut dysbiosis and their results were pretty impressive. Interestingly, the gut bacteria that this formulation increased are some of the same bacteria that are lacking in PwP. The formulation contains the following ingredients :

Active Ingredients

Each 5g of NC Gut Relief powder contains:

Cumerone® 30.37 mg

Equiv. Curcumin 6.38 mg

Glutamine 2.5 g

Quercetin 200 mg

Glucosamine Hydrochloride 415.05 mg

Aloe Vera fresh leaf

Equiv. Aloe Vera fresh leaf 500 mg

Peppermint Oil 3 mg

Slippery Elm (Ulmus rubra)

Stem Bark Inner Powder 500 mg

Guar Gum 100 mg

Pectin 100 mg

Dibasic Sodium Phosphate 260 mg

Here is a link to the study :

sciencedirect.com/science/a...

Here is a link to the product that was used in the study :

natonic.com.au/en/nutrition...

Art

chartist profile image
chartist

Currently as of 8/25/2021 I am 98% clear. The gas is still there, but seems to have less ups and more downs which is good, but the abdominal pain has decreased significantly, which seems in line with the FMT study results. My results overall have been very good, but the rate of improvement has clearly declined now and improvement occurs at a much slower pace than when I started on this regimen.

I don't know if I will make it to 100% clear within the 12 week schedule I am working toward, but the improvements are very substantial and at a level that I have not seen in over a decade and I feel very fortunate for the improvements. I am currently in the 8 to 9 week range of this test. There are still a few stubborn areas that are very slow to clear, but seem to be trending down. My skin tone also seems to be significantly more even which is nice because psoriasis leaves plenty of discolorations on the skin once the psoriasis starts to diminish and those discolorations have significantly diminished. I believe they are referred to as post inflammatory hyperpigmentation and hypopigmentation with some areas showing darker and some areas showing lighter, but both types are noticeably diminished.

My bowel movements are daily and smooth with little effort at all. Overall, gas production seems to be on a downward trend, but still there. That's it for now.

Art

Kia17 profile image
Kia17 in reply tochartist

👍

chartist profile image
chartist

This clear and interesting article, although not about Fecal Microbiota Transplantation (FMT), explains many reasons why FMT would be quite helpful for PwP. It further exemplifies why Short Chain Fatty Acids (SCFAs) are likely to be quite useful for PwP, a point that I am a true believer in and I feel that this article also helps to support my theory about a potential repetitive pro-health cycle involving the interplay between SCFAs and melatonin! This article further illustrates the role of gut inflammation and how it may potentially lead to PD over time. The gut brain connection as well as the role of the gut microbiome and SCFAs is becoming clearer and clearer.

psychiatryadvisor.com/home/...

This review article discusses how the melatonergic pathway is hindered via reduced serotonin in PD and results in increased inflammation, oxidative stress, nitrosative stress, gut dysbiosis and increased gut permeability. In studies, melatonin and or SCFAs work against all of these contributors to disease pathology.

pubmed.ncbi.nlm.nih.gov/276...

The role of melatonin in PD is also becoming clearer and this is why I feel that melatonin is one of the main reasons why people can have PD for a decade or more before symptoms appear strong enough to validate a diagnosis of PD, because melatonin is working effectively along side SCFAs against PD for that long until the melatonin levels and SCFA levels decline from age as well as from PD itself to a point where they are no longer able to maintain good control of the disease . It would likely be a somewhat similar situation in many age related diseases where melatonin and SCFA levels decline with age allowing the disease to advance to a place where symptoms become readily apparent and melatonin and SCFAs are no longer able to maintain control of the disease process at their lower levels.

These points are part of why I think the theory of the repetitive pro-health cycle between melatonin and SCFAs is a very real possibility.

Art

chartist profile image
chartist

Just a brief update on how my self experiment is going. Since I started this experiment, my blood pressure has been very slowly declining. At a recent visit to my primary, I mentioned this to him and he looked up my blood pressure history. After reviewing it he asked me if I would like to try lowering my blood pressure medication and I said, yes! He told me he would like to reduce it by 25%, but that the medication was not available in that size pill, so he said lets try a 50% reduction as the medication was available in that size. So I just started this reduction yesterday and will report back later on how that goes. My doctor told me that if my blood pressure goes up too high, I can always go back to the higher dose, but so far it seems fine!

I was wondering what was causing my blood pressure decrease and just a quick check suggests that melatonin, thiamine and pistachios can cause this effect, but I am going to rule out melatonin as the reason because I have been taking high dose melatonin at 106 mg or more per night for about a year now and never saw this benefit previously which suggests that either the pistachios, thiamine mononitrate or both are the reason for this benefit!

As far as the psoriasis, I am still at 98% clear!

Art

in reply tochartist

98% clear is amazing! I've been meaning to ask about quantity of pistachios. I've (coincidentally) been snacking on them, but it is only a small handful of shelled nuts. How much are you eating?

chartist profile image
chartist in reply to

I use a little cup like restaurants use for ketchup and ranch dressing. When filled to the very top it holds 4 ounces of water. I fill this to overflowing with pistachios with shells on. I eat 4 of these little cups per day.

Art

in reply tochartist

Thanks! ha, I even have one of those. :D

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