Urolithin A (mitopure) and Palmitoylethanolamide and Akkermansia muciniphila

[Bolt_Upright]

Congratulations to John_morris71 for confirming Mitopure really does have 500 mg of Urolithin A healthunlocked.com/cure-par...

John got me poking around Urolithin A and something caught my eye. Only about 40% of people have the bacteria needed to turn pomegranate juice into Urolithin A. So... I noticed this:

Direct supplementation with Urolithin A overcomes limitations of dietary exposure and gut microbiome variability in healthy adults to achieve consistent levels across the population nature.com/articles/s41430-...

"Of note was also the increased abundance of Akkermansia muciniphilia in the microbial high UA producer group compared to the low and non-producers"

And it reminded me of something else that had crossed my eye: Palmitoylethanolamide: A Natural Compound for Health Management

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

"PEA may contribute to correcting the effects of dysbiosis. In an induced inflammation state, such as vitamin D deficiency in mice, intraperitoneal administration of PEA increases the level of commensal bacteria such as Akkermansia muciniphila (protective effects against obesity and diabetes), Eubacterium (microbiome regulatory properties) and Enterobacteriaceae [83]. Moreover, exogenous administration of PEA relieves chronic and acute GIT inflammation via its action on PPAR-α in the colon [84]. For these reasons, PEA is becoming an increasingly popular topic in microbiome research."

So... PEA boosts Akkermansia muciniphila. Akkermansia muciniphila boosts UA.

So maybe if I keep taking my PEA, and drink some pomegranate juice, I won't have to pay for that super expensive Mitopure!

[park_bear]

edit - misunderstanding deleted

[John_morris71 in reply to park_bear]

I am still trying to figure out and may have found some sort of explanation. (Not an endorsement)

I am suspecting that they are showing the PEAK MEAN of Plasma levels of Urolithin A Glucoronide after taking Mitopure 500mg and not how much of it is contained in 500mg of the sachet. To the naked eye, looks like it is somewhere close to 475 ng/ml in that bar graph.

Please let me know if it makes sense.

As detailed below in the excerpt from the article

nature.com/articles/s41430-...

Direct oral supplementation with Urolithin A delivers significantly higher levels than PJ

In the PJ intervention, the baseline (T0) mean UA glucuronide levels were 5.48 ± 19.97 ng/mL, slightly increasing to 12.84 ± 36.34 ng/mL at the 6 h time point and rising to 110.47 ± 131.6 ng/mL 24 h following PJ intake.

In comparison, during Mitopure supplementation, the mean baseline (T0) levels of UA glucuronide were 9.57 ± 47.78 ng/mL; at 6 h UA glucuronide concentration PEAKED in circulation to 480.75 ± 238.03 ng/mL and then declined to 255.52 ± 129.38 ng/mL 24 h after Mitopure intake (Fig. 4A and Supplementary Table 4).

The absolute change in UA glucuronide levels from baseline to T24 (primary outcome of study) between PJ and Mitopure supplementation was investigated to determine plasma levels of UA a day following intake.

[park_bear in reply to John_morris71]

OK . That makes sense. Peace.

[John_morris71 in reply to park_bear]

So one problem solved.

Now how to we solve the cost problem, even after a 10% discount is available on the website. LOL

Buying a lotto ticket today!

[park_bear in reply to John_morris71]

Yes, one issue out of the way. However, every study of UA in Parkinson's that I have seen pretreated with UA before applying the toxicant. This is not a valid model of Parkinson's. I saw one clinical study of but only of healthy adults.

[Bolt_Upright]

DAMN DAMN DAMN DAMN DAMN

"levels of Akkermansia were significantly increased in feces of PD patients compared to control groups in four studies,52, 55, 57, 60 with particular mention to the increase in Akkermansia muciniphila." ncbi.nlm.nih.gov/pmc/articl...

So I guess we don't need PEA to boost our Akkermansia muciniphila. I don't think this means PEA is bad for us (but I was a lot happier when I thought boosting Akkermansia muciniphila was a good thing).

[Sydney75 in reply to Bolt_Upright]

So I assume the presence of this bacteria is bad for PD. Yet it is stated to lower inflammation for metabolic diseases. I did not read the entire article, I researched Akkermansia bc I did not know the term. This is what makes supplementing so difficult, what benefits one disorder can be harmful to another. Really have to hunt down all angles, using PEA to reduce nerve pain (meh).

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

Akkermansia muciniphila is a mucin-degrading bacterium commonly found in human gut. A. muciniphila has been inversely associated with obesity, diabetes, inflammation, and metabolic disorders. Due to its highly promising probiotic activities against obesity and diabetes, A. muciniphila has drawn intensive interest for research and development in recent years. A number of human and animal studies have shown that the abundance of A. muciniphila in the gut can be enhanced through dietary interventions. The present review focuses on evidence-based dietary strategies of improving A. muciniphila abundance in the gut by critically appraising up-to-date available human and animal intervention studies on A. muciniphila growth and their impact on risk factors of obesity and diabetes. Their potential mechanisms in promoting A. muciniphila are also discussed along with the discussions of mechanism of action for A. muciniphila to exert probiotic functions.

[Bolt_Upright in reply to Sydney75]

I will take a guess that Akkermansia muciniphila is higher in PD patients because PwP have inflammation and the Akkermansia muciniphila is increasing to help it. Just taking a guess.

[Hidden in reply to Bolt_Upright]

Helping in what sense? Just clarifying. Helping as in reducing inflammation or increasing Akkermsnsia in a negative way? Maybe I need to dive back in to this one to reassess?

[Bolt_Upright in reply to Hidden]

My guess is PD raises inflammation and Akkermansia muciniphila is increasing to help lower the inflammation.So people with PD have increased Akkermansia muciniphila, and PEA boosts Akkermansia muciniphila, but Akkermansia muciniphila lowers inflammation, so the fact that PEA increases Akkermansia muciniphila is not necessarily a bad thing.

[Hidden in reply to Bolt_Upright]

Oh no! I’m taking it and I think it is why my shoulder is hurting less. 😞

[Bolt_Upright in reply to Hidden]

I don't think the increasing Akkermansia muciniphila is a bad thing. That is my HS degree talking. I am still taking it. Hoping it is disease modifying.

[Hidden in reply to Bolt_Upright]

It’s notIt’s a good thing! I was just doing a post

[Hidden]

Yes indeed! Thank you John Morris! Please when contemplating this supplement consider that multiple senolytics should not be used at once or indefinitely.

[Awyn]

Very interesting.

ccraspberry- To clarify… when cautioning “that multiple senolytics should not be used at once or indefinitely” you are referring to the Urolithin, not the PEA, correct? As far as I can discover, wherein PEA may assist in eliminating senescent cells by the shear nature of it’s anti-inflammatory role as a neuroprotective mediator, it is not a senolytic.

Bolt- With regard to the PEA powder you have ordered, how are you planning to administer for best absorption, since it is insoluble in water? I read that because one of the natural substances it can be derived from are peanuts, that mixing in peanut butter is one way. Others…straight on the tongue with a juice chaser (POM makes sense), sprinkled on fruit, with yogurt, …or, in a capsule, the capsule being the easier delivery however may not fully absorb once in the stomach/gut, i.e. perhaps the more wasteful way. Would love to know how you plan to take it…and if you experiment with different deliveries, which way, over time, gives you the best, most noticed, effects.

Also…have you read anything about the role of PEA if also taking Quercetin, which IS known for senolytic properties?

[Bolt_Upright in reply to Awyn]

So I joined this FB PEA group: facebook.com/groups/1620388...

They may have ideas.

I noticed last night that if I take my Licorice Root Extract by itself it sticks to the roof of my mouth. I am thinking of mixing the licorice with the PEA so they both stick to the roof of my mouth.

[Bolt_Upright]

So... i had this thought this morning:

1: PwP have higher counts of Akkermansia muciniphila.

2: Akkermansia muciniphila degrades mucin in the intestines.

3: Mucin makes up mucus in the intestines.

4: PwP have less mucin/mucus in the intestines.

Conclusion: There is SOMETHING in the mucus in the intestines that should not be there, or should not be there at the level it is there. The body is trying to rid itself of it with higher counts of Akkermansia muciniphila.

So... can we help clear whatever it is the Akkermansia muciniphila is trying to clear? Or should we find a way to get the Akkermansia muciniphila to simmer down? I don't know where this leads.

And most importantly: I HAVE A HIGH SCHOOL DEGREE AND AM FREQUENTLY WRONG.

[MoJoe2]

The enzyme responsible for the conversion is not available. A Swiss company can supply Urolithin A directly. Do a Google. While you are at it Google "CGP Blackcurrants"

[Bolt_Upright]

HU permits editing

[MoJoe2]

Thanks.