Posts made by Mauritio

" TPH1 is highly expressed in SBNETs and many cancer types. TPH1 knockdown cells and telotristat treated cells showed similar growth rates as control cells in vitro . However, TPH1 knockdown cells formed smaller tumors in vivo and tumors were less vascularized. Although Tph1 inhibition with telotristat showed no effect on tumor cell growth in vitro , Tph1 inhibition reduced tumor formation in vivo . Serotonin inhibition in combination with other therapies is a promising new avenue for targeting metabolic vulnerabilities in NENs."

• https://pubmed.ncbi.nlm.nih.gov/37066322/

@Kasper said in Methionine/Cysteine restriction increases longetivity AND energy expenditure:

FGF21

FGF21

The benefits of MR are almost exclusviely downstream from FGF21. ("...mice lacking FGF21 fail to exhibit metabolic responses to protein restriction...")
https://pubmed.ncbi.nlm.nih.gov/35393401/
Interestingly FGF21 fails to have effects when the longevity gene klotho is silenced, so FGF21's effects seem to depend on klotho.
https://pubmed.ncbi.nlm.nih.gov/23209629/

• Ketogenic diets decrease FGF21 (and klotho) as per this study, so they are not good for replicating MR
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4431718/

• Low protein diet increases FGF21 more, but high protein diet decreases liver fat more
  https://raypeatforum.com/community/threads/high-protein-diet-reduces-hepatic-fat-than-low-protein-diet.35461/

• Low carb, high protein diet decreased FGF21 by 54%
  https://pubmed.ncbi.nlm.nih.gov/38379856/

• Molecular hydrogen increases FGF21
  https://pubmed.ncbi.nlm.nih.gov/21293445/

• high sucrose diet increases FGF21
  https://pubmed.ncbi.nlm.nih.gov/28886439/

• Concentric exercise, in this case, treadmill uphill walk variations, increase FGF21 by 66% in 2 weeks in humans
  https://pubmed.ncbi.nlm.nih.gov/22701542/

@hypercashoidism said in The pro-metabolic effects of apple polyphenols:

@Mauritio i'm still not sure since i remember reading that 'theory of everything' reddit post a while back which theorised that procyanidin works through increasing intracellular degradation of DHT through the increase of an enzyme i forgot the name of. In that case i'm not sure if that's something i want, i'm more interested in better eyebrows and facial hair which more DHT breakdown would antagonise

Balding is a metabolic disease. And this thread offers 10 different mechanisms on how procyanidin helps with that, if that's not enough and you rather rely on some post you read some time ago that you vaguely remember, then I dont know what to tell you.

"...hippocampal neurogenesis were lower in mice fed an ERGO-free diet than in those fed the control diet. Furthermore, ERGO supplementation to achieve the control diet ERGO levels reversed these effects and restored ERGO concentrations in the plasma and hippocampus."

https://www.nature.com/articles/s41538-024-00250-5

Interesting that bacteria can break down AND synthesize ergothioneine, depending on the type of baceria.

"Herein we describe two enzymes from actinobacteria that cooperate in the specific oxidative degradation of ergothioneine. The first enzyme is an iron-dependent thiol dioxygenase that produces ergothioneine sulfinic acid. A crystal structure of ergothioneine dioxygenase from Thermocatellispora tengchongensis reveals many similarities with cysteine dioxygenases, suggesting that the two enzymes share a common mechanism. The second enzyme is a metal-dependent ergothioneine sulfinic acid desulfinase that produces Nα-trimethylhistidine and SO2 . The discovery that certain actinobacteria contain the enzymatic machinery for O2 -dependent biosynthesis and O2 -dependent degradation of ergothioneine indicates that these organisms may actively manage their ergothioneine content."

• https://pubmed.ncbi.nlm.nih.gov/38095354/

@hypercashoidism said in The pro-metabolic effects of apple polyphenols:

@questforhealth anyone else have an opinion on this? i always thought the same. even if procyanidin does work for hair loss i'm not that interested if it just works through being anti-DHT

Have you read this thread ? lol

@cs3000 said in Ergothioneine - amino acid for life extension.:

https://www.biorxiv.org/content/10.1101/2024.04.10.588849v1.full

And that was after 2 weeks only.

"On average control diet-fed mice ran 0.73 km per hour during the dark phase of an entire week, while EGT diet-fed mice ran 0.87 km per hour, reflecting a ∼19% increase in exercise performance during their active phase (Fig. 4B). Moreover, at peak activity EGT diet-fed mice were able to run ∼28% faster (Average 24.8 m per min) than control diet-fed mice (Average 19.4 m per min) (Fig. 4C, Fig. S4B)."

@cs3000 said in Ergothioneine - amino acid for life extension.:

very nice, thanks. love to see it when studies include solo groups vs normal controls, that catalase increase is wild

Yes, me too. Also interesting that Ive never come across this amino acid, ever. No mention of it on the RPF as well. Yet it has been known for at least a century.
Absolutely, and the overexpression of CAT to mitochondria also resulted in an increase in life span of about 20% IIRC, so that might be the most important factor here.

@cs3000 said in Ergothioneine - amino acid for life extension.:

(builds up over time, glutathione helps recycle it)

Yes, that is noteworthy that the body likes to retain it as much as possible. Almost as if it would store it for when times are bad. Which is why some scientists call it a "stress vitamin" because it is needed in times of stress otherwise not so much. Hence why knockout animals only experience issues when they are stressed.

• https://pubmed.ncbi.nlm.nih.gov/34619979/

@cs3000 said in Ergothioneine - amino acid for life extension.:

the half life on this thing lol wtf "It is not metabolized to any notable extent in mammalian tissues, the half-life of dietary ET being approximately 1 month" , very curious compound

Wow, although yesterday I read that while there is only 4% excretion , they found two likely metabolites. But not sure anymore where I read that.

@cs3000 said in Ergothioneine - amino acid for life extension.:

Its cycling between oxidized and reduced

That's exactly what methylene blue is doing as well.

I would just go for the supplement ,otherwise you'd have to eat a ton of mushrooms everyday. And I dont think I had any major issues with cellulose. And for trying it out ,it should be ok.I can only find the life extension supplement .

@questforhealth said in The relationship between Candida infections and heavy metal toxicity:

Might be making you more hypo, I know some people say oranges make them hypothyroid and if citrus pectin is made form oranges...

For me it has benefited thyroid health so much, I'm naturally almost hyperthyroid and it's making me feel better and better and I have such an appetite now, I can eat so many organs and meats and vegetables and dairy and fruits I'm just eating everything in sight, I must have been very deficient

mercury causes hashimotos like symptoms iirc, not sure about other metals

lol if oranges made me hypothyroid, I Ithink Id have noticed by now

ERG protects PUFAs from beeing oxidized and helps to maintain Vitamin E levels.

"Oral administration of 70 mg l-Ergo/kg body weight of rats for 7 days prior to the injection of ferric-nitrilotriacetate protected the fatty acids against oxidation, with notable protections directed to: 20:5 (eicosapentaenoic acid) (23%), 22:6 (docosahexaenoinic acid) (30%), 20:3 n6 (eicosatrienoic acid) (22%), 20:4 (arachidonic acid) (25%), 18:2 linoleic acid (25%) and 18:1 oleic acid (14%) in the kidney. The protection of 20:5, 20:3 n6 and 18:1 in the liver by 32%, 20% and 11%, respectively, were statistically significant. l-Ergothioneine significantly reduced kidney and liver levels of conjugated dienes and conserved the concentrations of α-tocopherol and glutathione in the kidney and liver in the ferric-nitrilotriacetate/l-ergothioneine treated rats."

• https://www.sciencedirect.com/science/article/abs/pii/S0261561403001080

This study is very interesting, because not only does it show that Ergothioneine removes the detrimental effects on reproductive health, caused by a cancer drug, but it also shows that it increases sperm health for healthy individuals as well (compare control vs L-erg group)

The effect on motility, abnormal morphology and dead cells is quite strong.

This table probably holds the key to its life enhancing capabilities: it almost trippled the catalase levels and almost halfed the MDA level (PUFA metabolite, which is very inflammatory).
The increase in catalase has been shown in another study to have remarkabe life extension effects (https://pubmed.ncbi.nlm.nih.gov/15879174/)

ERG was able to increase the Testosterone levels of the healthy control group by about 40%

• https://scholar.google.com/scholar_lookup?journal=J+Pharm+Biol+Sci&title=L-ergothioneine+supplement+protect+testicular+functions+in+cisplatin-treated+Wistar+rats&author=D.+Ayobami&author=O.+Olaniyan&author=M.+Salihu&author=K.+Illesanmi&volume=14&issue=1&publication_year=2019&pages=6-13&

"ET is found in most, if not all, tissues of laboratory rats and mice despite there only being trace levels of ET in their diet [4,15], indicating efficient uptake and retention of this nutrient. "

"...lower blood levels of ET have been associated with incidence of several disorders including Parkinson disease (PD) [19], mild cognitive impairment (MCI) [20], Crohn's disease (CD) [21] and frailty [22], while correspondingly higher levels of blood ET are correlated with lower risk of cardiometabolic disorders and associated mortality [23] and lower prevalence of peripheral neuropathy [24]. "

"A study of healthy males in Saudi Arabia found that blood levels of ET increase from infanthood to teenage years, peaking at early adulthood, again suggesting the possible importance of ET for human development [59]."

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113028/#bib9

Very solid results on the life extension front here.

Ergothioneine seems like an interesting amino acid, working as an anti-oxdidant mostly, but has many other MoAs as well.

21% increase in average life span is pretty decent and comparable to aspirin or deprenyl/selegiline.

It also supresses several age related marker and issues, so it not only increases life- but also healthspan.

• https://link.springer.com/content/pdf/10.1007/s11357-024-01111-5.pdf

@Crypt-Keeper said in Ursolic acid: anti-serotonin,anti-estrogen, pro-dopamine and more:

I remember a long time ago Patrick Arnold was releasing this substance as a muscle building and fat burning supplement. There was some initial hype but after people tried it (for those effects) it never really went anywhere.

Interesting, I guess if people expected it to work like steroids and DNP, then you're setting yourself up for disappointment of course.

@Jakeandpace said in Ursolic acid: anti-serotonin,anti-estrogen, pro-dopamine and more:

Your really loving apples lately

Theres a lot to love

Ursolic acid

It is found in apple peels and there some supplement versions of it although they are still rare.

1. Its derivatives are TPH-inhibitors, so it might be as well

• https://pubmed.ncbi.nlm.nih.gov/25930119/

2.It increases dopamine receptors D1 and D3 gene expression and enhances life span

• https://pubmed.ncbi.nlm.nih.gov/33352493/

3. Again pro-dopamine and anti-depressive

• https://pubmed.ncbi.nlm.nih.gov/22940588/

4. It boosts ATP 3-fold, increases muscle satellite cells

• https://pubmed.ncbi.nlm.nih.gov/25976755/

5. It inhibits estrogen

• https://pubmed.ncbi.nlm.nih.gov/25088993/

6. Pro-liver, pro-muscle. Increases UCP1

• https://pubmed.ncbi.nlm.nih.gov/22745735/

I have noticed 2-3 times in the days after I take MCP that my T3 dose has to be increased.

No this could be a positive or negative scenario, not sure.

The negative interpretation would be that it made me more hypothyroid.

The positive interpretation is that it made me able to tolerate more T3.

I tend towards the latter, since I always had issues increasing my T3 dose. If I went too high I would get hypo symptoms. I attributed it to the state of my liver.

So me beeing able to tolerate more T3 could mean that my liver is in a better state. And since I only take a weekly dose of MCP this would suggest that there is a semi-permanent effect of it.
I'll keep observing it.

@pineapple said in Estrogenic effects from t3 and progesterone:

@Mauritio what did you do to tolerate t3? Im skinny but cant handle even a dose smaller than what you mentioned, get same side effects. Now that you tolerate it better, what benefits is it giving you? did you solve any health problems with using t3? The whole idea from what I read is it should reduce estrogenic symptoms and edema, so I can't really figure out how it does the opposite in some people

For me it was improving liver health by loosing weight.

It increased my life quality a lot: increased energy while lowering adreanline, increased calories I could eat by about 20-30%, increased mood, lowered edema, better hormonal health, etc... all of those and probably more.

It gives you the estrogenic symptoms because it is not beeing metabolized properly. Im not sure what exactly it is, but too much T3 gives me hypothyroid symptoms and that seems to be happening to you, too. (Maybe its reverse T3?)
Thats why Ray was often talking about the RIGHT amount of thyroid that will do xyz, because the wrong amount can either cause no improvement or even worsening. T3 dosage is not easy to figure out for some people.

@pineapple said in Estrogenic effects from t3 and progesterone:

Anyone else who gets really severe estrogenic effects from small doses of t3 or progesterone? Breast growth (male), edema, immediate gain of pounds of weight (water?), emotional, depression... Even 1 mcg of t3 or just a few milligrams of progesterone causes it and it takes weeks to go away from just a single dose of either one

why is this happening? any input appreciated

I have experienced that and I am relatively certain that this has to do with suboptimal liver function.
I still experience edema , mood swings and depression when I mess up my T3 dose or liver function.
The "Peat diet" is great with a good liver ,but can lead to weight gain and other issues quickly, when liver function is suboptimal.

BTW I had to start out with 0.1mcg of T3 because that was all I could tolerate. And even that I could only tolerate after I had lost 20kg which leaned out my liver.
Thyroid requirements can vary drastically.

• https://raypeatforum.com/community/threads/pufa-deficiency-is-actually-a-symptom-of-vitamin-b6-deficiency.5934/

• https://raypeatforum.com/community/threads/efad-symptoms-most-probably-caused-by-a-biotin-deficiency.15453/

• https://raypeatforum.com/community/threads/eating-pufa-makes-my-skin-healthier-why-is-this-happening.52369/post-976686