Ergothioneine - amino acid for life extension.

cs3000

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

stimulates mitochondria respiration & more in diet boosts exercise performance
https://www.biorxiv.org/content/10.1101/2024.04.10.588849v1.full

Humans and mice obtain EGT exclusively from their diet. Despite only trace levels of EGT in standard mouse diets (5.6 ng/mg), rodents can show high basal level of EGT in their tissues (mouse liver 80.7 ng/mg), indicating efficient EGT uptake

(builds up over time, glutathione helps recycle it)
,

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

Its cycling between oxidized and reduced sulfur takes place non-enzymatically and is facilitated by the intrinsically tautomeric structure of the molecule. These properties suggest a role for ET as a bulwark, a final defense for cells against oxidative damage. Its stability may help mitochondria cope with otherwise overwhelming stresses encountered even during relatively physiologic metabolism.
Endogenous levels of ET vary, attaining millimolar concentrations in tissues that are typically exposed to marked oxidative stress such as blood cells, the lens of the eye, liver and bone marrow. In the bovine lens, ET concentrations, about 7 mM, 10 exceed those of glutathione, generally regarded as the most abundant endogenous antioxidant. In the bovine cornea, ET concentrations are 14-fold higher than those of glutathione, suggesting that it is the principal antioxidant in this tissue.
When acting as an antioxidant, its SH group is oxidized but very rapidly reduced because of the unique tautomeric structure of the molecule. By contrast, glutathione is often almost totally depleted in the face of oxidative stress.
following administration of radiolabeled ET to rats, mitochondrial accumulation was higher than in any other particulate subcellular compartment.
ET might be uniquely involved in the protection of mitochondrial DNA from the superoxide generated in the course of the electron transport cycle.
Because of its highly charged nature, ET does not readily diffuse out of cells. In our own experiments a variety of cell lines labeled with [3H]ET retain most of the radiolabel for many hours even after repeated washing with fresh media
In summary, ET is a most unusual amino acid with substantial antioxidant efficacy. The existence of a physiologic ET transporter is responsible for high tissue levels.
For all these reasons ET appears to be an important physiologic cytoprotectant which probably merits designation as a vitamin.

theres a small amount of supplements ~~but have microcrystalline cellulose. eh might outweigh but pretty sure that fucks with the gut~~ microcrystalline cellulose should be fine for the gut actually, silicon dioxide is the concerning 1

Aside from mushrooms main dietary source looks to be chicken liver. nothing major but builds over time.
and apparently spirulina is high in it up to 0.8 mg per g dry weight https://www.sciencedirect.com/science/article/abs/pii/S0308814611009344 and raised catalase here (but dose is water extract) https://pubmed.ncbi.nlm.nih.gov/21697639/ and in humans 500mg x 4 raised catalase into 30 and 60d https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320919/table/tab5/?report=objectonly
high in vit K , medium-high in iron, random sampling apparently low enough in heavy metals at reasonable doses , ~5g maybe up to 5mg per g of chlorophyll also,

... but high in beta carotene (~1mg per g) , 3300iu in 1mg retinol. conversion all over the place but say 4:1 equivalent, would be 800iu vit a per g of spirulina which is pushing it with grams considering the extra from diet

The vitamin A equivalency ratio for β-carotene to vitamin A is currently estimated as 12:1, by weight (12 μg β-carotene is equal to 1 μg retinol), for plant sources of β-carotene in a mixed diet. The ratio is based on ∼17% absorption of β-carotene from a mixed diet (6 μg plant β-carotene = 1 μg pure β-carotene) and a conversion ratio to vitamin A of 2:1 (2 μg β-carotene = 1 μg retinol)

that estimates ~12:1 average though for plant sources which would be a lot better, 200iu vit a per gram. 5g 1000iu and maybe gets you 3mg ergothioneine daily building up over time
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10535605/ active at 0.1mg/kg orally so <1mg heq , potent

Mauritio

@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 .

Mauritio

@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)."

Mauritio

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/

Mauritio

"...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

Mauritio

ERGO can protect against social defeat.

"...ergothioneine prior to and during the SDS (social defeat stress) paradigm had a preventative effect on SDS-induced depressive behaviors, such as social avoidance and depression-like sleep abnormalities, particularly those of rapid eye movement sleep."

Not only that, I already mentioned that some gut bacteria can synthesize ergothioneine. One of them is L. Reuteri. It can increase testosterone dramatically and is anti-inflammatory. Well, another benefit can be added to the list now! Hans made an interesting video on it.

Youtube Video

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256047/

Mauritio

I took my first tablet yesterday.

It increases muscle fullness and I am feeling more androgenic. I think it is good for liver health. Had some bile dumps and felt a sense of relief after.

I am currently adjusting my thyroid dosage and everbody who did that before knows that can be a pain in the ass and you might have to go through a few days of suboptimal thyroid function. Ergothioneine definitely helped with that and relieved the low mood and lethargy associated with hypothyroidism. It also made me more active during the day, but sleep was very refreshing.
Verbal fluency seems increased.
The only downside is hair loss is a bit increased. But not strongly.

I can only encourage people to try it. Given its long half life it might be taken only 1 or twice a week since the body accumulates it similarly to the fat soluble vitamins.

wrl

Ergothioneine: A Stress Vitamin with Antiaging, Vascular, and Neuroprotective Roles?

https://www.liebertpub.com/doi/full/10.1089/ars.2021.0043

Mauritio

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

Ergothioneine: A Stress Vitamin with Antiaging, Vascular, and Neuroprotective Roles?

https://www.liebertpub.com/doi/full/10.1089/ars.2021.0043

Good one.

It also seems to have cosmetic benefits .

"ET accumulates in skin cells and not only prevents oxidative damage but also facilitates DNA repair in UV-irradiated cells (80). For these reasons, ET has been included as an ingredient in several skin care products and cosmetics."

Ismail

@Mauritio bud, you still taking this? If so, how’s it going? Which brand/product are you taking?

Mauritio

I've only tried it a few times. It felt pretty good, but unfortunately increased my hair loss.

Ismail

@Mauritio oh no! Sorry to hear that bud! I guess you had no choice but to stop.

CrumblingCookie

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

I've only tried it a few times. It felt pretty good, but unfortunately increased my hair loss.

I wonder whether this could be related to the glutathione system. Perhaps that needs to step up accordingly. Would some 1:1 Glycin and NAC and some xx mg ascorbic acid do the trick?
If that hair loss for you really knocks through within only two days of taking ET it's an undesired but actually very convenient marker.

DavidPS

I get mine from L-reuteri (see) and I have not had any negative side effects.

Store bought mushrooms are most likely grown in manure contaminated with waste from industrial processing of cattle and the like.

cs3000

nice ergothioneine overview
https://nutritionfacts.org/video/dietary-sources-of-the-longevity-vitamin-ergothioneine/

**even eating 20g of white button mushroom daily gives a good amount with good effect (1mg), thats already bumped up a bit but for variation in amounts could go 30g, likely sorts ergothionine effects that japanese are getting with their great healthspans

-> 2 servings of mushrooms a week = 1/2 the odds of cognitive impairment

https://www.researchgate.net/publication/346870796_Is_ergothioneine_a_'longevity_vitamin'_limited_in_the_American_diet
(i think their estimates are off going by absolutes, when u look at the doses that have effects and the amounts in foods that arent mushrooms, but if their relative amounts are close its interesting) @luke

The reason it says 1mg for USA is because its including the mushroom consumers, which are only 10% of the people surveyed, so skews the number upward. if they hit the 1mg i think they'd be closer to italy ireland france

Doi: //doi.org/10.1080/10807039.2015.1104241

also this

recent longitudinal unbiased metabolomic study conducted in Sweden involving over 3200 adult men and women consuming a health-conscious food pattern at baseline sought to identify blood metabolites that could predict a lower risk of cardiovascular disease(CVD) and overall mortality(17). Out of 112 metabolites measured at baseline, they found that plasma ERGO levels were the most strongly associated with decreased risk of CVD and reduced mortality after 21⋅4 years of follow-up

Mauritio

@cs3000 that's interesting. I might try ergo again, it start eating mushrooms again!

It's a no brainer if you look at the data...

Luke

@cs3000
Nice find. Another reason to eat mushrooms.

Gut-cleaning effects
aromatase inhibtors
good Ergothioneine source
nutritious in general
If I remember correctly, Dr. Peat also talked about an antihistamine effect

DavidPS

@Luke - I like the list. I would add that it might also delay the onset of MCI.

The Association between Mushroom
Consumption and Mild Cognitive
Impairment: A Community-Based
Cross-Sectional Study in Singapore (2019)

cs3000

@DavidPS

**But there's a potential problem getting it through mushrooms, https://pmc.ncbi.nlm.nih.gov/articles/PMC8329194/#Sec2 mushrooms antagonistic to androgen receptor
they stop DHT increasing androgen receptor in multiple tissues & can lower vs controls in some tissues

ive noticed a flat mood effect from mushrooms before
heq low amounts 1g-1.5g of white button mushroom water extract (so probably not the ergo, likely b-glucans which are found in way higher amounts)

(the beta glucan content has effects ~250mg here , closely matching white button https://pmc.ncbi.nlm.nih.gov/articles/PMC11467013/#ctm270048-sec-0070)

shiitake has 1g/10g cooked b-glucan

here a b-glucan lowered estrogen in the prostate where elevated (normalized in prostate and also normalized low testosterone / AR doi: 10.1039/c4fo00472h ) there's an anti androgen receptor effect pretty potent across tissues by earlier study though using mushroom water extract

mainly because of the high beta glucan content

Here white button mushroom lowered AR in vitro, but in the mice tumors in vivo AR expression didn't lower, even tho tumors shrank (at least short term) (tho its not healthy tissue like the 1st study showed)
https://pmc.ncbi.nlm.nih.gov/articles/PMC8542389/#S17

*maybe a supplement is best if doesnt also include the mushroom powder.
or taking 2g spirullina , if dont respond well to androgen reducing stuff

--
also for ppl eating, wondered if microwaving destroys the ergothionine, nope all ergothioneine stays intact
https://www.jstage.jst.go.jp/article/fstr/25/1/25_115/_pdf/-char/en
Best not to boil them 2/3 of the ergothioneine gets drained
Roasting is good and frying should be ok too can pour the fat into the food

DavidPS

@cs3000 = Thanks for all the information. I do not like all the fuss associated with boiling mushrooms as Dr. Peat advised. I am mostly interested in ergothioneine rather than the mushrooms themselves.

Peatbot.com: To cook mushrooms safely and effectively, particularly white button mushrooms, it is recommended to boil them. Here is a detailed method:

Preparation: Clean the mushrooms thoroughly to remove any dirt or debris. You can slice them if desired, but whole mushrooms can also be used.

Boiling: Place the mushrooms in a pot of water and bring it to a boil. It is suggested to keep them at the boiling temperature for at least an hour to ensure safety and maximize the health benefits.

Alternative Cooking Method: While boiling is recommended, you can also fry them in butter for flavor. However, it is still advised to boil them first to reduce any potentially harmful substances.

Cooking Time: Although mushrooms may be safe after boiling for 15 to 20 minutes, cooking them for up to an hour is recommended to ensure they are thoroughly cooked and safe to eat.

This method helps to reduce the agaritine content, a compound found in mushrooms, which decreases significantly with prolonged boiling.