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Ergothioneine - amino acid for life extension.

Literature Review
ergothioneine life extension
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  • M
    Mauritio @cs3000
    last edited by Mauritio Apr 21, 2024, 9:18 AM Apr 21, 2024, 9:11 AM

    @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 .

    Dare to think.

    My X:
    x.com/Metabolicmonstr

    1 Reply Last reply Reply Quote 0
    • M
      Mauritio @cs3000
      last edited by Apr 21, 2024, 9:27 AM

      @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)."

      Dare to think.

      My X:
      x.com/Metabolicmonstr

      1 Reply Last reply Reply Quote 0
      • M
        Mauritio
        last edited by Apr 24, 2024, 5:37 AM

        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/

        Dare to think.

        My X:
        x.com/Metabolicmonstr

        1 Reply Last reply Reply Quote 0
        • M
          Mauritio
          last edited by Apr 24, 2024, 5:46 AM

          "...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

          Dare to think.

          My X:
          x.com/Metabolicmonstr

          1 Reply Last reply Reply Quote 0
          • M
            Mauritio
            last edited by May 1, 2024, 8:13 PM

            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/

            Dare to think.

            My X:
            x.com/Metabolicmonstr

            1 Reply Last reply Reply Quote 0
            • M
              Mauritio
              last edited by May 3, 2024, 9:32 AM

              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.

              Dare to think.

              My X:
              x.com/Metabolicmonstr

              1 Reply Last reply Reply Quote 0
              • W
                wrl
                last edited by May 3, 2024, 10:51 AM

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

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

                M 1 Reply Last reply May 4, 2024, 3:26 PM Reply Quote 0
                • M
                  Mauritio @wrl
                  last edited by May 4, 2024, 3:26 PM

                  @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."

                  Dare to think.

                  My X:
                  x.com/Metabolicmonstr

                  I 1 Reply Last reply Jul 8, 2024, 1:02 AM Reply Quote 0
                  • M Mauritio referenced this topic on Jun 9, 2024, 1:10 PM
                  • I
                    Ismail @Mauritio
                    last edited by Jul 8, 2024, 1:02 AM

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

                    1 Reply Last reply Reply Quote 0
                    • M
                      Mauritio
                      last edited by Jul 8, 2024, 8:44 PM

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

                      Dare to think.

                      My X:
                      x.com/Metabolicmonstr

                      I C 2 Replies Last reply Jul 8, 2024, 9:07 PM Reply Quote 0
                      • I
                        Ismail @Mauritio
                        last edited by Jul 8, 2024, 9:07 PM

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

                        1 Reply Last reply Reply Quote 0
                        • C
                          CrumblingCookie @Mauritio
                          last edited by Jul 8, 2024, 10:46 PM

                          @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.

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                          • D
                            DavidPS
                            last edited by Jul 9, 2024, 9:11 AM

                            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.

                            ““Effective health care depends on self-care” - Ivan Illich, 👀
                            ☂️

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                            • L Luke referenced this topic on Jan 7, 2025, 1:43 PM
                            • C
                              cs3000
                              last edited by cs3000 Jan 7, 2025, 5:44 PM Jan 7, 2025, 4:45 PM

                              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

                              ea5eaf68-8018-44fe-9955-2751652555da-image.png

                              196e4715-3e16-4aee-b1bf-28fb4cc0e6c7-image.png
                              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
                              b4ce2850-6529-47dd-834c-cb5880416b48-image.png
                              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

                              "world," as a source of new perceptions
                              more https://substack.com/@cs3001

                              "Self-organizing systems decay only if they have assimilated inertia and — with a little support of the right kind— the centers of degeneration can become centers of regeneration"

                              M 1 Reply Last reply Jan 7, 2025, 9:08 PM Reply Quote 0
                              • M
                                Mauritio @cs3000
                                last edited by Jan 7, 2025, 9:08 PM

                                @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...

                                Dare to think.

                                My X:
                                x.com/Metabolicmonstr

                                C 1 Reply Last reply Jan 9, 2025, 12:13 PM Reply Quote 0
                                • L
                                  Luke
                                  last edited by Jan 8, 2025, 6:58 AM

                                  @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

                                  I've never been a big party attender, but I never went to a party where I didn't probably offend most of the people there by talking about what I was interested in. (Ray Peat)

                                  D 1 Reply Last reply Jan 8, 2025, 1:19 PM Reply Quote 0
                                  • D
                                    DavidPS @Luke
                                    last edited by Jan 8, 2025, 1:19 PM

                                    @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)

                                    3e1dce5a-4791-446d-80a3-0da0eb5e5681-image.png

                                    ““Effective health care depends on self-care” - Ivan Illich, 👀
                                    ☂️

                                    1 Reply Last reply Reply Quote 0
                                    • C
                                      cs3000 @Mauritio
                                      last edited by cs3000 Jan 9, 2025, 1:19 PM Jan 9, 2025, 12:13 PM

                                      @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
                                      ca97198f-3390-4db2-ae75-ed78f3a41ad6-image.png
                                      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)
                                      66f4987c-ae55-4909-8884-a0d5b5db3a42-image.png
                                      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
                                      ecf7b568-e9cb-4c99-8616-edb8e6963a5f-image.png
                                      990fe169-7b5f-438f-99c9-c636020b7ed9-image.png

                                      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

                                      19140609-e0ff-4998-a24f-710b345c766f-image.png

                                      *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

                                      59365cb1-b7dd-40ca-aeb3-aebf09c5561f-image.png

                                      "world," as a source of new perceptions
                                      more https://substack.com/@cs3001

                                      "Self-organizing systems decay only if they have assimilated inertia and — with a little support of the right kind— the centers of degeneration can become centers of regeneration"

                                      D 1 Reply Last reply Jan 9, 2025, 1:16 PM Reply Quote 0
                                      • D
                                        DavidPS @cs3000
                                        last edited by Jan 9, 2025, 1:16 PM

                                        @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:

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

                                        2. 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.

                                        3. 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.

                                        4. 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.

                                        ““Effective health care depends on self-care” - Ivan Illich, 👀
                                        ☂️

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                                        • C
                                          cs3000
                                          last edited by cs3000 Jan 9, 2025, 2:20 PM Jan 9, 2025, 1:55 PM

                                          Another good one ,
                                          gives weight to ergo as the main compound in mushrooms that gives the main cognition improving effects vs b-glucans

                                          giving mice deficient diet for 5 weeks
                                          then refeeding 3x a week for 2 weeks (2mg/kg or 20mg/kg)

                                          discrimination index (DI), an indicator of learning and memory ability
                                          restored by either amount (and higher than controls) , took 2 weeks

                                          5ba56789-bc58-4d3e-882d-68a13729c039-image.png
                                          (smaller amounts likely work the same too just with a longer buildup , amounts build to 4 weeks its half life)

                                          https://pmc.ncbi.nlm.nih.gov/articles/PMC10847428/#Sec2

                                          something interesting is their hippocampal levels didnt restore to controls at 2mg/kg vs 20mg/kg by 2 weeks, but still got the effect. i wonder how much mice usually get & where from. ive seen adding 0.5mg/kg bw to normal mice diet gave behavioral improvements in another study posted here

                                          neurogenesis
                                          33ea6482-3a77-46d3-b78a-21eb9acf6efa-image.png

                                          "world," as a source of new perceptions
                                          more https://substack.com/@cs3001

                                          "Self-organizing systems decay only if they have assimilated inertia and — with a little support of the right kind— the centers of degeneration can become centers of regeneration"

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