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    Ergothioneine - amino acid for life extension.

    Scheduled Pinned Locked Moved Literature Review
    ergothioneinelife extension
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    • LukeL Offline
      Luke
      last edited by

      @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)

      DavidPSD 1 Reply Last reply Reply Quote 0
      • DavidPSD Offline
        DavidPS @Luke
        last edited by

        @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

        A mind is like a parachute. It doesn’t work if it is not open. 👀
        ☂️

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        • cs3000C Offline
          cs3000 @Mauritio
          last edited by 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
          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

          "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"

          DavidPSD 1 Reply Last reply Reply Quote 0
          • DavidPSD Offline
            DavidPS @cs3000
            last edited by

            @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.

            A mind is like a parachute. It doesn’t work if it is not open. 👀
            ☂️

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            • cs3000C Offline
              cs3000
              last edited by cs3000

              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

              "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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              • cs3000C Offline
                cs3000 @Mauritio
                last edited by cs3000

                there's human trials

                cognitive improvement
                https://www.ls-corporation.co.jp/wp-content/uploads/2022/10/ergothioneine_congitive.pdf

                and over 1 year, with people aged > 60
                https://www.medrxiv.org/content/10.1101/2024.07.08.24310085v1.full.pdf

                f92ec67d-100b-4fa5-a512-86ba1002478b-image.png
                at 6 months, and still gaining at 12 months

                . Following ET intake, an increase in Z-scores was observed in RAVLT assessments (immediate and delayed recalls), which evaluates learning ability and memory (Figure 4a&b). In contrast, no significant increase was observed in Z-scores across all NCA components, in the subjects given the placebo.
                Block design scores, which assess visual-motor coordination and problem-solving skills, declined over time in both ET and placebo groups (Figure 4g). Although not measured at baseline, Z-scores of SDMT (written format) in the ET group showed a trend to increase from visit 7 to visit 14 (Figure 4i)

                (at 4 weeks visit 1 ergo group also had a better lymphocyte-neutrophil ratio)
                dec0b3e9-1154-4776-acb4-5b5f54bd831c-image.png

                "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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                • C Offline
                  CrumblingCookie @Mauritio
                  last edited by CrumblingCookie

                  bump

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

                  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,

                  This effect by ERG (/ ETG) was likely due its property of chelating intracellular iron?
                  It enriches in mitochondria and the nucleus where it exerts protective action against iron and copper ions by binding them in a harmless way, i.e. without them undergoing the Fenton reaction. Therefore also protecting against ferroptosis and cuproptosis.
                  The effects of hippocampal neurodifferentiation are reminiscent of the benefits of low dose lithium.

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                  • DavidPSD Offline
                    DavidPS
                    last edited by DavidPS

                    A Review of Novel Antioxidant Ergothioneine: Biosynthesis Pathways, Production, Function and Food Applications (2025)

                    4329e282-e579-4852-8027-46910f8494fd-image.png

                    A mind is like a parachute. It doesn’t work if it is not open. 👀
                    ☂️

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                    • DavidPSD Offline
                      DavidPS
                      last edited by DavidPS

                      If you want to get Ergothioneine in whole foods, you should intentionally consider branching out beyond the button mushrooms. Supplements are the easiest route to get the pure form. You can start at five milligrams a day, whether that's mushrooms or whether that's a supplement.

                      9e8dd608-531f-4e8a-9ef3-bdfed24e0eeb-image.png

                      A mind is like a parachute. It doesn’t work if it is not open. 👀
                      ☂️

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                      • DavidPSD Offline
                        DavidPS
                        last edited by

                        Ergothioneine alleviates osteoporosis via the ROS-MAPK signaling Axis (2025)

                        Highlights

                        Ergothioneine (EGT) inhibits osteoclastogenesis via ROS reduction and RANKL-induced MAPK suppression.

                        EGT downregulates NFATc1 and c-Fos while upregulating Ho-1, Catexpression.

                        EGT combines antioxidant and anti-osteoclastic activity properties with a high safety profile

                        EGT effectively mitigates trabecular bone loss in OVX mice by reducing TRAP-positive osteoclast activity.

                        EGT effectively treats osteoporosis via ROS reduction and osteoclast inhibtion.

                        A mind is like a parachute. It doesn’t work if it is not open. 👀
                        ☂️

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                        • DavidPSD Offline
                          DavidPS
                          last edited by

                          Ergothioneine and exercise: A match made in (cognitive) heaven? (2025)

                          Highlights

                          • Ergothioneine accumulates in high-stress organs to protect against oxidative stress, inflammation, and mitochondrial damage.

                          • Higher ergothioneine levels associate with improved cognition and supplementation shows promise for memory and neuroprotection.

                          • Physical exercise enhances neuroplasticity, cerebral perfusion, and cognitive performance through distinct mechanisms.

                          • The combined effects of ergothioneine and exercise on cognition are untested, representing a key direction for future research.

                          A mind is like a parachute. It doesn’t work if it is not open. 👀
                          ☂️

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                          • DavidPSD Offline
                            DavidPS
                            last edited by

                            The Effect of Ergothioneine Supplementation on Cognitive Function, Memory, and Sleep in Older Adults with Subjective Memory Complaints: A Randomized Placebo-Controlled Trial (2025)

                            Abstract

                            Ergothioneine is a diet-derived antioxidant with emerging evidence of neuroprotective benefits, but no dose-ranging study has evaluated its effects in healthy older adults. In this 16-week randomized, double-blind, placebo-controlled trial, 147 adults aged 55–79 with subjective memory complaints received ergothioneine (10 mg or 25 mg/day ErgoActive®) or placebo. The primary outcome was the change in composite memory (CNS Vital Signs). Secondary outcomes included other cognitive domains, subjective memory and sleep quality, and blood biomarkers. At baseline, participants showed slightly above-average cognitive function (neurocognitive index median = 105), with plasma ergothioneine levels of median = 1154 nM (interquartile range = 889.9). Plasma ergothioneine increased by ~3- and ~6-fold for 10 mg, and ~6- and ~16-fold for 25 mg, at weeks 4 and 16, respectively (p < 0.001). 25 mg ergothioneine showed a within-group improvement in composite memory at week 4 (p < 0.05), although this was not sustained. Reaction time improved in both groups, dependent on time. Other domains showed null or limited effects. Subjective prospective memory and sleep initiation improved dose-dependently, with significant effects at 25 mg (p < 0.05). Liver function improved and a within-group increase in telomere length was noted. In conclusion, ergothioneine supplementation was safe and well tolerated, with evidence suggesting some benefits in this cohort of healthy older adults. Longer trials in individuals with lower baseline ergothioneine or cognitive function are warranted.

                            4ac86e7b-a668-461a-adad-aa8891d4c572-image.png

                            A mind is like a parachute. It doesn’t work if it is not open. 👀
                            ☂️

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