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    Random, interesting studies

    Literature Review
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    • MauritioM
      Mauritio @CrumblingCookie
      last edited by

      @CrumblingCookie they don't make studies like this anymore...

      Dare to think.

      My X:
      x.com/Metabolicmonstr

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      • MauritioM
        Mauritio
        last edited by Mauritio

        Some interesting stuff on pentoxifylline

        -" PTX completely restored bone mass, bone strength and bone mineral properties by an anabolic mechanism. PTX has the potential to become an oral osteogenic drug for the treatment of post-menopausal osteoporosis."
        https://pubmed.ncbi.nlm.nih.gov/30858147/

        • https://doi.org/10.1016/j.biopha.2021.112399

        • https://pubmed.ncbi.nlm.nih.gov/21748765/

        • https://lowtoxinforum.com/threads/some-pentoxifylline-studies.10437/post-345653

        • https://www.reddit.com/r/Nootropics/comments/1k6l3u7/pentoxifylline_makes_me_intelligent_again/

        • https://pubmed.ncbi.nlm.nih.gov/10506631/

        • https://lowtoxinforum.com/threads/evaluation-of-the-effect-of-pentoxifylline-on-sleep-deprivation-induced-memory-impairment.10310/

        • https://lowtoxinforum.com/threads/chorionic-morphine-naltrexone-and-pentoxifylline-effect-on-hypophyso-gonadal-hormones-of-male-rats.10305/

        • https://www.reddit.com/r/LongHaulersRecovery/s/mh5AO1rOBA

        Ray Peat:

        "The use of nitric oxide for treating pulmonary
        hypertension is deflecting interest from generally
        safe substances, such as magnesium, oxybutyrate,
        pentoxifylline, progesterone, DHEA, testosterone,
        and thyroid hormone, and directing attention
        away from the various factors that cause the
        pulmonary hypertension of adults as well as
        newborns. "

        "Although caffeine, if it’s combined with hypoglycemia and stress, will increase lipolysis and free fatty acids, several of the methylxanthines, including caffeine, theophylline, and pentoxifylline, can protect against capillary leakage, probably by a variety of antiinflammatory actions, including inhibition of nitric oxide synthesis (Bereta, et al., 1994).”

        Dare to think.

        My X:
        x.com/Metabolicmonstr

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        • L
          lobotomize-me
          last edited by lobotomize-me

          opinions on CDS Chlorine Dioxide?

          1 Reply Last reply Reply Quote 0
          • MauritioM
            Mauritio
            last edited by

            "At 3 weeks after tumor transplantation, the fish oil diet and the safflower oil diet had induced, respectively, 10- and 4-fold more metastases (number) and over 1000- and 500-fold more metastases (size) than were found in the livers of rats on the low-fat diet. "
            https://pubmed.ncbi.nlm.nih.gov/9699661/

            Dare to think.

            My X:
            x.com/Metabolicmonstr

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            • MauritioM
              Mauritio
              last edited by Mauritio

              CATALASE

              Been looking into catalase again.

              1.Thyroid hormones increase catalase.
              https://lowtoxinforum.com/threads/thyroid-hormone-increases-anti-oxidant-enzymes-glucocorticoids-lower-them.49877/

              I found this clip of Ray talking about it very useful. Often peaters will dogmatically oppose anti-oxidants, because "you want oxidation", but as Peat says here, anti-oxidants like T3, will inhibit the random harmful oxidation in the ETC and keep the electrons flowing, so actually more, good oxidation can happen.
              Youtube Video

              2.Catalase knock out mice experience increased lipogenesis and ER stress.
              https://pubmed.ncbi.nlm.nih.gov/31877356/

              Dare to think.

              My X:
              x.com/Metabolicmonstr

              1 Reply Last reply Reply Quote 1
              • MauritioM
                Mauritio
                last edited by Mauritio

                Unexpected, but DHT and other androgens increase mice susceptibility to Candida fungal infections.
                Giving them estrogen or gonadectomizing the mice removed those effects.

                Not sure what's the MoA here.
                But certain bacteria increase and metabolize androgens, so maybe androgens can be used as food by those bacteria, thereby increasing the bacteria:fungus ratio.
                Bacteria and fungi are constantly in competition, so if you increase bacteria you're lowering the total fungi load in the gut. That's why, if you lower bacteria via an antibiotic for example, you might get a fungal infection .
                Can't think of another mechanism .

                https://pmc.ncbi.nlm.nih.gov/articles/PMC7358272/

                Dare to think.

                My X:
                x.com/Metabolicmonstr

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                • L
                  lobotomize-me
                  last edited by

                  @Mauritio
                  androgens suppress the immune system, estrogen cranks it up.

                  this is how androgens (t / dht) mess with suppress it and reduce inflamation

                  they reduce TNF‑α and iNOS → less nitric oxide, weaker kill power

                  Boost IL‑10 and TGF‑β → “calm down” signals, inducing healing instead of immune responsiveness

                  they slow neutrophils: weaker ERK, less leukotrienes, poorer phagocytosis + NETs.

                  Th1 / Th17 T‑cells drop → less IFN‑γ, IL‑17, so fewer cells to fight fungi.

                  Net result: mice on high dht / t clear Candida badly → bigger infection.

                  Why estrogen (or castration) flips it

                  Without androgens, macrophages + neutrophils go full throttle.

                  Estrogen pushes Th1 / Th17 up, more IFN‑γ & IL‑17, and thus they neutralize fungi better

                  So ovariectomized females or castrated males plus estrogen handle Candida better

                  Microbiome guess
                  Yes, some gut bugs eat androgens and compete with fungi, but here the infection was IV and response changed within days. Fast switch caused immune modulation, and not a big microbiome shift.

                  MauritioM 1 Reply Last reply Reply Quote 1
                  • MauritioM
                    Mauritio @lobotomize-me
                    last edited by

                    @lobotomize-me Great explanation , thanks.

                    Dare to think.

                    My X:
                    x.com/Metabolicmonstr

                    1 Reply Last reply Reply Quote 0
                    • L
                      lobotomize-me
                      last edited by

                      @Mauritio 👍

                      1 Reply Last reply Reply Quote 0
                      • L
                        lobotomize-me
                        last edited by lobotomize-me

                        @Mauritio

                        Sodium butyrate increases seratonin

                        : Peripheral (gut) serotonin: In vitro and in vivo studies show that butyrate stimulates tryptophan hydroxylase‑1 (TPH1), the rate‑limiting enzyme for serotonin synthesis in intestinal enterochromaffin cells. Low concentrations of sodium butyrate (0.5–1 mM) increased TPH1 mRNA expression in human EC cells by 2.5–3.5‑fold; high concentrations (>2 mM) suppressed TPH1. A review notes that butyrate in the gut lumen can activate a zinc‑finger transcription factor (ZBP‑89) and stimulate serotonin production in enterochromaffin cells.

                        Central (brain) serotonin: In mice exposed to chronic unpredictable stress, sodium butyrate treatment alleviated depression‑like behaviours and increased brain serotonin (5‑HT) concentration and brain‑derived neurotrophic factor (BDNF) levels. A gene‑expression study in rats showed that sodium‑butyrate‑induced HDAC inhibition downregulated the 5‑HT₂A receptor in the brain and another study reported up‑regulation of 5‑HT₁A receptor mRNA when sodium butyrate was combined with estrogen therapy (data from behavioural tests) – suggesting receptor‑level modulation rather than direct synthesis of serotonin

                        SB prevented behavioural deficit made by CUMS
                        by raising seratonin and BDNF
                        https://pubmed.ncbi.nlm.nih.gov/26957230/

                        Increase seratonin under stress:
                        https://pubmed.ncbi.nlm.nih.gov/18817816/

                        https://pmc.ncbi.nlm.nih.gov/articles/PMC4396604/

                        "When mice were treated with antibiotics to deplete gut microbiota, serotonin levels dropped significantly.

                        Recolonization of the microbiota or administration of SCFAs restored normal 5-HT levels in the colon"

                        This means sodium butyrate could be the pathway, gut bacteria use to trigger serotonin production⬇️

                        https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.1035538/full

                        L 2 Replies Last reply Reply Quote 0
                        • L
                          lobotomize-me @Mauritio
                          last edited by

                          @Mauritio have been taking sr 9011 for a week or so which is a strong agonist of reverb/Clock haven't been feeling much other than increased base bpm and easier time changing my sleep schedule (which is helpful as I usually go to sleep late and now it gives me the motivation to go to sleep early)

                          1 Reply Last reply Reply Quote 1
                          • MauritioM
                            Mauritio
                            last edited by

                            The case for nattokinase for varicose veins

                            It seems that varicose veins display an increased concentration of fibrin(ogen) and inflammatory cytokines.
                            Fibrin increases clotting.
                            When I asked Peat if there was any medical danger of varicose veins he said that it probably slighlty increased the risk for clotting.
                            So that checks out as well.

                            Nattokinase is very good at dissolving fibrin and its also an ACE inhibitor, so generally anti-inflammatory. So it seems worth checking out as a treatment.

                            Sources:
                            1)https://pubmed.ncbi.nlm.nih.gov/1986710/
                            2)https://pubmed.ncbi.nlm.nih.gov/32529904/
                            3)https://pubmed.ncbi.nlm.nih.gov/9017960/
                            4)https://pubmed.ncbi.nlm.nih.gov/26100448/

                            Dare to think.

                            My X:
                            x.com/Metabolicmonstr

                            sunsunsunS 1 Reply Last reply Reply Quote 0
                            • sunsunsunS
                              sunsunsun @Mauritio
                              last edited by

                              @Mauritio an average sized man eating 2 packages of natto (45g x 2) on an otherwise empty stomach actually gets a supplement level of nattokinase into the blood iirc

                              1 Reply Last reply Reply Quote 0
                              • MauritioM
                                Mauritio
                                last edited by Mauritio

                                "Notably, prostaglandin E2 (PGE2) can promote the formation of a Candida biofilm. Recently, the inhibition of PGE2 has received much attention. Studies have shown that cyclooxygenase (COX) inhibitors, such as aspirin, ibuprofen, and indomethacin, combined with fluconazole can significantly reduce Candida adhesion and biofilm development and increase fluconazole susceptibility; the MIC of fluconazole can be decrease from 64 to 2 μg/ml when used in combination with ibuprofen. "
                                https://pmc.ncbi.nlm.nih.gov/articles/PMC5138225/

                                Dare to think.

                                My X:
                                x.com/Metabolicmonstr

                                1 Reply Last reply Reply Quote 1
                                • MauritioM
                                  Mauritio
                                  last edited by

                                  "In vitro, 5-HT inhibits rat prostate branching through down-regulation of androgen receptor (AR). "

                                  "...Tph1 knockout mice present higher prostate mass and up-regulation of AR when compared to wild-type,..."

                                  https://www.nature.com/articles/s41598-017-15832-5

                                  Dare to think.

                                  My X:
                                  x.com/Metabolicmonstr

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                                  • MauritioM
                                    Mauritio @Mauritio
                                    last edited by Mauritio

                                    @Mauritio said in Random, interesting studies:

                                    It seems to come down to age as well.
                                    Here it gets interesting: if you're under 65 and eating a high protein diet, that is strongly associated with death, cancer and diabetes . Over 65 it seems to be protective !

                                    "...aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer and diabetes mortality..."
                                    https://pmc.ncbi.nlm.nih.gov/articles/PMC3988

                                    Another pointer in this direction.
                                    Young mice experienced a 17% decrease in life span when methionine was increased, for old mice it didn't change anything.
                                    So maybe there is an age related effect of protein on the body.
                                    If that's true (and that's still a big if), then im starting to wonder how good Rays low protein phase was shortly before his death, given his advanced age.

                                    "The lifespan of old mice was unchanged by feeding 0.05M methionine. Young mice, however, experienced a 16.9% decrease in their average lifespan and a decreased maximum lifespan when given supplemental methionine. "
                                    https://www.sciencedirect.com/science/article/abs/pii/0531556584900494

                                    I have previously speculated that the mechanism might have to do with the immune system, since a low protein diet can lower thymus weight and that is possibly worse than additional protein in old age .

                                    It could also have to do with heavy metals since amino acids have heavy metal cheating properties and heavy metals tend to accumulate in old age.
                                    https://www.sciencedirect.com/science/article/abs/pii/S2210271X25000076#:~:text=Introduction,4]%2C [5].

                                    Dare to think.

                                    My X:
                                    x.com/Metabolicmonstr

                                    1 Reply Last reply Reply Quote 1
                                    • MauritioM
                                      Mauritio
                                      last edited by

                                      Thyroid Hormone-Induced Expression of the Hepatic Scaffold Proteins Sestrin2, β-Klotho, and FRS2α in Relation to FGF21-AMPK Signaling
                                      https://pubmed.ncbi.nlm.nih.gov/28895643/

                                      Dare to think.

                                      My X:
                                      x.com/Metabolicmonstr

                                      1 Reply Last reply Reply Quote 0
                                      • L
                                        lobotomize-me @lobotomize-me
                                        last edited by

                                        This post is deleted!
                                        1 Reply Last reply Reply Quote 0
                                        • L
                                          lobotomize-me @lobotomize-me
                                          last edited by

                                          @lobotomize-me said in Random, interesting studies:

                                          @Mauritio

                                          Sodium butyrate increases seratonin

                                          : Peripheral (gut) serotonin: In vitro and in vivo studies show that butyrate stimulates tryptophan hydroxylase‑1 (TPH1), the rate‑limiting enzyme for serotonin synthesis in intestinal enterochromaffin cells. Low concentrations of sodium butyrate (0.5–1 mM) increased TPH1 mRNA expression in human EC cells by 2.5–3.5‑fold; high concentrations (>2 mM) suppressed TPH1. A review notes that butyrate in the gut lumen can activate a zinc‑finger transcription factor (ZBP‑89) and stimulate serotonin production in enterochromaffin cells.

                                          Central (brain) serotonin: In mice exposed to chronic unpredictable stress, sodium butyrate treatment alleviated depression‑like behaviours and increased brain serotonin (5‑HT) concentration and brain‑derived neurotrophic factor (BDNF) levels. A gene‑expression study in rats showed that sodium‑butyrate‑induced HDAC inhibition downregulated the 5‑HT₂A receptor in the brain and another study reported up‑regulation of 5‑HT₁A receptor mRNA when sodium butyrate was combined with estrogen therapy (data from behavioural tests) – suggesting receptor‑level modulation rather than direct synthesis of serotonin

                                          SB prevented behavioural deficit made by CUMS
                                          by raising seratonin and BDNF
                                          https://pubmed.ncbi.nlm.nih.gov/26957230/

                                          Increase seratonin under stress:
                                          https://pubmed.ncbi.nlm.nih.gov/18817816/

                                          https://pmc.ncbi.nlm.nih.gov/articles/PMC4396604/

                                          "When mice were treated with antibiotics to deplete gut microbiota, serotonin levels dropped significantly.

                                          Recolonization of the microbiota or administration of SCFAs restored normal 5-HT levels in the colon"

                                          This means sodium butyrate could be the pathway, gut bacteria use to trigger serotonin production⬇️

                                          https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2022.1035538/full

                                          @Mauritio

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