Berberine Berberine activates thermogenesis in white and brown adipose tissue and increases UCP1; PMID 25423280 Berberine increases testosterone but also prolactin. There might be a sweet spot between 50-100mg/kg (rat dose) where you get minimal prolactin increase with a significant testosterone increase. Maximal T increase was almost 100% https://link.springer.com/article/10.1007/s44345-024-00007-3#Fig2 Berberine sometimes receives criticism because some studies show that it can inhibit mitochondria. Which is true it can:" "...inhibit mitochondrial respiratory complex I” in vitro PMID 18285556 Although in this study it had a positive effect on mitochondria in vivo; it increases mitochondria numbers and prevented mitochondrial dysfunction, which was accomplished via AMPK and SIRT1 activation. "Furthermore, we observe that the prevention of mitochondrial dysfunction by BBR, the increase in mitochondrial biogenesis, as well as BBR-induced AMPK activation, are blocked in cells in which SIRT1 has been knocked-down." PMID: 22027215 "...extended the lifespan ... of naturally aged mice by ~16.49%” PMID 31773901 This study reported an increase in the NAD+/NADH ratio. PMID: 22027215 Berberine made someone on the RPF able to tolerate milk. https://lowtoxinforum.com/threads/does-anyone-here-use-berberine-regularly.41514/post-669774 Increases SERT; lowers serotonin https://pubmed.ncbi.nlm.nih.gov/21647174/

@Mauritio pharma grade is 99.5% +

@pondfountain chronic caffeine consumption negates the Ach-increasing effects of caffeine. Chronic caffeine treatment reduces caffeine but not adenosine effects on cortical acetylcholine release The results indicate that prolonged consumption of high doses of caffeine causes changes in the responsiveness of cholinergic neurons to caffeine. The change is not shared by adenosine, through whose recognition sites caffeine is believed to act. It is therefore possible that the adaptive changes following repeated caffeine administration involve either only the coupler-transducer mechanism activated by the antagonist, or effects unrelated to receptors.

You’ll see that, in addition to any androgen binding to GR, you’ll have two potent anti-catabolic factors: mTOR and PGC-1α; GR negatively regulates both To put it very simply, REDD1 negatively regulates mTOR, and FOXO1 is largely regulated by PGC-1α. Although they function “separately,” they can converge since REDD1 not only inhibits mTOR but also increases FOXO1. You can make them resistant to catabolism by inhibiting FOXO1, and abolish the effects of GCs by inhibiting REDD1. Not surprisingly, type 1 fibers—rich in mitochondria and OXPHOS—are resistant to stress-induced atrophy (glucocorticoids, energy deprivation, etc.) but are also resistant to hypertrophy. Glycolytic fibers, on the other hand, which are prone to energy deficits because they have few mitochondria and rely on glycolysis, are sensitive to stress but are also sensitive to hypertrophy due to greater GR and AR density. [image: 1786057988696-d19493b6-4e2d-43de-ad03-f365e0eb848c-image.jpeg]

@Ena Re: antifungal/antimicrobial effect of lovastatin. It looks like lovastatin (LOV) potentiates other antifungals rather than having that effect by itself. "LOV single treatment was unable to inhibit C. albicans strains except the ERG3 and ERG11 double mutant. LOV and itraconazole (ITZ) combination was capable of inhibiting the C. albicans planktonic cells and biofilms synergistically including the ITZ resistant mutants." --- From the abstract to Lovastatin synergizes with itraconazole against planktonic cells and biofilms of Candida albicans through the regulation on ergosterol biosynthesis pathway.

There is also morphogenic resonance going on of the Ray Peat ideas thoughts energetic expressions consciousness and all. The more of us talking about these ideas working towards pro metabolic higher metabolic lives etc… we are spreading these ideas into the Aether and scientists influencers kids people are getting seeded these ideas and they resonate with them. Resonance, it happens constantly in culture, through marketing magic but also just by morphogenic fields. I mean people are trending towards rays ideas because they are more or less the right direction of full spectrum truth. And big brains like Georgi and some of the folks here are broadcasting electron flow awareness out to the universe! Grab a tank of co2 and a glass of milk and tune in! Plagiarism is constantly an annoying part of life also.

@sunsunsun Yeah but the point is that the spoons are inaccurate for the exact reason you mentioned XD as well as density etc

@haidut I am wondering if it is really inflammation that is causing mitochondrial dysfunction and not the other way around. I have a large store of bacteria that I keep having to kill and each time there is a kill plenty of endotoxins are released and they are a major source of inflammation. And it suppresses mitochondrial activity to the point that even the conversion of cholesterol to pregnenolone and downstream prosuction of hormones and steroids are very much affected. To such effect that taking hormones like thyroid and pregnenolone and progesterone can hardly make a dent. I had to inhibit the nfkb inflammatory response using turmeric and black pepper in order to see my cholesterol level go down and my hormonal production go up. But it is hard to keep endotoxins low when there is a large colony of pathogenic microbes and in my case it is feom periodontal infection having translocated to my vascular and lymphatic system where it get more embedded over time especially as it gets protected by biofilms. One way I see out of this conundrum of killing pathogens by relying on our endogenous ROS from our own innate immune system and from use of pharma antibiotics or herbal antibacterials,, which all end up producing endotoxins; is to engage antibacterial peptides such as LL-37 in neutrophils and macrophages - to kill pathogens with the benefit of not leaving behind endotoxins that both inflame and cause oxidative stress. More sunshine to produce high levels of Vitamin D (50-80 ng/dl) together with plenty of butyric acid in the gut gives the body a high endogenous supply of LL-37 to achieve effective antimicrobial activity without endotoxic side effects.

L-form, aka protoplast or spheroplast, yeasts and fungi are likely the much more widespread and pressing issues next to biofilms. IMO of a more widespread importance than the specialty case of additional biliary survival as per this thread's original topic. Such L-form variants (predominated by filamentous Aspergillus, plus Candida parapsilosis and others) were found in autistic children, and often their mothers yet not in healthy controls. Acquisition of the L-forms especially during gestation and infancy is suspected to confer a particular kind of life-long immunological blindness to these. Dysbiotic microbiota in autistic children and their mothers: persistence of fungal and bacterial wall-deficient L-form variants in blood, 2019 An according collection of case studies, albeit with a strong conflict of interests (authors are heavily involved in Mosaic Diagnostics, formerly Great Plains Laboratory, with their urine organic acid tests): Case Study: Rapid Complete Recovery From An Autism Spectrum Disorder After Treatment of Aspergillus With The Antifungal Drugs Itraconazole And Sporanox, 2020 The seemingly most powerful antifungal combination discovered so far which targets the fungal membranes and therefore equally well any L-form persister fungi variants is Itraconazole or Posaconazole + a HIV protease inhibitor like Atazavir (+Ritonavir as a systemic inhibitor of degradation via Cyp3A4 to boost ATV's impact. RTV can be very cheap; thus no biggie): Enhanced antifungal activity of posaconazole against Candida auris by HIV protease inhibitors, atazanavir and saquinavir, 2024 There are a few more studies published on combinations like this without the particular use of spheroplasts but on "normal" fungi, too. Such combos also overcome aquired resistancies by upregulated efflux pumps (CDR1/2) and the filaments and biofilm abilities. @sunsunsun

So then, Mitolipin to the rescue

Looks like Picard's work supports the "rate of living theory". For example, in his Cellular allostatic load is linked to increased energy expenditure and accelerated biological aging hypermetabolism, defined as "increased energy expenditure", it is concluded that "a robust and specific temporal association be­tween hypermetabolism and premature cell death, aligning with pro­spective observations in the human literature where hypermetabolism increases mortality risk. Finally, our experimental modulation of OxPhos and total J_ATP suggest that total energy expenditure, rather than flux through mitochondrial OxPhos, may have a particularly influential ef­fect on cellular aging". Hmm... but the references that they use could be mined further for some gems.