@Ray-Van-Winkle well I'm not a scientist yet but maybe I could go into this stuff in the future. This peating journey has given me about a thousand ideas of things that could be tested and studied... might try find more papers on this

@haidut This is so hard for me to understand. Especially when the language revolves around the idea of receptors. Once I get into that world, it just seems like an expert, not necessarily referring to you, is explaining to me some arcane terms in quantum physics. I could be wrong here, but isn't the idea of receptors something that came off the mechanical model based on a Cartesian model that is at odds with the concept of a life force or field model that sees life than more than just something that can be reduced to a mechanical model? What I can relate to in concept is our organs, and the kidneys being just one of them, as being a collection of tissues. Tissues are composed of cells, and cells that are healthy are governed by a balance. When there is balance, there is an abundance of well-directed energy that keeps cells and tissues and organs functional with a minimum of stress. With stress at minimal levels, the organ does not have to adapt to stresses that create conditions for organs to calcify and to develop fibrosis. And when the kidneys do not undergo calcification and fibrosis, it stays very functional. As when it is supplied with necessary inputs such as oxygen and sugar, and it makes good use of them by having an environment that is supportive of productive and beneficial processes. An environment free of toxins, with microbes always present that are not harmful but commensal that is free from infection, and an optimal acid-base balance that allows each cell in the organ the regulation of calcium ingress and egress, with potassium doing its role in regulating calcium entry in the cell (that can only be achieved with having the pH levels that only good sugar-based mitochondrial metabolism can unfailingly provide with an abundance of CO2 production) and with the calcium being spirited out of the cell as it pairs with CO2 as bicarbonate to keep internal calcification from developing. I like this kind of explanation nor only because it addresses my need as a child in me to satisfy what is the cause of an effect. As I can understand it better and I can apply it in other situations. But I find it hard to understand aldosterone in how it acts as its presence has never been explained without me saying "oh I am not worthy." and I better move on and leave it to the experts. The kidneys and how it get so sick that there is CKD is such a mystery to us all. And we end up using some formula called the eGFR in it's various versions to determine how much deep into CKD we are from stage 1 to 5. Relying on a formula that is so simplistic involving only the input of creatinine, age, sex, and race to determine kidney health. In reality, eGFR means "estimated," and this estimate is so wide in its variance to render it practically worthless for diagnosis, but still doctors forget to treat it as an estimate, and see it as the gold standard in the absence of something better. Just one way the practice of medicine is more an art than a science, and as an art competes with economics for distinction in the Nobel hall of infamy, only bested by the Peace Prize with its laureate, Barack Obama. Yes, the use of pregnenolone and progesterone is good and I have no objection to their use. But in the context that these steroids and hormones are already part of the cast of actors in a body running on optimal sugar metabolism, wouldn't they be redundant in a healthy individual? And shouldn't they be seen as temporary crutches to use while the long term direction is to guide the patient towards being metabolically independent from the use of progesterone and pregnenolone?

Tissue-specific effect of colitis on protein synthesis in mice: impact of the dietary protein content "As previously reported, acute inflammation severely affects colon metabolism by stimulating protein anabolism [4, 9, 18]. Because colon protein content was not modified along the colitis course and resolution despite a higher protein synthesis rate, this increase in biosynthesis might reflect colon repair after epithelium erosion, with possibly a higher epithelial cell loss in the lumen. The locally induced inflammation is known to provoke an increased amino acid need for protein synthesis in the colon, not only when inflammation is maximal (day 7–10) [19], but also likely during the healing process. This increase, notably at a time when dietary daily intake was reduced, could have been compensated by amino acids supplied by other tissues, such as muscle. A reduced protein synthesis in muscle would also spare amino acids for increased protein synthesis in the colon, liver and spleen. Indeed, muscle is a major contributor to restore protein and energy losses in situations where protein catabolism is manifest such as starvation [20], acute injury [21] or chronic inflammation [9]." "The present study shows that the protein metabolism modifications are modulated by the dietary protein content. The moderately high-protein diet (P30%), which has been recently shown to improve epithelial repair after an acute colitis episode [14], was associated with a lower protein synthesis rate, restoring initial level in colon compared to the two other diets [14% and 55% protein]. It is noteworthy that several colitis induced alterations were restored earlier with P30 diet consumption compared to the two other diets, such as body weight, caecal protein content, spleen and muscle protein synthesis rates. These changes coincided with the recovery of P30-fed mice that showed less inflammation and bacterial translocation (as evidenced by measuring the circulating LPS-BP concentration [14]) and faster colon repair in accordance with an earlier restoration of initial protein synthesis colon as shown in the present study." "Our finding that the P30 diet restores rapidly and sustainably the initial (before colitis induction) colon protein synthesis can be related to our previous study in which we showed that P30 diet improved (when compared to the P14 diet) the colonic mucosal healing process by accelerating inflammation resolution, increasing epithelial repair, reducing permeability, and inducing epithelial hyperproliferation [14]. This suggests that the P30 diet, by furnishing an increased amount of amino acids, helps in the restoration of the colon epithelium, thus explaining the less active protein synthesis at this site. However, the relative amount of amino acids that is devoted to the restoration of the colonic epithelium remains to be determined when compared to other amino acid-consuming processes involved in inflammation. We previously showed that a specific mixture of amino acids given to rats after colitis induction was able to improve the colon regeneration/re-epithelialization, and this amelioration was found to coincide with a reduction of the stimulated protein synthesis rate in the colon when compared to control animals not receiving the amino acid mixture [23]. In sharp contrast, by further increasing the protein content in the diet (P53), we did not observe in this study any effect on the colon protein synthesis rate when compared to the P14 diet. This result can be ascribed to the deleterious effects of the P53 diet on the disease activity index, both in intensity and duration after a DSS challenge [14]. The reasons that would explain how a very high-protein diet consumption, although furnishing more amino acids is counterproductive after colitis induction, are not clear. One possibility is that by increasing the protein content in the diet, a larger amount of the dietary and endogenous protein escapes digestion in the small intestine, and thus reaches the large intestine. As a consequence, the microbiota produces an increased amount of amino acid-derived metabolites, some of which (hydrogen sulphide, ammonium, p-cresol) being known to be deleterious for the colonic epithelial cells, notably in terms of energy metabolism [24]." "In conclusion, our study highlights the severe impact of acute colonic inflammation not only on the metabolism of proteins in the splanchnic area, but also in the peripheral tissues. The ability of the P30 diet to restore a normal protein synthesis in the colon may correspond to its documented beneficial effect on mucosal healing. In addition, the recovery of the initial protein synthesis rate in the various tissues in the period of time following colitis induction appears to be modulated by the amount of protein in the diet, with the P30 diet being more effective than the P53 diet."

@oldchem It's rampant.

@haidut So glad I didn’t decide to do SSRI’s for hypochondria. It felt like I had chronic fatigue and I was losing my mind. I was very close to trying out SSRI’s but glad I didn’t and trusted in myself and my judgement. I may trial BCAA’s and see if they have an effect on me. So far thyroid, biotin, Niacinamide, thiamine and aspirin have been my greatest and most powerful tools. Really powerful stuff. Don’t do too well on progesterone I suspect because I’m male.

I am not sure it is that easy with NAC. Anecdotes are often incredible. It is a (weakish) biofilm buster, scavenges aldehydes, interacts with heavy metals (iirc positively) along with what you already mentioned increasing glutathion. There is alot more to it and i think its magic as with most things lies in the right application at the right time. Most chronic ill people i speculate have a bad persistent infection going on where NAC has its place. In that sense it would help the energetic situation as its helping dealing with toxins and pathogens. As for a more general statement in healthy people i could see it being a net negative? Even more so what one should consider doing to offset negative outcomes that could come with longterm use (ive been taking it for half a year now)

@questforhealth From this perspective yes. I personally prefer raw milk, but have not had noticeable issues with ultra pasteurized homogenized milk. However, if drinking lower quality milk, it can’t hurt to get a little extra folate, either from supplements or food.

@Appa Well said. Very much lines up with my experience and I couldn't help but notice the similarities with SSRI's on mood, behavior, sleep, appetite. It turns you into a zombie. Cypro made me sleep, hungry, and foggy. Never liked it. Now I have these unwanted side effects long term... that I'm thinking of correcting with a serotonin agonist. Any recommendations for an agonist?

Trace Element Speciation in Food ↳ [54] Iron and Zinc Compounds in the Muscle Meats of Beef, Lamb, Pork and Chicken "Figure 1 shows that the soluble zinc in all meats is distributed between five main components. The first zinc peak corresponds to the exclusion volume of the column (molecular weight approximately 130 000) and therefore represents high molecular weight zinc. The zinc in this peak is possibly associated with a-macroglobulin which has a molecular weight of 820 000 and is known to account for one-third of all plasma zinc.[30] Zinc peak II eluted in the same volume as the reference protein, transferrin, at a molecular weight of 76 000. Transferrin is known to bind a small amount of plasma zinc.[30] The third zinc peak is very large and eluted at a molecular weight of approximately 65 000. Some, if not all, of the zinc in this peak is probably bound to albumin (molecular weight 67 000). Albumin is one of the sarcoplasmic proteins of meat[31] and is the predominant form of zinc in plasma.[30] Zinc peak IV is also large and eluted at a molecular weight of approximately 35 000. This peak probably consists of the zinc metallo-enzyme carbonic anhydrase which has the same molecular weight, is a major soluble form of zinc in liver,[32] and accounts for nearly all the zinc found in erythrocytes.[30] The fifth zinc peak eluted in a volume corresponding to low molecular weight compounds (< 12 000). The fractions from zinc peak Vb reacted with ninhydrin which suggests that this peak consists of zinc bound to amino acids.[19] Fractions from peak Va showed no reaction with ninhydrin and therefore probably consist of zinc bound to small peptides." [image: 1710812258296-5a53761c-680e-43b4-8835-c7df9d5d7917-image.png]

@questforhealth the problem seems to be that you’ll never approach 1mg of vitamin K2 from most foods. The most concentrated source is natto and even though it does have about 600mcg per the most common serving size, most people here won’t touch it because it’s a soybean food containing significant PUFA; also the form is MK-7 not MK-4, which is viewed as a disadvantage by most

@Kvothe said in Vitamin A increases T3 by more than 60% in humans!: Some dude posted this study on RPF. In rats, an equivalent dose was enough increases TSH and suppress T3. I personally experienced that anything over an extra 5.000IU can be suppressive for a mildy hypothyroid person. https://link.springer.com/content/pdf/10.1007/s00394-022-02945-5.pdf [image: 1710202886357-0db5dde3-7db7-4cfb-8447-a8fe77b96aba-grafik.png] Well that dude (sinatra) probably has the study from this thread here (https://bioenergetic.forum/post/12395) where I posted it a few days before him, it's interesting that he did not post the main study of this very thread or any of the other pro-vitamin A things I posted. The HED of about 30k IU per day is still realtively high. And i agree that this can make you hypo, which peat has said for decades. On the other hand the study, which this thread is about (human study, not rat) shows clear benefits in a similar dosage.

Thanks for sharing. Activation of the PXR/SXR is an interesting thing in and of itself. It increases phase 1,2 and 3 detoxification in the liver and increases CYP3A4. Other ligands are for example: progesterone, 5aDHP or bile acids. The authors of this study hypothesize that the liver-regenerating capabilites of Vitamin K2 were reliant on PXR-activation. All the nucelar "X" receptors are really interesting, the FXR probably beeing my favorite. PXR/SXR also upregulates a protein that takes up and excretes prostaglandins. So vitamin K leads to less PUFA/prostaglandin metabolites and damage.

@Master Too bad but thanks anyway Master.

How's your thyroid, what's your waking up temp? It's probably not good since your sleep is bad.