Relevant for many and thank you as always. This info will be passed on.

Also, if b.i. progesterone actually maintained or reduced the size of a meningioma.

Hello, Jorge (or your bot). That these vitamins increase the risk of cancer complications is not a reason to avoid supplementation, but to be more cautious with them. One suggestion was to offer B-vitamins in separate products, something like: Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism Mitochondrial function and toxicity: role of B vitamins on the one-carbon transfer pathways But it's challenging to have a clear separation of vitamins because of interrelationships. Pyridoxin was excluded from their 'energy metabolism' group, but it's directly involved in glycogen use and the transaminases to prepare amino acids for oxidation. Biotin was included, but associated with anabolic functions, and one of the catabolic pathways would be dependent on the vilified (adenosyl)cobalamin. If all came down to an energy problem, the nucleotides of the energy-releasing coenzymes involve folate in their syntheses. Cancer Cells Tune the Signaling Pathways to Empower de Novo Synthesis of Nucleotides [image: 1726443780475-0fa521f5-78b7-4401-88c7-079d8641aa8d-image.png] Growth-promoting substances don't just fuel cancer, they're also needed for cell and tissue regeneration. Supplementation is discouraged for folate, cobalamin, and choline (or betaine). We know that the message is reaching a community that doesn't consume a lot of leaves (foliage→folate), nor legumes. The availability of folate in oranges is arguably lower than expected. Properties of Food Folates Determined by Stability and Susceptibility to Intestinal Pteroylpolyglutamate Hydrolase Action Tipping the reliance in favor of folate-cobalamin over choline might yield extra glycine, that can be formed for every folate cycled. The simultaneous restriction of these vitamins, along with a predisposition to their insufficiency, malabsorption syndromes, and the adoption of a diet low in methionine doesn't seem promising. Do we have indications that the population is adequate in the anabolic vitamins and can afford a restriction? Because the typical consumption and positive reactions to supplementation suggest otherwise. Not only a deficiency of any vitamin tends to predispose to cancer, but cancer is not the only disease to worry about. Cardiovascular problems and infections are major threats. Digestion weakens in advanced age and disease, making it helpful to have available these vitamins in purified form. The issue here is that you're leaving for other vendors to do the dirty job of guaranteeing adequacy in a considerable number of people that would benefit from the carcinogenic nutrients.

Thank you for sharing this interesting new angle. It fits very well with the recent interest in the connection between antibiotics and AD. In the last three years, several large studies looking at the efficacy of antibiotics have been started, and they should probably yield some very interesting results. In the end, it all comes down to your gut and endotoxins.

@haidut said in Pregnenolone (P5) may treat for COVID-19, by increasing dopamine: Given that the mechanism of action reported by the study (dopamine enhancement) is so generic, the findings of the study possibly apply to other respiratory viral infections (URTI) too Dopamine was quite important in renal function the last time I checked, renal function quite important to the RRAS, the RRAS quite important to the "spike protein" (an ACE2 inhibitor, allegedly). It's highly likely to me that it does apply to other URTI. In which case I wonder why we're using the word "covid". Other means to walk believing masses back are available.

@stag I wonder if their theories can be shown on blood tests. Although I know how Dr. Peat feels about free T4 and free T3 labs, an rT3 might be good to track in such cases. My rT3 indeed does go down when I increase my T3 while taking T4/T3. Thank you for sharing this - I will look into their therapies further.

@haidut Your work is much appreciated! What do you think of using ALCAR (Acetyl-L-carnitine) to raise dopamine? From personal experience it seems to be able to do this on an empty stomach. Here is one study -that begs the question what kind of electrical sim were they using?: Effect of acetyl-L-carnitine on the dopaminergic system in aging brain *Abstract We studied the effect of acetyl-L-carnitine (ALCAR) on dopamine release and the effect of long-term acetyl-L-carnitine treatment on age-related changes in striatal dopamine receptors and brain amino acid levels. In striatal tissue that had been incubated with [3H]dopamine, acetyl-L-carnitine increased the release of [3H]dopamine evoked by electrical stimulation. In striatal tissue from aged mice administered acetyl-L-carnitine for 3 months, the release of [3H]dopamine evoked by electrical stimulation was higher than that of its aged control; the release after a second stimulation was similar in the two groups. There was a significant decline in the number of D1 striatal dopamine receptors with age. The Bmax was 51% lower in 1.5-year-old mice than in 4-month-old animals. Administration of acetyl-L-carnitine for 3 months diminished the reduction in the binding of [3H]SCH-23390. [3H]Spiperone binding to D2 receptors was not decreased with age and was not affected by acetyl-L-carnitine treatment. Age-related decreases in levels of several amino acids were observed in several brain regions. Acetyl-L-carnitine lessened the reduction in the level of taurine only in the striatum. The findings confirm the multiple effects of acetyl-L-carnitine in brain, and suggest that its administration can have a positive effect on age-related changes in the dopaminergic system.*

interesting do you agree with this tier list? https://bioenergetic.forum/topic/2838/protein-tier-list

@haidut Interesting. I looked for success markers along the stated timeframe of 6 months in the study's full text but the authors did not disclose any details. Would be great to contact them and ask if anybody here would be so forthcoming? As in: How was the success measured and did those measures improve gradually or was it switch-like at about 6 months or earlier? Has anybody looked into this 2021 study from Hungary below? Post Orgasmic Illness Syndrome (POIS) and Delayed Onset Muscle Soreness (DOMS): Do They Have Anything in Common? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392034/ They argue for a complex system of energy depletion, mitochondria dysfunction and also a polyamine depletion (by expulsion) for the crucial spermidine levels in neurons in combination with odd stress signalling patterns. There could be a unique case for spermidine supplementation. And the participation of a long-term manifestation of changes in the endocannabinoid and opioid system. And much more. For some odd reason there even seems to be succesful, positive interaction between hCG injections and spermidine and POIS? By the authors' establishing ties of a common multifactorial pathogenesis between POIS and delayed onset muscle soreness I wonder whether either of these two are 'special' manifestations of a general CFS, mitochondrial, energy, neuronal, autonomic dysfunction.

@Mauritio said in Vitamin A and D deficiency increases liver cancer: o for anyone thinking vitamin A and D are poisons maybe ingest some Vitamin E at least. I’d like to point out some inadequacy to remind: High levels of vitamin E alpha (only one dimer) affect retinol binding protein (RBP). Excessive vitamin E could increase the concentration of vitamin A in liver by inhibiting RBP synthesis in hepatocytes. We need 20-25 mg vitamin E per day, according to Chris Masterjohn. So I won’t take 400 UI every day but every 72 hours (+/ 2x/wk.), 3x if inflammation. There is U-shape effect with retinol: An excess of vitamin A (or a vitamin D deficiency) prevents the formation of heterodimers: essentially homodimers (RXR-RXR) will be formed, leaving the VDR unoccupied and inactive. Zoëhlo (Pharmacologist). A deficit in Fe Zn Vit E or protein can exhaust the carriage, the storage and the use of vitamin A. Useful links: Vitamin A is one of the Keys to a Tolerant Immune System? (in French, translator needed) https://mirzoune-ciboulette.forumactif.org/t721-vitamine-a-la-cle-dun-systeme-immunitaire-tolerant#6555 Vitamin A works as an estrogen antagonist The greatest use of vitamin A is at the level of production of pregnenolone, progesterone and the other steroid hormones associated with youth. “Vitamin A is for the production of pregnenolone, progesterone, and the other youth-associated steroids”. http://raypeat.com/articles/articles/alzheimers2.shtml

Thank you — much appreciated. Very interesting find. Of course, we don’t know if people who are healthy and live longer are more grateful for their situation…or if it’s the gratitude that causes them to live longer.

@Milk-Destroyer [image: 1725179348192-96f7d62d-035a-4d37-94fd-670e78ccdc5e-image.png]

@Butter-Girl very interesting. Thank you.

@haidut said in Niacinamide improves bone health and reduces fat synthesis: Two of the features of aging thought to be unavoidable are brittle bones and increased visceral fat, both of which (alone or in combination) are a major contributing factor for the increased mortality seen with aging. As it turns out, both these features are apparently driven by decline in metabolism/OXPHOS, which is driven primarily by a relative NAD+ deficiency (i.e. low NAD+/NADH ratio), and supplementation with NAD+ precursors such as niacinamide may be able to stop/reverse them. https://www.xiahepublishing.com/2835-6357/FIM-2023-00046 https://www.eurekalert.org/news-releases/1054674 “…Recent studies indicate that oxidative phosphorylation plays a critical role in osteogenesis, the process by which new bone is formed. During osteogenic induction, cells shift their energy metabolism from glycolysis to mitochondrial oxidative phosphorylation, increasing respiratory enzymes, mitochondrial DNA copy number, oxygen consumption, and intracellular ATP content​. Bone morphogenetic protein 2 (BMP2) has been shown to trigger metabolic adaptations in mesenchymal stem cells (MSCs), characterized by successive activation of glycolysis and oxidative phosphorylation​. NAD+ levels and the NAD+/NADH ratio are crucial for mitochondrial function, linking cellular metabolism to transcriptional events and signaling pathways. Nicotinamide mononucleotide (NMN), a key NAD+ intermediate, promotes osteogenesis and reduces adipogenesis in MSCs, protecting bone from aging and damage.” Via: http://haidut.me/?p=2604 Niacinamide and Weight Loss: Niacinamide Has Striking Antiobesity Effects https://www.onedaymd.com/2022/07/low-dose-niacinamide-has-striking.html

@Ecstatic_Hamster

I think this lines up generally with PUFAs/increased serotonin/increased cortisol being associated with ASD (autism spectrum disorder) symptoms. Very nice that you keep collecting these studies! Not specifically related to PUFA, but more to the endotoxin part, I have noticed that a lot of people I know with ASD have somewhat of a "pot belly". The evidence here is of course anecdotal, but I was wondering if this could be bloatedness associated precisely with endotoxin? The correlation with increased bacterial activity in the gut seems likely via the serotonin/cortisol connection in people with ASD, and I guess increased bacterial activity could lead to bloating. It would also line up with what you have mentioned for long distance runners in this connection, the "subclinical Cushing's disease", if I'm not mistaken. Could you kindly comment if you consider this makes sense? Much appreciated!