@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!

For anyone researching the related topics of myopathy, muscle weakness/endurance, NAD and lactate, be sure to check out the RP forum for more info. There you'll find info on how Thiamine and especially Niacinamide can be helpful.

Good post https://raypeatforum.com/community/threads/war-is-coming-in-2024-be-prepared.52436/post-999500

@haidut This is a different angle on Vitamin C I had never thought about. As the molecule is very close to glucose, vitamin C could take on the properties of glucose and be used by the body for energy as needed by our immune system to counter pathogens. On this alone, I have a newfound respect for vitamin C that goes beyond its usual association to being an antioxidant. I have been monitoring my oxygen saturation every night for 3 years already, and I follow with interest the nightly spO2 charts (at 4 second intervals), and see the effects of phagocytosis by neutrophils and macrophages using respiratory burst, which consume plenty of oxygen that lead to sharp temporary drops in spO2. Even eosinophils consume large amounts of oxygen to produce ROS that spewed at larger pathogens. Energy is needed for these white blood cells to protect us from pathogenic insults, and it is plausible that vitamin C does as much as glucose does to provide an emergency boost to strengthen our immune system. [Don't know how to attach an image here. Unless it is in the form of a url]

@haidut I think that adopting just another Peaty routine to my nutritional lifestyle has helped me. This routine is in eating well cooked leafy greens. The vitamin K, as well as calcium and magnesium, has helped me. I had been eating leafy greens for quite some time now, and when I had bronchitis, I put myself in a year long downward cycle that involved heart failure. From being at the ICU, I thought my recovery would be difficult, if not impossible. But I am now back to having healthy lungs and a healthy heart, like I was before. It speaks to having a lifestyle that prepares one to bounce back from a heart failure easily. Having all the nutrients we need met, and by eating whole foods, is the simplest way to be resilient. Vitamin K is just one nutrient though. We need them all, and I for one, like to keep things simple. And for me, the simplest lifestyle is to have all our nutritional needs met by food, clean air, and sunshine. I used to rely on supplementation when I lived in the US, but before I came back to the Philippines, I vowed to stop all supplementation and make food my medicine. Except for vitamin E and C and some B vitamins, I have no deficiency to worry about and my body has been more resilient. Vitamin K from leafy greens is adequate. I don't have a reason to want K2 supplementation. But if I ever go back to live in the US, I may have to rely on more supplementation given that I don't trust the food ecosystem there to be able to supply nutrients adequately. It is very much a wasteland of industrial food.

@haidut I have to get a lot of sun exposure at or around mid-day sun to get the most vitamin D produced by the skin and eyes. I started this right before my cat my ankle and since I never had a bite wound on the skin on top of an ankle bone, I didn't know until know how to heal from such a wound. It's been 3 months since that bite and it's only now thst the wound is closing. I think the myelin sheath may have been damaged when my body was exposed to a week of taking orally cinnamon bark oil. This left me ataxic and I walk like drunk and have drop foot. Megadosing thiamine is somewhat effective, but something is still lacking to fully heal. I think vitamin D may be all that's needed to effect the healing on a damaged myelin sheath. When my ankle wound heals, I will resume a daily midday sun exposure of about an hour in my koi pond, where I am exposed to the sun. It may take a while, but I hope that vitamin D is the missing ingredient in my recovery from ataxia.

@haidut Empathy is a tricky process, especially in our culture that negates it. It requires good health, and ample biological energy. If the organism is faced with a detrimental situation in which most of the energy is required to keep itself alive, less energy can be used for the perception of other minds. In Mind and Tissue Ray talks about forming a "dominant" for other people as a brain process for acquiring impressions of other people`s internal life. It is probably one of the most energy-requiring process in the cerebral cortex, and something like endotoxin should be able to switch it off almost immediately. “You know, the hardest thing in the world for a person may be to free himself of his double, his automatic tendency to see himself, his faults, his shortcomings, his secret deviance in everyone he meets; but even more difficult is to liberate himself from the constant company of his double! And only from the moment when the double is overcome is the road open to free communication with another! "It is then for the first time that mind, heart, and word are revealed, making it possible truly to hear what it is that makes the person one has encountered tick….An open heart and open and intelligent hearing detect and understand in the other that which the individual had been unaware of in himself, and which merely dully exhausted and tormented him from some undiscovered part of his insides!" (Ukhtomksky)