@ZackVegas I wasn't taking about a "nutrient," I was talking about the studies. They don't have much application to real world humans. If, for the sake of argument, we presume that Omega 3 and Omega 6 are "essential," it's obvious they wouldn't be needed in the diet in every case. Someone who has 20 pounds of stored Omega 6 and Omega 3 certainly wouldn't need them in the diet every day, or even need to consume them for very long periods of time. And even then, Omega 6 and 3 are basically unavoidable in anyone who eats food. You aren't "determining anything". What would you recommend if an individual has the following symptoms of EFA deficiency? These symptoms are very much prevalent in common people with "normal feeding": • Dermatological: Dry, scaly, or flaky skin (xerotic or eczematous dermatitis), periorificial dermatitis, and loss of skin elasticity. • Hair and Nails: Hair loss (alopecia), brittle or dull hair, and weakened nails. • Healing and Immunity: Poor wound healing and an increased risk of frequent infections due to a weakened immune system. • Developmental (in Infants and Children): Growth delays, failure to thrive, and potential intellectual impairment. • Other Signs: Thrombocytopenia (low blood platelet count), anemia, and fatigue or brain fog. The study in no way proves that. That's an interpretation, but not necessarily correct. They may have simply needed more fat in general, or simply more calories. Feel free to dismiss every single EFA studies like this or "extreme cases". Again, the fact that the study shows that 25% of patients on an extreme protocol of a purified diet for 6 months didn't develop "EFA deficiency" shows that this condition is nothing to be concerned with for any human or animal that actually eats food, and raises the question of if Omega 6 and 3 are "essential" in any context. They didn't develop "EFA deficiency" from measurement of triene to tetraene ratio, you can check if they're getting the "higher metabolism" positive effects, without EFA deficiency symptoms. Kinda like how you keep citing TPN studies over and over? Even if I did it's better than you telling people to deprive themselves of nutrients they might need based on the study that is literal one human. There are other studies done with very low fat diets. Walter Kempner used The Rice Diet with many people, and didn't seem to have any issues with so called "EFA Deficiency." https://pubmed.ncbi.nlm.nih.gov/1200726/ Some patients stayed on the diet a year or more. You cite a study of massively obese patients not needing fat in the diet for prolonged period, which probably to your logic isn't an "extreme case". There's also a medical study Angus Barbieri who didn't eat for a year, does that apply to everyone? TPN is a purified diet, and will be missing a lot of vitamins, minerals, cofactors, and such. As I pointed out earlier, it might even be missing sufficient calories in some cases. The levels of included vitamins and minerals could be insufficient as well. Where do you get the information on TPN? TPN is used to feed sick and even near-death people, there's almost no missing nutrients in TPN. I'm sure researchers take calories into account in TPN studies.

@secondkelping Glad the shedding is already easing up. Peat talked about this on the Get Fit with Jodelle podcast in 2022: "Scalp massage definitely helps hair loss from a variety of causes." The way he described it was keeping your fingertips planted on the scalp and wiggling them so the skin moves around. Then he said "That kind of 15 minutes per day amount of massage can very significantly improve hair growth." How long are your sessions now? Would like to hear how the vitex goes too.

@LunaticRed Peat liked uric acid more than most people do. In his caffeine article he wrote "Uric acid, synthesized in the body, is both a stimulant and a very important antioxidant," and said part of how it works is "by modifying the activity of the enzyme xanthine oxidase, which in stress can become a dangerous source of free radicals. Caffeine also restrains this enzyme." So my guess is the muscle protection comes from calming xanthine oxidase during heavy exercise, and dropping uric acid is the part I'd be wary of long term. Did any of the papers compare it with caffeine or theophylline?

@alfredoolivas i rememeber reading it is needed for clearing oxidated dopam from synapses

Useful link on B6 vitamin in relation with neurotransmitters (In French, translator required). a) https://mirzoune-ciboulette.forumactif.org/t2032-effets-de-la-vitamine-b6-sur-les-neurotransmetteurs b) Moderate sensory neuropathy caused by vitamin B6 Reducing brain inflammation with vitamin B6 https://mirzoune-ciboulette.forumactif.org/t2038-neuropathie-sensitive-moderee-par-la-vit-b6 Excerpt: “For individuals suffering from brain inflammation—whether mediated by disease, medications, or adverse vaccine reactions—vitamin B6 could potentially dampen inflammatory cascades and improve quality of life.” Chandler MARRS, PhD

@thebiooracle said: He wrote that it tends to locally activate thyroid secretion "by a variety of mechanisms, increasing cyclic AMP and decreasing serotonin in thyroid cells, for example, and also by lowering the systemic stress mediators." Interesting, thyroid mostly expresses PDE8, same form mostly present in leydig cells, inhibition of which significantly raises testicular steroidogenesis.

Have to add that after acid-base balance is restored, magnesium intake can be used to regain and sustain OXPHOS.

Point Shear Wave Elastography and the Effect of Physical Exercise, Alcohol Consumption, and Respiration in Healthy Adults We found that LSM (liver stiffness measurement) increased significantly following physical exercise, observing clinically significant differences (≥1 kPa) in 1 in 5 subjects. Our study thus supports previous findings, strengthening the hypothesis that physical strain prior to LSM results in significantly higher LSM values and should be avoided prior to measurement. To our knowledge, only one other study has previously investigated the impact of exercise on LSM 8 , but includes only 7 participants. The study found a significant LSM increase 0 and 5 min after activity, while it returned close to baseline values after 10 min. Pulse increase during physical strain has been linked to increased blood flow through the liver, further suggesting that blood redistribution may increase LSM. In line with this, we observed that the increase in exercise-induced LSM was restricted to subjects with a pulse increase >40 bpm, whereas individuals with a low pulse increase (≤40 bpm) did not show signs of increasing LSM after activity, suggesting that only strenuous exercise inducing a high heart rate affects LSM values. Hence, 10 min of rest prior to LSM may be superfluous in most subjects if strenuous exercise is avoided. The low number of individuals (n=9) and short observation time following exercise preclude definitive conclusions, and further studies are warranted to strengthen recommendations regarding rest prior to LSM. Gender differences found in our study, i. e., significant LSM increase observed in males and not in females, also warrant further study to allow conclusions. https://pmc.ncbi.nlm.nih.gov/articles/PMC7723471/

@haidut Ray Peat had a line in his CO2 article that fits this. Naked mole rats and queen bees both live in closed spaces where the CO2 gets up to around 5 or 6 percent, and he wrote "Since queen bees and mole rats live in the dark, I think their high carbon dioxide compensates for the lack of light. (Both light and CO2 help to maintain oxidative metabolism and inhibit lactic acid formation.)" Did the preprint test the infrared at different CO2 levels, or is the CO2 part only in the model so far?

@haidut Ray Peat said almost this in his cholesterol article: "One of the basic functions of cholesterol seems to be the stabilization of mitochondria, preventing their destruction by stress." He tied the synthesis side to energy too: "Serious stress lowers ATP, magnesium, and carbon dioxide. When ATP and intracellular magnesium are decreased, cholesterol synthesis increases." In this study the cells ramped up production once the ER ran short. Did they check whether that ramp-up tracked the cells' ATP, or was the ER shortage enough by itself?

@haidut Ray Peat wrote in his meat physiology article that "an excess of estrogen has been commonly associated with sarcopenia, muscular dystrophy, and atrophy of the skeletal muscles," and that meat scientists were the only people he knew of who called estrogen an anabolic steroid. He also had a cardiolipin point that fits the aging part: in young animals one site of cardiolipin holds palmitic acid, and "After that, as the animal's respiratory activity declines, the palmitic acid is replaced by linoleic acid." Did the paper look at what was in the cardiolipin that was left in the old muscle, or only how much of it there was?

@thebiooracle No, it does not. The data on human diets is not there. P.S. This paper is available as a free PDF download.

Peat called endotoxin "One nearly ubiquitous source of inappropriate excitation and energy depletion" and motor neurons have those really long axons to keep running. Was LBP already high when people were diagnosed, or did it climb as the disease went on?

@AlphaZance said: Stoichiometric Limitation: One molecule of Vitamin E quenches one peroxyl radical before needing to be recycled by Vitamin C or Glutathione. It protects the surrounding bis-allylic motifs as long as active Vitamin E levels are maintained. Hi, Thanks for the post. I've been searching for additonal info, trying to connect the dots. (8 pages docx for an article on my forum). Here is a no-conventional aspect: There is a bidirectional save effect between AA and tocos. Translation of an excerpt: Bidirectional recycling: Once Vitamin E is regenerated (recycled by ascorbic acid), its membrane anchoring allows it to act as a shield; this not only exerts a sparing effect on the nearby ascorbic acid but also enables a bidirectional exchange. The precise mechanism of this reciprocal support remains a complex biochemical challenge, yet the outcome is clear: the two molecules protect and sustain each other amidst the oxidative storm.

@haidut said: ... it may very well be helpful for cancer too. The reason to use B3 in this study was explained, in part, by its prior use for skin cancer prevention: "In a phase III randomized, placebo-controlled trial by Chen et al, [8] oral nicotinamide administered at 500 mg BD for 12 months was safe and effective in reducing the incidence of nonmelanoma skin cancer and actinic keratoses in individuals who were at high risk. " [8] Chen AC, Martin AJ, Choy B, et al. A phase 3 randomised trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med 2015; 373(17):1618–1626. doi: https://doi.org/10.1056/NEJMoa1506197

@haidut Interesting find -- thankss! Yet another reason to keep the glucose uptake high and to avoid metabolic stess. From this paper's concluding passages [bold-facing is mine]: "These results also have implications for therapeutic strategies that manipulate cyst(e)ine availability. Intracellular cysteine became toxic at concentrations of approximately 1–1.5 mM (Extended Data Fig. 4l), substantially above its normal systemic abundance. In fasting human plasma, free cysteine and cystine are present at approximately 10 µM and 80 µM, respectively, with total cyst(e)ine reaching ~250 µM (refs. 31,32). Thus, the toxic threshold is unlikely to be reached through bulk plasma exposure but may be approached in cells with unusually high cyst(e)ine uptake or impaired cysteine disposal. One such example would be cancers with constitutive NRF2 activation that accumulate cysteine beyond biosynthetic demand through upregulation of SLC7A11, promoting the formation of cysteine-derived conjugates that may serve as a detoxification route [33]. Cysteine or NAC has also been reported to induce cell death in glioblastoma and other cellular contexts, particularly during metabolic stress¹¹,³⁴. Our study suggests that, when this buffering capacity is exceeded, or under conditions of metabolic stress such as glucose limitation, excess cysteine becomes deleterious. Conversely, cystine supplementation can enhance tissue regeneration and stem-cell function in some settings.³⁵. Such findings are therefore likely to depend on the capacity of the receiving cells to metabolize or safely dispose of the resulting cysteine. Cysteine damages the mitochondrial electron transport chain via iron–sulfur protein loss, leading to cells relying more on glycolysis for ATP production and trying to uptake more glucose (Extended Data Fig. 4b). This would explain why glucose starvation is synthetically lethal with high cyst(e)ine as exemplified by disulfidptosis, although this death cannot be rescued by iron chelation [10]. Although this process shares features with ferroptosis, it occurs despite elevated GSH and suppressed lipid peroxidation, defining a distinct form of mitochondrial iron-dependent cell death (Extended Data Fig. 4m). Together, these results position thiol imbalance as a central metabolic vulnerability and underscore the importance of both limiting cysteine accumulation and promoting its safe disposal to maintain cellular homeostasis. "