@user73636 Di Bella method is very successful in many difficult cancers It usues somatostatin and melatonin. http://www.metododibella.org/it/Archivio-Newsletter.html https://www.metododibellaevidenzescientifiche.com/2022/05/03/mdb001-di-bella-et-al-2018/ Il sinergismo di somatostatina, melatonina, retinoidi, vitamin E, D3, C, inibitori prolattinici ed estrogenici, microdosi metronomiche di ciclofosfamide, ha incrementato sopravvivenza, risposte obiettive, performance status, in 297 casi di carcinomi del seno – The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer

@user73636 1 cup of chocolate chips has 15.691g of stearic acid. I think this fusion is just the result of fixing a deficiency. there are lots of foods with decent amounts of stearic acid in them.

Yes, these might interest you: Oxidation of hydrogen sulfide by Quinones: How polyphenols initiate their Cytoprotective effects ‘Antioxidant’ berries, anthocyanins, resveratrol and rosmarinic acid oxidize hydrogen sulfide to polysulfides and thiosulfate: A novel mechanism underlying their biological actions Alteration of the Gut Microbiome in Inflammatory Bowel Disease

Compounds that inhibit lactate overproduction are usually beneficial, but relying on oxaloacetate for this is not ideal. Pyruvate carboxylase is required for glutamine-independent growth of tumor cells (PC synthesizes oxaloacetate) In case of oxaloacetate supplementation, delivery is the first challenge because most of the dose is metabolized in the liver after absorption. For esterified forms, the fraction that reaches target cells is likely overestimated, especially when tissue circulation is poor. Malate dehydrogenase (MDH) interconverts malate and oxaloacetate, and this enzyme is also part of the malate-aspartate shuttle (MAS) that you mention. [image: 1772751634940-d34ce921-acea-4633-9653-639c96f9838f-image.png] ⠀(10.1101/cshperspect.a040543) The figure shows some potential concerns: Cytosolic NAD reoxidation by MDH can promote glycolysis, but without reliably improving mitochondrial metabolism for further oxidation. Increased demand for NAD+ relative to ATP drives aerobic glycolysis Extra oxaloacetate (OAA) may not convert into malate as expected. Aspartate is another component of the shuttle and is a reaction away from oxaloacetate (GOT/AST is bidirectional). [image: 1772751647814-4f7a93ec-7e75-4c6a-a1ad-ae54d314276c-image.png] ⠀(10.1016/j.ymgmr.2023.100967) An Essential Role of the Mitochondrial Electron Transport Chain in Cell Proliferation Is to Enable Aspartate Synthesis Supporting Aspartate Biosynthesis Is an Essential Function of Respiration in Proliferating Cells Oxaloacetate enters mitochondria hydrogenated as malate. Recovering oxaloacetate on the mitochondrial side depends on sufficient NAD⁺ (also shown on the figure), which may be scarce and prioritized for other reactions, such as that of KGDHc. Recovery of oxaloacetate from malate in mitochondria doesn't guarantee its reaction with acetyl-CoA. It may instead support glutamate metabolism by accepting its amino group, yielding ketoglutarate for KGDHc (↻) or IDH (↺). One route doesn't exclude the other, as a fraction of ketoglutarate can undergo oxidative decarboxylation (releasing CO₂) and the other reductive carboxylation (incorporating CO₂), Supporting glutamate metabolism in forward function: Oxaloacetate + glutamate ←{GOT}→ Aspartate + Ketoglutarate Ketoglutarate –{KGDHc}→ Succinyl-CoA ←{STK}→ ATP + Succinate A portion of oxaloacetate-derived malate can also be converted to fumarate in reverse TCA cycle operation. Oxaloacetate → Malate → Fumarate → Succinate [image: 1772751671369-3224a3ed-9ba4-4586-bbab-57e75c344b76-image.png] ⠀(10.3389/fendo.2012.00022) This way, oxaloacetate helps to generate ketoglutarate to support mitochondrial fermentation and non-respiratory ATP synthesis with minimal oxidation. In addition, fumarate may be used as a substitute to deficient oxygen, accepting electrons from the respiratory chain sourced from ketoglutarate itself, dihydro-orotate, etc. (Oxaloacetate +) Glutamate → Ketoglutarate → Succinate ← Fumarate ← Oxaloacetate Succinate accumulation becomes comparable to lactate. Both metabolites are exported as fermentation end-products together with an extra H⁺, contributing to extracellular acidification. [image: 1772751690253-15d16b6b-0813-45e0-8bb1-7fecd96f1d33-image.png] ⠀(10.1080/17590914.2024.2422268) "Succinate-stabilized HIF-1a" reinforces PDHc inhibition, giving another reason not to assume that extra oxaloacetate and CoA release will serve PDHc, because they may just as well promote fatty acid oxidation. If oxaloacetate condenses with acetyl-CoA, that doesn't commit it oxidation either; oxaloacetate can serve as a carrier to export excess acetyl groups to support lipid synthesis. As for pyruvate and its multiple metabolic fates, even discounting lactate and oxaloacetate in this context, we can't assume that pyruvate routing to the chronically inhibited PDHc will prevail over supporting an upregulated pathway, such as in metabolizing abundant glutamate via GPT/ALT, which remains expressed outside the liver. Pyruvate + H⁺ + CoA + NAD⁺ –{PDHc}→ Acetyl-CoA + CO₂ + NADH + H⁺ Pyruvate + ⇈Glutamate ←{GPT}→ Alanine + Ketoglutarate This is another potential route that would supply ketoglutarate without depending on glutamate oxidation, sparing oxidative capacity to keep KGDHc running.

[image: 1772655639415-injust.jpg] Adjustment to what.

@Mauritio i have not but planning on it

@lobotomize - Thanks, another reason to proceed with caution.

Dihydromyricetin in the management of diabetes and its complications: a narrative review Managing diabetes mellitus (DM) and its long-term complications remains a major global health challenge. Dihydromyricetin (DHM), a natural flavonoid abundant in Ampelopsis grossedentata and Hovenia dulcis, has attracted increasing attention for its multi-target anti-diabetic properties. Growing evidence indicates that DHM improves glucose metabolism, alleviates oxidative stress and inflammation, regulates autophagy and cell death, and exerts beneficial effects in DM and a range of related complications, including diabetic nephropathy, cardiomyopathy, cognitive impairment, and wound healing impairment, and other related complications. Overall, this review provides an overview of preclinical research on DHM in DM and its main complications, emphasizing its therapeutic benefits and underlying molecular mechanisms.

silicon chelates aluminum *edit posted that b4 reading your whole post

@user73636 Quoting Wikipedia: https://en.wikipedia.org/wiki/Diisopropylamine_dichloroacetate#:~:text=DADA is formed by combining diisopropylamine with dichloroacetic acid. It is chemically related to pangamic acid (formerly known as "vitamin B15")%2C which may convert to DADA and diisopropylamine in the body.[4] Pangamic acid = ester of D-gluconic acid (the sugar-acid part) N,N-dimethylglycine (DMG) (the amino-acid part) Pangamic acid, stomach acid quickly breaks the ester bond and you get free DMG + free gluconic acid.

I believe a stack of B5 + carnitine + OAA/malate High carb low fat Eating leaner meat cuts Lower bcaa intake And focusing on odd chain fats (produce less acetyl coa) would be a great way to lower the acetyl coa/coa ratio further increasing the activity of pyruvate dehydrogenase Also eat foods rich in nad precursors as the nad/nadh ratio is also important for pdh/pdk ratio malate and OAA can not only help pull acetyl-CoA into the TCA cycle (Krebs cycle) to make energy, which frees up CoA. They also help turn NADH back into usable NAD+. (TCA Cycle Pull) OAA mixes with acetyl-CoA to start the cycle, releasing free CoA each turn . Malate turns into OAA inside mitochondria, keeping OAA stocked so the cycle keeps running smoothly.

Get your eggs in! Spinach also is rich in lutein. Interestingly, cooking it doesn't degrade the lutein content. And having calcium with the spinach is two-fold beneficial: block oxalate absorption enhance lutein absorption by 30 to 40%

@Ecstatic_Hamster said in Does low TSH correlate with longevity and health: What do you think about this and why? I think that a low TSH is associated with health, especially when it occurs naturally without pharmaceuticals or exogenous hormones. I do not think that a low TSH is associated with longevity; but I think that a high TSH is associated with increased mortality (a shorter duration in lifespan). So there is an incentive to keep TSH low or at least on the low side of the normal range. As to the 'why", I have not read the literature but I have a general analogy. First, there has been an explosion in the number of people with Type II diabetes and the term adult onset diabetes is no longer appropiate since children also develop Type II diabetes. The general cause for this explosion is our modern lifestyle (with many non-ancestral components) which has over stimulated our hormonal insulin secretion. And for the analogy, lifestyle promotes high ISH (insulin secreting hormone). It takes years of high ISH before diabetes is diagnosed. [image: 1771780870851-e3378664-92f2-4d65-a6f7-8b80cc3897c1-image.png] I am wondering if high TSH will eventually result in thyroid problems, that is thyroid resistance and the lucrative medical manangement thereof. There are hotlinked references about thyroid resistance at the end of this article. Thyroid hormone resistance and its management (2016)

@haidut There are many ways to deplete GSH in cancer cells e.g. arsenic AI Arsenic exposure causes significant glutathione (GSH) depletion by increasing reactive oxygen species (ROS) and directly binding to sulfhydryl groups, leading to oxidative stress and reduced antioxidant capacity in blood and tissues. Depletion of GSH sensitizes cells to arsenic-induced apoptosis, frequently utilized in cancer therapies (e.g., leukemia) to enhance the efficacy of arsenic trioxide. Mechanisms of Arsenic-Induced Glutathione Depletion Oxidative Stress: Arsenic exposure increases ROS, which consumes GSH, a crucial cellular antioxidant. Direct Binding: Arsenic binds directly to glutathione and other thiol-containing proteins. Inhibition of Synthesis: Exposure can reduce essential raw materials for GSH synthesis, such as cysteine and glutamate. Enzyme Activity: While glutathione-S-transferase (GST) activity might increase in response to stress, it often results in a net decline of the GSH pool. Significance of GSH Depletion Increased Toxicity: Lowered GSH levels render cells more vulnerable to arsenic toxicity. Cancer Therapy: GSH depletion (e.g., via Buthionine sulfoximine, BSO) enhances arsenic trioxide's ability to kill cancer cells, as shown in leukemia studies. Reduced Detoxification: Impaired GSH levels impair the body's ability to methylate and excrete arsenic. Consequences and Mitigation Oxidative Damage: Depletion causes significant decreases in brain and blood protective enzymes like superoxide dismutase (SOD) and glutathione peroxidase (GPx). Therapeutic Approaches: Antioxidants or chelators, such as MiADMSA, have been shown to be effective in restoring GSH levels and reducing ROS induced by arsenic. gold nano-particles https://www.sciencedirect.com/science/article/abs/pii/S138589472501232X auranofin -indirectly https://pmc.ncbi.nlm.nih.gov/articles/PMC8777575/ silver nano-particles https://www.sciencedirect.com/science/article/abs/pii/S0378427410017984 https://thesilveredge.com/clinicalstudies/ selenite and selenate https://pubmed.ncbi.nlm.nih.gov/10406889/