Low-dose aspirin slashed dementia risk by 70% in certain people, study shows. Researchers at Monash University in Australia went back to the ASPREE trial, a large study in which older adults took either a daily low-dose aspirin or a dummy pill (placebo). They analyzed the genetic data of more than 13,500 participants and gave each person a "polygenic score", a combined measure of many small gene variants, linked to how many platelets their blood makes. Platelets are the tiny cells that help blood clot. In the 20% of people with the highest platelet scores, just 1% of those on aspirin developed dementia, compared with 3.3% of those on placebo, about 70% lower risk. Earlier trials found aspirin didn't prevent dementia when everyone was considered together, so this points to a hidden group who might benefit, and to platelet biology as a new lead in dementia research. The signal wasn't tied to known Alzheimer's risk genes. But the same high-score group also had more major bleeding on aspirin, 4.4% vs 2.1% on placebo. This is a subgroup finding that still needs confirming in a dedicated trial. Do not start taking aspirin to prevent dementia on your own: daily aspirin can cause serious bleeding, so talk to your doctor first. source: Fransquet, P. D., Yu, C., Tran, C., Hussain, S. M., Brodtmann, A., Tonkin, A. M., Nelson, M. R., Ryan, J., McNeil, J. J., & Lacaze, P. (2026). Platelet count polygenic scores may modify the effect of aspirin in primary prevention of dementia. Alzheimer's & Dementia, 22(9).

The humble mushroom in your fridge has a hidden winter superpower: it is a biological satellite dish designed to trap the sun. Mushrooms contain a compound called ergosterol. It is virtually identical to the cholesterol in human skin. When hit by ultraviolet light, it instantly transforms into pure Vitamin D. In the summer, leaving mushrooms in the sun for 15 minutes skyrockets their Vitamin D levels by over 1,000%. They retain that potency for days in the fridge and survive the heat of a searing pan. It is a living hack for human vitality. But right now, we are in the depths of winter. The angle of the earth has locked us under a weak sky. The UV index is flatlining, and window glass completely blocks the remaining UVB rays. If you leave your mushrooms on an indoor windowsill today, nothing happens. To activate them in the winter, you have to shift the physics: 1. Slice them thin: You need maximum surface area. 2 Flip them over: The gills contain the highest concentration of ergosterol. Point them directly at the sky. 3. Go outdoors: Glass is a barrier. They need direct, unfiltered contact. 4. Extend the time: The winter sun is weak. Give them 2 hours minimum. If the sky is completely grey, hack the system. Placing a reptile UVB lamp over sliced mushrooms indoors for an hour triggers the exact same evolutionary chemistry. Nature doesn't stop operating in the dark seasons. It just requires you to understand the geometry.

He drove his wife to one of the best hospitals in America for a planned caesarean. A routine one. Her second. Charles Johnson watched her blood collect in a catheter bag for ten hours while he asked for help. Kira Johnson died at 2:22am. Cedars-Sinai, Los Angeles, 12th April 2016. Kira Johnson was 39. She spoke five languages, raced cars, ran marathons. The caesarean was scheduled. Everything about it was routine. Her son Langston was delivered at midday. By the afternoon her husband could see blood in her catheter. He told a nurse. He was told they would check. He asked again. And again. A CT scan was ordered and then not performed. He has described being told, at one point, that his wife was simply not a priority right now. He stood in a corridor for ten hours asking people to look at his wife. They took her back to theatre just after midnight. There were three litres of blood in her abdomen. She died shortly after. Her son Langston was twelve hours old. Charles Johnson has spent the decade since as one of the most effective advocates in American maternal health. He founded 4Kira4Moms. He has testified before Congress. The federal Black maternal health legislation introduced in recent years carries work he pushed for. He talks about one thing more than any other, and it is not the medicine. It is the ten hours. He was standing right there, in the building, awake, articulate, asking. And it made no difference at all.

ADHD in older adults raised the odds of later cognitive impairment more than fourfold. Higher daytime light cut dementia risk. The shared axis is sunrise light on solar time. It advances the master clock, sets the nocturnal melatonin window, and times the mitohormetic ROS pulse that restores mitochondrial membrane potential. Miss that cue and the repair window for high-flux attention and memory circuits compresses. ADHD liability (clinical or genetic) marks lower tolerance for the mismatch. The light study showed larger protection precisely where the margin is already narrow—evening chronotypes, high nighttime light, APOE ε4. Pair it with darker nights, especially in winter. Absolute risks stay modest. Both studies are observational. The numbers keep pointing to the same daily contrast. Head to my bio for 1 on 1 consultation

Over the last two decades, ordinary U.S. citizens have come to see themselves in different struggles when in fact we all face the same challenges. In this essay, I present how we got to where we are, and the foundation of the solution. We have more in common than not. Read free!

Things that are connected: US live-streaming the firing squad execution of a paraplegic in a wheelchair. The public calling CPS on celeb parents with disabled babies & demanding their removal. US states bringing back forced institutionalization in private equity-owned institutions. US removes disability protections & cuts off disability services, as we’re systematically disabled by unmitigated pandemics & no one can afford healthcare. US/Canada euthanizing the disabled, poor, & mentally ill. Netherlands just euthanized a baby. Very obvious increases in ableist content, beliefs & behaviors, after we learned cognitive disabilities in the US have increased by over 40% since 2019 & the RECORD disability we’ve ignored since 2020 continues to increase. There is no funding & no help for the rapidly increasing disabled population, which is YOUNG & GROWING YOUNGER, only institutionalization to enrich private equity & certain premature death. Human life has been fully devalued. Bad things are upon us & even worse things are coming. All together now: This is a Business Model. In the end, they’re going to kill us.

BREAKING: my latest test finds that 8g of vitamin B5 per day dropped post-ruck lactate from over 656 to 23 in two weeks WHILE DOUBLING THE WORKLOAD. B5 also improved: - Pyruvate (-96%) - Alanine (-76%) - less pyruvate spillover - Citrate (undetectable → in range) - Kreb cycling working better - Hippuric acid (23x higher) - better benzoic acid clearance - Orotic acid (-88%) - less ammonia

TTFD is one of the best things for fixing many gut issues, brain fog and chronic fatigue, but it needs cofactors to work properly. If cofactors are missing, it can hurt you in the long term. Here is the exact architecture to unlock the therapeutic power of TTFD without precipitating functional collapse👇 1. The Transporter-Independent Bypass Standard water-soluble thiamine salts rely on rate-limiting active transport proteins (SLC19A2 and SLC19A3) that downregulate under inflammation and hypoxia. TTFD possesses a lipid-soluble mercapturic structure that bypasses these transport gates entirely. It diffuses passively across cell membranes, penetrates the blood-brain barrier, and saturates intracellular compartments independent of metabolic friction. 2. The Clinical Upstream Leverage Once inside the cell, TTFD targets the primary rate-limiting enzymes of bioenergetic metabolism: Pyruvate Dehydrogenase (PDH), converting glycolytic pyruvate into Acetyl-CoA to clear cellular lactic acidosis. Alpha-Ketoglutarate Dehydrogenase (KGDH), unlocking the rate-limiting turn of the Krebs cycle. Transketolase, driving the Pentose Phosphate Pathway to generate NADPH for antioxidant defense and myelin synthesis. Acetylcholine synthesis via the PDH axis, directly rebooting vagus nerve motor output, gastric motility, the migrating motor complex (MMC), and resolving chronic dysautonomia or POTS. 3. The Glutathione Extraction Trap: To release free thiamine into the cytoplasm, TTFD requires the cleavage of its prosthetic disulfide bond. This enzymatic cleavage consumes reduced intracellular glutathione (GSH). In an internal system already burdened by oxidative stress, high-dose TTFD acutely strips the remaining GSH pool, triggering immediate mast cell destabilization, chemical sensitivity, and sudden detox flares. 4. The Phosphorylation Stall Free thiamine is biologically inert. It must be converted into active Thiamine Pyrophosphate (TPP) by the enzyme Thiamine Pyrophosphokinase (TPK1). TPK1 is strictly dependent on intracellular magnesium. If magnesium is depleted, TTFD accumulates as an unphosphorylated intermediate, stalling cellular energy production while accelerating systemic receptor agitation. 5. The Intracellular Ion Shift (Refeeding Dynamics) Unlocking a paralyzed PDH complex forces immediate, high-velocity glucose oxidation. Rapid glycolysis drives circulating potassium and phosphorus out of extracellular fluid and directly into cells. Without potassium repletion, patients experience functional hypokalemia: severe muscle weakness, ectopic heartbeats, resting tachycardia, and autonomic panic. 6. The Obligate Cofactor Architecture Chelated Magnesium Magnesium is the non-negotiable coenzyme required for TPK1 to synthesize active TPP. It stabilizes ATP within the mitochondrial matrix and buffers NMDA receptor channels against sudden glutamate flux. Administer bioavailable magnesium hours before escalating TTFD. Active Riboflavin (B2 / R5P) Riboflavin in its active Flavin Adenine Dinucleotide (FAD) state is required by Glutathione Reductase to recycle oxidized glutathione back into reduced GSH. Saturating the FAD pool ensures the disulfide cleavage of TTFD does not deplete cellular antioxidant defenses. You can also add GlyNAC for extra Glutathione. Potassium Repletion Dietary and supplemental potassium buffers the sudden intracellular electrolyte shift driven by accelerated glucose metabolism. Maintaining serum potassium prevents cardiac palpitations and terminates paradoxical adrenaline dumps. Balanced Methylation and B-Complex Support Unlocking transketolase and downstream dehydrogenase enzymes spikes consumption of Niacin (NAD+) and methyl donors. A fully methylated, balanced B-complex ensures secondary metabolic pathways do not bottleneck downstream. Other Cofactors: Molybdenum (Sulfite Clearance) and Selenium (Glutathione Peroxidase Axis). 7. The Unresolved Gap Supplying magnesium, potassium, and riboflavin buffers the TTFD entry pathway, but it does not address why your baseline bioenergetic engine failed initially. If your cellular respiration is paralyzed by heavy metal displacement, peripheral thyroid resistance, chronic endotoxemia, or electron transport chain Complex I/IV stall, forcing pyruvate into the mitochondria with TTFD will merely build up upstream pressure against a locked metabolic door. Treating downstream coenzyme deficiencies while ignoring the primary systemic bottleneck guarantees persistent functional collapse. - Chronic fatigue, gut issues and brain fog all trace back to stalled mitochondrial respiration and nutrient deficiencies. DM me 'PROTOCOL' with your biggest bottleneck and what you’ve already tried. I will break down the exact step-by-step pathway to fix it.

The top 0.1% of US households now own 15% of all household wealth, a record high. Meanwhile, the bottom 50% own just 2%. The wealth gap has never been wider.

This has been known for several years. Several doctors treat long Covid AND vaccine injury by a complex dance involving several blood thinners and anti-coagulants. Sharyl Attkinson has featured a couple on her show including follow-up stories.

A striking 54% increase in excess deaths in young adults aged 18 -44 in 2021. Middle-aged adults were ~26% above, and all ages were ~18% above in 2021. From 2022 onward, the excess deaths in children aged 0-17 from disease ranged ~12-17% above baseline, through 2024. According to mECfS IACC PAIS distortionists, these DEAD CHILDREN are NOTHING NEW.

While you sleep, your brain's white matter is charging up like a battery Myelin, the insulation around your nerve fibers, has been considered a passive structural component that speeds up signals. A new hypothesis from @FScholkmann and colleagues proposes it's actually an energy storage system that fills up during sleep and powers your neurons throughout the day. The paper, published in Progress in Biophysics and Molecular Biology, presents a radical reimagining of what myelin does beyond speeding up electrical signals along nerves. What is myelin? Myelin is the fatty sheath that wraps around nerve fibers like insulation around electrical wires. It's produced by specialized cells called oligodendrocytes in the central nervous system and makes up about 40% of your brain's volume. Traditionally, myelin's job has been simple: speed up nerve signals and provide structural support. This new hypothesis suggests it does something far more dynamic. The proton capacitor hypothesis The researchers propose myelin functions as a proton capacitor, meaning it stores energy in the form of protons (hydrogen ions) that accumulate during sleep and get released during wakefulness to produce ATP, the cell's energy currency. Think of it like a rechargeable battery. During sleep, myelin charges up by accumulating protons. During wakefulness, those protons flow through ATP synthase enzymes embedded in myelin, generating the energy neurons need to function. The mechanism involves two abundant myelin proteins: Myelin basic protein (MBP) sits between myelin layers and contains amino acids (lysine, arginine, histidine) that can absorb and hold protons. It functions as the energy storage component. Proteolipid protein (PLP) spans the myelin membrane and contains serine and threonine amino acids that form efficient proton conductors, creating pathways for protons to flow from storage sites to ATP synthase. How the charging cycle works During sleep, your myelin is actively storing energy. Specialized molecules in myelin pump protons (think of them as tiny charged particles) into storage proteins, like filling up a battery. During this phase, no energy is being used, just stored. When you wake up, the system switches into discharge mode. Those stored protons flow through protein channels to enzymes that convert them into ATP, your cells' usable energy form. This ATP travels through tiny tunnels called gap junctions directly into nerve fibers, where it powers your brain's activity. The researchers calculated that the amount of protons a small cube of myelin can hold matches exactly what your brain would need during 8 hours of wakefulness. The storage capacity and the daily demand align. The molecular sleep switch A naturally occurring molecule called oleamide acts as the on/off switch for this system. Throughout your waking hours, oleamide gradually accumulates in your brain. When it reaches a certain level, it closes those gap junctions, the tunnels that deliver ATP from myelin to nerve fibers. Once the tunnels close, your neurons can't access the energy supply. Neural activity drops. You get sleepy. With the delivery system shut down, myelin switches from discharge mode to charging mode. While you sleep, oleamide slowly breaks down. When enough of it clears out, the gap junctions reopen, ATP starts flowing to neurons again, and you wake up. This explains why you can't just decide to stay awake indefinitely. As oleamide builds up during the day, it eventually forces the system offline whether you want it to or not. Sleep isn't optional, it's a programmed metabolic requirement driven by molecular accumulation. How myelin produces energy without the usual machinery Here's where it gets strange: myelin can make ATP (cellular energy) even though it doesn't contain the typical power plants that cells use to generate energy. Normally, structures called mitochondria produce nearly all of a cell's ATP. But myelin has very few, if any, complete mitochondria. So how does it make energy? The researchers propose that mitochondria send small cargo packages carrying energy-producing equipment to the myelin. These packages fuse with myelin membranes and drop off the machinery, allowing myelin to produce ATP on its own. Think of it like getting a portable generator delivered to a remote cabin. You don't need a full power plant on site, just the essential equipment to generate electricity locally. The bigger the battery, the less time spent charging The researchers examined 23 different mammal species and discovered something remarkable: animals with more white matter (the brain tissue that's 95% myelin) need less sleep. Here's the pattern: • Bats have tiny brains with minimal white matter and sleep 20 hours a day • Humans have moderate white matter and sleep 8 hours a day • Elephants have massive white matter and sleep just 3.5 hours a day The logic is straightforward. More myelin means greater energy storage capacity. With a bigger battery, you need less time plugged in to fully recharge. The pattern suggests that more myelin provides greater energy storage capacity, reducing the time needed to recharge. Less myelin means longer recharging periods are required. This relationship also appears within humans across the lifespan. White matter volume peaks between ages 30-50, the same period when sleep duration reaches its minimum. Both follow inverted U-shaped curves over the human lifespan. Even sex differences align: women have less white matter than men and require more sleep on average. Experimental support The hypothesis draws on experimental work showing: • Isolated myelin vesicles consume oxygen and synthesize ATP via oxidative phosphorylation • Myelin vesicles exposed to NADH retain an energy charge that's later used for ATP synthesis when ADP and phosphate are added • Longer exposure to NADH produces more ATP in subsequent phases • This matches the predicted two-phase system: charging during simulated sleep, discharge during simulated wakefulness Sleep deprivation studies show myelin thickness decreases when animals are kept awake, consistent with discharge without adequate recharging time. Marathon runners show notable reductions in myelin after intense physical activity, suggesting the energy reserves get depleted during sustained neural and physical exertion. Key takeaways: • Myelin may function as a proton battery, storing energy during sleep and releasing it during wakefulness • Two myelin proteins (MBP and PLP) form a coupled system: one stores protons, the other conducts them to ATP synthase • Sleep duration correlates with white matter volume across 23 mammalian species • Oleamide, a natural sleep inducer, closes the gap junctions that deliver ATP from myelin to axons • Myelin contains functional mitochondrial components delivered via mitochondrial-derived vesicles • The human brain requires approximately 8 hours to fully recharge myelin's proton storage capacity • Sleep deprivation leads to measurable myelin degradation Limitations and open questions This remains a hypothesis requiring direct experimental validation in living systems. The calculations provide plausibility but don't prove the mechanism operates as proposed. Key questions: • Can proton accumulation and discharge be measured directly in myelin during sleep/wake cycles? • Does blocking this proposed system prevent normal sleep function? • How does this mechanism integrate with other established functions of sleep? • Can therapeutic interventions targeting this system improve sleep quality or neurological function? The challenge is that protons moving between membrane-bound buffers without entering free solution is difficult to measure experimentally. Why this matters If validated, this hypothesis fundamentally reframes our understanding of sleep. Rather than viewing sleep as a period when the brain passively recovers, it positions sleep as an active metabolic phase when the brain's white matter systematically stores energy for the next waking period. It also elevates myelin from a passive structural element to an active metabolic organizer that administers energy distribution to neurons. The framework could explain why myelin disorders often involve fatigue and why conditions affecting white matter integrity produce cognitive deficits even when gray matter remains intact. The identification of oleamide as the molecular switch controlling this cycle points to a natural compound that's been overlooked as a potential sleep therapeutic despite decades of evidence. The convergence of structural data (protein composition and positioning), metabolic data (oxygen consumption and ATP synthesis in myelin), molecular data (oleamide and gap junctions), and cross-species data (white matter volume and sleep duration) creates a compelling case that myelin plays a previously unrecognized role in sleep energetics. Whether this represents the primary function of sleep or one component of a multi-system process remains to be determined. But the hypothesis provides testable predictions and a mechanistic framework for understanding the metabolic foundations of the sleep-wake cycle.

our HR director showed me our company’s hardship loan applications this morning. a senior analyst on our team applied for an advance after finding out she was pregnant. she and her husband already have two kids. he works night shifts at a warehouse. she works 50 hours a week for us. they ran the numbers: another child meant $1,800/mo in childcare plus a bigger apartment they couldn't afford. so they made the agonizing decision to get an abortion. then the healthcare system hit them: out-of-pocket procedure: $750. out-of-network ultrasound: $420. unpaid days off work: $300. they literally had to apply for a corporate payroll advance just to pay off the medical debt from terminating a pregnancy they couldn't afford to keep. we don't have a functional middle class. we have an economy where people are priced out of having families and then forced into debt just to opt out.

How could cGAS- Sting activation may play a role in MECFS and long covid? The cGAS-STING (cyclic GMP-AMP synthase–stimulator of interferon genes) pathway is a critical component of the innate immune system that senses cytosolic double-stranded DNA (dsDNA). While it traditionally defends against viral and bacterial invaders, its chronic or aberrant activation by self-DNA (such as leaked mitochondrial DNA) is increasingly recognized as a major driver of chronic fatigue, post-viral syndromes, and neuroinflammation. [1, 2, 3] In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and closely related conditions like Long COVID, cGAS-STING activation could play a pivotal role through several overlapping physiological mechanisms: [4, 5] 1. Mitochondrial Dysfunction and "Self-DNA" Leakage ME/CFS is heavily linked to cellular energy stress, impaired ATP production, and mitochondrial dysfunction. When mitochondria are damaged or undergo severe homeostatic stress (such as during the physical exertion that triggers Post-Exertional Malaise, or PEM): • The mitochondrial permeability transition pore (mPTP) can open, allowing mitochondrial DNA (mtDNA) to escape into the cytoplasm. • The cGAS protein misidentifies this leaked cytosolic mtDNA as a foreign pathogen, triggering the STING pathway and inducing a persistent, systemic inflammatory state without an active infection. [4, 5, 9] 2. Sustained Neuroinflammation and Microglial Activation One of the hallmark features of ME/CFS is neuroinflammation, particularly in autonomic and sensory-gating regions of the brain. • In the central nervous system, cGAS-STING activation occurs predominantly in microglia (the brain's resident immune cells). • Overactivation of this pathway in microglia drives the chronic release of Type I interferons (IFN-I) and pro-inflammatory cytokines (like IL-6 and TNF-α). This can cause low-grade, persistent neuroinflammation, contributing directly to cognitive dysfunction ("brain fog"), unrefreshing sleep, and sensory hypersensitivity. [1, 9, 10, 11, 12, 13] 3. Exaggerated Innate Immune Responses and Long COVID Overlap Recent multi-omics data in ME/CFS patients reveals a severely heightened and exaggerated innate immune response. • Research into Long COVID—which shares significant pathological and clinical overlap with ME/CFS—has demonstrated abnormally high expression levels of cGAS, STING, and IFN-α long after the acute viral infection has cleared. • This indicates that a viral or bacterial trigger can lock the cGAS-STING axis into a permanent "on" position, transitioning from an antiviral response into a chronic autoinflammatory loop. [15] 4. Direct Contribution to Behavioral and Metabolic Fatigue Emerging animal and translational models have begun directly linking the cGAS-STING pathway to the sensation of profound fatigue: • Preclinical studies on fatigue models show that cGAS-STING activation alters mitochondrial and metabolic gene expression in the liver. • When researchers pharmacologically block STING activation (using targeted antagonists), it mitigates systemic inflammatory signatures and significantly improves voluntary physical activity and energy levels. [3, 16] 5. Amplification of Chronic Pain Many ME/CFS patients experience widespread muscle aches and chronic pain. Downstream effectors of cGAS-STING activation include the NLRP3 inflammasome and NF-κB pathways. These downstream targets actively promote peripheral and central sensitization, directly amplifying chronic pain pathways and tissue hypersensitivity. [17, 18] Summary of Potential Mechanism in ME/CFS Are you looking at this from a research perspective, or are you exploring potential therapeutic targets (like STING inhibitors or mitochondrial protectants) currently being discussed in the chronic illness community? AI responses may include mistakes. [1] sciencedirect.com/science/ar… [2] pmc.ncbi.nlm.nih.gov/article…

Your brain switches between glucose, lactate, ketones, and fatty acids throughout the day to match energy demand. In Alzheimer's disease, this fuel flexibility is progressively lost. A Journal of Neurochemistry review reveals why the brain gets metabolically stuck. Alzheimer's disease has long been characterized by reduced glucose metabolism visible on brain scans. The standard interpretation was that neurons couldn't access enough fuel. But a new framework from researchers at the University of Kentucky proposes something different: the brain isn't starving for energy. It's locked into a rigid metabolic program that can't adapt to changing needs. Metabolic flexibility describes the ability of cells to sense, access, and switch between different fuel sources based on availability and demand. In a healthy brain, neurons primarily use glucose. But they can also run on lactate produced by support cells called astrocytes. During fasting or ketogenic diets, both neurons and glia can use ketones. Fatty acids provide another backup fuel source. This fuel switching happens constantly. After a meal, the brain uses glucose. During sleep, it may shift toward lactate and ketones. Under metabolic stress, cells activate alternative pathways to maintain energy production. The system stays flexible, matching fuel use to functional requirements. In Alzheimer's disease, this adaptability breaks down. The review argues that AD is fundamentally a disorder of metabolic inflexibility where cellular metabolism gets actively reprogrammed to support inflammatory and disease-associated processes at the cost of neuronal function. Alzheimer's disease doesn't progress in a straight line of declining metabolism. It unfolds in two distinct phases that seem contradictory. In the early stages, often years or decades before symptoms appear, the brain actually burns more glucose than normal. This hypermetabolism comes from immune cells ramping up their energy consumption to fight inflammation. Think of it as the brain running hot, immune cells working overtime. Later, in the stages when cognitive decline becomes apparent, the pattern flips. The whole brain shifts into hypometabolism, burning less glucose than it should. This is the energy collapse, where neurons can't get enough fuel to maintain normal function. By this point, the metabolic machinery that would allow cells to adapt has broken down. The shift from early hypermetabolism to late-stage collapse follows a biphasic trajectory: • Early stage: Immune cells and support cells burn excessive glucose to fuel inflammation • Late stage: Brain-wide energy shortage as neurons lose access to fuel The brain's immune cells, called microglia, drive this metabolic shift. When they detect damage, they switch to a faster way of burning glucose that prioritizes speed over efficiency. This helps them respond to threats quickly. But once locked into this mode, they consume glucose at rates that starve nearby neurons of fuel. Support cells called astrocytes normally convert glucose into lactate and deliver it to neurons as fuel. In Alzheimer's disease, these cells stop making lactate and start hoarding glucose for themselves instead. The fuel pipeline to neurons shuts down. Both cell types lose their flexibility. They get stuck burning fuel in ways that support their own inflammatory responses but cut off the energy supply that neurons need to function. This metabolic rigidity creates a vicious cycle. When cells can't switch fuels flexibly, they get stressed. That stress increases production of amyloid-β plaques and tau tangles, the hallmark proteins of Alzheimer's disease. These proteins trigger more inflammation, which locks cells even deeper into their rigid metabolic programs. The damage spreads beyond individual cells. Neurons become overactive when they can't meet energy demands, throwing off the brain's excitation-inhibition balance. Network connectivity breaks down. Sleep fragments. Cognitive function declines as the whole system fails to coordinate. System-level consequences include: These cellular-level changes show up as system-wide brain dysfunction: • Neurons fire erratically when starved of energy, disrupting communication patterns • The default mode network, critical for memory and self-referential thinking, loses connectivity • Sleep architecture deteriorates, reducing the brain's ability to clear waste during rest • Memory, attention, and executive function decline as metabolic failure spreads across brain regions Here's what makes this framework different from viewing Alzheimer's as simple energy failure: the metabolic programs are initially adaptive. Microglia activate glycolysis because it helps them respond to damage. Astrocytes shift fuel use to support their own functions under stress. These are protective responses. But they become chronically maladaptive. What works as a short-term stress response traps the brain in a metabolic state that can't support normal neuronal function. The longer these programs run, the more rigid they become, and the harder it is for cells to switch back to flexible fuel use. The critical insight from the review: metabolic inflexibility may be reversible. Unlike permanent structural damage, metabolic programs can potentially be reprogrammed. The authors propose that restoring metabolic flexibility could mitigate amyloid and tau pathology, reduce neuronal loss, and improve functional outcomes. Evidence supporting reversibility comes from preclinical studies testing metabolic interventions. Ketogenic diets, which force the brain to use ketones instead of glucose, have shown some cognitive benefits in animal models and small human trials. Compounds that enhance mitochondrial function or shift cells away from pure glycolysis are being tested. Other approaches target specific aspects of metabolic inflexibility. Drugs that improve insulin signaling in the brain could help cells take up and use glucose more effectively. Interventions that reduce microglial inflammation might allow these cells to return to more balanced metabolic programs. Enhancing the astrocyte-neuron lactate shuttle could restore an important fuel pathway. The review synthesizes human neuroimaging data showing regional patterns of hypometabolism that correlate with cognitive decline, cerebrospinal fluid studies demonstrating altered metabolite profiles, and animal research revealing the cellular mechanisms behind these changes. Clinical trials are actively testing metabolic interventions. Some focus on dietary approaches like ketogenic diets or medium-chain triglycerides that boost ketone availability. Others test drugs that improve glucose metabolism or mitochondrial function. Results so far have been mixed, but the framework suggests timing matters. Early intervention, before metabolic programs become too rigid, may be critical. The view of Alzheimer's disease as a disorder of metabolic inflexibility reframes how we think about disease progression. It's not just about plaques and tangles accumulating. It's about the brain's support systems getting stuck in metabolic states that prioritize inflammation over neuronal support, speed over efficiency, and short-term survival over long-term function. Those choices, made at the cellular level, compound over time. They create an environment where neurons can't get the fuel they need in the forms they can use. Network function deteriorates. Cognitive abilities decline. The brain collapses energetically not because fuel is absent, but because the metabolic machinery to access and use it flexibly has been dismantled. Restoring that flexibility means more than just providing alternative fuels. It means helping cells regain the ability to switch between fuels based on need, rebalancing the metabolic priorities of glia to support rather than compete with neurons, and breaking the feed-forward cycles that lock the brain into rigid metabolic programs. Whether this approach translates into effective therapies remains to be determined. But redefining Alzheimer's disease as metabolic inflexibility rather than simple metabolic failure opens new intervention points at stages of disease where structural damage may still be limited and metabolic programs potentially reversible.

Keep getting "high" serum B12 on your bloodwork? If you have a chronic illness (or autism) it is likely that this is a "paradoxical b12 deficiency". It needs to be TREATED. "The major cause of Paradoxical Vitamin B12 Deficiency appears to be lack of functional vitamin B2, which may occur due to overt vitamin B2 deficiency in a person's diet, Hypothyroidism, or due to lack of adequate intake of Iodine, Selenium and/or Molybdenum, which in turn leads to insufficient production of the two active forms of vitamin B2, namely FMN and FAD. FMN and FAD both have critical roles in cycling and maintenance of activity of vitamin B12, particularly methyl B12." Don't IGNORE this!!! It is not a meaningless result. Doctors are not taught about this and most will ignore it. Don't let this slide. @subversivepsych Is a great account to follow for information on b12 and chronic illness. vitaminb12deficiency.info/pa…

On this day 49 years ago, 30 year old Steve Biko was beaten to death by South African police. Biko had been a medical student himself. The police who killed him were not the only ones responsible for his death, but so are the doctors who were supposed to care for and advocate for him while he was in custody. Dr. Ivor Lang examined him while he was slurring his speech, not moving his body properly, and not making urine. Dr. Lang falsified records, certifying that he found "no evidence any abnormality or pathology". Dr. Benjamin Tucker, the chief district surgeon, also then examined Biko. He consulted with Dr. Colin Hersch who was concerned about brain injury and ordered a test of the fluid around Biko's brain and spine. The test showed enormous amount of blood (a normal test of this fluid would have no blood). Drs Lang and Hersch falsified medical records to indicate the test result was "normal". At times some of the doctors did recommend transfer to hospital, which the police denied. Biko collapsed. Dr. Tucker signed off on transferring him over 1,000km away. Biko was transferred with no medical monitoring, no medical escort, and handcuffed and without clothing, in the back of a police vehicle. No medical handover was given to the receiving medical team and Biko did not get any significant medical treatments. He was left completely alone and unmonitored and died on the floor of his cell. South Africa's professional physician bodies found no misconduct on the part of the doctors involved in Biko's death. 7 years later, a group of doctors took the South African Medical and Dental Council to the Supreme Court who ruled against the council, forcing them to hold disciplinary hearings. Dr. Tucker was found guilty of disgraceful conduct and was stripped of his license. He was reinstated years later. Dr. Lang was found guilty of improper conduct. He received a mild caution. He kept working until his retirement. There were no findings against Dr. Hersch and no action was taken against him. Steve Biko was killed by a violent racist system, from the police, to the doctors, and the medical organizations that protected them. But he left us with his words and he left us with his legacy. It is up to us to continue his work of dismantling systems of oppression and building a world we believe in. He has had a great impact on my own thinking, like millions of others. May he rest, and may his legacy continue to grow through us all.

Goodness. I was not expecting that!

I'm a patient. Whether I'm alive in ten years depends on how fast science moves, and nothing moves it faster than AI. Chasing a problem for the understanding, not the answer, is beautiful. It's also a preference held by people whose lives don't depend on the answers arriving. I think every scientific field is about to face a question it has never had to say out loud. Is the work for the people outside the field whose lives it changes, or is it for the people inside it, who get to spend their lives on the most satisfying kind of thinking there is? For most of history you never had to choose, because the satisfaction drove the work and the benefit came along behind it. When you're the patient the two come apart, because the benefit stops being an abstraction and becomes you. Every year a cure arrives later, people who would have lived instead die. We don't really count them, because we're very good at separating deaths from doing and deaths from not doing. Clinical trials are the clearest example. Keeping a risky combination therapy away from a dying patient protects them from a death by action while quietly accepting a death by inaction, and we weight the first heavily and barely count the second. Slowing AI down works the same way. Pushing the cure for most major diseases from the next decade to the one after is not a careful default. It kills people, it's just that nobody has to sign their name to it. Banning frontier AI in any meaningful capacity would be a decision to let millions of people die on schedule. The better path is infrastructure, meaning verified access for good actors, government capacity to audit what the leading systems are doing, and real consequences for labs that cut corners. On the letter itself, the mathematicians are right about the specifics. A proof announced in 88 hours with no proper writeup and no credit to the work it stands on is a bad way to do mathematics. But that's an output problem rather than a speed problem. Require the model to cite prior work and write the full argument and it's fixed within a quarter. What the letter is really protecting is a culture, and I understand that, but I still think the weight falls on adaptation rather than protection. Traditions built over centuries matter a great deal and they still aren't worth millions of lives. The job for mathematics now is to become the field that turns machine-generated results into ideas humans can actually understand and use, which is still mathematics, and might be the most important version of it. If the machines eventually get better at that too, I'd look at retirees. Most go through a period of agitation and then slowly lose the belief that meaning requires a nine to five. They keep reading, keep learning and keep arguing about ideas, they just stop doing it for a paycheck. I don't think that's a tragedy. I think it might be where all of this ends up. So for anyone weighing how fast this should go, put the hidden deaths from delay next to the visible risks from action every time. It's the only way to account for everyone with a stake in this, including the ones who won't be around to complain if we get the timeline wrong.

The powers that be know exactly what they are doing and what the consequences are. I know this post is related to the current UK situation but it has played out in Canada for years already. First you create/legislate poverty. Disabled people receive so little help from the government in Canada that it would not be possible to actually survive on their disability pension outside of a "skid row" type situation. Try to imagine living on ~1,250 CDN a month (yes, a MONTH). Now try and imagine how you would do this if you were disabled and thus had many extra medical expenses. Then you remove safeguards from the Assisted Death and MAID legislation so that 'poverty' or lack of resources becomes a grey area - if a disabled person cannot survive outside of extreme poverty - well...it is obvious this will heavily play into a decision for MAID/AD. Make sure this is not a point were MAID could be denied if poverty was obviously contributing to the decision.