Sanders

@JohnStamos @bobsaget @TheTonyAwards @BroadwayLeague @TheWing Love this tweet from Bob Saget, november 11, 2021: I truly believe in my heart of hearts, that we should tweet other people the way we’d like to be tweeted.

I call it the “poor man’s gut transit test “ It is a surrogate marker of whole gut transit time. You should see the corn in your stool within 24 hours. So who should perform the corn test? A better question is who should not perform the corn test? Anyone allergic to corn

Millions of people got sick, then got sicker — and then stopped getting better. They came back with normal labs. Unremarkable imaging. And the quiet suggestion that maybe the problem wasn't biological. Long COVID didn't just introduce a new illness. It exposed how modern medicine responds when suffering can't yet be measured. Modern healthcare systems struggle with: - Illness without measurable biomarkers - Symptoms that fluctuate and defy categorization - Patients — especially women — whose suffering outpaces the science - Chronic complexity in a system built for acute resolution What Long COVID revealed was already there. Patients with ME/CFS, fibromyalgia, and dysautonomia (like POTS) had been describing this reality for decades. Long COVID just made it impossible to ignore. In this essay, I explore: - Why Long COVID exposed cracks in medicine that existed long before the pandemic - How "we can't explain this" quietly became "this may not be real" - Why chronically ill patients already knew this story - How a system built for acute disease failed millions with chronic illness - Why Long COVID's research funding is catastrophically misaligned with its actual harm - And what medicine still owes the patients it dismissed open.substack.com/pub/brittanija…

Bacterial Extracellular Vesicles/ Blood Brain Barrier / Gut Health / Intestinal Permeability / Probiotcs / BDNF describe how BEVs from pathogenic bacteria disrupt intestinal barrier integrity by targeting tight junction proteins, activating pro-inflammatory PRR signaling, and inducing epithelial apoptosis, while BEVs from probiotic and commensal bacteria confer barrier protection, enhance mucin secretion, and promote immune homeostasis. Evidence is reviewed demonstrating that BEVs can traverse both the intestinal epithelium and the blood-brain barrier (BBB), delivering bioactive cargo—including LPS, bacterial amyloids, and regulatory RNAs—that promote neuroinflammation and aggregate pathology in Alzheimer's and Parkinson's disease models. Conversely, probiotic-derived BEVs exert neuroprotective effects through modulation of serotonergic signaling, BDNF expression, and anti-inflammatory pathways. Bacterial-derived extracellular vesicles as master regulators of intestinal barrier function, neurodegenerative diseases and metabolic health sciencedirect.com/science/articl…

Microbiome / Mitochondria / Oxygen Regulation / SCFA / Immunity The bidirectional dialogue between mitochondria and the human microbiota—the mitochondria–microbiome axis—plays a pivotal role in regulating host metabolism, immune signaling, and overall physiological homeostasis. Growing evidence underscores the role of microbial metabolites—including short-chain fatty acids, secondary bile acids, and lipopolysaccharides—as direct modulators of mitochondrial bioenergetics, redox balance, and inflammatory cascades. Conversely, mitochondrial integrity governs the microbial landscape by regulating local oxygen tension, modulating immune-mediated selection, and secreting metabolic byproducts that shape commensal populations. Disruptions to this bidirectional crosstalk are linked to a diverse pathological spectrum. These include metabolic syndromes like obesity, type 2 diabetes, and NAFLD; neurodegenerative disorders such as Parkinson's and Alzheimer's; and systemic inflammatory conditions, notably inflammatory bowel disease and various autoimmune pathologies. Therapeutic interventions designed to modulate this axis—ranging from targeted probiotics, dietary interventions, and mitochondrial boosters—offer significant potential for reinstating physiological homeostasis. Molecular Dialogues in the Mitochondria–Microbiome Crosstalk: Metabolites, Signaling, and Immunity onlinelibrary.wiley.com/doi/abs/10.100…

That means their effects may extend beyond glucose regulation, appetite, and weight. “Beyond weight” does not mean metabolism is irrelevant. It means metabolism may be the entry point into: * neuroinflammation * synaptic plasticity * brain connectivity * cognition * emotional regulation

GLP-1 receptor agonists are not just weight-loss drugs. They sit at the intersection of metabolism, inflammation, neuroplasticity, and cognition. That is why their relevance to metabolic psychiatry is becoming harder to ignore. 🧵👇

🧵Your Favourite Treatment Isn’t the Whole of Psychiatry 🚨1/16 
This image shows the range of targets we deal with in psychiatry. And it also shows why psychiatry becomes ‘dangerous’ when one target becomes the whole model. There are broadly 3 layers of targets. Let’s explore 👇

Vitamin B12 is absorbed through two pathways. The first is intrinsic factor, a protein produced by parietal cells in the stomach. IF binds B12 in the small intestine and carries it across the gut wall via a receptor called cubilin in the distal ileum. This pathway is efficient but has a hard ceiling: it saturates at roughly 1.5 µg per dose. No matter how much B12 you swallow beyond that, IF cannot carry any more. The second pathway is passive diffusion. About 1 to 2% of any oral dose diffuses across the intestinal lining without IF, and this occurs along the entire length of the gut. At dietary doses, this pathway is negligible. At supplement doses, it becomes the primary route of absorption. Adams et al. (1971, Scand J Gastroenterol) measured whole body retention of radiolabeled cyanocobalamin at different doses. At 1 µg, roughly 50% was retained. At 5 µg, about 20%. At 25 µg, just over 5%. The NIH Office of Dietary Supplements reports approximately 2% absorption at 500 µg and 1.3% at 1,000 µg. The fraction drops dramatically. But the total amount absorbed keeps rising. At 1 µg you absorb about 0.5 µg. At 1,000 µg you absorb roughly 13 µg total, of which approximately 10 µg comes from passive diffusion alone. The RDA is 2.4 µg. Even the backup pathway, working at 1% efficiency, delivers more than four times your daily requirement from a single pill. This is the basis for high-dose oral B12 as an alternative to injections in patients who lack intrinsic factor. The NIH notes that high-dose oral supplementation "may be another treatment option" for pernicious anemia, though injections remain standard first-line therapy and the available randomized controlled trials comparing the two approaches are considered limited in quality. One important nuance: absorbing B12 into your bloodstream is only the first step. After absorption, B12 must bind to a transport protein called transcobalamin to reach your cells. This complex, holotranscobalamin, is the biologically active fraction. It represents only about 20 to 30% of the total B12 circulating in your blood. The remaining 70 to 80% rides on a separate protein called haptocorrin, which does not deliver B12 to most tissues. This is why serum B12 can be misleading as a status marker. A person can have a "normal" total serum B12 level while their holotranscobalamin, the fraction that actually delivers B12 to cells, is low. Methylmalonic acid is a more sensitive functional marker because it rises when cellular B12 is genuinely insufficient, regardless of what total serum B12 shows. Absorption determines how much B12 enters your blood. Transport determines how much reaches your cells. Testing only total serum B12 measures neither of these processes accurately. Adams et al., Scand J Gastroenterol, 1971 NIH Office of Dietary Supplements, 2024 Allen et al., J Nutr, 2018

Orexin / Dysautonomia Dysautonomia, a disorder of the autonomic nervous system, shares significant overlap with orexin (hypocretin) system dysfunction, which regulates wakefulness, energy, and autonomic functions. Deficiencies in orexin, found in narcolepsy, cause autonomic instability—including tachycardia and blood pressure dysregulation—suggesting that the loss of this neurotransmitter contributes to impaired cardiovascular control. Orexin System & Autonomic Regulation Orexin is produced in the hypothalamus and regulates essential "multi-tasking" functions that are often impaired in dysautonomia patients: Autonomic Control: Orexin modulates breathing, blood pressure, thermoregulation, and heart rate, especially in res ponse to stress. Energy & Metabolism: It helps manage energy balance and metabolism. Arousal: It maintains wakefulness, and its lack results in fatigue, excessive daytime sleepiness, and brain fog. Dysautonomia & Orexin Dysfunction Overlap Fatigue & Sleep Disorders: Disruptions in the orexin system are linked to conditions like Long COVID and chronic fatigue, causing symptoms such as severe fatigue and sleep disturbances. Cardiovascular Dysfunction: Narcolepsy (a prime orexin deficiency disorder) shows autonomic dysfunction, including elevated heart rates and a "nondipping" blood pressure profile (blood pressure not decreasing at night). Neuroinflammation: Neuroinflammation is thought to damage orexin neurons in certain conditions, leading to both fatigue and dysautonomic symptoms.MCAS & Autonomic Dysfunction: Mast Cell Activation Syndrome (MCAS), often linked to EDS and POTS (types of dysautonomia), includes symptoms of autonomic dysregulation such as tachycardia, flushing, and nocturnal histamine surges. Potential Therapeutic Implications Research into orexin-related treatments, such as orexin agonists (to boost levels) and antagonists (to improve sleep quality), is an emerging area for managing fatigue and autonomic symptoms in conditions beyond narcolepsy, though this is considered experimental. Orexin in Respiratory and Autonomic Regulation, Health and Diseases - PubMed share.google/inDZT7Hzpq8fOO…

Your body makes collagen constantly. But the version it assembles first isn't finished. Before collagen can hold its shape, an enzyme has to modify specific amino acids in the chain. That enzyme needs vitamin C to work. Here's what vitamin C actually does: it enables the chemical modification (hydroxylation) that allows three collagen chains to lock together into a stable triple helix. Without that modification, the collagen structure is so weak it falls apart below body temperature. Literally. Unhydroxylated collagen melts at about 24°C. Your body runs at 37°C. The only thing keeping your collagen intact at body temperature is the modification that vitamin C makes possible. This is why scurvy causes bleeding gums, loose teeth, poor wound healing, and joint pain. Your body is still making collagen. It just can't hold together. Vitamin C isn't recycled in this process. It's consumed each time. Your supply has to be continuously replenished. Most collagen supplement studies co-administer vitamin C. The ones that don't rarely account for baseline vitamin C status. If you're taking collagen without adequate C, you're supplying the raw material without the tool that finishes it. Sources: Peterkofsky, Am J Clin Nutr, 1991. Shoulders & Raines, Annu Rev Biochem, 2009

She wasn’t misdiagnosed because it was complicated. She was misdiagnosed because people stopped looking. “It's in your head” shouldn’t be the end of the conversation—it should be the beginning of deeper investigation. Patients aren’t the problem. The lens is. #MedicalGaslighting #PatientAdvocacy

Nose-to-brain axis: mechanistic links between nasal microbiome dysbiosis, neuroinflammation, and brain disorders "Nasal dysbiosis promotes neuroinflammation and blood–brain barrier disruption... Microbial imbalance is linked to Alzheimer’s, Parkinson’s, MS, and psychiatric disorders." ibroneuroscience.org/article/S0306-…

Magnesium isn't the key or the lock. It's the spring inside the lock that makes the mechanism turn. When insulin binds its receptor, the receptor activates an internal kinase that phosphorylates itself. That switch kicks off the chain that tells GLUT4 to bring glucose into the cell. The switch requires magnesium. Suárez et al. showed this directly in rats. Magnesium-depleted animals had normal insulin binding, normal GLUT4 levels, structurally intact hardware. But receptor autophosphorylation dropped 50% and insulin sensitivity fell with it. The signal was weakened, not the parts. Two large meta-analyses of prospective cohorts confirm the pattern. Dong 2011: 14% lower type 2 diabetes risk per 100 mg/day, across 536,000 people. Fang 2016: 19% lower per 100 mg/day, across over 1 million people. Observational, not proof of causation, but consistent with the mechanism. The RDA is 310-420 mg/day. Roughly half of US adults don't meet it. Suárez, Diabetologia 1995: pubmed.ncbi.nlm.nih.gov/8582534/Dong, Diabetes Care 2011: pubmed.ncbi.nlm.nih.gov/21868780/Fang, BMC Medicine 2016: pubmed.ncbi.nlm.nih.gov/27927203/

Famotidine blocks H2 receptors. Your body has four types of histamine receptor. In mast cell activation, one blocker is not a strategy. The acid improves. Everything else the cell is doing continues. H1 drives flushing, hives, nasal congestion, and a share of the anxiety spectrum. First-generation H1 blockers (hydroxyzine) and second-generation (cetirizine, fexofenadine) cover this receptor. Missing H1 blockade leaves most of the daily MCAS load untreated. H2 drives gastric acid secretion. Famotidine, ranitidine (where still available), cimetidine. Often the only receptor blocked in primary care, because reflux is the presenting complaint. Useful, incomplete. H3 modulates neurotransmitter release in the brain. Linked to brain fog, sleep disruption, and appetite regulation. No standard blocker in routine practice, but the receptor exists and the symptoms correlate. H4 drives immune cell recruitment and chemotaxis. Part of why MCAS flares feel systemic rather than local. H4 antagonists are investigational but relevant to the mechanism picture. Combine H1 and H2 blockade, add mast cell stabilization (cromolyn, ketotifen), identify triggers, support DAO. Cover the cell, not one receptor. Follow @Covid_institute for mechanism-based MCAS workup.

Not all PTSD reflects the same neurobiological pattern. Some presentations are predominantly hyperaroused. Others are predominantly dissociative.  This distinction has direct clinical implications:🧵👇

WMHs are linked to increased risk of: - stroke - cognitive impairment - impaired mobility - depression - death They are increasingly understood as a marker of brain frailty.

Meds don't work consistently for 71% of Americans with high blood pressure. Why? They don't fix the factors that give you high blood pressure in the first place. Here are 7 tips to lower your blood pressure naturally:🧵 1. Get more magnesium and potassium

7 things your child will remember about you forever… And it’s not what you think. Not the toys. Not the money. Not the big moments. It’s the small, everyday things. Read this carefully 🧵

Most people who take CoQ10 think of it as an antioxidant. It is one. But that is not the most important thing it does. CoQ10 is the only lipid-soluble mobile electron carrier in the inner mitochondrial membrane. The electron transport chain has four protein complexes fixed in the membrane. Complex I accepts electrons from NADH. Complex II accepts them from FADH2. But neither can pass those electrons directly to Complex III. They hand them to CoQ10, which physically shuttles across the lipid bilayer to deliver them. Complex III passes them to cytochrome c, the second mobile carrier, which delivers them to Complex IV. Complex IV reduces oxygen to water. The proton gradient pumped by Complexes I, III, and IV powers ATP synthase to produce ATP. Without CoQ10, the chain breaks between Complex I/II and Complex III. Electrons have nowhere to go. Proton pumping stops. ATP production stalls. This is not an antioxidant function. This is the core mechanism of aerobic energy production. CoQ10 is predominantly synthesized endogenously through the mevalonate pathway, the same pathway that produces cholesterol. HMG-CoA reductase is the rate-limiting enzyme of the pathway. Statins inhibit HMG-CoA reductase. That is how they lower cholesterol. It is also how they lower CoQ10. An updated meta-analysis by Qu et al. (2018) pooled 12 RCTs with 1,776 participants and found statins significantly reduced circulating CoQ10. The reduction was present across statin types, intensities, and durations. Both lipophilic and hydrophilic statins showed the effect, with no significant difference between them. This is consistent with what the biochemistry predicts: the pathway is shared. On top of statin-induced depletion, CoQ10 in human heart tissue declines naturally with age. Kalén et al. (1989) measured CoQ10 concentrations in myocardial tissue and found levels peak around age 20, decline by more than 30% by age 40, and drop approximately 50% by age 80. The organ with the highest energy demand loses half its electron carrier over a lifetime. A 2025 meta-analysis by Kovacic et al. (Journal of Nutritional Science, 7 RCTs, 389 patients) found CoQ10 supplementation significantly reduced statin-associated muscle symptoms measured by pain intensity. This is the most current pooled data on clinical outcomes. One important nuance: while plasma CoQ10 depletion from statins is well established, whether intramuscular CoQ10 drops proportionally is inconsistent. Some studies found no change or even increases in muscle tissue CoQ10 during statin treatment. The plasma reduction may partly reflect reduced LDL particles, which are the primary carriers of CoQ10 in blood. The clinical significance of depletion beyond muscle symptoms remains debated. Roughly 200 million people worldwide take statins. The mevalonate pathway that produces their target also produces the electron carrier their mitochondria depend on. The mechanism is not controversial. The clinical implications are still being debated Sources: pubmed.ncbi.nlm.nih.gov/2779364/ pubmed.ncbi.nlm.nih.gov/30414615/ pubmed.ncbi.nlm.nih.gov/41158831/