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Sleep doctor says taking melatonin without understanding what it does can cause serious harm to your body “Melatonin is by prescription only almost everywhere outside the United States. Melatonin is a hormone. There’s a reason you can’t go to CVS and get testosterone and estrogen, right? Hormones affect the...

80,499 görüntüleme • 3 ay önce •via X (Twitter)

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The only thing worse than Homeopathy? Scientists on the internet without any knowledge on clinical medical practice, selling supplements that they endorse, using misinformation masquerading as "solid peer reviewed science." Check this video out, when Huberman bullshits everyone in just half a minute on the Joe Rogan Experience Podcast. Before I go on, please remember this The Bullshit Asymmetry Principle, also known as Brandolini’s Law, states that the amount of energy needed to refute bullshit is an order of magnitude bigger than that needed to produce it. Which means, I have to put extra effort just to debunk the 36 seconds of that podcast. First, a little about sleep disorders Sleep disorders are of different types and due to different causes. The diagnosis is simply not "I can't sleep" and so here, take this sleep cocktail. Many patients come with sleep disorders that are associated with other conditions. For example, cirrhosis patients have sleep disorders that require management with ammonia lowering therapies and severe cases can only be reversed with a liver transplant. Patients with alcohol use disorders have sleep disorders that require management with de-addiction therapies along with sedatives. Sleep disorders in the ICU set up has different causes. People with mental health disorders have associated sleep disorders. Certain sleep disorders have no identifiable causes and are called "idiopathic." Which means, coming on a podcast and blindly giving out a "sleep cocktail" to millions of viewers, who may be suffering from a sleep disorder which has an as yet unidentified cause, is one of the most foolish things one can do. And Huberman, not being an actual clinical doctor, makes that exact mistake. Huberman claims (very generally and casually), melatonin helps you to go to sleep, but does not maintain sleep. But "solid peer reviewed" studies have much more to say about melatonin. Melatonin improved sleep onset latency and total sleep time in children/adolescents with neurodevelopmental disorders. Melatonin also improved and sleep onset latency and total sleep time in adults with delayed sleep phase disorder. Treatment with melatonin has positive effects on sleep quality in adults with respiratory diseases, metabolic disorders, primary sleep disorders, not with mental disorders, neurodegenerative diseases and other diseases. This meta-analysis demonstrated that melatonin decreases sleep onset latency, increases total sleep time and improves overall sleep quality. Another large meta-analysis showed that melatonin dosing and timing matters: for circadian phase advancement, an earlier time and smaller dose, but for sleep quality/consolidation a larger and later dose seemed appropriate. See here: So melatonin does increase total sleep time, total sleep quality and reduces time to sleep and has beneficial effects in specific groups of patients. Now the "solid peer reviewed studies" on the cocktail - which Huberman claims on three supplements - magnesium threonate, apigenin and L-theanine. Unfortunately, such "solid peer-reviewed papers" DO NOT EXIST. Lets see. Magnesium supplements: First of all, there is no conclusive evidence that magnesium, dietary or supplemented has any actual effect on sleep. Randomized clinical trials showed an uncertain association between magnesium supplementation and sleep disorders. See here: Forget sleep, magnesium has absolutely no evidence for involvement even in mood disorders. See here: This review confirms that the quality of literature is substandard for physicians to make well-informed recommendations on usage of oral magnesium for older adults with insomnia. See here: Apigenin (from Chamomille): The possible sleep inducing effects of apigenin is still speculative. There are absolutely no solid peer reviewed studies or evidence for benefits of apigenin in sleep as Huberman claims. See here: A randomized, double-blind, placebo-controlled pilot trial showed that chamomille DID NOT have conclusive effects on sleep. See here: Even better, a systematic review and meta-analysis of randomized trials and quasi-randomized trials showed that there was very little evidence to show effect of chamomille on insomnia. See here: L-theanine supplements: There is absolutely NO study or data to suggest that L-theanine is useful for sleep induction, improving sleep quality or increasing total sleep time. The only studies that are of "better quality" shows that L-theanine "maybe" useful in reducing anxiety/ stress levels due to caffeine at night. See here and here The only other "study" on L-theanine which was done on mice and not humans showed effects only on brain related biomarkers and were not applicable in the clinical sense to humans - And coming to SOLID EVIDENCE on the "Huberman cocktail" - there is absolutely nothing in published literature to confirm that it works and there is no convincing mode of action of this cocktail in humans. A large systematic review and meta-analysis showed that Cognitive-Behavior Therapy for Insomnia was the best and not some random supplements proclaimed on a podcast by half-baked scientists who are full time supplement sellers. See here: There are basic scientists, with no or half-baked clinical practice knowledge, trying to sell you a bunch of useless supplements that they endorse for a paid-commission, using "science-sounding" words without any practical, rational or logical meaning; and push untested and unregulated therapies that are NEVER recommended, approved or promoted by any active, medical, scientific clinical societies worldwide. They are worse than pseudoscience peddlers. Be aware of where you find your health information. There is pseudoscience, but then there is also another terrible type of misinformation: BAD SCIENCE.

TheLiverDoc™

475,648 görüntüleme • 2 yıl önce

WHY YOU WAKE UP IN THE MIDDLE OF THE NIGHT Your brain has 20,000 neurons clustered in the hypothalamus. They form the suprachiasmatic nucleus. This is your master clock. It's been running since before birth. At 25, this clock kept you unconscious until morning. At 65, the same clock runs on less melatonin, weaker signals, and a rhythm that physically shifted 2-3 hours earlier. It fires a wake signal between 2-4 a.m. Four systems inside your body shifted with age. They converge at the same hour every night. The thoughts that arrive at 3 a.m. feel different from the same thoughts at 3 p.m. because your brain runs a different program in the dark. The part that would normally tell you those thoughts aren't emergencies is still asleep. THE CLOCK MOVED FORWARD The suprachiasmatic nucleus generates a near 24-hour rhythm controlling when you feel alert and when you feel sleepy. In young adults, peak sleepiness arrives around 11 p.m. Peak alertness arrives around 9-10 a.m. Blue light at 480 nanometers activates melanopsin cells in the retina. These cells send signals directly to the suprachiasmatic nucleus, synchronizing your clock to the day-night cycle. With age, the clock shifts earlier. This is circadian phase advance. The sleepiness signal arrives at 7-8 p.m. instead of 11 p.m. The wake signal arrives at 3-4 a.m. instead of 6-7 a.m. The entire sleep-wake window moves forward 2-3 hours. The suprachiasmatic nucleus itself degrades. Neurons deteriorate. The amplitude of the circadian signal weakens. Peaks become shallower. Troughs become less deep. The radio station loses transmitter power until the signal becomes fuzzy and inconsistent. The clock's sensitivity to light cues diminishes through two mechanisms. The aging lens yellows and thickens, filtering more blue light before it reaches the melanopsin cells. The suprachiasmatic neurons themselves respond less robustly to whatever signal does arrive. Weaker input through a cloudier window. Less responsive neurons processing that input. The clock drifts. When the circadian clock drifts without strong light cues, it drifts earlier. Phase advance is the default direction of an unanchored aging clock. MELATONIN COLLAPSED The pineal gland releases melatonin at night to initiate and maintain sleep. This hormone declines with age. The pineal gland calcifies gradually over decades, reducing functional tissue and capacity to produce melatonin. By 65, nighttime melatonin levels can be one-third to one-quarter of what they were at 30. Sometimes less. Melatonin doesn't just initiate sleep. It maintains depth and continuity across the full night. When melatonin is low, sleep is shallower, more fragmented, more vulnerable to interruption. Even if you fall asleep at a reasonable hour, low melatonin cannot hold you through to morning. Your body tries to put you to sleep at 8 p.m. and wake you at 3 a.m. That's a 7-hour sleep window. It might be enough sleep for your shifted clock. But you fight the 8 o'clock drowsiness. Social life, television, family, habit. You stay up until 10 or 11. The clock doesn't adjust to your social schedule. It fires the wake signal at 3 regardless. The clock runs on light and biology, not preferences. You lost 2-3 hours from the front of your sleep window by staying up late. The alarm still goes off on the original schedule. The 3 a.m. waking isn't a malfunction. It's your shifted clock doing exactly what it was programmed to do. This is social jet lag. The gap between your biological clock time and your social clock time creates the same physiological mismatch as flying across two or three time zones. Your body is in one time zone. Your social life is in another. The drowsiness you fight at 8 p.m. is your body's genuine sleep onset signal. The waking at 3 a.m. is your body's genuine wake signal. The problem isn't the signals. The problem is overriding one without being able to override the other. There's a compounding factor. The shifted clock means your body wants to sleep earlier. The reduced melatonin means it cannot hold sleep as deeply or as long. You're caught between two problems: a clock that fires the wake signal too early and a chemical supply that cannot maintain the sleep signal through the full night. Even if you went to bed at 8, the reduced melatonin might still fail to hold you past 3 or 4. The clock shifted the window. The melatonin shrank it. DEEP SLEEP DISAPPEARED Sleep cycles through stages roughly every 90 minutes. Light sleep, deeper sleep, deeper sleep, then REM. The stage that matters most for feeling rested is slow-wave sleep, stage N3, the deepest phase. Brainwaves drop to large, slow delta oscillations at 0.5-4 hertz. During slow-wave sleep, the glymphatic system activates. Cerebrospinal fluid flushes through brain tissue along channels that open when neurons shrink slightly during deep sleep. This clears metabolic waste: adenosine, the molecule that builds sleep pressure during the day, and amyloid beta proteins, the plaques associated with Alzheimer's disease. Growth hormone pulses during N3. Tissue repair peaks. Memory consolidation occurs. The hippocampus replays the day's experiences and transfers them to long-term cortical storage. This is the sleep that makes you feel like you actually slept. At 25, roughly 20% of the night is spent in slow-wave sleep. By 65, that drops to 10-15%. By 75, some people get almost none. My sleep tracker tells me that I almost never get less than 30%... and I'm 60. It is possible to have restorative deep sleep no matter what your age is. In my case even at lower sleep duration. High energy availability alsp plays a big role. The slow wave generating circuits in the medial prefrontal cortex usually deteriorate with age, producing weaker and less frequent delta oscillations. The deep sleep itself becomes shallower. The waves are smaller. The duration shorter. The restorative process is less complete. If deep sleep is the period when the brain clears amyloid beta, then reduced deep sleep means reduced clearance. Less deep sleep leads to more amyloid, which leads to less deep sleep, which leads to more amyloid. The relationship is bidirectional and self-reinforcing. If you never feel fully rested no matter how many hours you spend in bed, if 8 hours produces the recovery that 6 hours used to produce, if you wake in the morning with the sense that something was missing from the night, the missing component may be slow wave sleep. The hours were there. The depth was not. Slow-wave sleep that remains concentrates in the first half of the night, the first two to three sleep cycles. By 2-3 a.m., most of the deep sleep budget has been spent. What remains for the second half of the night is lighter stage one and stage two sleep, interspersed with REM. Light sleep has a dramatically lower arousal threshold. Stimuli that would not have registered during slow-wave sleep can push you above the waking threshold in light sleep. A slight temperature change in the room. A bathroom urge from a bladder that fills faster with age. A noise from outside. Even the natural shift in body position. You wake at 3 a.m. partly because the sleep you're in at 3 a.m. is physiologically different from the sleep you're in at midnight. The fortress walls got thinner as the night progressed. By 3 o'clock, you're sleeping behind a screen door instead of a vault. You could sleep through thunderstorms at 30. Now you wake at the sound of a refrigerator cycling on. The physics isn't about the noise. It's about the stage of sleep you're in when the noise arrives. At midnight, during slow-wave sleep, your arousal threshold is high. The brain runs delta waves that suppress responsiveness to external stimuli. At 3 a.m. in stage 1 or stage 2, the threshold has dropped to a fraction of its midnight level. The same sound that the sleeping brain would have filtered at midnight wakes you at 3 because the brain is no longer running the program that filters it. CORTISOL ARRIVED EARLY Your body runs a cortisol rhythm called the cortisol awakening response. In the final hours of sleep, the adrenal glands begin increasing cortisol output, preparing the body for waking. Mobilizing glucose into the bloodstream. Priming the immune system for the day's pathogens. Raising blood pressure and heart rate toward daytime operating levels. In a young adult, this cortisol rise begins around 4-5 a.m. and peaks roughly 30-45 minutes after waking. With age, the rise begins earlier. 2-3 a.m. in many older adults. Low-carb diets can also trigger a relatively strong cortisol release, waking you up early.. The same circadian phase advance that shifted the sleep-wake window also shifted the cortisol curve. Every rhythm the suprachiasmatic nucleus controls moves in the same direction. Cortisol alone doesn't wake you. But combined with already light sleep and a shifted circadian clock, the cortisol rise adds a third signal, pushing you toward wakefulness at precisely the hour when the other two systems have already weakened your defenses. Three systems converging on the same window. The clock says wake up. The sleep stage says the walls are thin. The cortisol says the body is preparing for morning. All three signals arrive at 3 a.m. Not by coincidence. All three are governed by the same shifted circadian master clock. If the waking comes at almost exactly the same time every night, not randomly scattered across the early morning hours but clustered within the same 30-minute window, that precision is the signature of a circadian event. Cortisol is antagonistic to melatonin. The two hormones suppress each other. Cortisol inhibits melatonin production. Melatonin suppresses cortisol. In a young person with high melatonin and correctly timed cortisol, the two hormones hand off smoothly. Melatonin dominates the night. Cortisol rises toward morning. The transition is seamless. In an aging body with depleted melatonin and early-arriving cortisol, the handoff happens too soon. When cortisol starts rising at 2-3 a.m. and melatonin is already low, the biochemical conditions for staying asleep collapse. The melatonin that should be holding you under is insufficient. The cortisol that should not be arriving for another two hours is already here. Two hormones that are supposed to hand off like relay runners, one finishing as the other begins, instead collide in the same hour because both shifted on the same aging clock. The balance tips toward waking. THE WORST THOUGHTS ARRIVE When you wake at 6-7 a.m., cortisol is high, light enters your eyes, and your prefrontal cortex comes online in its task-oriented mode. You think about what to do, what to eat, where to go. Executive function engages. The thinking is directed, practical, forward-looking. Problems that exist at 7 a.m. feel like problems to be solved. Manageable, bounded, addressable. When you wake at 3 a.m. in the dark with no tasks to perform and no light to signal daytime, a different network activates. The default mode network. The brain's self-referential processing system fires in the absence of external input and directed task. This is the rumination network. It runs replays of conversations you had years ago. It generates worry scenarios about events that may never happen. It revisits regrets from decades past with a vividness that feels more real than memory should. It rehearses confrontations that will never take place. It asks questions that have no answers at any hour, let alone at 3 a.m. At 3 a.m., the default mode network has nothing competing with it. No light. No task. No external stimulation. No social interaction. And the executive prefrontal cortex that would normally evaluate, contextualize, and override the rumination is still partially offline. The prefrontal cortex is the last brain region to fully activate upon waking. It requires light exposure and time to reach full operating capacity. This is the region that says this thought is not an emergency. This worry is not proportionate to reality. This problem can wait until morning and will look different then. At 3 a.m., that region is sleeping while the default mode network runs at full power. You're awake enough to think. But the thinking is the uncontrolled, self-referential, catastrophizing kind. The system that controls and contextualizes thought has not caught up with the system that generates it. The worry loop feels more intense at 3 a.m. than the same thoughts would feel at 3 p.m. because the brain regions that regulate emotional response and assign proportionality are not yet operational. You're running the worry software without the control software. The thoughts feel urgent and catastrophic because the part of your brain that would tell you they are neither is still asleep. The thoughts are not true in the way they feel true. They're running on hardware that cannot evaluate them yet. The 3 a.m. thoughts have a specific quality that daytime worry doesn't. A sense of certainty. Of inevitability. Of problems being larger and solutions being fewer than they actually are. The distortion isn't emotional. It's architectural. The brain regions that generate worry are online. The brain regions that evaluate worry are not. By 7 a.m., when the prefrontal cortex has fully activated and light has entered the eyes and cortisol has reached its appropriate peak, the same problems that felt catastrophic at 3 a.m. feel manageable. Nothing changed about the problems. Everything changed about which brain regions are processing them. If you've lain in the dark at 3 a.m. and felt that your problems were larger, your regrets sharper, your fears more certain than they would be by breakfast, that wasn't weakness. It wasn't anxiety disorder. It was the default mode network running without prefrontal supervision, amplified by cortisol that arrived early, in a brain that had already run through its deep sleep budget and could not pull you back under. Four systems, all doing what the physics of aging programmed them to do, all converging on the same hour. Subscribers have access to detailed practical applications of remedies in a second attached post.

Metabolic Uncle

12,138 görüntüleme • 4 ay önce

The problem with most supplements is the deuterium they deliver. Stephanie Seneff, MIT researcher: "People are loading up on supplements that are actually hurting them — they're not supplying the low deuterium resource that would have happened if it had been biological." Most supplements are made in chemistry labs. The molecules are chemically identical to their natural counterparts. But they lack one critical property: deuterium depletion. Deuterium is a heavy form of hydrogen that damages ATPase pumps in the mitochondria. Melatonin is the clearest example. Your gut produces 400x more melatonin than your pineal gland — most of it inside mitochondria. Seneff: Melatonin is not primarily a sleep hormone. It is a deuterium depletion system. Here's the mechanism: Gut microbes produce hydrogen gas that is 80% deuterium depleted. That gas feeds a chain of conversions — producing methyl and acetyl groups that are severely low in deuterium. Those methyl and acetyl groups get attached to serotonin, converting it into melatonin. Each melatonin molecule now carries depleted hydrogen — ready to be delivered to the mitochondria. Inside gut cells (enterocytes), an enzyme called CYP2C19 strips the methyl group off melatonin. Each time it does, it releases four molecules of deuterium-depleted water directly into the mitochondria — protecting the ATPase pumps that generate your cellular energy. Four depleted water molecules. Per cycle. To the ATPase pumps that need them most. When melatonin is made synthetically — which is virtually all commercial melatonin — the methyl and acetyl groups come from bulk chemicals made in a lab. Random high deuterium content. The biological depletion step never happened. Your body cannot tell the difference. Sleep improves. Antioxidant effects occur. But the deuterium depletion cycle doesn't run. The mitochondria don't get what they actually need. The short-term benefit masks the long-term harm. The TMAO (Trimethylamine N-oxide) evidence: TMAO is a marker for deuterium toxicity — deuterium-loaded methyl groups accumulating systemically. People who ate eggs — no TMAO increase. People who took synthetic choline supplements — elevated TMAO. The mechanism: enzymes that metabolize methyl groups can detect deuterium — and refuse to process it. The trimethylamine survives in the gut. Gets oxidized in the liver. Becomes TMAO in the blood. The same problem applies to: N-acetylcysteine (NAC) — the acetyl group is low deuterium from gut microbes, unpredictable when synthetic. Choline bitartrate — Seneff: "If you're taking choline bitartrate, you need to stop." Methionine — methionine-deficient rats lived longer in one study. Seneff's interpretation: methionine restriction extended lifespan not because methionine itself is harmful — but because the rats stopped receiving deuterium-loaded synthetic methionine. Their gut microbes produced it naturally — low deuterium. The rats getting synthetic methionine wrecked their mitochondria with deuterium-enriched methyl groups. The deficient rats didn't. Methylated B vitamins — likely synthetic, likely the same problem. The studies testing these supplements never account for the fact that they're synthetic. They have no idea that's even a variable worth measuring. What to do instead: - Get methionine from meat, fish and eggs — not synthetic amino acid supplements. - Get choline from eggs and animal foods — not choline bitartrate. - Get tryptophan from food — chicken, turkey, beef, pork, fish, eggs, hard cheeses (parmesan, cheddar). Your gut microbes convert it through the biological pathway naturally, producing depleted melatonin the way biology intended. One study: tryptophan loading increases serum melatonin 4-fold — even in rats without a pineal gland, confirming the melatonin was gut-sourced not pineal-sourced. - Animal fats — butter, tallow — are among the lowest deuterium foods available. Derived from acetate produced by gut microbes from deuterium-depleted hydrogen gas. The same pathway that makes biological methyl groups low in deuterium. - Eat certified organic. Glyphosate disrupts the gut microbiome — which disrupts the entire deuterium management system upstream. - Fermented foods support acetate production and the whole chain. Whenever the food is fermented, the microbes are making nutrients that are low in deuterium. - Keep your gut microbiome healthy. It is your primary deuterium management system. Seneff is 78 years old. Still writing papers. Mentally sharp. Doesn't take any supplements. "I don't take any supplements. None of these organic molecules. None." The supplement industry sells you the molecule. They don't sell you the mechanism biology built into the production process.

no.mind

88,753 görüntüleme • 4 ay önce