A 2022 LessWrong post on orexin and the quest for more waking hours argues that orexin agonists could safely reduce human sleep needs, pointing to short-sleeper gene mutations that increase orexin production and to cavefish that evolved heightened orexin sensitivity alongside an 80% reduction in sleep. Several commenters discussed clinical trials, embryo selection, and the evolutionary puzzle of why short-sleeper genes haven’t spread.
I thought the whole approach was backwards, and left a comment:
Orexin is a signal about energy metabolism. Unless the signaling system itself is broken (e.g. narcolepsy type 1, caused by autoimmune destruction of orexin-producing neurons), it’s better to fix the underlying reality the signals point to than to falsify the signals.
My sleep got noticeably more efficient when I started supplementing glycine. Most people on modern diets don’t get enough; we can make ~3g/day but can use 10g+, because in the ancestral environment we ate much more connective tissue or broth therefrom. Glycine is both important for repair processes and triggers NMDA receptors to drop core temperature, which smooths the path to sleep.
While drafting that, I went back to Chris Masterjohn’s page on glycine requirements. His estimate for total need is 10 to 60 grams per day, with the high end for people in poor health. [1] I had just written that glycine lowers core temperature. What if those are connected?
Is fever what happens when you are too glycine-depleted to fight infection through the more precise mechanisms glycine enables?
Glycine helps us sleep by cooling the body
The established explanation for glycine improving sleep is that it lowers core body temperature. Glycine helps activate NMDA receptors in the brain’s master circadian clock (the suprachiasmatic nucleus, or SCN). [2] This causes blood vessels near the skin to widen, dumping heat from the core to the surface. The body needs its core temperature to drop in order to fall asleep, and glycine accelerates that drop. In rats, surgically destroying the SCN eliminates glycine’s sleep-promoting and temperature-lowering effects.
Glycine cleans our mitochondria as we sleep
Your mitochondria produce energy, and as a byproduct they generate reactive oxygen species (ROS), chemically aggressive molecules that damage proteins, lipids, and DNA. ROS accumulate during wakefulness. Amber O’Hearn’s 2024 paper “Signals of energy availability in sleep” synthesizes the evidence that this accumulation is a key signal driving the need for sleep: wakefulness generates ROS, ROS buildup triggers sleep, and sleep clears them.
A Drosophila study tested multiple short-sleeping mutant lines with mutations in unrelated genes. All were more vulnerable to oxidative stress than normal flies. When the researchers forced normal flies to sleep more, those flies survived oxidative stress better. And when they reduced ROS specifically in neurons, the flies slept less, as if the need for sleep had partly gone away. Their conclusion: oxidative stress drives the need for sleep, and sleep is when the body does its oxidative cleanup.
The body’s main intracellular antioxidant is glutathione, a small molecule made from three amino acids: glutamate, cysteine, and glycine. If you are glycine-deficient, you cannot make enough glutathione, you clear ROS more slowly during sleep, and you need more sleep to achieve the same degree of clearance. That is a complete mechanistic chain from glycine deficiency to increased sleep need, and it is entirely independent of the NMDA temperature pathway.
Most people could use more glycine
Glutathione synthesis is rarely limited by glutamate, often limited by cysteine, and in the human tissues where glycine has been measured, limited by glycine as well. [3]
Glycine is classified as a “non-essential” amino acid because the body can make it, primarily from another amino acid called serine. But the body only produces about 3 grams per day. Meléndez-Hevia et al. (2009) estimate that the body needs roughly 10 grams more glycine per day than it can synthesize, because glycine is consumed in enormous quantities by the production of glutathione, creatine, heme, purines, bile salts, and collagen. Illness and injury may increase demand further: infection drives glutathione consumption, [4] tissue damage drives collagen synthesis, [5] and the liver’s phase II detoxification pathways consume glycine directly to conjugate toxins for excretion. [6]
In the ancestral environment this was not a problem. Traditional diets included connective tissue such as skin, tendons, cartilage, and bone broth, all rich in collagen, which is about one third glycine by amino acid count and one quarter by weight.
One group of researchers estimated that most people adapt to this deficit by reducing collagen turnover, letting damaged collagen accumulate with age, and that this may contribute to arthritis, poor skin quality, and other consequences of aging. Others have noted that markers of glycine deficiency appear in the urine of vegetarians, people on low-protein diets, children recovering from malnourishment, and pregnant women.
Fever is plan B for fighting infection; glycine supports plan A
Fever slows pathogen replication, makes immune cells move faster and multiply more, helps them engulf pathogens more effectively, triggers the production of protective stress-response proteins, and speeds antibody production. But it is metabolically expensive (roughly 10 to 13% increase in metabolic rate per degree Celsius) and causes significant collateral discomfort and tissue stress.
Glycine enables several cheaper alternatives to the same functions.
Peripheral macrophages are immune cells that eat pathogens and coordinate the inflammatory response. They have glycine-sensitive chloride channels (GlyR) on their surfaces. When glycine binds these channels, it calms the cell down: chloride flows in, shifting the cell’s electrical charge in a way that suppresses the calcium signaling needed to produce inflammatory molecules. These inflammatory molecules are called cytokines (the important ones here are TNF-alpha, IL-1-beta, and IL-6), and they are what drive the fever response. Glycine dampens the production of these pro-inflammatory cytokines while increasing production of the anti-inflammatory cytokine IL-10. [7]
Pyroptosis is a form of inflammatory cell death where immune cells fighting an infection blow themselves up, releasing their inflammatory contents into surrounding tissue. This is useful for eliminating pathogens but causes collateral tissue damage. Glycine prevents the final membrane rupture during pyroptosis without blocking the internal machinery that kills the pathogen inside the cell. The cell still dies—pores form, membrane potential is lost—but the inflammatory contents are not immediately released into surrounding tissue, potentially deferring the resulting acute inflammation until after the crisis. In animal sepsis models, glycine treatment has reduced hepatic damage and sometimes improved survival. [8]
Then there is the extracellular matrix. Collagen, the most abundant protein in the body, forms the structural matrix of tissues and acts as a physical barrier against pathogen spread. Collagen is one-third glycine. A three-year study of 127 volunteers (not randomized or blinded, so take it cum grano salis) found that among the 85 who took 10 grams of glycine daily, only 16 had viral infections, all in the first year and with reduced severity and duration. The control group reported no change in infection frequency. The proposed mechanism is that adequate glycine supports collagen turnover, maintaining the extracellular matrix as a mechanical barrier against viral invasion.
A glycine-replete organism can fight infection through these targeted mechanisms and does not need to escalate as aggressively to raising core temperature. A glycine-deficient organism cranks the thermostat higher and longer.
Elevated temperature directly impairs pathogen replication. Bacteria really do grow slower at 39°C (102°F) than at 37°C (98.6°F). No survivable amount of glycine changes that biochemistry. But the degree and duration of fever may be substantially modulated by glycine status, because many of the things fever accomplishes systemically (immune cell function, inflammation control, tissue protection) are things glycine accomplishes through targeted molecular mechanisms.
This leads to a testable prediction: people with high glycine and glutathione status should mount lower fevers for equivalent infections while maintaining equivalent or better outcomes. I am not aware of anyone having studied this directly, because nobody frames the question this way. But the mechanistic pieces are all published. Some are well-established (glycine’s role in glutathione synthesis, macrophage chloride channels), others more preliminary (the ECM/infection study). They are just sitting in different literatures (sleep biology, amino acid metabolism, innate immunology, pyroptosis research) and nobody has connected them.
Glycine’s cooling effect via the SCN is unrelated to its immune benefits
Remember the NMDA temperature pathway from the beginning of this essay, the one that made me notice the coincidence? It turns out to be a red herring as a link between sleep and immunity. The sleep pathway (glycine acting on NMDA receptors in the SCN to cool the core) and the immune pathway (glycine acting on chloride channels on macrophages to prevent pyroptosis) are completely independent. They involve different receptors, different cell types, and different organ systems.
So when I noticed that glycine lowers temperature and that sick people need more glycine, I was right that they were connected, but for none of the reasons I initially thought. The NMDA pathway had nothing to do with it. I had a true belief (“glycine, temperature, and illness are linked”) that happened to be true, but my justification (“because NMDA receptors and thermoregulation”) was wrong. A Gettier case!
But the wrong reason led me to the right question.
Glycine turns out to be a legitimate antipyretic after all
In rabbit experiments, glycine injected directly into the brain’s fluid-filled cavities reduced fever caused by two different triggers: substances released by white blood cells during infection (leukocytic pyrogen) and prostaglandin E2, which is the specific molecule the brain’s thermostat uses to raise the temperature setpoint during illness. This is a different operation from the sleep-onset mechanism. The sleep pathway lowers the thermostat from 37°C (98.6°F) to 36.5°C (97.7°F) to help you fall asleep. The antipyretic effect prevents the thermostat from being cranked up to 39°C (102°F) during infection.
So glycine suppresses fever directly (which might confound the testable prediction above), and unrelatedly lowers core temperature before sleep, and unrelatedly improves specific immune response in ways that reduce the infection-related inflammation that raises body temperature. Three independent pathways, with no apparent mechanistic connection, all drawing on the same pool of one simple, cheap amino acid that modern diets undersupply.
Practical considerations
Glycine powder is cheap, roughly 2 to 3 cents per gram. It is mildly sweet and dissolves easily in water. There is no known toxicity at supplemental doses aside from gastrointestinal upset at high doses. For most people, 10 to 15 grams per day in divided doses (some with meals, some before bed) would address the estimated deficit. Three grams before bed is the dose studied for sleep improvement specifically.
This is not comprehensive nutritional advice. For instance, cysteine is the other bottleneck for glutathione production, and people who eat little animal protein or are acutely ill may benefit from supplementing NAC (N-acetylcysteine) alongside glycine.
Alternatively, you can eat the way your ancestors did: bone broth, skin-on poultry, oxtail, pork rinds, and other collagen-rich foods. One gram of collagen for every ten grams of muscle meat protein roughly restores the ancestral glycine-to-methionine ratio.
Before reaching for a pharmaceutical intervention to override a biological signal, it is worth asking whether the signal is accurately reporting a problem you could fix with inputs. Orexin tells your body about its energy metabolism. Fever tells your body about its immune status. If you are not providing the substrates those systems need to function, the signals will reflect that, and the right response is to supply the substrates, not to shoot the messenger.
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Masterjohn’s range draws on several sources. The ~3g/day endogenous synthesis figure and ~10g/day shortfall estimate come from Meléndez-Hevia et al. 2009, a peer-reviewed metabolic flux analysis that explicitly accounts for glycine recycling in the procollagen cycle. 3g before bed is the dose studied for sleep improvement (Inagawa et al. 2006, Yamadera et al. 2007). 15g gelatin before exercise doubled a collagen synthesis marker in blood (Shaw et al. 2017). 0.8 g/kg/day (about 60g for a 75kg person) has been used in multiple double-blind schizophrenia trials targeting NMDA receptor modulation, where it was well tolerated over the study period and produced significant reductions in negative symptoms (Heresco-Levy et al. 1999, 2004).
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How does dietary glycine reach the SCN if the blood-brain barrier keeps glycine out? The SCN sits adjacent to the third ventricle, and glycine enters the brain primarily via the blood-CSF barrier rather than by crossing the blood-brain barrier into parenchyma. Kawai et al. 2012 found that oral glycine in rats passively diffused into the CSF (reaching concentrations about 100× lower than plasma) and was distributed among periventricular structures. At 2 g/kg oral dosing, CSF glycine rose above the ED50 for NMDA receptors. The schizophrenia application, by contrast, targets cortical NMDA receptors deep in brain parenchyma behind the BBB proper, which is why it requires doses as high as 60g.
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Glutathione is assembled in two steps: glutamate-cysteine ligase (GCL) combines glutamate and cysteine, then glutathione synthase (GS) adds glycine. Each step has a Km — the substrate concentration at which the enzyme runs at half speed, and below which output is increasingly sensitive to supply. The ratio of measured concentration to Km indicates how saturated each step is. Glutamate (GCL step): Km ~1.7 mM; intracellular glutamate is 2–4 mM in rat liver and 6–12 mM in human brain gray matter (ratio ~1.2–7×); above Km in every tissue measured. Cysteine (GCL step): Km ~0.15–0.35 mM (range reflects rat vs. human enzyme preparations); intracellular cysteine is 0.15–0.25 mM in rat liver (ratio ~0.4–1.7×); near Km and often limiting; brain cysteine is kept low and is widely considered limiting for brain glutathione synthesis. Glycine (GS step): Km ~0.9 mM; intracellular glycine is 1.5–2 mM in rat liver (ratio ~1.7–2.2×, above Km), ~1.1 mM in human brain gray matter (~1.2×, borderline), ~0.1 mM in human brain white matter (~0.1×, severely below Km), and 200–500 µM in human serum and red blood cells (~0.2–0.6×, well below Km); whether glycine limits glutathione synthesis depends on the tissue. Sources and caveats: The rat liver concentrations are from nutritionally optimized lab rats; the human numbers are from people eating ordinary Western diets. The rat-to-human comparison confounds organ, species, and diet. GCL Km from Richman & Meister 1975; rat liver concentrations and GS Km from Griffith 1999 as reported in Wu et al. 2004; human red blood cell glycine from Kumar et al. 2023; human brain glycine from Choi et al. 2009; human serum amino acids from Pitkänen et al. 2003.
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Whole-body glutathione utilization in healthy adults is about 25 µmol/(kg·h) (Wu et al. 2004), which for a 70 kg person works out to roughly 3.2g of glycine per day consumed by glutathione turnover alone. Under metabolic stress this rate increases substantially: Darmaun et al. 2005 found a 1.7× increase in glutathione fractional synthesis rate in poorly controlled type 1 diabetics, which would bring the glycine demand from glutathione to roughly 5.4g/day.
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Meléndez-Hevia’s flux model estimates that baseline collagen turnover is the single largest consumer of glycine at roughly 14.5g/day of the ~15g total need. Injury increases local collagen synthesis dramatically: Zhou et al. 2013 measured a 480% increase at day 2 and 860% at day 7 in rat muscle at the wound site compared to undamaged tissue in the same animal. These are local rates at the injury site; the whole-body glycine increment from wound healing has not been quantified directly, and would likely vary with the wound.
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Glycine conjugation is a standard phase II detoxification pathway: the liver attaches glycine to aromatic and acyl compounds to make them water-soluble for excretion. In isovaleric acidemia, a rare metabolic disorder that produces an abnormally large load of one such substrate, glycine at around 200 mg/kg/day (roughly 14g for a 70kg person) has been used therapeutically to clear the toxic metabolites (Tajima et al. 2018).
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Microglia, the macrophages that reside in the brain, respond to glycine differently. Hendriks et al. 2010 found a pro-inflammatory response mediated not by GlyR but by neutral amino acid transporters (NAATs) that aren’t even glycine-specific. The blood-brain barrier keeps free amino acid levels low in brain parenchyma, where microglia reside. (That’s why the doses of glycine to treat schizophrenia have to be as high as 60g — you’re trying to modulate NMDA receptors across widespread cortical tissue, which requires forcing glycine through the BBB into parenchyma.) So this pathway is not relevant to dietary glycine supplementation.
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Bruck et al. 2003 found that glycine reduced liver enzyme levels, TNF-alpha, histologic damage, and mortality (p<0.001) in a mouse endotoxemia model (LPS + d-galactosamine). A rat two-hit sepsis model (ischemia/reperfusion followed by endotoxin challenge) found that glycine reduced liver damage and the inflammatory response but did not decrease mortality.
Bone broth soup seems to be a traditional home remedy for feverish colds and flu-like respiratory illness. This is true cross culturally and many different cultures seem to converged on it being a good treatment.
It’s 33% of the amino acids in collagen counting amino acids. It’s less if you count them by weight/mass as glycine is lighter than other amino acids. Connective tissue also contains a lot besides collagen, so 33% is overcounting it on that front as well.
That sentence sounds like different people estimated the requirement with some saying you need 10 gram and others say you need 60 gram. Your link mainly seems to show that there’s one blogger who thinks that the needs are in that range.
When trying to reproduce the 10 gram number myself, I get the impression it counts the total need of glycine in a normal state for bodily processes against dietary consumption while ignoring the amount of glycine that gets freed by the breakdown of the body own proteins including collagen. A lot of collagen production is collagen turnover where old collagen (sometimes damaged by AGEs) gets replaced with fresh new collagen where the individual glycine can in principle be reused.
In some cases that might be beneficial but NAC supplementation can decrease muscle hypertrophy, so supplementing NAC per default when not ill probably only should be done when it’s well-thought out and not just by random supplement consumption.
This was a mistake on my part and I’ll correct the article.
Masterjohn’s lower bound of 10g matches Meléndez-Hevia et al. 2009, which explicitly accounts for glycine recycling, while 60g is the highest dose used in schizophrenia treatment. He didn’t cite sources in the linked piece, though, so I’ll add a footnote with the sourcing I could find.
I haven’t been able to find evidence that typical oral supplement doses of NAC meaningfully reduce hypertrophy. I did find one paper reporting that an NAC infusion can blunt some ROS signaling after exercise, and a 2017 meta-analysis found no benefits from NAC supplementation on exercise performance, but I can’t find evidence of harm at oral doses.
I still endorse the very limited recommendation I made that people with specific reason to think they have elevated need or meaningfully limited supply of cysteine “may benefit” from the supplement.
Having thought about NAC a bit more, I think I agree with you. The one paper about the signaling seems to be less important than the actual observed effect in exercise. Additionally, even if given NAC to a normal person who has a glycine deficit leads to more glutathione synthesis at the cost of less collagen synthesis which could have a negative effect on hypertrophy that concern is less if you just supply both NAC and glycine.
Also, on the upper end of that range, this would mean that ~50-60% of an average person’s daily protein intake should consist of glycine, which seems incredibly unlikely.
If you read further and look at the footnote to the 10-60 claim this is answered.
But also I revised the post to make more accurate and clearer claims in response to criticisms
Not directly relevant to the schizophrenia doses (for reasons I noticed after I initially published the post), but maximum useful uptake of protein (and other structural inputs like cholesterol) can go up a lot in extreme cases; physicians reported good results from administering 35 eggs per day to severe burn victims to help them heal, which amounts to 210g/day of protein just from eggs, 314/day total, for people who aren’t even huge or on anabolic steroids. Followup here.
In 1971, the FDA wrote:
I know very little about glycine and the FDA is often overcautious, but at minimum I think if you are suggesting readers to supplement glycine then you should address the fact that the FDA rescinded its GRAS designation.
The 1971 GRAS rescission was a precautionary regulatory action during a broad FDA review of GRAS substances. The regulation (21 CFR 170.50) cites unspecified animal studies at “high levels” and concern about increasing industrial use of glycine as a food additive.
I did not rely on glycine’s historical GRAS status in the first place, and I don’t think it’s reasonable to ask me to put words in the FDA’s mouth about why glycine was shifted from one category of permissible food ingredients to another category of permissible food ingredients in order to argue with them.
I have not been able to identify which pre-1971 studies the FDA was referring to, and neither apparently have subsequent reviewers. The rescission did not amount to an across-the-board ban; glycine is currently permitted for certain food uses under later regulations (21 CFR 172.320).
The most plausibly concerning animal finding I’ve found is a 1994 carcinogenicity study (Kitahori et al.) that found renal papillae necrosis in Fischer 344 rats given 2.5% or 5.0% glycine in drinking water for 108 weeks. Those concentrations work out to roughly 6-12 g/kg/day in rats, which scales to roughly 70-150g/day in a human. Fischer 344 rats are known for high rates of spontaneous chronic progressive nephropathy, a renal disease with no strict human counterpart, which complicates interpretation of renal findings in this strain. A follow-up study by the same group (Kitamura et al. 1996) found that glycine at 5% did not promote chemically initiated urinary lesions, while sodium aspartate did, suggesting the original renal findings may have been about chronic osmotic or pH stress from very concentrated solutions rather than glycine toxicity per se. The authors of a later 2013 study (Shibui et al.) reached the same interpretation.
That 2013 study, specifically designed to establish a toxicity threshold, found no adverse effects at the maximum tested dose of 2 g/kg/day (scaling to ~23g/day in humans). Human schizophrenia trials have used 30-60g/day for weeks to months; the main reported side effects are gastrointestinal.
(Update: This does not seem to have been the key)
This is a very interesting post to me in general and extra interesting because this may hold the key to what’s going on with some mysteriously-good-sleep I’ve been experiencing.
I recently had a couple random absurdly good nights of sleep. Like, I don’t remember feeling so energized, refreshed, healthy, good etc after a night of sleep as I did these couple nights. Two back to back nights in particular were perfect and extremely strong signal, but I think there have been a few other mornings I woke up before my alarm feeling better than expected. I have been trying and failing to figure out what caused this
the context that makes this interesting: I was in the tail end of a covid infection, and I’d been taking s-acetyl l-glutathione (SAG) and N-acetylcysteine (NAC) off and on during it (covid depletes glutathione and this is associated w/ worse outcomes). I unfortunately don’t know exactly when I was taking SAG and NAC but it would fit with the good sleep nights appearing to be happening at random since I was taking them off and on and not paying attention for any possible effect.
Anyways, this is not necessarily the explanation for my extremely good sleep nights but it’s the most likely hypothesis I have currently, still probably <30% likelihood
Thankfully I can test that hypothesis pretty clearly to my satisfaction by just taking glutathione enhancers for a week or so. The good nights of sleep were so abnormally good that getting more of them would be an extremely clear signal.
So, I expect to be testing this out this week, and I’ll try to remember to report back with the outcome.
Thanks for making this interesting post and the possible lead on what was causing the very good sleep!
It’s always gratifying to learn that the information I offered helped someone orient, and especially gratifying to get that validation so quickly. Please let me know what you find out.
Sadly I did not manage to replicate those great nights of sleep
Still, loved your post :)
Any updates?
I was unable to replicate those good nights of sleep
Curated. I was personally more excited for the “glycine and/or cysteine maybe help with sleep” suggestion than for the fever reduction speculation, although the latter is an interesting idea.
I haven’t done a super deep epistemic spot check here[1] but I did a few rounds of asking LLMs and colleagues whether the claims checked out (which warned that the evidence for some of them isn’t very robust and some are misleading[2]).
But this is a genre of post I’d like to see more of – a nice practical combo of engaging with science literature while reasoning about underlying mechanisms, and what sort of goals actually make sense. And, it provides both an immediate practical takeaway as well as an interesting path for further study.
There’s also a bit of an interesting connection between “treating the symptom vs disease” and “addressing an indicator vs the underlying phenomena”, with parallels to other Benquo work about not destroying information and ability to communicate (in more classical social/intellectual contexts). I don’t have an immediate takeaway from that but feel a vague sense that it added some depth to an existing frame.
I find myself curious whether the original orexin post was a major motivator for this post, or if Benquo would have likely written this up anyway. (Regardless, I appreciate a 4 year old post getting some followup)
[1] We don’t have time to vet curations at a “serious review” level
[2] In particular, the claims about “body produces 3 grams a day, and needs 10-60 grams” are coming from a few low powered studies that aren’t all studying the same thing. And, the post focuses more on glycine than on cysteine and I’m not sure why. See full llm transcript.
Thanks for the independent check. I like the prompt you used and just used it to do an extra fact-checking pass of another draft post.
I too am more interested in the “treat the underlying cause, not the signal” thing that led directly to “glycine for reducing sleep need”, than the rabbit hole I went down about glycine and fever. I just thought the rabbit hole led somewhere productive (a much more detailed and therefore credible picture of glycine’s relation to sleep need), so I figured I’d share it; without that rabbit hole you just get my quoted comment, which I agree is more valuable word for word, but also isn’t the sort of thing that gets curated as a front-page post. (You could of course fix the incentive problem by curating my comment instead if the system allowed for that.)
To answer the question about motive: the story I told in this post is pretty much complete. I had recently started supplementing glycine for idiosyncratic metabolic reasons, but had no plans to write anything up until I got a crazy idea I decided to check out. In the course of checking it out I realized I had the material for an interesting article, so here it is!
By my count there are eight complaints in the Claude transcript you shared. I looked into all of them: three warrant corrections, two are plausible but wrong on closer inspection, and three are complaints where I can’t figure out what I should have done differently.
Corrections I’m making:
1. The 10-60g range conflates nutritional shortfall with pharmacological dosing. The 10g comes from Meléndez-Hevia et al. 2009, a metabolic flux analysis of what the body needs for normal function. The 60g is the dose used in schizophrenia trials targeting NMDA receptor modulation in the brain. Glycine is an obligatory co-agonist at NMDA receptors, and massive oral doses are needed to force enough across the blood-brain barrier to increase brain glycine levels. The schizophrenia application is fundamentally pharmacological, not supraphysiological compensation for unusual glycine need. I think the sourcing footnote itself is not misleading, but summarizing this in the body text as “Estimated total requirements” collapses an important distinction. I’ll think about how to fix that.
2. The pyroptosis description overstates macrophage integrity. “The macrophage can do its job without self-destructing” is too strong. The cell still dies. Pores still form in the membrane and the cell loses membrane potential. Glycine prevents the final membrane rupture that releases inflammatory contents into surrounding tissue, but the macrophage doesn’t survive. The inflammatory damage is deferred, not eliminated, which can still matter in acute infection, but the essay implies the macrophage walks away intact.
3. The essay says “macrophages have glycine-sensitive chloride channels” without specifying which macrophage populations. The anti-inflammatory chloride channel pathway (GlyR) operates in peripheral macrophages (Kupffer cells, alveolar macrophages) responding to infection and endotoxin. But Hendriks et al. 2010 found that microglia, macrophages that live exclusively in the brain, respond to glycine pro-inflammatorily via a mechanism that is not mediated by GlyR. Although microglia express GlyR subunit mRNA, Hendriks found that the immunomodulatory effect was GlyR-independent and instead operated through neutral amino acid transporters (NAATs), which aren’t even glycine-specific. NAATs respond to alanine, serine, glutamine, proline, and other small neutral amino acids. So the microglia aren’t responding to glycine per se; they’re responding to free amino acids, which the blood-brain barrier works hard to keep out. (That’s why schizophrenia treatment has to use oral glycine doses as high as 60g to force enough glycine into the brain to do anything interesting.)
The essay’s argument about infection and inflammation holds for the peripheral macrophages it’s actually about, but the prose needs to specify that rather than saying “macrophages” unqualified.
Criticisms that are plausible but wrong:
4. Glycine vs cysteine as glutathione bottleneck. The fact-check complains this “oversimplifies a contested area where cysteine is traditionally considered the primary rate-limiting substrate” and asks why the post focuses more on glycine than cysteine.
The post focuses on glycine because it’s about glycine. It’s investigating a specific question (“is fever a symptom of glycine deficiency?”), not writing a comprehensive guide to glutathione precursors. The essay says explicitly that it’s “not comprehensive nutritional advice” and immediately goes on to illustrate that by flagging cysteine as the other glutathione bottleneck, noting that people with limited cysteine intake or elevated need for it may benefit from supplementing NAC. That’s the essay doing exactly what you’d want it to do: acknowledging the limitation of its own scope and pointing readers toward what it isn’t covering, rather than pretending cysteine doesn’t matter.
As to why I personally am more interested in glycine right now, my reasons are:
I already knew about NAC for preventing respiratory tract infections or recovering from them faster.
I recently started supplementing glycine based partly on idiosyncratic metabolic defects that likely mildly to moderately impair my glycine synthesis, and partly based on estimates that typical Westerners could use more anyway, and got surprisingly-to-me strong almost immediate apparent benefits (though it’ll be clearer in a year whether this is real or just coincidence).
The estimates that typical Westerners could use more anyway persuaded me that glycine’s benefits might be of particular relevance to a general audience, while my impression (as discussed in the linked comment thread) is that people who get enough animal protein generally get enough cysteine for when they’re not sick or injured.
On oversimplification, the essay says “in many contexts, glycine is the bottleneck.” The counterargument offered is that in many cases cysteine is the bottleneck. Yes.
Your fact-check turned up some evidence for glycine specifically that I hadn’t referenced in the post. Glutathione is made in two steps: glutamate-cysteine ligase (GCL) combines glutamate and cysteine, then glutathione synthase adds glycine. Each enzyme-substrate pairing has a Km, the concentration at which the reaction runs at half its maximum speed, and below which its output becomes increasingly sensitive to how much of that substrate is available. Glutathione synthase’s Km for glycine is about 900 µM (Luo et al. 2000), while red blood cell glycine concentrations have been measured at 218-529 µM (Kumar et al. 2023) — near or below the Km, suggesting that glycine availability can materially influence glutathione synthesis rates. Glutamate is typically well above GCL’s Km (Lu 2013). Cysteine varies more, ranging from near to well above its Km (Lu 2013).
5. Gersovitz 45g/day vs Meléndez-Hevia 3g/day. The fact-check flags this as a discrepancy that “complicates the deficit narrative.” They’re measuring different things.
Gersovitz’s ~44g/day and Meléndez-Hevia’s ~3g/day are not in conflict. Gersovitz measured glycine appearing from all biosynthetic sources. Much of that 44g is glycine being converted to serine and back; it shows up in the flux measurement but doesn’t add net new glycine to the pool. Meléndez-Hevia measured net new glycine created via that same enzyme (serine hydroxymethyltransferase): about 3g/day. Comparing dietary glycine and new glycine production with irreversible consumption and loss from collagen turnover, Meléndez-Hevia estimates a glycine deficit of about 10g/day.
Complaints where I can’t figure out what I should have done differently:
6. O’Hearn paper status. The fact-check says I should have flagged that O’Hearn is an independent researcher publishing a review rather than original experimental work. The essay describes it as synthesizing evidence, which is what reviews do. The fact-check seems to think “paper” implies “original experiment by someone at an institution,” but I don’t.
As for “independent researcher,” in case that’s a complaint about qualifications and credentials, I’ll note that the paper was published in a peer-reviewed academic journal.
7. The 127-volunteer infection study. The fact-check acknowledges “the study exists and the post’s description is accurate,” then says it’s “very weak, even beyond what the post acknowledges,” complaining that the essay doesn’t mention that the study involves self-selected groups, self-reported outcomes, and no viral confirmation.
The post’s characterization of the study explicitly tags the unrandomized and unblinded nature of the study, advises the reader to take it with a grain of salt, and says “the control group reported no change in infection frequency,” which would seem to suggest self-reporting, and would seem to preclude formal viral confirmation.
This seems to me like an appropriate level of detail on the flaws of a study invoked as illustrative, not load-bearing. Should I really have spent extra words on the fact that the specific form of selection bias the study failed to prevent via randomization was self-selection?
8. Rabbit ICV glycine. The fact-check notes this is intracerebroventricular injection and questions its relevance to dietary supplementation. But the essay already says “glycine injected directly into the brain’s fluid-filled cavities.”
More importantly, the rabbit study is not presented in support of the primary argument, but to flag a potential confounder of the essay’s proposed experimental test.
Neat, appreciate the response.
As I was looking over the LLM-critique and deciding whether to curate, what I found was “Well, for many of the complaints the LLM made, the post does flag the epistemic status, and the LLM-complaint feels a bit off-base for ignoring that. But, in some of those cases, it did feel to me like the mood of the post didn’t quite convey the quality of the evidence, or something.”
(To be clear to everyone I also didn’t super vet the LLM critique either, and present it not as ‘these are all correct counterarguments’ but, well, here’s an LLM’s attempt at a critique, make of that what you will. I think you took it in the spirit it was given but felt like flagging)
I do think LessWrong should probably do more to highlight good comments, but, in this case I do think the post added something substantive over the comment, in highlighting more of the search process, how many different bits of evidence there were, and conveying an interesting implicit worldview.”
(Meanwhile the opening comment is listed at the beginning, so people can get the short payoff and dig into it if they feel like it)
The issues should be fixed now.
I’d like to congratulate you, specifically, for this curation note. It is high quality for two reasons. First, it helped me understand the article a bit before diving in. I think it is a very good practice to note the reasons behind the curation, and I’d like to see more comments like this (not all will need to be long or detailed). Plus, this comment appears before the text of the article on the email, but then it quietly appears on the comments on the site, so it does not hinder the navigation. Seems like the best of both worlds.
Thanks! Yeah we have been vaguely-meaning-for-awhile to make it so curation notes appear at the top of the curation email, and not got around to it. It seemed kinda important to convey my epistemic state for this particular post so I did some manual work to add it to the email as a one-of, but, maybe we’ll go ahead and add that feature soon.
The Claude transcript you sent isn’t to a share link, and doesn’t work for me. I’m confused though, because it seems like Benquo was able to open it?
Huh, I’m not sure what happened (I had deliberately made it a share link, I thought). Fixed it again.
Thanks!
I’m curious about mechanisms for some sort of community review of claims with potential downside effects.
I.e., it would be great to know if commenters are excited about the idea, if commenters have checked/discussed the idea in detail, if there’s a consensus on how likely the idea seems to be true and how likely it is to have downside effects.
A while ago, I looked into essential vs non essential amino acids. It turns out the data we have on this mostly comes from a guy doing elimination diet experiments on young male college students in the 1930s-50s. While the essential aminos remained essential on replication, the “non essential” ones are not actually ruled out as non essential. Many have been reclassified into “conditionally essential” based on certain disease, genetic, or stressor states.
But what I think would be interesting would be some kind of comprehensive model of all the tradeoffs among all the amino acids. Such as, which other aminos and other body resources does an amino synthesis consume; any byproducts made thereby; biological pathways clogged up by their cooption for synthesis; harmful and helpful body processes enabled by certain levels of a certain amino; and so on. Then you condition on various disease states, and expected changes for each state based on amino acid intake, and then you can have a whole Pareto frontier of amino acid intake profiles.
I wonder if a very rough draft of one could be put together with a week of directing LLMs to do research and model building. Seems like an interesting project!
Did you work on this project at all? I know there are posters full of metabolic diagrams, that are super fun to marvel at, but I have no idea what the state of the art is for attempting to (safely?) falsify or confirm the details based on personal eating habits, symptom tracking, sequencing one’s own genome, and so on.
It would be VERY COOL if a website existed where all the metabolic reaction rates like this could be numerically simulated, with tuning based on personalized data, and then the aggregated data rolled up into estimated summaries about how things usually work.
If the last time this stuff was rigorously “measured for reals with meals” was the 1930s to 1950s we might be able to advance the state of the art as a hobby, via online tools built by robot frens! ❤
Well, I’ll give it a shot! I have Claude chugging away doing the research now. No guarantees, especially since I have no biology training, but I’ll post it if I finish it!
I think it would be valuable to post if you don’t finish it too; there might be valuable intermediate products, and there might be valuable information about which subproblems are easy, hard, or impossible pending more physical experiments.
The mapping project would need to work out a way to represent complex feedback systems where only some of the causal relations are known at all, and only some of those are quantified with various degrees of validity. I haven’t seen a good solution, seems like a subproblem that could generalize nicely to other important cases.
If I was prompting an LLM agent, I would try to find a Systems Dynamics modeling tool the agent could interact with the file formats of somehow. LunaSim might work? Or OpenModelica? Or perhaps PathSim?
In the aughties, when I wanted to play with something best modeled this way I would download a “free for education” VenSim copy (but that (1) is still proprietary and (2) open source stuff exists now and (3) Vensim hasn’t been updated since ~covid so one of the other three is likely better).
What effects did you have from what dose of glycine, and how quickly did they kick in?
Colds immediately got noticeably shorter and milder and moderate sleep loss just didn’t bother me that much, you might say I had much more sleep credit to spend.
dose, tho?
5g in AM, 5g in PM, rounding up a bit. When I’m sick, double the dose plus 1⁄4 tsp NAC powder. in AM and PM.
This is quite cool!
It randomly explains why I haven’t had a fever in like 3 years because that’s how long I’ve been doing glycine supplementation for my sleep. I thought something might be wrong with me and my immune system since I used to get fevers before.
How much glycine are you taking?
I’ve been taking 5g before but I do around 8 now
I’m pretty sure I haven’t had a fever in 3 years too, and I’m a reasonably young man in decent physical condition who works as a doctor (or at least my poor lifestyle choices haven’t caught up to me yet).
That’s … a stronger effect than I expected. Whoa.
Well, n=1 and confounding factors and all that but yeah true. And also to be clear I had one fever a year ago but I do get sick maybe 10 times per year because I have a bad immune system in general.
Chicken soup with bone broth seems to be cross culturally a traditional treatment for acute respiratory tract infections. In Western Medicine, doctors like Pedanius Dioscorides in 60AD and Galen in the second century AD advocated it. Over in China in the second century BC Huangdi Neijing wrote about it in a key Traditional Chinese Medicine book. Through the work of an Egyptian Jewish doctor called Moses Maimonides in the 12th hundreds it became popular among the Jewish while being called “Jewish Pencilin” in the 20th century.
Gemini found differently formulations of the soup in the traditions of Philippines, Korea, China, North Africa, Iran, India, Thailand, West Africa, Levant, Greece, Mexico, Asia, West Africa and Peru.
While the evidence base could be better a literature review by Lucas et al found: Acute respiratory tract infections (ARTIs) are a significant global health burden, contributing to increased healthcare use, absenteeism, and economic strain. While clinical treatments exist, many individuals use traditional dietary remedies such as soup to relieve symptoms. [… Four studies (n = 342) met inclusion criteria. Interventions commonly included chicken-based soups with vegetables and herbs. Comparators varied (e.g., no treatment, water, or alternative soup). Findings showed modest reductions in symptom severity and illness duration (by 1–2.5 days).
Chiming in with another causal mechanism: hot soup lets off steam. Humid air in general plays nicer with our lungs, and can noticeably help when people are having a cough, or having trouble breathing. I sometimes use “just have them sit over a canteen of steaming-hot water” as a palliative for both issues.
Inhalation of humid air is a standard treatment for dealing with mucus better in medicine and pretty well studied. It does not cut illness duration by 1-2.5 days. If you look for example at the Mayo Clinic page for influenza treatments that does not rise to the level of standard recommendation.
I think it’s pretty stupid that when I was with pneumonia and influenza in the hospital I did not get heated water for my normal drinking water, but the effect sizes involved are smaller.
There are quite many ways to give people humid air, it does not explain why so many different traditions ended up with chicken broth soup in particular. The thing that distinguishes this specific kind of soup is the glycine, hyaluronan and a few other substances that exist in connective tissue and can be helpful supplements for connective tissue issues like wrinkles and joint pain.
Very interesting!
I started taking collagen half a year back and didn’t notice improved sleep. But my sleep is also hard to improve upon. I had less joint pain, which I was taking it for, but could also be explained by regression to the mean.
The main effect I am pretty sure about is that my finger nails started growing like crazy.
Good to know there are other reasons it might be a good idea to keep taking it.
What dose of collagen do you take when when did you take it? The 3gram of glycine in the sleep trials would be something like 15gram of collagen and they were timed to be taken right before going to sleep.
The recommendation is something like 10 gram and I probably roughly take that, but relatively spread out over the day (I mix it into a hot beverage). But as I said, I very rarely have any problems sleeping, so I don’t know what a positive effect on that would have looked like.
Shorter sleep periods and longer wake periods with no new health, mood, energy, or cognitive problems, or improved recovery from stressors like exercise, infection, or injury with no longer sleep periods.
Poultry and pork rinds will get you a bunch of linoleic fatty acid, which is a whole separate dietary villain.
If you eat 3 oz of plain pork rinds, you get 52g of protein and 26g of fat. Of that protein, 19% is glycine, 10g. Of that fat, 11% is linoleic acid, 2.9g, which is 16% of average American daily intake. Of course, you might be unusually adversely sensitive to linoleic acid, which would be a reason to get glycine some other way.
Chicken is a much less efficient glycine delivery vehicle. If you eat a pound of roasted skin-on chicken (roughly half a Costco rotisserie chicken) you get 125g of protein and 62g of fat. Of that protein, 6.5% is glycine, 8g. Of that fat, 19% is linoleic acid, 12g, which is 2⁄3 of the average American daily intake.
Chicken skin alone is even worse per unit of linoleic acid. If you eat 1⁄3 kg of roasted chicken skin (wow, that’s a lot), you get 67g of protein and 137g of fat. Of that protein, approximately 13% is glycine, 9g. Of that fat, 20% is linoleic acid, 27g, which is 1.5x the average American daily intake.
I didn’t know that until I looked up the numbers just now. It probably varies a lot based on what the animals are fed. Typical Chinese chickens are probably meaningfully better than the American ones on this metric, as the Chinese tend to prefer chickens that taste like chicken over ones bred to maximize meat yields above all else, though this is changing.
If you want to avoid linoleic acid, and want to get glycine from whole foods, best to do things like eat tendons and skimmed bone broth.
On linoleic acid as a “dietary villain,” I’m familiar with two plausible stories:
1 PUFAs generally as oxidative liability (via Masterjohn), which seems mechanistically tight but doesn’t seem to generate a clear observational signal so the effect size is probably small, though I can think of ways to save the hypothesis (snapshots of PUFA consumption may not reflect AUC or PUFA levels). This should only be a problem if you’re storing rather than burning PUFAs, so I’d expect a lot of heterogeneity in response depending on many other factors. It’s also not specific to LA except insofar as LA is a common PUFA in Western diets.
2 Brad Marshall’s torpor story. I looked into this a bit, and while there aren’t experimental results on humans, there are both positive and negative results in animals; the main negative one I found was Gerson et al. (2008). I’m skeptical of external validity as applied to a species that doesn’t have what seem to be the relevant physiological torpor mechanisms.
Am I missing something big here?
Glycine might turn out to be The Vitamin for me. I had ordered some prior to finding this essay and then forgot about it. Reading this made me take it the same day and also at a much higher dose than I otherwise would have.
I want to wait out a month, and possibly a year before reporting back too much, but the difference in my wellbeing and health is so far hard to overstate and it’s only been 1 week.
Thank you <3
Any update on how this has been going?
It’s still lasting! The most telling and direct sign that it is not placebo, is that variations in the dose directly affect my digestion.
I want to wait a bit longer before reporting in detail cause I started vit D and iron courses 4 weeks after I started glycine. I don’t know how much of an effect these have had but I hope to get them measured again once I finish the courses
I’ve been taking collagen and the exogenous antioxidant astaxanthin for a while and it’s definitely improved my sleep among other things.
I’ve ordered some glycine and plan to start taking 3g/day before sleep and see what happens. (I don’t plan to blind myself or deliberately measure anything. I guess my watch might have some stats that show changes?)
Night 1: I got to sleep quickly, woke briefly after 1 1⁄2 hours, woke up early again with muscle cramp (I expect this at least to be unrelated). I’d rate as “worse sleep than normal”. Didn’t notice myself being out of distribution for daytime alertness conditioned on sleep.
Night 2: got to sleep quickly, woke early, but sleep quality seemed fine. Not obviously out of distribution for alertness.
Nights 3-8: failed to keep detailed logs. I think I’ve slept quickly every night (good if related), and often woken up early (bad if related). Neither of those is very out of distribution. Been mildly sick which probably confounds things too. Inclined to keep taking it.
I should mention here that I think the “improve sleep onset” dose of 3g just before bed is calibrated for NMDA receptor stimulation, not the improved ROS clearance etc that would improve sleep quality, for which 10g/day (ideally broken up into at least 2 doses with meals) seems like a good place to start. I see no strong reason not to try both, though. And if you want to see over a slightly longer period what 3g/night does instead, that seems like good data to have anyhow.
“Got to sleep quickly” is the main immediate easy to recognize benefit I’d expect from the 3g dose just before bed (unless, of course, you already usually got to sleep quickly).
Yeah, I think I’ll keep trying 3g/night for a bit and then maybe explore 10g/day. That feels like a pretty inconvenient dose to be taking, but so it goes.
I had been wondering how much of the effect comes from the timing and how much comes from just getting more. There must be a time delay in the process of “glycine enters your stomach, makes its way into your bloodstream, gets incorporated into glutathione, and that helps clear ROS”. But I figured, sleep lasts a while, it could well be that the glutathione starts doing its work an hour after you take the glycine; and maybe if you take it earlier in the day, it’s all used in other things by the time you get to sleep.
But “no, 3g just before sleep isn’t enough at the right time to help with sleep” is also not surprising.
Glycine is water soluble and slightly sweet tasting. 10g readily solves in a glass of water.
As it’s sweet it does encourage your body to produce some insulin which could be an issue for some people but probably not for just trying it out for a few weeks for most people.
Bought 1kg of glycine due to this post, will post qualitative subjective feelings after trying it out for a couple weeks.
The slight sweetness made it really easy to form a habit of taking it daily
Pouring a small cup (~5g) in your mouth before adding water tastes funny, I won’t do it regularly
Update: I feel absolutely 0 subjective difference, which is probably expected? I couldn’t bother doing a proper self-experiment.
My process is 5g glycine in the morning (almost always) and 5g ~1h before sleep (sometimes, I forget ~50% of the time)
I was vegan for four years, and generally felt worse, but what ultimately got me to quit was getting a fever six times in the first six months of 2025. I did ~0 supplementation because I usually threw up my vitamins and because I find supplements aesthetically unappealing. (I have since strongly changed my mind on that second point). I am no longer vegan, but this article was validating to read nonetheless.
A couple of months ago, one of my doctors prescribed magnesium glycinate to alleviate visual migraines, but she said that it might also improve sleep. Happily, it helped with both. (...and several other conditions!)
The doctor implied that the primary benefit of magnesium glycinate over other magnesium supplememts was its gentler gastrointestinal effects, so I assumed that the improvement to my sleep was caused by the magnesium, not the glycinate. This essay caused me to question that assumption.
What dose did you take?
If I’m interpreting the label correctly, then it’s 200 mg of magnesium glycinate per day. The active ingredient is labeled as “Magnesium (as Magnesium Glycinate) 200 mg”.
That’s 1.4 gram of glycine, so half of the amount used in the studies for sleep. Probably, enough to have an effect.
Thank you. If I’m following correctly, then what I’ve been taking is 200 mg of magnesium itself, embedded in ~2 grams of magnesium glycinate. If so, then I was misinterpreting the label.
Yes, as I read it the label is saying that it’s 200mg magnesium and that’s in Magnesium Glycinate so there has to be the relevant amount of glycine. If there’s any uncertainty simply taking a photo of the label and asking your favorite chatbot is also great.
Asking CharGPT again it seems that 1.4 was somehow 200mg of magnesium is 1.4 magnesium Glycinate and that’s 1.24 glycine but the general principle holds.
Well, that’s less than one tenth the amount of glycine your body makes by itself and than one fiftieth the amount you’d need according to this post...
That’s a good point, although it still leaves a few hypotheses on the table:
The improvement was due to the magnesium, not the glycine.
I had a severe glycine shortage.
I misinterpreted the label. (i.e. 200 mg is actually the mass of the magnesium itself, so the amount of glycine is unknown.)
If 3 is right, then it’s 1.2 grams of glycine (magnesium glycinate is 14% magnesium by mass)
Generally, as I understand it, the convention is for that sort of text to mean it’s 200 mg of magnesium, not 200 mg of the compound.
1.4g is more than a tenth of the typical shortfall and there’s a lot of heterogeneity, but also total magnesium need is often estimated at half a gram, so 200mg is a large percentage of that.
This essay is much more interesting than the title indicates! (I hope you take that as a 90% compliment, 10% criticism. I’m rather bad a promoting my own work, so I’m not trying to condescend.)
What aspects of the post do you think it was a missed opportunity not to highlight?
I agree with them, and for me I very rarely get sick or fevers, and when I do they’re usually pretty minor, so I wouldn’t click on something about fevers. But I am really interested in ways to improve sleep, as well as discussion on amino acids and which are essential and which are “less essential”
Do you take antipyretics like NSAIDs or acetaminophen/paracetamol/tylenol when you get sick or for pain? If so, then you might not be aware of your unsuppressed baseline incidence of fevers.
No, I haven’t used any of those in a long time. When I get sick I generally just take it easy and ride it out. I don’t really get pain, but if I do (e.g. knees or feet hurt from running) I take it as a sign to do something differently (step lighter/not stomp feet) or just take it easier for a week or two.
I second HoVY’s points. The other point that should have made it into the title, in my opinion, is that medical interventions should target problems, not indicators of problems. (Your application of the idiom “don’t shoot the messenger” was especially clever, and I think you could have based the title around it.)
I was also impressed by your disentanglement of two additional means by which glycine prevents or lessens fevers, and your identification of this as a Gettier case, but I doubt that it belongs in the title.
May I suggest that you or somebody with the time to spare look into the link Glycine has with calming panic attacks and manic episodes. There is a connection to be made with NMDA receptors, improved sleep, and blood flow. Another interesting topic is it’s effect on depersonalization.
Great article by the way!
There’s a little relevant info in the footnotes.
There was a room in my parents’ house where I slept as a child, and even as an adult over 40, I fell asleep there as easily as I did as a child, although I constantly struggled with sleep in other places. When my mother died, my father moved, but I accidentally found a replacement – in my country house, on the edge of civilization, I sleep as well as I did as a child.
I think sleep problems are more a matter of switching from work mode to rest mode. I work remotely, and my bedroom is also my workspace. I can wake up at 4 AM and sit at the computer, and then go to bed at 3 PM – it’s terrible. I don’t think glycine will help me, no matter the dose.
I almost never have trouble getting to sleep; the glycine seems to improve the quality of sleep or reduce my need for it, which seems more likely to have to do with ROS clearance or possibly collagen repair than the NMDA signaling mechanism studied specifically for sleep onset.
But my utility function is different. I experience flow states periodically — and I want them more often. This is not an abstract wish: if it already happens, the conditions for it exist and can be studied.
I’d agree to an experiment — taking 0.3g of glycine before bed, as a chemist and understanding the mechanism
But the metric I’ll track isn’t sleep quality or morning alertness. It is the frequency and intensity of flow states over the following weeks.
If these variables turn out to be orthogonal — that is also a result.
Do you have any data on this use case?
I think you would want 3 g, not .3 g.
Your flow states won’t be nearly as productive if you’re getting bad sleep. Just noting. Sleep has a large effect on intelligence forany purposes. And the effect is underestimated subjectively.