I have a nasty condition called Restless Legs Syndrome which I can turn “on and off” by controlling the oxalate level in my diet. RLS is characterized by very unpleasant sensations in the legs which cause sufferers to move about restlessly, especially at bedtime. It took me 5 years of tracking my diet to identify oxalate as the offending substance. It took me several more years to find an explanation for why some “low oxalate” vegetables were problematic: because much of our fresh produce is sprayed either pre- or post harvest with oxalic acid solution to preserve “freshness and nutrients” during warehouse storage and transportation to the grocers. It took me several more years to piece together an explanation for why magnesium glycinate supplements caused return of my RLS discomforts by learning a few of the basic aspects of the citric acid cycle, etc., which you have explicated much more thoroughly in your wonderful article. Eventually I realized that, for me, gelatinous soups and stews were similarly problematic. This was in contradiction to the standard advice on websites offering guidance for low oxalate dieters which says that all meats and meat products are okay. As a result of my sharing of my insights on the rls.org discussion board for “Non-prescription Medicines, Supplements, Diet” under my user name of notnowdad many people have found relief from RLS without the scary medicines that are typically prescribed. After reading a lot of scientific articles I suspect that RLS is due to oxalate taking the place of carbonate in the binding of iron to transferrin which then causes the iron to become “locked up” such that it doesn’t get distributed around the body. Excessive endogenous production of oxalic acid is probably due to an inability to tolerate exposure to normal amounts of dietary fluoride, and most especially the toxic fluorocarbons in most non-stick cookware. Fluoride rich pesticide residues and fluorinated drugs are also to be avoided. Poor digestive tract handling of the eight common refined, bleached and deodorized cooking oils made from seeds can lead to the inappropriate presence of bile salts in the colon which causes damage to the colonic mucosa and results in increased vulnerability to dietary oxalate.
I'm a schizoid but I've never liked glycine. It makes my sleep restless, yet also puts me in a strange, somewhat impaired headspace if taken during the day. Taurine does much the same. L-Ornithine doesn't help so I don't think it's ammonia.
In contrast, Neboglamine (NMDA glycine site PAM), boosts my mood and isn't impairing, however, it also disrupts my sleep in a similar way to glycine if taken at night.
Thanks for your amazing work Chris, I have health anxiety and I read your articles and can’t imagine the amount of research you must cover,I don’t understand most of it but are fascinated by it,I know if I tried to utilize it it would most definitely improve my health in many ways but would increase my anxiety so I don’t act on it but I do appreciate what you do.cheers.
Do you believe that we can synthesize 100% of our glycine requirements with an adequate supply of THF?
How does your hypothesis that we can detoxify oxalate with biotin, folate, and B12 fit into this equation? If we can detoxify oxalate why do we bother excreting it, or do we only excrete it because we don't have optimal levels of these nutrients to detoxify?
What's covered here is known. Biotin/folate/B12 is my hypothesis, not demonstrated. Will evaluate further in the future. For now I will be writing an article on maximizing glycine synthesis but it is not all about thf.
Looking forward to the article of endogenous glycine synthesis. Curious if it will also touch on the importance of serine catabolism for mitochondrial nadph production, it is something that I have been trying to untangle for a while.
I've been trying to determine if I'm having a paradoxical reaction to glycine or if it's a stress response. I've been under extreme stress and experiencing significant grief which could be the culprit, but I'd like your input on what I'm experiencing.
Years ago when I wasn't under significant stress, magnesium glycinate caused significant insomnia.
Flash forward to recently, I started taking 3,000mg of glycine at night with my aspirin dose as recommended by many in the prometabolic community. I experienced significant insomnia. I have felt benefit from taurine and have taken it for many years. I'm not sure what to make of this. The one night I was able to sleep after taking glycine I didn't feel rested at all, but I know I slept because I vividly remembered numerous nightmares I experienced throughout the night.
We have found benefit to taking glycine. It has improved sleep and helped with brain clarity. We do not seem to have any oxalate problems. We do have migraines from a huge range of things such as pesticides (glyphosate = glycine + phospate I believe?), some essential oils (fragrances, specific phenols), artificial nitrates. Importantly, we have found glutamate (MSG and many other food sources especially grains and legumes) to cause inflammation and pain. We think the GABA - glutamate - glycine balance is important, and wonder about glycine's role in making glutathione. We had a very weird unpleasant reaction to NAC.
Thanks so much for the deep dive on glycine.. I am a big fan of this supplement in powder form and take 5g (teaspoon of powder in water) with 600mg NAC several times a week to stimulate natural glutathione production. Zero difficulties with this, so I believe that it’s metabolized correctly. I don’t do all the testing noted in your article since there have been no issues. I’m a believer that the good is not the enemy of the great - my supplementation may not be optimal, but I believe it’s better than nothing and hopefully I can get some of the longevity benefits mentioned in the early part of your piece without any issues. Cheers to you and keep the info coming!
Your posts are fascinating and so thought provoking they keep me revisiting many times. Thank you for always suggesting which other posts to revisit with you newest publications. I share with people everyday (no exaggeration) about you and things I have learned from you. Thank you also for the resources you provide.
For the past year or so I have been adding oral peptides (beyond collagen), glycine rich foods and increased attention to diet, exercise, stress and lifestyle but seen little improvement for my advancing hip osteoarthritis.
Have been advised long ago (by the biochemist who helped "recover" my now 27 y/o daughter from severe ASD), that my family should steer clear of folic and methyl folate. I have focused on TMG, L-serine, Methylcobalamin p-5-p, zinc, B6 & Udo's oil for EFAs. wondered if this (over the past 2 decades) has played a role in both my own and my immediate and extended family members health issues
We have a strong maternal history of osteoarthritis (as well as cancer, glaucoma, hyperhomocysteinemia, hypertension, stroke, some ASD, PD, schizophrenia and poor creatine tolerance).
My sister had her 1st hip replacement in her 30's (also when she acquired Guillan Barre after vaccinating for foster parenting)
Her healthcare has always been through KP and they told her never to take vaccines again (till C19). Then they told her to take the shot. This did not stop her from contracting it (2 or more times?) Add this to a poor diet, little exercise and high stress and she has had a long history of respiratory infections. I finally got her to test SAH:SAM her homocysteine was 22, now down to 10). Despite the above she never had hypertension or anemia, elevated CRP or poor LDL. Now she does?
Late last year she had a large pseudotumor (mostly) excised and had her failing, first hardware replaced. The mysterious "pseudo tumor" seems to be back. Her inflammation is through the roof and her WBC count is almost 3000. Her surgeon says he can see smoke but cant see the fire as there is no apparent bacterial infection. His investigations continue. Could it be viral?
I wonder if she is THF deficient, do not know her genome status, if she has misbehaving MDSCs and a poor response to her history of shots and infections.
As I said, osteoarthritis is now chasing me at 65, but I hesitate on surgery. Especially without understanding more about why I have it! Sure do not need to compromise my health so my doctor can send his kids to college with joints continuing to fail!
Thank you again for giving us hope and some tools for this endeavor. Will pursue testing and continue learning all I can. Looking forward to Romaine cocktails!
Duh..i'll go see what you've written about Vitamin A first. But I did want to ping you. This stuff is so complex. I can't follow it. But knowing that you dig into this stuff all the time has me at least keeping tabs in case something that comes up that may turn me onto a key supplement or vitamin. I recently joined a group where a member in it is suffering from Ritanitas Pigmentosa. Sounds like Vitamin A is the only real thing recommended to these people and that int he past it is assumed a Vitamin A deficiency is what led to a lot of sight issues and even blindness int he past. I'm curious if you ever looked into this condition and if it could be a Vitamin deficiency even in people that supplement if something is going wrong with how the Vitamen is used in the biochemical processes that vision requires. Would be curious what you would make of this, or what you would want to explore and test the levels of in such patients?
I have a nasty condition called Restless Legs Syndrome which I can turn “on and off” by controlling the oxalate level in my diet. RLS is characterized by very unpleasant sensations in the legs which cause sufferers to move about restlessly, especially at bedtime. It took me 5 years of tracking my diet to identify oxalate as the offending substance. It took me several more years to find an explanation for why some “low oxalate” vegetables were problematic: because much of our fresh produce is sprayed either pre- or post harvest with oxalic acid solution to preserve “freshness and nutrients” during warehouse storage and transportation to the grocers. It took me several more years to piece together an explanation for why magnesium glycinate supplements caused return of my RLS discomforts by learning a few of the basic aspects of the citric acid cycle, etc., which you have explicated much more thoroughly in your wonderful article. Eventually I realized that, for me, gelatinous soups and stews were similarly problematic. This was in contradiction to the standard advice on websites offering guidance for low oxalate dieters which says that all meats and meat products are okay. As a result of my sharing of my insights on the rls.org discussion board for “Non-prescription Medicines, Supplements, Diet” under my user name of notnowdad many people have found relief from RLS without the scary medicines that are typically prescribed. After reading a lot of scientific articles I suspect that RLS is due to oxalate taking the place of carbonate in the binding of iron to transferrin which then causes the iron to become “locked up” such that it doesn’t get distributed around the body. Excessive endogenous production of oxalic acid is probably due to an inability to tolerate exposure to normal amounts of dietary fluoride, and most especially the toxic fluorocarbons in most non-stick cookware. Fluoride rich pesticide residues and fluorinated drugs are also to be avoided. Poor digestive tract handling of the eight common refined, bleached and deodorized cooking oils made from seeds can lead to the inappropriate presence of bile salts in the colon which causes damage to the colonic mucosa and results in increased vulnerability to dietary oxalate.
One thing I have noticed though is when I lower my oxolate foods, my sulphur intolerance gets worse. The body is truly fascinating
I'm a schizoid but I've never liked glycine. It makes my sleep restless, yet also puts me in a strange, somewhat impaired headspace if taken during the day. Taurine does much the same. L-Ornithine doesn't help so I don't think it's ammonia.
In contrast, Neboglamine (NMDA glycine site PAM), boosts my mood and isn't impairing, however, it also disrupts my sleep in a similar way to glycine if taken at night.
Thanks for your amazing work Chris, I have health anxiety and I read your articles and can’t imagine the amount of research you must cover,I don’t understand most of it but are fascinated by it,I know if I tried to utilize it it would most definitely improve my health in many ways but would increase my anxiety so I don’t act on it but I do appreciate what you do.cheers.
Glycine causes anger and insomnia, plus makes me feel anhedonic. Thank you for your work Chris. Appreciate you so much
Do you believe that we can synthesize 100% of our glycine requirements with an adequate supply of THF?
How does your hypothesis that we can detoxify oxalate with biotin, folate, and B12 fit into this equation? If we can detoxify oxalate why do we bother excreting it, or do we only excrete it because we don't have optimal levels of these nutrients to detoxify?
What's covered here is known. Biotin/folate/B12 is my hypothesis, not demonstrated. Will evaluate further in the future. For now I will be writing an article on maximizing glycine synthesis but it is not all about thf.
Looking forward to the article of endogenous glycine synthesis. Curious if it will also touch on the importance of serine catabolism for mitochondrial nadph production, it is something that I have been trying to untangle for a while.
https://www.science.org/doi/10.1126/sciadv.1601273
https://www.nature.com/articles/s41589-023-01283-9
https://www.nature.com/articles/nature13236
I've been trying to determine if I'm having a paradoxical reaction to glycine or if it's a stress response. I've been under extreme stress and experiencing significant grief which could be the culprit, but I'd like your input on what I'm experiencing.
Years ago when I wasn't under significant stress, magnesium glycinate caused significant insomnia.
Flash forward to recently, I started taking 3,000mg of glycine at night with my aspirin dose as recommended by many in the prometabolic community. I experienced significant insomnia. I have felt benefit from taurine and have taken it for many years. I'm not sure what to make of this. The one night I was able to sleep after taking glycine I didn't feel rested at all, but I know I slept because I vividly remembered numerous nightmares I experienced throughout the night.
Any insight would be appreciated. Thanks!
We have found benefit to taking glycine. It has improved sleep and helped with brain clarity. We do not seem to have any oxalate problems. We do have migraines from a huge range of things such as pesticides (glyphosate = glycine + phospate I believe?), some essential oils (fragrances, specific phenols), artificial nitrates. Importantly, we have found glutamate (MSG and many other food sources especially grains and legumes) to cause inflammation and pain. We think the GABA - glutamate - glycine balance is important, and wonder about glycine's role in making glutathione. We had a very weird unpleasant reaction to NAC.
Thanks so much for the deep dive on glycine.. I am a big fan of this supplement in powder form and take 5g (teaspoon of powder in water) with 600mg NAC several times a week to stimulate natural glutathione production. Zero difficulties with this, so I believe that it’s metabolized correctly. I don’t do all the testing noted in your article since there have been no issues. I’m a believer that the good is not the enemy of the great - my supplementation may not be optimal, but I believe it’s better than nothing and hopefully I can get some of the longevity benefits mentioned in the early part of your piece without any issues. Cheers to you and keep the info coming!
Your posts are fascinating and so thought provoking they keep me revisiting many times. Thank you for always suggesting which other posts to revisit with you newest publications. I share with people everyday (no exaggeration) about you and things I have learned from you. Thank you also for the resources you provide.
For the past year or so I have been adding oral peptides (beyond collagen), glycine rich foods and increased attention to diet, exercise, stress and lifestyle but seen little improvement for my advancing hip osteoarthritis.
Have been advised long ago (by the biochemist who helped "recover" my now 27 y/o daughter from severe ASD), that my family should steer clear of folic and methyl folate. I have focused on TMG, L-serine, Methylcobalamin p-5-p, zinc, B6 & Udo's oil for EFAs. wondered if this (over the past 2 decades) has played a role in both my own and my immediate and extended family members health issues
We have a strong maternal history of osteoarthritis (as well as cancer, glaucoma, hyperhomocysteinemia, hypertension, stroke, some ASD, PD, schizophrenia and poor creatine tolerance).
My sister had her 1st hip replacement in her 30's (also when she acquired Guillan Barre after vaccinating for foster parenting)
Her healthcare has always been through KP and they told her never to take vaccines again (till C19). Then they told her to take the shot. This did not stop her from contracting it (2 or more times?) Add this to a poor diet, little exercise and high stress and she has had a long history of respiratory infections. I finally got her to test SAH:SAM her homocysteine was 22, now down to 10). Despite the above she never had hypertension or anemia, elevated CRP or poor LDL. Now she does?
Late last year she had a large pseudotumor (mostly) excised and had her failing, first hardware replaced. The mysterious "pseudo tumor" seems to be back. Her inflammation is through the roof and her WBC count is almost 3000. Her surgeon says he can see smoke but cant see the fire as there is no apparent bacterial infection. His investigations continue. Could it be viral?
I wonder if she is THF deficient, do not know her genome status, if she has misbehaving MDSCs and a poor response to her history of shots and infections.
As I said, osteoarthritis is now chasing me at 65, but I hesitate on surgery. Especially without understanding more about why I have it! Sure do not need to compromise my health so my doctor can send his kids to college with joints continuing to fail!
Thank you again for giving us hope and some tools for this endeavor. Will pursue testing and continue learning all I can. Looking forward to Romaine cocktails!
TV
I seem to react to glycine badly. The few times I've tried to use it I've had terrible depression. I figured it must just be me, but I did find a study that talked about glycine could be a trigger for major depression. https://neurosciencenews.com/major-depression-glycine-22905/#:~:text=A%20common%20amino%20acid%2C%20glycine%2C%20can%20deliver%20a,Institute%20for%20Biomedical%20Innovation%20%26%20Technology%20have%20found.
Duh..i'll go see what you've written about Vitamin A first. But I did want to ping you. This stuff is so complex. I can't follow it. But knowing that you dig into this stuff all the time has me at least keeping tabs in case something that comes up that may turn me onto a key supplement or vitamin. I recently joined a group where a member in it is suffering from Ritanitas Pigmentosa. Sounds like Vitamin A is the only real thing recommended to these people and that int he past it is assumed a Vitamin A deficiency is what led to a lot of sight issues and even blindness int he past. I'm curious if you ever looked into this condition and if it could be a Vitamin deficiency even in people that supplement if something is going wrong with how the Vitamen is used in the biochemical processes that vision requires. Would be curious what you would make of this, or what you would want to explore and test the levels of in such patients?
Thiamine deficiency results from Lactose Dehydrogenase (LDH) because B1 is its cofactor.
Lactic acidemia and Beriberi ... Fun!
A stammering person susceptible to sepsis.
for renal stone formers i take it glycine supplementation might be a no go?
I have the impression that I get migraines after supplementing glycine. Any idea why this could be?