Glycine Powerfully Lowers Cortisol

Shai Hulud

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I'm reacting very strangely to glycine.
Even at 1 g I will feel fatigued and very unsharp mentally the next day, but more like several days, slowly getting better. Also lowered mood and getting out of bed harder than usually (=very hard)
Taking Vitamin A palmitate once at 15,000 IU felt very similar, so this could be related.

On the other hand, I take TMG and have tried up to 8 g a day and get no problems. I'm homozygous for MTHFR C677T.
Did a dutch test last year and thyroid (TSH/T4/T3/antibodies). Thyroid was ok, cortisol seemed ok, but sex hormones were super high, especially estradiol.
Did an additional testing of SHBG and total testosterone, both again really high.
Also tracking my food intake, seeing that I don't consume enough glycine, especially since I probably loose a lot through my glycine buffer system (low 5-MTHF).
When I had the hormones tested (late in summer '17), I had also done an OAT test by great plains and it showed low 5-HT metabolites.

@haidut Can you help me out here? What is happening?


I have long suspected that inhibitory amino acids suppress cortisol release. The reason is that most of these inhibitory amino acids like glycine, taurine, beta alanine, theanine, etc are all GABA agonists. GABA agonist pharma drugs are used to treat Cushing syndrome and are very effective at lowering cortisol. However, up until today I did not have much evidence for such an effect of amino acids with the possible exception of theanine.
This study shows that glycine can acutely lower cortisol to about 20% of controls (i.e. 80% reduction). The study was done in chickens, so unfortunately the dosage conversion is a bit difficult to come buy but I think the results are valid given that glycine has also been shown to stop aging-related muscle loss and even cancer cachexia, both of which are mediated at least partially through elevated cortisol. So, if somebody knows how to convert doses from chicken to rodent or human please chime in. I have included a link that talks about doses of specific drugs for rodents, pigs, cats, dogs and birds and based on that conversion it looks like the effective dose in humans to achieve the cortisol-lowering effect could be as low as 70mg/kg. This dose is surprisingly close to the 1mmol/kg (75mg/kg) glycine that acutely lowered the glycemic response in humans by more than 66% without changing insulin levels. As you can see from the screenshot, glycine also lowered cortisol in chickens without changing insulin. In general, anything that lowers cortisol will lower blood sugar, so it is quite plausible that the cortisol-lowering effects of glycine are behind its beneficial effects on blood glucose, diabetes, obesity, bone health, and aging which I have posted about in separate threads on this forum.


Effects of orally administered glycine on myofibrillar proteolysis and expression of proteolytic-related genes of skeletal muscle in chicks. - PubMed - NCBI
"...The plasma corticosterone concentration was also decreased by glycine, but the plasma insulin concentration was unaffected. These results indicate that orally administered glycine suppresses myofibrillar proteolysis and expression of proteolytic-related genes of skeletal muscle by decreasing the plasma corticosterone concentration in chicks."


The domestic animals drug conversion link:
Veterinary Formulary

Another substance that also powerfully lowers cortisol is niacinamide and thus can synergize well with glycine to block the stress response.
Niacinamide Lowers Cortisol | Ray Peat Forum
 
OP
haidut

haidut

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I'm reacting very strangely to glycine.
Even at 1 g I will feel fatigued and very unsharp mentally the next day, but more like several days, slowly getting better. Also lowered mood and getting out of bed harder than usually (=very hard)
Taking Vitamin A palmitate once at 15,000 IU felt very similar, so this could be related.

On the other hand, I take TMG and have tried up to 8 g a day and get no problems. I'm homozygous for MTHFR C677T.
Did a dutch test last year and thyroid (TSH/T4/T3/antibodies). Thyroid was ok, cortisol seemed ok, but sex hormones were super high, especially estradiol.
Did an additional testing of SHBG and total testosterone, both again really high.
Also tracking my food intake, seeing that I don't consume enough glycine, especially since I probably loose a lot through my glycine buffer system (low 5-MTHF).
When I had the hormones tested (late in summer '17), I had also done an OAT test by great plains and it showed low 5-HT metabolites.

@haidut Can you help me out here? What is happening?

A dose of 1g glycine should not cause such effects, so it could be related to purity. I would try a spoon of gelatin, which has more glycine than that and see if it still causes the same issues.
 

nostalgic

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Will lower doses still result in reduced (but less so) cortisol levels? What doses did you start at?
 

Shai Hulud

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A dose of 1g glycine should not cause such effects, so it could be related to purity. I would try a spoon of gelatin, which has more glycine than that and see if it still causes the same issues.

I'm sure I responded, but my last post somehow got lost back then: I've tried glycine powder by myprotein, but also MagGlycinate by Kirkman (shouldn't that be pretty pure?). Wil try gelatine at some point, but really can't afford to be knocked out for severl days right now.
 

LCohen

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Why are you trying to megadose everything ? Too much of anything will harm rather than heal you.
 
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Watch out for symptoms of nausea from too much gelatin. Back in revolutionary France it was tried as food for the poor and most people refused to eat more than 50g a day due to the overwhelming nausea it caused when eaten long term. Their health did improve, especially bone health and ability to do hard work, and the latter genuinely thrilled the nobility. But if you consider that attempts as a type of randomized uncontrolled trial, it seems that gelatin may have a sweet spot in dose. Not sure if it is 50g but when I tried eating nothing but gelatin as my protein I did get the nausea after a week of 128g (4 boxes of Knox gelatin) a day.
Damn that’s a lot! Did it tank cortisol?
 

Xemnoraq

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I have long suspected that inhibitory amino acids suppress cortisol release. The reason is that most of these inhibitory amino acids like glycine, taurine, beta alanine, theanine, etc are all GABA agonists. GABA agonist pharma drugs are used to treat Cushing syndrome and are very effective at lowering cortisol. However, up until today I did not have much evidence for such an effect of amino acids with the possible exception of theanine.
This study shows that glycine can acutely lower cortisol to about 20% of controls (i.e. 80% reduction). The study was done in chickens, so unfortunately the dosage conversion is a bit difficult to come buy but I think the results are valid given that glycine has also been shown to stop aging-related muscle loss and even cancer cachexia, both of which are mediated at least partially through elevated cortisol. So, if somebody knows how to convert doses from chicken to rodent or human please chime in. I have included a link that talks about doses of specific drugs for rodents, pigs, cats, dogs and birds and based on that conversion it looks like the effective dose in humans to achieve the cortisol-lowering effect could be as low as 70mg/kg. This dose is surprisingly close to the 1mmol/kg (75mg/kg) glycine that acutely lowered the glycemic response in humans by more than 66% without changing insulin levels. As you can see from the screenshot, glycine also lowered cortisol in chickens without changing insulin. In general, anything that lowers cortisol will lower blood sugar, so it is quite plausible that the cortisol-lowering effects of glycine are behind its beneficial effects on blood glucose, diabetes, obesity, bone health, and aging which I have posted about in separate threads on this forum.


Effects of orally administered glycine on myofibrillar proteolysis and expression of proteolytic-related genes of skeletal muscle in chicks. - PubMed - NCBI
"...The plasma corticosterone concentration was also decreased by glycine, but the plasma insulin concentration was unaffected. These results indicate that orally administered glycine suppresses myofibrillar proteolysis and expression of proteolytic-related genes of skeletal muscle by decreasing the plasma corticosterone concentration in chicks."


The domestic animals drug conversion link:
Veterinary Formulary

Another substance that also powerfully lowers cortisol is niacinamide and thus can synergize well with glycine to block the stress response.
Niacinamide Lowers Cortisol | Ray Peat Forum
Its interesting this review, i remember seeing a few similar posts like this and anyway i just wanted to testify to the glycine statement,

I keep having these lactic acidosis shock like episodes whether its diabetes related or endotoxin my linbs start to seize up and lactic acid floods my body and i start to have these major panic attacks,

Anyway i remembered seeing posts like this on glycine so interestingly enough i add gelatin powder to my orange juice when this happens along with baking soda sugar and thiamine, and instantly or shortly after im back to a relaxed state and breathing deeply again,
I wouldnt say it puts me back at 100 percent but i can 100% agree with these posts on glycine, anytime i feel extreme surges of cortisol or stress, taking glycine in the form of gelatin powder stop it so fast and allows me to relax, its amazing seeing studies like this on glycine and then actually applying it to a situation, and seeing it work,

Glycine also seems to powerfully take the swelling in my liver area away, so i think im gonna keep some gelatin powder on me for emergencies when i need it! Good post!
 

Spartan300

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@Jake sullivan What form/brand of gelatin powder do you use?

Anything other than the stuff I have to soak then heat becomes really expensive to use in significant quantities.
 

Xemnoraq

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@Jake sullivan What form/brand of gelatin powder do you use?

Anything other than the stuff I have to soak then heat becomes really expensive to use in significant quantities.
Im not sure what brand it is because i get it from a bulk food store but if i go back to get more ill let you know, its like protein powder but gelatin i think its hydrolized gelatin powder but ill try and find the brand
 

johnwester130

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How much glycine is in 1 tbsp of Great Lakes gelatin? Are there other sources of glycine in food beside bone and gelatin?

glycine has uses that gelatin doesn't
for example glycine can be used in skin care products

glycine powder is used to remove biofilm from teeth
 

BearWithMe

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Glycine significantly improves my digestion, mood, sleep and skin quality. But every time I take it, it makes me tired and sleepy to the point of uncontrollably passing out. Even 250mg makes me unable to work and think for the rest of the day.

What could be the reason?
 
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@BearWithMe Just a guess: sam-e depletion and something to do with NMDA / calcium channels
 

HumanLife

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Glycine significantly improves my digestion, mood, sleep and skin quality. But every time I take it, it makes me tired and sleepy to the point of uncontrollably passing out. Even 250mg makes me unable to work and think for the rest of the day.

What could be the reason?
If I recall correctly it lowers blood sugar and has some insulin-like effects but don’t quote me on this. I take my collagen or glycine with a sugared drink so I can’t say I recall it ever made me tired.
 

youngsinatra

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Glycine significantly improves my digestion, mood, sleep and skin quality. But every time I take it, it makes me tired and sleepy to the point of uncontrollably passing out. Even 250mg makes me unable to work and think for the rest of the day.

What could be the reason?
Low cortisol
 

BearWithMe

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If I recall correctly it lowers blood sugar and has some insulin-like effects but don’t quote me on this. I take my collagen or glycine with a sugared drink so I can’t say I recall it ever made me tired.
It does feel like hypoglycemia. I'm always taking glycine with a large glass of orange juice, I'm having hypoglycemic tendencies even when not taking glycine, though.
 
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@BearWithMe Glycine has a similar action to niacinamide on the drainage of methyl groups and therefore can temporarily create these problems for you. The moment you consume a protein source with methionine you could solve ... NMDA receptors are very complex and I don't have the right requirements to explain but you must consider that glycine, aspartic acid and glutamic acid work here so you can be subject to excitement toxicity also from glycine rather than an inhibitory effect. This happens when the balance is shifted towards glutamate rather than GABA (inhibitory).
 

BearWithMe

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@BearWithMe Glycine has a similar action to niacinamide on the drainage of methyl groups and therefore can temporarily create these problems for you. The moment you consume a protein source with methionine you could solve ... NMDA receptors are very complex and I don't have the right requirements to explain but you must consider that glycine, aspartic acid and glutamic acid work here so you can be subject to excitement toxicity also from glycine rather than an inhibitory effect. This happens when the balance is shifted towards glutamate rather than GABA (inhibitory).
Hmmm, I have bad reactions to niacinamide too.

This is very interesting topic to research. Thank you very much!
 

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