15 replies to this topic

[sapentia]

I regularly take 5g (1 tsp) glycine prebed most every night. I have found it to help my sleep quality, and there is the additional benefit that is stimulates increased hGH release. There is also evidence for its beneficial impact on several neurological conditions.

Okay, so my 64 y/o healthy mother has difficulty sleeping most nights. I thought I would try giving her a 5g dose of glycine taken sublingually for 1 minute before washing it down with some water. Her reaction took me by surprise to say the least. The partial sublingual dosing likely explains the rapidity of the following reactions. First, within less than 2 minutes she had difficulty speaking. Very labored speech, slurred, and had a strange sensation in her tongue. Within a couple more minutes she began having fits of laughter for no apparent reason. In all honesty if I hadn't known better I would have thought her drunk (she had not consumed anything prior). The laughter passed after about 5 minutes and then she became much more subdued with slight nausea. I made sure that she stayed stable before leaving as she was going to sleep. I am sure there are many other symptoms I may not have caught or been aware of at the time.

I proceeded to do some searching on Google; the only thing I could find was potentially fatal hyponatremia as a reaction to hypotonic glycine solutions used for urologic irrigation. Reference

I am very interested in getting some feedback on the above as nothing I have read with regards to glycine supplementation mentions any type of serious side effects. I am aware of glycine's role with the NMDA receptor but am at a loss for explaining what happened.

[outsider]

Well glycine is an allosteric NMDA potentiator, nmda is one of the most important component of cognitive fonction and one of the last gate keeper of memory consolidation if I'm not mistaken and 5g looks like pretty high dose regardless of what you have read about schizophrenia. Some study only used 390 mg for other purpose. I myself start to get problems if I supplement with more than 1,5g of glutamine (the most abundant amino acid in the body by far) even if they sometimes talk about 30g dose, just as an example. And I believe the pharmacological world boost to the max sometimes when it comes to natural supplement until they get lots of side effects.

The nmda receptor needs magnesium to function properly, magnesium has inhibitory action so a lack of this mineral to protect it from working too much and a boost from glycine for working more could well be the reason of the imbalance if she was deficient with this mineral.

By the way when you are deficient in magnesium you can have difficulty sleeping with constipation.

Edited by outsider, 16 January 2011 - 12:16 PM.

[sapentia]

The nmda receptor needs magnesium to function properly, magnesium has inhibitory action so a lack of this mineral to protect it from working too much and a boost from glycine for working more could well be the reason of the imbalance if she was deficient with this mineral.

By the way when you are deficient in magnesium you can have difficulty sleeping with constipation.

Thanks for your thoughts. She actually gets plenty of magnesium to counteract her osteopenia. Apart from diet she gets 125mg (magnesium) twice a day from magnesium taurate with one dose being prebed, and she gets 380mg magnesium from an algae based product called Raw Calcium from Garden of Life. Including diet I would say she gets a full 1,000mg Mg/day.

I haven't read anything that supports such a low dose of glycine though. The AOR website recommends 15g-60g glycine per day spread over 3 or more doses. I think the schizophrenia groups used 40g-60g per day. I would personally consider 15g per day to be the maximum dose I would take. In this sleep study (Subjective effects of glycine ingestion before bedtime on sleep quality) they used a dosage of 3g.

Quick thought, many people have a glutamate (MSG) sensitivity/allergy and I think my mother may have an MSG sensitivity; if that is the case is it feasible that glycine could potentially trigger a similar reaction given that it is one of the two co-activation factors for the NMDA receptor?

[outsider]

The nmda receptor needs magnesium to function properly, magnesium has inhibitory action so a lack of this mineral to protect it from working too much and a boost from glycine for working more could well be the reason of the imbalance if she was deficient with this mineral.

By the way when you are deficient in magnesium you can have difficulty sleeping with constipation.

Thanks for your thoughts. She actually gets plenty of magnesium to counteract her osteopenia. Apart from diet she gets 125mg (magnesium) twice a day from magnesium taurate with one dose being prebed, and she gets 380mg magnesium from an algae based product called Raw Calcium from Garden of Life. Including diet I would say she gets a full 1,000mg Mg/day.

I haven't read anything that supports such a low dose of glycine though. The AOR website recommends 15g-60g glycine per day spread over 3 or more doses. I think the schizophrenia groups used 40g-60g per day. I would personally consider 15g per day to be the maximum dose I would take. In this sleep study (Subjective effects of glycine ingestion before bedtime on sleep quality) they used a dosage of 3g.

Quick thought, many people have a glutamate (MSG) sensitivity/allergy and I think my mother may have an MSG sensitivity; if that is the case is it feasible that glycine could potentially trigger a similar reaction given that it is one of the two co-activation factors for the NMDA receptor?

Ok hummm at first I wanted to talk about too much calcium could counteract magnesium absorption and metabolism. When I took 1g calcium for 2 days I could not sleep until I got even more magnesium. It was very fast acting and you wont find that kind of information unless in testimonials since calcium is believed to be the answer to everything while it is not the case at all. A balance in calcium magnesium like 1/1 is much more important because without magnesium calcium cannot be well used in the body anyway. But yeah looks like it is not the problem after all.

Ok she could benefit from glutamine since it is the precursor to gaba and gaba is the most inhibitory neurotrasmeter (you need B6 to convert) in the brain that balance glutamate and it is the most abundant amino acid in the body by far and if people knew how much glutamine is released in the blood after exercise maybe they would never exercise again even if it is a known fact that exercise is a great nootropic. In my opinion there is no problem there. I say that because glutamine is the precursor to both glutamate and gaba. But it is up to you to chose what you think is good in the end.

[outsider]

I regularly take 5g (1 tsp) glycine prebed most every night. I have found it to help my sleep quality, and there is the additional benefit that is stimulates increased hGH release. There is also evidence for its beneficial impact on several neurological conditions.

Okay, so my 64 y/o healthy mother has difficulty sleeping most nights. I thought I would try giving her a 5g dose of glycine taken sublingually for 1 minute before washing it down with some water. Her reaction took me by surprise to say the least. The partial sublingual dosing likely explains the rapidity of the following reactions. First, within less than 2 minutes she had difficulty speaking. Very labored speech, slurred, and had a strange sensation in her tongue. Within a couple more minutes she began having fits of laughter for no apparent reason. In all honesty if I hadn't known better I would have thought her drunk (she had not consumed anything prior). The laughter passed after about 5 minutes and then she became much more subdued with slight nausea. I made sure that she stayed stable before leaving as she was going to sleep. I am sure there are many other symptoms I may not have caught or been aware of at the time.

I proceeded to do some searching on Google; the only thing I could find was potentially fatal hyponatremia as a reaction to hypotonic glycine solutions used for urologic irrigation. Reference

I am very interested in getting some feedback on the above as nothing I have read with regards to glycine supplementation mentions any type of serious side effects. I am aware of glycine's role with the NMDA receptor but am at a loss for explaining what happened.

Ok I think I got the answer, by pure coincidence, I was not looking to find it, I just wanted to know what was the role of zinc upon the brain and from my recent experimentations since 4 days, its pretty deep. Just give your mother some zinc, it's a fundamental mineral anyway. Increase my sex drive quite substantially as goods as any aphrodisiacs if not better. Now I know why oysters are great for sex, they have the highest concentration of zinc and now I know why you can become crazy if you masturbate too much, its full of zinc. "Zinc is undoubtedly the most important mineral as far as your semen production is concerned."


http://www.articlesb...lity-56138.html

Required for a healthy male reproductive system and sperm production.
Zinc is required for the production of testosterone and zinc content in the prostate gland and sperm is higher than in any other body tissues.
A deficiency of zinc is associated with numerous sexual problems, including sperm abnormalities and prostate disease.
Zinc helps to maintain semen volume and adequate levels of testosterone; keeping sperm healthy.


Anyway here is the thing:

Modulation of excitatory synaptic transmission by glycine and zinc in cultures o

ID Forsythe, GL Westbrook, ML Mayer

The monosynaptic EPSP between cultured hippocampal neurons is mediated by activation of 2 classes of excitatory amino acid receptors. Kainate or quisqualate receptors generate a fast conventional EPSP, while NMDA receptors mediate a slow, voltage-sensitive EPSP. Recently, 2 substances have been shown to modulate the activity of the NMDA receptor-channel complex: glycine increases the probability of channel opening, while zinc acts as a noncompetitive antagonist. Since these substances are present in the CNS and thus may function as neuromodulators, we have examined their role in excitatory synaptic transmission in hippocampal cultures using the whole-cell-patch-recording technique. The slow, NMDA-receptor-mediated EPSP was strikingly dependent on the presence of a conditioning substance that gradually accumulated in the extracellular fluid during a 30 min incubation in physiological saline. Washout of the conditioned medium eliminated the slow EPSP, and perfusion with physiological saline containing 1 microM glycine restored the slow EPSP to control levels. Furthermore, conditioned medium collected from astroglial-only cultures also potentiated the response to NMDA. Zinc (20-50 microM) overcame the potentiation of the response by glycine and resulted in a reversible block of the slow EPSP, providing the first evidence for a direct action of zinc on excitatory synaptic transmission. Our results show that the expression of the slow EPSP may be subject to regulation by several endogenous substances: positive modulation by glycine (or a glycine-like substance), which can be released from astroglial cells, and negative modulation by physiological levels of zinc.(ABSTRACT TRUNCATED AT 250 WORDS)


Also


http://www.medicalne...icles/57359.php

Betz and his colleagues wrote that "The data presented in our paper disclose a pivotal role of ambient synaptic [zinc ion] for glycinergic neurotransmission in the context of normal animal behavior." They also concluded that their results implied that manipulating synaptic zinc levels could affect the neuronal action of zinc, but that such manipulation "highlights the complexity of potential therapeutic interventions," which could cause an imbalance between the excitatory and inhibitory circuitry in the central nervous system.

[tham]

That is why I have stressed that you should
always start off with a minimal dose on any
new supplement.

This is particularly important with the elderly,
who may be compromised in many of their
metabolic enzymes - anything can happen.

Compromised liver and kidney function in
the elderly would have made it extremely
risky to give a high dose of an amino acid.


Five grams is a horrendous amount to give
to someone pushing 70. You are lucky
nothing further serious happened.


I always took this precaution with the many
supplements I had given my father, starting
with a quarter to half a tablet or capsule, and
moreover only every two or three days.
Most times I am the guinea pig first.


Even if she not genetically predisposed to
nonketotic glycine encephalopathy, your mum
may well have a deficiency of glycine
decarboxylase, or some other component of
her glycine cleavage system.


http://en.wikipedia....cleavage_system



" Excess glycine in the brain and CSF results
in serious medical problems, including
encephalopathy, hence the name of the disorder. "

" ...... episodes of delirium "

" ..... expressive speech deficit "

http://en.wikipedia...._encephalopathy


Glycine provokes lipid oxidative damage and
reduces the antioxidant defenses in brain cortex.

http://www.ncbi.nlm....t_uids=18830815


Blindness Due to Non-Ketotic Hyperglycinemia.

http://www.journalar...8&startpage=641


" .... a progressive lack of energy (lethargy),
..... life-threatening problems with breathing. "

http://ghr.nlm.nih.g...-encephalopathy


http://www.ehow.com/...t-seizures.html

Edited by tham, 24 January 2011 - 09:43 AM.

[sapentia]

That is why I have stressed that you should
always start off with a minimal dose on any
new supplement.

This is particularly important with the elderly,
who may be compromised in many of their
metabolic enzymes - anything can happen.

Thank you for your reply Tham. It seems that the issues are dependent upon a person having non-ketotic hyperglycinemia. Looking at the parameters for this condition the only type my mother could even possibly have is atypical or mild glycine encephalopathy. Looking at the symptoms for this form leads me to believe that she does not suffer from this either.

As far as the dosing, nothing I read gave any indication that a 5g dosing was detrimental in any way whatsoever. I clearly see the danger in light of a potentially having NKH. I can note that I have since given my mother a 2g dosage of glycine which did not manifest any negative effects.

I am curious as to the study in which glycine provoked lipid oxidative damage in young rats. I am unable to read the full study, but are we assume these were healthy young rats without non-ketotic hyperglycinemia? I personally take glycine so if it causes increased oxidative damage independently of non-ketotic hyperglycinemia I would find that very relevant for myself and many others who take it. I did note that melatonin negated the oxidative damage.

[withdrawn]

Sorry to dig out this old post - but I have been taking large concentrations of magnesium glycinate these past 2 years and I have noticed a heavy decline in my mental abilities.

The links that tham provided :

" Excess glycine in the brain and CSF results
in serious medical problems, including
encephalopathy, hence the name of the disorder. "

" ...... episodes of delirium "

" ..... expressive speech deficit "

http://en.wikipedia...._encephalopathy


Glycine provokes lipid oxidative damage and
reduces the antioxidant defenses in brain cortex.

http://www.ncbi.nlm....t_uids=18830815


Blindness Due to Non-Ketotic Hyperglycinemia.

http://www.journalar...8&startpage=641


" .... a progressive lack of energy (lethargy),
..... life-threatening problems with breathing. "

http://ghr.nlm.nih.g...-encephalopathy

Do you think that maybe these are the symptoms I have currently experiencing? Is this even possible via magnesium glycinate supplementation?

Edited by withdrawn, 09 February 2013 - 01:42 PM.

[formergenius]

Bumping this because I've started taking 800mg/kg as of today, amounting to a total of 57.6 grams.
I've had no adverse reactions to this dose, aside from some nausea and sedation, after which I've slept great.
Reasons for supplementing: attempt to mitigate depersonalization and derealization (dissociative symptoms) via NMDAR activation.
Should I be concerned about this with no adverse events present? I figured it would be fine given the use of this dosage regimen in schizophrenia.
Perhaps I'll cut down to 400mg/kg to play it safe. Anyone have any input on this?

[KryptonStratos]

bump

[formergenius]

Discontinued high dosage due to almost vomiting. I now take a teaspoon at night. Not sure if it's helping, but it doesn't hurt.

[blood]

Sorry to dig out this old post - but I have been taking large concentrations of magnesium glycinate these past 2 years and I have noticed a heavy decline in my mental abilities.

The links that tham provided :

" Excess glycine in the brain and CSF results
in serious medical problems, including
encephalopathy, hence the name of the disorder. "

" ...... episodes of delirium "

" ..... expressive speech deficit "

http://en.wikipedia...._encephalopathy


Glycine provokes lipid oxidative damage and
reduces the antioxidant defenses in brain cortex.

http://www.ncbi.nlm....t_uids=18830815


Blindness Due to Non-Ketotic Hyperglycinemia.

http://www.journalar...8&startpage=641


" .... a progressive lack of energy (lethargy),
..... life-threatening problems with breathing. "

http://ghr.nlm.nih.g...-encephalopathy

Do you think that maybe these are the symptoms I have currently experiencing? Is this even possible via magnesium glycinate supplementation?

I would hope that the amounts of glycine contained in magnesium glycinate supplements would be safe for healthy people who should be able to catabolise normal amounts of dietary glycine.

Long shot - I suppose it is conceivable that you are showing the early signs of a late onset non-ketogenic hyper-glycinemia, where first symptoms apparently may include mental decline in school years or early adulthood:

No To Shinkei. 2002 Dec;54(12):1068-72.
[Late-onset nonketotic hyperglycinemia: a case report].

[Article in Japanese]
Hasegawa T, Shiga Y, Matsumoto A, Takeda A, Itoyama Y.

Source

Department of Neurology, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.

Abstract


We report a 66-year-old woman who developed mental deterioration in her school days, and progressive gait disturbance, dysarthria and bradykinesia in her 40s. Her parents were consanguineous, and the two of her brothers were suspected to have the allied disorder. On physical examination, she was short-statured and high-arched palate was observed. Neurological examination revealed dementia, abnormal eye movement, dysarthria, spastic paraparesis with hyperreflexia, bilateral Babinski signs, cerebellar ataxia and dysuria. Brain MRI showed marked hypoplasia of corpus callosum with dilatation of lateral ventricles and cerebral sulci and significant cerebellar atrophy. Amino acid analyses showed significant elevation of glycine without ketosis in serum, cerebrospinal fluid, and urine, which lead us to the diagnosis of late-onset nonketotic hyperglycinemia(NKH). NKH is known to be a rare autosomal recessive metabolic disorder primarily caused by deficient activity of various components of the mitochondrial glycine cleavage system. Onset of the disease occurs most often in early infancy, however, later-onset variants have been described. Usually, late-onset NKH only manifests mild mental deterioration, character change, seizure, ataxia or spastic paraparesis, which sometimes makes difficulty in differentiating this disease from other hereditary cerebellar ataxia or spastic paraparesis. In addition, many structural brain abnormalities have been reported accompanied with NKH, and especially, agenesis or hypoplasia of corpus callosum is the most characteristic feature in this disease. Therefore, we emphasized that amino acid analyses should be considered in any patients who have cerebellar ataxia or spastic paraparesis of unknown cause with these neuroradiological findings.

PMID: 12599524 [PubMed - indexed for MEDLINE]

What other supplements were you taking? A multivitamin with trace elements? Consumption of copper-containing multivitamins have been linked to markedly accelerated cognitive decline in older folks.

You should probably consult with a doctor over your concerns.

Edited by blood, 17 November 2013 - 07:55 AM.

[Coffeee]

ok here it goes, i took about 40 grams of this as my first dose......

 

3 years later my dick still dosent work properly, did i give my self major brain or heart damage?

 

 

I am partially retarded, I am lucky i didnt drop dead after taking this much but i thought it would help with my retardation and my body for bodybuidling, it was from hard rhino, which has no reccomended dosage on the label, some kid died from a caffine overdose from the same company because it sells these powders in huge bads with no reccomended dosing.....

Edited by Coffeee, 02 March 2016 - 04:24 AM.

[AlexCanada]

Any updates on Glycine?  I notice greater clarity of thought a few hours after dosing but also increased desire to sleep.  There is some sedating effect at times.  

[Nate-2004]

Most of the glycine benefits from what I understand are sleep quality related. This is why I take it just before bed.

[Tom Andre F. (ex shinobi)]

I think people should make the 23andme test prior to consume glycine then, if not in the case of the nonketonic hyperglycinema, can run into it as it proven to help with increased lifespan. Also interesting to see that this alzeimer model mice actually got stable glutamate in the brain but have decreased level of glycine.. so im still studying in what way it could be that bad. I see mainly benefit for now...

 

https://www.alzheime...1627-X/abstract