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"Glutamine is Harmful"...Relationship with Ammonia and Astrocytes.

Ema

Senior Member
Messages
4,729
Location
Midwest USA
Super interesting article...

Glutamine: A Trojan Horse in Ammonia Neurotoxicity
http://onlinelibrary.wiley.com/stor...zm&s=3679d7a22fe6be66918c3c6dc74188cc01b535e4

Mechanisms involved in hepatic encephalopathy still remain to be defined. Nonetheless, it is well recognized that ammonia is a major factor in its pathogenesis, and that the astrocyte represents a major target of its CNS toxicity.

In vivo and in vitro studies have shown that ammonia evokes oxidative/nitrosative stress, mitochondrial abnormalities (the mitochondrial permeability transition, MPT) and astrocyte swelling, a major component of the brain edema associated with fulminant hepatic failure. How ammonia brings about these changes in astrocytes is not well understood.

It has long been accepted that the conversion of glutamate to glutamine, catalyzed by glutamine synthetase, a cytoplasmic enzyme largely localized to astrocytes in brain, represented the principal means of cerebral ammonia detox- ification. Yet, the “benign” aspect of glutamine synthesis has been questioned.

This article highlights evidence that, at elevated levels, glutamine is indeed a noxious agent. We also propose a mechanism by which glutamine executes its toxic effects in astrocytes, the “Trojan horse” hypothesis. Much of the newly synthesized glutamine is subsequently metabolized in mitochondria by phosphate-activated glutaminase, yielding glutamate and ammonia. In this manner, glutamine (the Trojan horse) is transported in excess from the cytoplasm to mito- chondria serving as a carrier of ammonia.

We propose that it is the glutamine-derived ammonia within mitochondria that interferes with mitochondrial function giving rise to excessive production of free radicals and induction of the MPT, two phenomena known to bring about astrocyte dysfunction, including cell swelling.

Future therapeutic approaches might include controlling excessive transport of newly synthesized glutamine to mitochon- dria and its subsequent hydrolysis. (HEPATOLOGY 2006;44:788-794.)
 
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Ema

Senior Member
Messages
4,729
Location
Midwest USA
@Ema - I think the key phrase is " at elevated levels" glutamine can be harmful, and this is true of any nutrient, that it can be harmful at elevated levels.

Glutamine can also be very beneficial and actually can help remove excess ammonia (http://umm.edu/health/medical/altmed/supplement/glutamine)

I've been taking glutamine for almost 8 months with no problem.
The dose always makes the poison.

My point is that it's probably not a good idea to supplement willy-nilly with things like glutamine because they don't always work like they are supposed to in our population.

Glutamine made me feel much, much worse almost immediately and I've tried it several times. It doesn't help with my elevated ammonia at all and in fact seems to make the symptoms much worse.

This is probably because I have excessive glutamate. Many with MECFS have dyregulated glutamate and thus should be careful with glutamine, in my opinion.

I have elevated glutamate, GABA and glycine on neurotransmitter testing as well as elevated ammonia. So clearly something in that pathway is off, for me and many others, that is not solved by pouring more glutamine into the mix.
 
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halcyon

Senior Member
Messages
2,482
I thought I read somewhere that people with ME likely have glutamine deficiency. It's a non-essential amino acid, but it is thought to become conditionally essential during times of injury and illness.

Perhaps I was thinking about this, which isn't exactly about ME patients but could apply.

I take around 6g of it a day with no apparent negative effects.
 

Mary

Moderator Resource
Messages
17,334
Location
Southern California
The dose always makes the poison.

My point is that it's probably not a good idea to supplement willy-nilly with things like glutamine because they don't always work like they are supposed to in our population.

Glutamine made me feel much, much worse almost immediately and I've tried it several times. It doesn't help with my elevated ammonia at all and in fact seems to make the symptoms much worse.

This is probably because I have excessive glutamate. Many with MECFS have dyregulated glutamate and thus should be careful with glutamine, in my opinion.

I have elevated glutamate, GABA and glycine on neurotransmitter testing as well as elevated ammonia. So clearly something in that pathway is off, for me and many others, that is not solved by pouring more glutamine into the mix.

We are all so very different. glutamine is good for me. And I seem to be low in both GABA and glycine, both of which help me with sleep. So what's hurting you is helping me.

You are right - we shouldn't take things willy nilly, but I think it does a disservice to just state that "glutamine is harmful" in your title. Methylfolate has helped many many people here, and there are many who can't tolerate it, but it would be misleading to do a post stating that it was harmful, period.

You're providing good information which is important - it's just not the whole story.
 

Mary

Moderator Resource
Messages
17,334
Location
Southern California
It's a direct quote from the paper.

Yes, which talks about elevated levels, not glutamine per se, according to the summary you provided (I tried clicking on your link to the paper but was denied access). That's why your title is misleading. I wish it said "glutamine can be harmful" or "excess glutamine is harmful", something like that.

Again, elevated anything can be harmful, which otherwise would not be.
 

Ema

Senior Member
Messages
4,729
Location
Midwest USA
Yes, which talks about elevated levels, not glutamine per se, according to the summary you provided (I tried clicking on your link to the paper but was denied access). That's why your title is misleading. I wish it said "glutamine can be harmful" or "excess glutamine is harmful", something like that.

Again, elevated anything can be harmful, which otherwise would not be.
But that's not what the article says. It says it is harmful. It's not (necessarily) my opinion though it does certainly line up with my experience with glutamine.

I'll add some quotes to the title to clear up that I am quoting directly.

Thanks for letting me know the link was broken. I always enjoy debating articles with people who haven't actually even read them.
 

Misfit Toy

Senior Member
Messages
4,178
Location
USA
I can only give what happened to me which was when I was on Glutamine back in 2013, I found it to cause me intense anxiety. I have high ammonia. I am not sure if it worsened this. I wrote about it a few years ago. I was a mess.

I think Yucca helps with high ammonia and moly..that's what I have been told, plus charcoal, I believe.
 

PeterPositive

Senior Member
Messages
1,426
Well... poor glutamine, does it deserve all the flak? :D
It's the only thing that has helped bringing my bowel's secretory IgA from non-existent to the upper range and fighting GI parasites.

It also seems to have improved the immune system, in general.

To be honest I've had some insomnia-related issues with the initial doses of Glutamine, so I adopted the usual low-and-slow way for some time, and I got used to it. Currently I am taking 2-3 grams a day with no ill effects.

If I had to shoot a specific amino acid I'd shoot L-Tyrosine. That's a major anxiety booster for me :ill:

cheers