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Glutamine and Neurotoxicity?


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#1 ampa

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Posted 18 August 2010 - 11:41 PM


I'm confused regarding the safety of glutamine supplementation. Below is a link to a letter written by neurosurgeon Russell L. Blaylock, M.D., in which he argues that glutamine supplementation increases brain glutamate, resulting in glutamate-induced excitotoxicity. Additionally, he states that increased brain glutamine increases free radical production and impairs mitochondrial function.

http://articles.merc.../glutamine.aspx

Dr. Blaylock was responding to the following statement by Dr. Robert Crayhon:

"Also, the idea that supplemental glutamine is all metabolized to glutamate is simply not the case. Have you ever seen a patient with MSG sensitivity? The symptoms these patients have are the symptoms of excess glutamate: headaches, nausea, dizziness, and this is something I have never seen nor seen reported with high dose glutamine. The body is very good at controlling the Glutamine-Glutamate pathway, which requires B6. I have had many discussions with cell biologist PhDs about this idea that glutamine turns to glutamate at will, and they all say that this is a misstatement, and are particularly critical of Russell Blaylock for making this error in his book.

After all, why doesn't the glutamine all just turn to GABA? Then glutamine would not over excite your neurons, it would put you to sleep. Glutamine clearly does neither".


So who's correct here? Does glutamine supplementation lead to excess brain glutamate (and hence its neurotoxicity)? This certainly seems possible given their interchangeability, and would be concerning as glutamine supplementation is not uncommon.

And hello...this is my first post :)

Edited by chrono, 26 August 2010 - 11:30 PM.
formatting


#2 mwestbro

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Posted 20 August 2010 - 04:39 PM

It seems unlikely that glutamine would produce excitotoxicity given these results:

Intensive Care Med. 2006 Nov;32(11):1741-6. Epub 2006 Sep 23.

Intravenous glutamine supplementation to head trauma patients leaves cerebral
glutamate concentration unaffected.

Berg A, Bellander BM, Wanecek M, Gamrin L, Elving A, Rooyackers O, Ungerstedt U,
Wernerman J.

Karolinska University Hospital, Huddinge, Sweden.

OBJECTIVE: There is reluctance to use glutamine-containing i.v. nutrition for
neurosurgical patients, as this may result in elevated intracerebral glutamate
levels, which are thought to be associated with neuronal injury and cell
swelling, causing an increase in ICP and an unfavourable outcome. As general ICU
patients benefit from i.v. glutamine supplementation in terms of reduced
mortality and morbidity, neurosurgical patients might also be candidates for such
treatment, if the possible relation between i.v. glutamine supplementation and a
possible increase in cerebral glutamate could be sorted out. DESIGN AND SETTING:
The study protocol had a crossover design with a 24h treatment period and a 24h
placebo period in random order. Treatment was a glutamine containing dipeptide,
L-alanyl-L-glutamine 200mg/ml, for 20h; placebo was saline. The rate of infusion
was 0.125ml/kg/h, which is equal to 0.34g/kg of glutamine over the 20h period.
Microdialysate was collected for analysis in 120min portions. The flow through
the microdialysis catheter was 0.3microl/min. SUBJECTS: Patients with severe head
trauma (GCS<or=8; n=15) on routine monitoring, including intracerebral
microdialysis, were randomly assigned to treatment followed by placebo or placebo
followed by treatment. MEASUREMENTS AND RESULTS: Glutamine infusion increased
plasma glutamine concentration by 30%, but not plasma glutamate concentration.
Intracerebral glutamate was unaffected in median values and in all individual
patients. CONCLUSION: Intravenous glutamine in clinically relevant doses leaves
cerebral glutamate unaffected. This opens the possibility of evaluating the
effects of i.[Symbol: see text]v. glutamine supplementation upon outcome for
neurosurgical ICU patients.


PMID: 17001467 [PubMed - indexed for MEDLINE]

Note that intravenous glutamine is likely to produce a MUCH larger increase in plasma concentrations than any oral supplementation.
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#3 hamishm00

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Posted 21 August 2010 - 07:22 AM

What about aspartic acid supplementation? Any risk of excitotoxicity with supplementation? If so, do we have any idea of what amounts / dosages might bring on the toxicity.
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#4 hamishm00

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Posted 21 August 2010 - 07:25 AM

Btw Blaylock has always comes across as a crank IMO.
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#5 ampa

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Posted 21 August 2010 - 02:18 PM

It seems unlikely that glutamine would produce excitotoxicity given these results:

Intensive Care Med. 2006 Nov;32(11):1741-6. Epub 2006 Sep 23.

Intravenous glutamine supplementation to head trauma patients leaves cerebral
glutamate concentration unaffected.

Berg A, Bellander BM, Wanecek M, Gamrin L, Elving A, Rooyackers O, Ungerstedt U,
Wernerman J.

Karolinska University Hospital, Huddinge, Sweden.

OBJECTIVE: There is reluctance to use glutamine-containing i.v. nutrition for
neurosurgical patients, as this may result in elevated intracerebral glutamate
levels, which are thought to be associated with neuronal injury and cell
swelling, causing an increase in ICP and an unfavourable outcome. As general ICU
patients benefit from i.v. glutamine supplementation in terms of reduced
mortality and morbidity, neurosurgical patients might also be candidates for such
treatment, if the possible relation between i.v. glutamine supplementation and a
possible increase in cerebral glutamate could be sorted out. DESIGN AND SETTING:
The study protocol had a crossover design with a 24h treatment period and a 24h
placebo period in random order. Treatment was a glutamine containing dipeptide,
L-alanyl-L-glutamine 200mg/ml, for 20h; placebo was saline. The rate of infusion
was 0.125ml/kg/h, which is equal to 0.34g/kg of glutamine over the 20h period.
Microdialysate was collected for analysis in 120min portions. The flow through
the microdialysis catheter was 0.3microl/min. SUBJECTS: Patients with severe head
trauma (GCS<or=8; n=15) on routine monitoring, including intracerebral
microdialysis, were randomly assigned to treatment followed by placebo or placebo
followed by treatment. MEASUREMENTS AND RESULTS: Glutamine infusion increased
plasma glutamine concentration by 30%, but not plasma glutamate concentration.
Intracerebral glutamate was unaffected in median values and in all individual
patients. CONCLUSION: Intravenous glutamine in clinically relevant doses leaves
cerebral glutamate unaffected. This opens the possibility of evaluating the
effects of i.[Symbol: see text]v. glutamine supplementation upon outcome for
neurosurgical ICU patients.


PMID: 17001467 [PubMed - indexed for MEDLINE]

Note that intravenous glutamine is likely to produce a MUCH larger increase in plasma concentrations than any oral supplementation.


Thank you for posting this information. It is very helpful and appreciated!

#6 kilgoretrout

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Posted 26 August 2010 - 04:00 AM

Large amounts of glutamine are used by millions of athletes, and its given to thousands of trauma patients in hospitals, and its used by many sufferers of conditions that affect the gut like HIV and IBS.... there is no epidemic of brain damage Ive heard as a result of all this usage.

Blaylock is an egoistical QUACK. Ignore him completely. Glutamine has been known to be extremely safe and beneficial even in huge doses for decades. Some jerks just try to make a name and career for themselves by issuing panicky warnings about all sorts of junk about which they are wrong.

#7 chrono

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Posted 26 August 2010 - 11:35 PM

Below is a link to a letter written by neurosurgeon Russell L. Blaylock, M.D., in which he argues that glutamine supplementation increases brain glutamate, resulting in glutamate-induced excitotoxicity. Additionally, he states that increased brain glutamine increases free radical production and impairs mitochondrial function.

Unfortunately he omitted any references to the "numerous recent studies" which supposedly prove his point. I guess he assumes that his rhetoric is comprehensive and authoritative, or that the amazon link to a basic textbook does the job.

#8 outsider

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Posted 29 August 2010 - 10:15 AM

Wow this pretty much close the debate for glutamine, at least, for now. I used glutamine for gut health for 5 weeks and never noticed any cognitive/mood change.

#9 Ark

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Posted 31 August 2010 - 07:50 AM

IMHO it would take years of a diet saturated to see any sort of notable effect of any kind on the brain. As for aspartic acid everything I've come across tells me to stay away if you care about optimal brain function, its no cyanide pill but its not the direction of supplementation I'd recommend to anyone who I gave a crap about. ;-) I feel like they'll put anything in a pill these days and this new body building fad of loading aspartic acid is pretty nuts,if you ask me.

Edited by Ark, 31 August 2010 - 07:51 AM.


#10 Nate-2004

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Posted 15 June 2018 - 01:13 PM

Thanks, the OP's post helped me get past a point of understanding here in regards to how glutamate functions and the glutamine-glutamate cycle, hopefully with respect to essential tremor which I struggle with.



#11 Believer

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Posted 15 June 2018 - 03:36 PM

It definitely is neurotoxic if you have the common gene defect that affects the enzyme which breaks down glutamate to gaba. Glutamine turns to glutamate but it unable to be effectively reduced to gaba and thus dangerous levels of glutamate circulates in the brain.

This results in symptoms of autism and I suffer from these symptoms if I ingest glutamate, glutamine, caffeine, etc.

Basically it's autistic rage fits, itchy skin, inability to focus, weird voice effect, extreme ocd, etc. All mediated via mGluR5.

After a while all of these symptoms tend to turn into deep relaxation and sleepiness, probably because eventually the glutamate is finally converted to gaba.



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#12 Nate-2004

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Posted 16 June 2018 - 03:36 PM

I wrote my hypothesis here.

 

https://www.reddit.c...oil_hypothesis/






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