L-Glutamine - An Overview
Glutamine is the most abundant and versatile amino acid in the body.
This makes it one of the most fundamentally essential factors in protein synthesis, metabolism, glutamate production, and many other functions.
Glutamine is the precursor of glutamate (Glu) and γ-aminobutyric acid (GABA), which are the main excitatory and inhibitory neurotransmitters, respectively, within the brain.
This means that glutamine plays a huge role in the function and regulation of mental processes.23Walls AB, et al. The glutamine-glutamate/GABA cycle: function, regional differences in glutamate and GABA production and effects of interference with GABA metabolism, Neurochem Res. 2015
And as the most abundant amino acid, glutamine concentration is 10- to 100-fold more than any other.25Labow BI, Souba WW, Abcouwer SF. Mechanisms governing the expression of the enzymes of glutamine metabolism–glutaminase and glutamine synthetase, J Nutr. 2001
Researchers estimate that endogenous glutamine production is between 40 to 80 g/day in the average human.26Newsholme EA, Parry-Billings M. Properties of glutamine release from muscle and its importance for the immune system, JPEN J Parenter Enteral Nutr. 1990
Bodybuilders and athletes have been using glutamine for years as a performance enhancer. But glutamine may also be taken as a nootropic supplement for:
- Memory and learning
- Concentration and focus
- Stress relief
High-quality research on L-glutamine’s specific nootropic effects tend to be scarce in this respect, but there is some evidence that it could be a worthwhile addition to your nootropic stack.
What Does L-Glutamine Do?
L-Glutamine For Memory And Learning
In one trial, rats that supplemented with glutamine, aspartic acid, and arginine saw enhanced memory and learning ability, as well as higher brain nitric oxide synthase (NOS) activity.
It also seemed to modulate the activity of N-methyl-D-aspartate (NMDA) receptors, a system heavily involved in memory formation.
1Jing H, Cheng Y, Li S, Zhang G.. Effects of glutamate and glutamine on learning and memory of rats, Wei Sheng Yan Jiu. 2000
One study suggests that glutamine (combined with insulin) increased the expression of PI3K in cells at high glucose levels.
2Caijuan Wang, et al. Glutamine Enhances the Hypoglycemic Effect of Insulin in L6 Cells via Phosphatidylinositol-3-Kinase (PI3K)/Protein Kinase B (AKT)/Glucose Transporter 4 (GLUT4) Signaling Pathway, Med Sci Monit. 2018
Enhancing PI3K-Akt signaling in the central nervous system can improve memory in mice and human trials.3Gabbouj S, et al. Altered Insulin Signaling in Alzheimer’s Disease Brain – Special Emphasis on PI3K-Akt Pathway, Journal or Front Neurosci. 2019
These studies provide a more theoretical basis for the idea that glutamine can potentially improve learning ability.
Conversely, a double-blind, randomized, placebo-controlled study suggests that glutamine can alter cortical excitability (mental activity).
Still, they could not find any direct evidence that it can improve sequence learning.4Bryant J. Jongkees, et al. Influences of glutamine administration on response selection and sequence learning: a randomized controlled trial, Sci Rep. 2017
Another study, with adult women, shows that glutamine supplementation in combination with exercise shows improvement in overall executive function but no changes in operational memory.
5Dayane Cristina de Souza, et al. The Effect of a Short Period of Supplementation with Glutamine Dipeptide on the Cognitive Responses after a Resistance Training Session of Women with HIV/AIDS: A Randomized Double-Blind Placebo-Controlled Crossover Study, BioMed Research International. 2018
L-Glutamine As An Anti-depressant
Lower levels of glutamine correlate with cases of major depressive disorder.6Choudary PV, et al. Altered cortical glutamatergic and GABAergic signal transmission with glial involvement in depression, Proc Natl Acad Sci U S A. 2005
In a preliminary trial of 43 adults affected by different forms of depressive, neurasthenic, and dissociative illnesses, glutamine indicates clear antidepressant properties.
The researchers noted that “since 1-glutamine is noticed being a precursor of GABA, this fact itself could explain its antidepressive properties.”7Cocchi R. Antidepressive properties of I-glutamine. Preliminary report, Acta Psychiatr Belg. 1976
Glutamine has also been shown to alleviate symptoms of depression in mice.8AYounghyurk Lee, et al. Glutamine deficiency in the prefrontal cortex increases depressive-like behaviours in male mice, J Psychiatry Neurosci. 2013
One mouse study concluded that depressive behaviors evoked by chronic stress were due to hypoactive glutamatergic neurons in the medial prefrontal cortex.
Low levels of glutamate and glutamine caused this, according to researchers.
They concluded that supplementing with glutamine can be used as an alternative antidepressant to increase glutamatergic neurotransmission.9Son H, et al. Glutamine has antidepressive effects through increments of glutamate and glutamine levels and glutamatergic activity in the medial prefrontal cortex, Neuropharmacology. 2018
L-Glutamine For ADHD
Researchers found low glutamine in adults with ADHD versus adults without. So, there is a possibility that supplementation may help treat ADHD.10S Maltezos, et al. Glutamate/glutamine and neuronal integrity in adults with ADHD: a proton MRS study, Transl Psychiatry. 2014
However, keep in mind that there have not been any clinical trials that directly indicate glutamine can improve symptoms of ADHD. There is some anecdotal evidence that this may be the case, but further research is needed.
L-Glutamine For Exercise And Physical Performance
L-glutamine is a popular supplement among bodybuilders, and there is clinical evidence that it can improve some aspects of physical performance.
Two trials saw a significant increase in both Human Growth Hormone (HGH) and growth factor-I (similar to insulin) after supplementing with L-glutamine.
This could have a significant effect on athletic ability as well as muscle growth and recovery.11Arwert LI, Deijen JB, Drent ML. Effects of an oral mixture containing glycine, glutamine and niacin on memory, GH and IGF-I secretion in middle-aged and elderly subjects, Nutr Neurosci. 200312Welbourne TC. Increased plasma bicarbonate and growth hormone after an oral glutamine load, Am J Clin Nutr. 1995
Because exercise like heavy weightlifting depletes l-glutamine stores, many weightlifters and bodybuilders use this supplement to build muscle.
L-Glutamine For Gut And Immune System Health
L-glutamine can be a majorly beneficial supplement for supporting gut health and immunity.
Glutamine reduces pro-inflammatory cytokine production in the intestines, which plays a major role in the pathogenesis of inflammatory bowel disease (IBD).13Coëffier M, et al. Influence of glutamine on cytokine production by human gut in vitro, Cytokine. 2001
L-Glutamine has been shown to increase zonulin production, which regulates gut permeability.
This can also help prevent leaky gut, which can lead to dysregulated immune function and autoimmunity.14Clément L’Huillier, et al. Glutamine, but not Branched-Chain Amino Acids, Restores Intestinal Barrier Function during Activity-Based Anorexia, Nutrients. 2019
Glutamine is also considered “fuel for the immune system.”
Low blood concentration may impair immune cell function, resulting in poor clinical outcomes and increased risk of mortality.15Rodas PC, et al. Glutamine and glutathione at ICU admission in relation to outcome, Clin Sci (Lond). 2012
How L-Glutamine Works In The Brain
The entire human body uses glutamine. The lungs, liver, brain, skeletal muscles, and adipose tissue all synthesize glutamine.
Glutamine is abundant in the central nervous system, where it participates in a variety of metabolic pathways.
Does Glutamine Increase GABA?
Its primary role in the brain is as a precursor of the neurotransmitter amino acids: the excitatory amino acids, glutamate and aspartate, and the inhibitory amino acid, γ-aminobutyric acid (GABA).
Glutamate is also the precursor of glutamine itself. The Glutamate/glutamine/GABA cycle is one of the most significant, most important, and most energy-intensive systems in the brain.
Glutamine is synthesized from glutamate and ammonia in astrocytes, in a reaction catalyzed by glutamine synthetase.16Martinez-Hernandez A, Bell KP, Norenberg MD. Glutamine synthetase: glial localization in brain, Science. 1977
Newly synthesized glutamine is transferred to neurons and hydrolyzed by phosphate-activated glutaminase (PAG) to give rise to glutamate, a portion of which may be synthesized into GABA.
So, glutamine synthesis in astrocytes and its transport to neurons promotes glutamatergic and GABA-ergic transmission.
Glutamine also appears to affect neurotransmission directly by interacting with NMDA receptors.
Also, glutamine appears to modulate the synthesis of the gaseous messenger, nitric oxide (NO), by controlling the supply to the cells of its precursor, arginine.17Albrecht J, et al. Roles of glutamine in neurotransmission Neuron Glia Biol. 2010
Glutamine appears to be the main respiratory fuel for rapidly dividing cells.18Lacey JM, Wilmore DW. Is glutamine a conditionally essential amino acid?, Nutr Rev. 1990
Glutamine is used throughout the body for many important functions, but if the body is under particular stress or compromising situations, the liver will consume it and degrade its efficacy.
These situations can include low carbohydrate intake, extreme exercise, or disease.19Cooney G, Curi R, Mitchelson A, Newsholme P, Simpson M, Newsholme EA. Activities of some key enzymes of carbohydrate, ketone body, adenosine and glutamine metabolism in liver, and brown and white adipose tissues of the rat, Biochem Biophys Res Commun. 1986 20Tan HWS, et al. Glutamine metabolism regulates autophagy-dependent mTORC1 reactivation during amino acid starvation, Nat Commun. 2017 21Newsholme P. Why is L-glutamine metabolism important to cells of the immune system in health, postinjury, surgery or infection?, J Nutr. 2001
If the high glutamine degradation in these tissues persists, a large number of metabolic pathways and mechanisms that depend on glutamine availability are affected.
This results in cognitive impairment and immunosuppression.
22Curi R, et al. Glutamine-dependent changes in gene expression and protein activity, Cell Biochem Funct. 2005
L-Glutamine Potential Side Effects
Long term glutamine supplementation appears to be safe.
Doses of L-glutamine up to 21 grams daily appear to be well tolerated. Reported adverse reactions are mainly gastrointestinal and not common.
We strive to bring you the most up to date, research-based information about L-Glutamine and other nootropics.
Something we missed? Do you use L-Glutamine? Share your thoughts and experiences in the comments below.
About the author:
Erik Levi is a co-founder of HolisticNootropics.com and a certified holistic nutritional therapy practitioner.
As an NTP Erik takes a nutrition first approach to health. He has worked with many different people to help them use nutrition to optimize their quality of life.
Erik believes that mental health is a physiological process and cognitive enhancement is not something that can be achieved by just taking some pills with good Amazon reviews.
Instead, true cognitive enhancement comes with the right balance of nutrients, movement, and gratitude. Erik continues to stay up to date with the most current nootropic and holistic health research and promises to deliver the best solutions possible.
You can check out his personal health blog/podcast/YouTube Channel all under the name Holistic A-Hole.