Glutamine, the most abundant amino acid in the human body, is non-essential (you make it yourself) and is found in both animal and plant protein; cancer cells are 'addicted' to glutamine, which converts to glutamate, a fuel for cancer.
Glutamine and glutamate - so, what’s the difference?
i) Glutamine
Glutamine is a non-essential amino acid (a building block for protein). It is found in both plant and animal protein. You make it yourself in your muscles in very large quantities and it is the most abundant amino acid in your body. Glutamine helps in gut function, brain function, the immune system, amino acid production; and glutamine donates its nitrogen for the synthesis of nucleotides and hexosamines, producing glutamate in the process. Where nitrogen is needed by the body - for example, in wound repair - a third of this comes from glutamine. Stress and certain drugs can deplete it and muscle wastage is a common result.
Glutamine and gut repair - Glutamine is widely credited with helping to ’heal’ the gut. It can repair damaged cells in the gut wall and is also an important amino acid source for immunoglobulin production and the immune system inside the gut.
Glutamine and the brain - Glutamine is the most abundant amino acid in the central nervous system (CNS) and plays a central role in brain function. It serves as a primary precursor for both excitatory neurotransmitters (glutamate and aspartate) and the inhibitory neurotransmitter GABA, making it essential for maintaining the balance between neural excitation and inhibition.
Be clear - you can't just cut glutamine
If glutamine is low - if you are under stress, illness, or injury, glutamine becomes 'conditionally essential', meaning the body’s demand exceeds its production. Disruptions in glutamine metabolism, such as reduced glutamine synthetase activity, are linked to neurological and psychiatric disorders including epilepsy, hepatic encephalopathy, Alzheimer’s disease, schizophrenia, and depression.. Your body will make it to replace shortfall.
ii) Glutamate
Glutamate (also known as glutamic acid) is also a non-essential amino acid - you make this one too.
It can come into the body in a variety of ways - for example, in protein or as MSG, mono-sodium glutamate. It can be provided intact or in bonded form. Glutamate can also be made as the breakdown product from a number of compounds - importantly from glutamine, but also from folic acid/folate and from glucose. And glutamate is widely present in all our protein stores in our muscles.
Glutamate is also essential for brain and nervous function. Glutamate is the primary excitatory neurotransmitter in the human brain and central nervous system It is the major transmitter in nerves. People with more glutamate receptors tend to have higher IQs. However, glutamate uptake by the brain across the Blood Brain Barrier is very low. The vast majority of glutamate is as a result of conversion from glutamine as neurons cannot make glutamate from glucose inside the brain; indeed there are pools of glutamine and glutamate in the brain. Glutamate plays a critical role in learning, memory, cognition, and synaptic plasticity, with over 90% of excitatory synaptic connections in the brain relying on glutamate.
Where glutamine is the source of glutamate, the conversion is aided by glutaminase enzymes.
Where glutamate is the source for glutamine production, the latter is usually made via the enzyme glutamine synthetase. This reaction occurs mainly in the brain and other tissues, helping to regulate nitrogen balance and support various metabolic functions.
So, at first sight it looks like glutamine and glutamate are interchangeable, only differing in their specific effects.
Glutamine, glutamate and cancer
Glutamine and cancer - Cancer cells exhibit "glutamine addiction," consuming 10–100 times more glutamine than normal cells to support rapid proliferation. This occurs because glutamine serves as a nitrogen and carbon source for the biosynthesis of nucleotides, fatty acids, and non-essential amino acids (1).
Glutamine keeps the TCA cycle running - the TCA cycle, also known as the Citric acid cycle or Krebs cycle, is a series of biochemical reactions that generate energy in the mitochondria of the cell, and glutamine's cellular up take is linked to a number of very specific genetic transporters and to the good health of the mitochondria.
Bottom line - You need sufficient glutamine to keep energy production running smoothly and prevent illness as we reported above.
Glutamate and cancer - There is already clear evidence that glutamate receptors are found on cancer cells. But there's more.
Once inside the cell, glutamine is converted to glutamate by the enzyme glutaminase. Glutamate is the fuel for the cancer cell, not glutamine. After glucose, glutamate is usually the secondary fuel. - if cancer cells cannot get enough glucose they can switch to glutamate. In prostate cancer and brain tumours, glutamate can be more important than glucose as a fuel.
Glutamate is further metabolised to α-ketoglutarate (α-KG), inside the cell, which enters the TCA cycle to generate ATP, and support biosynthesis of proteins, nucleotides, and lipids. It also fuels the production of Glutathione (GSH), a major antioxidant that helps cells manage oxidative stress, and supports NADPH production, which is essential for redox homeostasis and fatty acid synthesis.
In the brain, glioma cells seem to have more than their fair share of glutamate receptors, and now there are studies showing that so do other cancer cells.
In prostate cancer, blocking glutamate can stop the cancer feeding and restrict progression. Another study linked higher blood glutamate levels to higher Gleeson scores and a more aggressive prostate cancer.
In breast cancer, glutamate can disrupt homeostasis, and pathological conditions including pain. Breast cancer cells secrete high levels of glutamate, and this is linked with more bone metastases.
Now we are reaching the tipping point. Do people really believe you can lower glutamine in the body by restricting protein consumption? Given you can make glutamine yourself, and deficiency makes you ill, this is incredibly unlikely (2).
However, reducing and blocking the production of the cancer fuel glutamate seems to have far more potential.
Sure enough, scientists have been looking at ways of cutting glutamate production to stop cancer in its tracks!
For example, Elena S. Reckzeh and her team have shown that by using a high potency glucose uptake inhibitor called Glutor, they can stop cancer cells using glucose. This causes them to turn to their back up fuel, glutamate. Since is converted from glutamine by the enzyme glutaminase, Reckzeh's team simultaneously used a glutaminase inhibitor (CB-839). This prevented the enzyme glutaminase converting glutamine to the cancer fuel glutamate.
And she found that stopping glucose uptake and simultaneously inhibiting glutamate production causes cancer cells to stop growing and spreading.
Go to: Cutting glucose and glutamate starves cancer to death
10 natural compounds that inhibit glutaminase
However, no glucose uptake drugs nor glutaminase inhibitor drugs have been approved to date by the FDA, because they say they are too risky. I'd agree with that.
However, it would appear relatively easy to cut glucose consumption and, to a degree, starve cancer cells (The Atkin's Diet would do that), but simultaneously, as the researchers above did, you must try to inhibit the glutamine to glutamate conversion. And we know this causes a 'metabolic crisis' in the cancer cell.
Can you reduce glutamate? Cut out bone broth might be a start. Other foods high in glutamate include parmesan cheese, soy sauce, fish sauce, and cured ham.
Are there natural compounds that can inhibit glutaminase? Well, yes. For example, there has already been research with 3 foods - Ursolic Acid/Holy Basil, Curcumin and Resveratrol which were shown to deprive prostate cancer of its fuel (glutamate) and restrict growth..
10 foods that have been shown to block glutaminase in research.
- EGCG (Green tea)
- Curcumin (Turmeric root)
- Lycopene (Tomatoes)
- Ursolic Acid (Holy basil, rosemary, pistachio nuts)
- Resveratrol (Red grape skins)
- Honokiol, magnol (Magnolia Bark Extract)
- Graviola (Soursop)
- Sulforaphane (Sprouting seeds)
- Valerian
- Withanolide (Ashwagandha)
The Ketogenic Diet
Professor Thomas Seyfried and Dr. D’Agostino have championed the Ketogenic Diet with several cancers such as brain cancer.
Seyfried, in his major review on the Ketogenic Diet in 2012, which we covered at CANCERactive, agreed that sometimes, people who were on an almost nil carb diet had their cancer cells turn to glutamate as an energy source, so he also used low protein as a main plank of the Ketogenic Diet. While carbs are limited to just 2% of total calorie consumption, protein is limited to not much more: 8%.
But I worry this is nonsense.
Believing that you can restrict glutamine levels without becoming ill and/or driving natural production in the body to compensate for the shortfall is a non-starter. And I am already full of it, in my muscles, brain and so on.
As we have said, glutamate is the cancer cell fuel and if a cancer cell wants glutamate, it can rob adjacent cells. As I told Seyfried when we were both speaking at an International Conference, you can try to block glutamine all you want but it's glutamate you really need to stop because it is a fuel for cancer cells.
Understandably, at CANCERactive, we have been getting a lot of confused people with questions on this. I’m not surprised ordinary folk are confused, though. In my searches I found even top scientists in peer-reviewed research papers were using the word glutamine when it should have been glutamate!
The Truth is that there is clear evidence that cancer cells have large numbers of glutamate receptor sites - and there is a good number of research studies showing that glutamate is definitely a fuel for cancer. If you have cancer, frankly, you’d be wise to try to block the enzyme glutaminase, which causes glutamine to ferment into glutaminase. Seyfried went back to the USA and came up with DON.
6-Diazo-5-oxo-L-norleucine (DON), an unconventional amino acid having a structure similar to that of L-glutamine, was first isolated in the 1950's from Streptomyces bacteria. 1,2 DON broadly blocks glutamine-reactions in cancer cells, and has shown robust efficacy in both preclinical cancer models and exploratory clinical studies.
If you want to try to stop cancer, cut the two fuels glucose and glutamate - your 'empty glucose' consumption, and your glutamine to glutamate conversion enzyme with some of the 10 compounds above, like Holy Basil (Tulsi), Curcumin and Resveratrol.
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References
1. Rethinking glutamine metabolism and the regulation of glutamine addiction by oncogenes in cancer; Rui Ni et al; Front. Oncol., 07 March 2023; Sec. Cancer Metabolism; Volume 13 - 2023
2. Glutamate and Its Role in the Metabolism of Plants and Animals; Maria Stolarz, Agnieszka Hanaka; MDPI July 1st 2025