Glutamine is an amino acid found in both animal and plant protein; it is the most abundant amino acid in the human body - it is non-essential, you make it yourself in your muscles from where it supplies other organs; 25% is found in your brain. Glutaminase is an enzyme that converts glutamine into glutamate, a secondary fuel for cancer cells.
Glutamine and glutamate - so, what’s the difference?
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 the body. Glutamine helps in gut function, brain function, the immune system, amino acid production and in times of stress. Stress and certain drugs can deplete it and muscle wastage is a common result. Where nitrogen is needed by the body - for example, in wound repair - a third of this comes from glutamine.
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 inside the gut, and hence the immune system.
Glutamate (also known as glutamic acid) is also a non-essential amino acid. 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.
But in the body it can also be made as the breakdown product of a number of compounds - yes, 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. 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.
Where glutamine is the source for glutamate, it is produced by glutaminase enzymes.
Glutamine, glutamate and cancer
There is already clear evidence that glutamate receptors are found on cancer cells. Glutamate is a secondary fuel if cancer cells cannot get enough glucose.
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.
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.
Scientists are 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 gluatmate. The source for that is the glutamine found throughout the human body. So Reckzeh's team simultaneously used a glutaminase inhibitor (CB-839). This prevented an enzymes glutaminase converting glutamine to the cancer fuel glutamate. 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
So glutamate, a secondary fuel for cancer cells, is made from glutamine by glutaminase enzymes. And the researchers above used a glutaminase inhibitor, CB-839. However, no glucose uptake drugs nor glutaminase inhibitors have been approved to date by the FDA, because they are too risky.
It would appear relatively easy to cut glucose consumption and, to a degree, starve cancer cells, but simultaneously, as the researchers above did, you must try to inhibit the glutamine to glutamate conversion. This causes a 'metabolic crisis' in the cancer cell.
Are there natural compounds that can inhibit glutaminase? Well, yes. For example, there has already been research with 3 foods used against prostate cancer.
Go to: Three foods starve prostate cancer of glutamate
Here are 10 foods that can block glutaminase in research.
- EGCG (Green tea)
- Curcumin (Turmeric root)
- Lycopene (Tomatoes)
- Ursolic Acid (Holy basil, pistachio nuts)
- Resveratrol (Red grape skins)
- Honokiol, magnol (Magnolia Bark Extract)
- Graviola (Soursop)
- Sulforaphane (Sprouting seeds)
- Valerian
- Withanolide (Ashwagandha)
The Ketogenic Diet
Professor Seyfried and Dr. D’Agostino have championed the Ketogenic Diet with brain cancer. The origins of the diet came from child Epilepsy, where children have more fits with greater carbohydrate consumption.
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 uses low protein as part of the Ketogenic Diet. While carbs are limited to just 2% of calories consumption, protein is limited to not much more: 8%.
But this is a non-sense. Believing that restricting glutamine consumption will restrict glutamine levels in the body is a non-starter. I am already full of it,; in my muscles, brain and so on. If a cancer cell wants glutamate, it can go next door and rob adjacent cells. Given every 16-year old biology student knows it is a non-essential amino acid, were I to have depleted levels, I might start to experience muscle wastage and my glutamine production system in my body would kick in to raise levels.
But we also know that protein also feeds the mTOR pathway for cancer progression - high protein diets in cases of cancer are not particularly clever anyway. mTor is linked to a signaling pathway controlling growth or repair in the body. To up regulate the mTor pathway, you need to limit protein consumption. This has been shown to increase longevity and reduce cancer levels.
Limited protein, not just limiting glutamine, might be the real health-positive if you have cancer.
Go to: Why the Keto diet is fundamentally flawed
A Diet for Cancer - The Rainbow Diet
We have been consistent since 2004 on our views on the best anti-cancer diet:
We advocate the Rainbow Diet - and in 2019, just as in 2018, it was voted 'The Healthiest Diet in the World', and, 'The Best Plant-Based Diet' by professors (diabetes, heart disease) and nutrition experts. The basis is:
- Low carbohydrate consumption, which is only whole,
- Plus lowish protein (and switch meat to fish where possible),
- Plus high good fats (EVOO, avocado, nuts and seeds, fish oils), at least 70:30 over bad fats (saturated fats like dairy, coconut oil etc.)
- Plus, high levels of colourful vegetables because they have bioactive compounds, like polyphenols, with Epigenetic benefits that can correct cancer cells.
Above all, this is a natural diet that has proven health benefits across 300 or more years. It is not hard to adopt, and easy to continue with.
If you have cancer, eating beef bone broth and high protein may not be wise
Beef bone broth (which contains high levels of glutamine) is often claimed to be 'good for you’ and is plugged by people like Ty Bollinger from 'The Truth about Cancer' series in the USA. But an expert on their 2016 video series previously said that glutamate drove cancer. How can they advocate opposites?
Understandably, 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 can definitely be a fuel for cancer. If you have cancer, frankly, you’d be wise not to touch beef bone broth. Nor, as we say above, too much protein in general.
Glutamine, glutamate and cancer – the bottom line
1. If you have cancer, stick to the Rainbow Diet. We loaded our 93rd research study in March 2020. The colourful Mediterranean Diet protects and corrects.
2. Focus on healing your gut without glutamine if you have cancer
Go to: Heal your Gut - Heal your Body
3. If you want to beat cancer, cut your 'empty glucose' consumption, and simultaneously try to cut your glutamine to glutamate conversion with the 10 compounds above.