Glutamine: The Surprising Link to Prostate Cancer -thoughts?

Posted by hanscasteels @hanscasteels, Jan 19 3:30pm

A groundbreaking study published in ASN Neuro reveals a significant breakthrough in cancer research. This research shifts the paradigm in cancer biology, establishing glutamine fermentation as a critical metabolic pathway. By targeting the dual dependency on glucose and glutamine, this approach offers the potential to revolutionize cancer treatment and significantly reduce mortality rates. For the first time, it demonstrates that amino acid fermentation, particularly of glutamine, plays a pivotal role in the dysregulated growth of tumor cells. This discovery advances our understanding of cancer metabolism and has profound implications for treatment strategies.

Key Findings:
Glutamine as a Primary Fermentable Fuel:
Among all 20 amino acids tested, glutamine uniquely promotes robust tumor growth in both mouse and human glioblastoma cells.
Glutamine is metabolized into succinate through a fermentation process, even in the absence of oxygen and glucose.

Non-Oxidative Energy Production:
Tumor cells produce ATP through mitochondrial substrate-level phosphorylation, independent of oxidative phosphorylation.
This process persists in the absence of glucose, oxygen, or functional oxidative phosphorylation pathways (e.g., when inhibited by cyanide).

Mechanistic Insights:
Labeling experiments with C13-glutamine confirm the production of C13-succinate as a fermentation end product.
This demonstrates that tumor cells depend on glutamine fermentation rather than traditional respiration for energy.

Synergistic Role of Glucose and Glutamine:
Tumor cells exploit the synergy between glucose and glutamine metabolism to sustain rapid, dysregulated growth.

Clinical Validation:
In vivo experiments show that targeting both glucose and glutamine metabolism, combined with nutritional ketosis, dramatically reduces tumor growth with minimal toxicity.

Implications:
Revisiting Warburg's Hypothesis:
While Warburg identified cancer as a mitochondrial metabolic disease, this study clarifies that tumors utilize two fermentable fuels—glucose and glutamine—for survival and growth.
The study challenges the traditional view that oxygen consumption in tumors is linked to ATP production through oxidative phosphorylation.

Treatment Strategies:
Combining dietary interventions (e.g., ketosis) with therapies targeting glucose and glutamine metabolism offers a promising, low-toxicity approach to cancer management.

The findings provide a blueprint for addressing major cancers, including lung, colon, bladder, and breast cancer, which exhibit similar metabolic traits.

This research shifts the paradigm in cancer biology, establishing glutamine fermentation as a critical metabolic pathway. By targeting the dual dependency on glucose and glutamine, this approach offers the potential to revolutionize cancer treatment and significantly reduce mortality rates.

Interested in more discussions like this? Go to the Prostate Cancer Support Group.

northoftheborder | @northoftheborder | Jan 19 4:01pm

Thanks for sharing that.

According to the Cleveland Clinic, all cells need glutamine as fuel, but cancer cells tend to hog it, sometimes not leaving enough for the others. Our bodies produce it naturally in addition to getting it from food. It can also be helpful for recovering from chemo. Search for "Cancer" here:
https://my.clevelandclinic.org/health/articles/glutamine
Glutamine is not something we can easily avoid, since our healthy cells would die without it. However, perhaps many early studies like this, taken together, will eventually lead to a way to starve the cancer cells without starving the healthy ones.

In the meantime, sadly, we're stuck using other ways to inhibit prostate cancer growth, like ADT and ARSIs.

bens1 | @bens1 | Jan 20 5:48am

...and although our body produces it, glutamine also comes from meat, dairy, eggs, tofu and select vegetables. It also helps with muscle recovery.

heavyphil | @heavyphil | Jan 20 7:14am

You are going down rabbit holes again, Hans….be already beat the crap out of this.
Avoiding glutamine is like a human being avoiding oxygen….which, by the way, also fuels cancer.
But like you, I also continue to be drawn to these “astonishing” discoveries to then find out they are not much at all.

northoftheborder | @northoftheborder | Jan 20 8:14am

They're interesting to me as early previews of directions treatments might take in 10+ years. For example, researchers already knew that cancer cells have a voracious appetite for glutamine, and the paper @hanscasteels shared might have further refined some aspect of that knowledge (I don't have the knowledge to evaluate).

Perhaps some day they'll find a genetic treatment that reprogrammes cancer cells so that they can't "digest" glutamine and end up starving. Who knows? It's no practical use to clinicians and patients yet, but it could be one step in a long path towards a future treatment. 🤞

wandyfisher | @wandyfisher | Jan 20 8:44am

Much of the diet information I’ve encountered says that unlike many cancers that feed on sugar, prostate cancer feeds on animal fats and that fruits, cruciferous veggies, fish and fiber are the things you want in your diet.

hanscasteels | @hanscasteels | Jan 20 8:47am

In reply to @wandyfisher "Much of the diet information I’ve encountered says that unlike many cancers that feed on sugar,..." + (show)

Indeed. It seems to me that we are where we are today due to the trial and errors of those that struggled and endured before us. Hopefully we can play the same role in support of our sons and grandsons should they be afflicted with the same disease.

wandyfisher | @wandyfisher | Jan 20 8:51am

Link to an fun watch on sugar vs fat: https://youtu.be/-PyqazlkpCE?si=0a3Uh2-qbOdeMGme

trusam1 | @trusam1 | Jan 20 8:59am

Magic silver bullet #3,267...

hanscasteels | @hanscasteels | Jan 20 9:58am

In reply to @trusam1 "Magic silver bullet #3,267..." + (show)

I don’t think anyone is implying that this is a magic bullet. Perhaps it’s yet another stepping stone to find a treatment devoid of the consequences we struggle with today. At least, most of us

bjroc | @bjroc | Jan 20 10:22am

There is always this
https://gamechangersmovie.com/
which does NOT touch on prostate cancer or even anything prostate but does have a urologist talking about animal fats + meat and what it does to men. It is on netflix or paid youtube I think and other places

Meat has all these in it from either being naturally in the meat or from cooking it:
Heterocyclic amines
TMAO (Trimethylamine N-Oxide)
Heme iron
Neu5gc (N-Glycolylneuraminic acid )
AGEs (Advanced glycation end products )