Glutamine Enhances the Anti-Cancer Potency of TNF, Tumor Necrosis Factor
"He just stopped dying". Those words continue to be burned in my brain. I just can't stop thinking about this remarkable story.
http://grouppekurosawa.typepad.com/grouppe_kurosawa_natural_/2008/04/he-just-stopped.html
An elderly man, probably in his 70s, with terminal pancreatic cancer takes 50 grams of glutamine a day for 30 days and walks out of a Hospice. "He just stopped dying".
In the new autophagy cytotoxic protocol, I recommended a minimal dose of 50 grams of glutamine a day. But this dose may be too low. The elderly man referenced above probably did not weight very much. Therefore, for a large person like myself (250 pounds) 50 grams is probably therapeutically inadequate. But who knows. I do know that you cannot overdose on a natural amino acid like glutamine.
This is the bottom line question. Did this man get better because
1. Glutamine provided nutritional value.
2. Glutamine enhances the uptake of nutrients from the GI tract.
3. Glutamine enhances immune functioning.
4. Glutamine and its metabolite glutamate promoted cancer cell death.
I believe the correct answer is ALL of the above.
Everyone who is sick or under excessive stress is defacto glutamine depleted. Regardless of diet, when tissues are stressed they consume glutamine at a rapid rate. Although glutamine is considered a non-essential amino acid, the scientific literature is clear that this is BS. Glutamine is a critically important amino acid and in HIGH concentrations it can induce necrosis, autophagy and apoptosis in cancer cells.
I have already written extensively about the use of glutamine in the treatment of cancer. Now we know that the metabolism of glutamine also directly promotes cancer cell death. Consider the following...
TNF or tumor necrosis factor is THE most potent natural anti-cancer agent known. In proper concentrations, it promotes necrosis, autophagy and apoptosis. Unfortunately, TNF is also toxic to normal cells so it cannot be administered via an IV injection.
We know that low levels of chronic inflammation promotes the development of cancer. One of the inflammatory agents is TNF. In high concentrations, TNF kills cancer cells. However, in low chronic concentrations, such as that present in tumors, TNF promotes cancer cell growth and survival. With the use of high oral doses of glutamine, we should be able to enhance the anti-cancer potency of TNF that is normally present in tumors.
Consider the following diagram.
http://grouppekurosawa.typepad.com/grouppe_kurosawa_natural_/2008/04/you-must-print.html
On the right, glutamine blocks NF-kappaB activation by interfering with PI-3K/AKT signaling and by promoting the synthesis of HSP70, an inhibitor of IKK.
The apoptosis pathway described on the left is a tad simplistic. In order for TNF to induce mitochondrial damage, oxidative stress must be initiated.
If the oxidative stress pathway is impaired (respiration), TNF cannot kill a cancer cell. The production of superoxide radicals by respiration is of fundamental importance in the initiation of necrosis, apoptosis and autophagy by TNF.
Glutamine is metabolized by respiration. If glutamine is depleted in the culture media of cancer cells, respiration is impaired and the cells become desensitized to the killing powers of TNF. Glutamine is not an ordinary amino acid. It plays many roles in cellular metabolism. Until recently, I did not realize that the metabolism (oxidation) of glutamine in the mitochondria promoted oxidative stress and eventual death in cancer cells. The lack of glucose in the culture media does not desensitize cancer cells to TNF.
Remember Coleys Toxin? This bacterial extract promoted necrosis in highly malignant cancer cells by stimulating the secretion of TNF. We really don't need to stimulate further TNF release, a potentially dangerous procedure. But we do need to increase the cytotoxic potential of the small amounts of TNF present in all cancer lesions.
I can't stop thinking about that elderly gentleman with terminal pancreatic cancer who "walked" out of a hospice after taking 50 grams of glutamine daily for 30 days. There is NO question that this extremely sick individual had almost no glutamine in his body. This is true of all cancer patients. Unfortunately, due to my stupidity we have no feedback information on his condition. Did the high glutamine dose clinically affect his pancreatic cancer? Considering what we know about the anti-cancer properties of glutamine, I would venture to say that it did. How could it not? I don't think this is a case where glutamine simply provided nutritional support. Something else is going on.
In summary, glutamine blocks the ability of TNF to induce NF-kappaB signaling and cancer cell survival. It also directly promotes cell death by inducing mitochondrial oxidative stress. Also, don't forget that glutamate, a metabolite of glutamine, inhibits the uptake of glutathione into the mitochondria. This further destabilizes the mitochondria and enhances the cytotoxic efficacy of TNF.
Stay tuned...
Grouppe Kurosawa, Medicine in the Public Interest
At NaturalVigor.com:
Glutamine Ethyl Ester
L-Glutamine
N-Acetyl L-Glutamine
Which?
Posted by: satx2 | May 09, 2008 at 05:41 PM
Simple L-glutamine. The common amino acid.
Posted by: Dr. Steve Martin | May 09, 2008 at 07:30 PM
I am upping my dose and also doing topical. I found a store locally that carries NOW brand USP l-glutamine free-form (non-peptide bonded) for slightly less than I can buy it from the GK source since the $4.95 postage knocks it slightly over. It's nice to have it available right here, but hope it's the quality I need. I remain very excited about glutamine. The higher doses I am finally taking seem to be knocking down the inflammation some similarly to what the SS did which at the moment I am not taking, tho I expect to resume as soon as my lung drain implant has healed. Don't want any bleeding.
Posted by: Thea Hardy | May 10, 2008 at 04:49 PM
I'm waiting a quote for many products AIE/NaturalVigor.com
BulkNutrition.com:
1000 grams L-Glutamine Powder $24.99
1000 grams Arginine Base $34.99
Posted by: satx2 | May 10, 2008 at 10:00 PM