Glutathione and cancer???

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Homer

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Has anyone seen the recent article published in Nature that says that "Supplementation with GSH (Glutathione) rescues cancer cell survival and growth in cystine-deficient conditions". In reading over it, it's above my head and I couldn't figure out if the form (liposomal, reduced, oral, injectable) mattered but running through AI determined the amount given to laboratory mice would be the equivalent of 13000mg per day for a 70kg subject. Has anyone seen a better breakdown or similar findings??

Catabolism of extracellular glutathione supplies cysteine to support tumours - Nature

Catabolism of extracellular glutathione by γ-glutamyltransferases supports tumour growth and survival, and pharmacological targeting of these enzymes slows tumour growth.

www.nature.com
 
Homer said:
Has anyone seen the recent article published in Nature that says that "Supplementation with GSH (Glutathione) rescues cancer cell survival and growth in cystine-deficient conditions". In reading over it, it's above my head and I couldn't figure out if the form (liposomal, reduced, oral, injectable) mattered but running through AI determined the amount given to laboratory mice would be the equivalent of 13000mg per day for a 70kg subject. Has anyone seen a better breakdown or similar findings??

Catabolism of extracellular glutathione supplies cysteine to support tumours - Nature

Catabolism of extracellular glutathione by γ-glutamyltransferases supports tumour growth and survival, and pharmacological targeting of these enzymes slows tumour growth.

www.nature.com
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On one level (before this study), gluta seems no different than other antioxidant supplements being a bad idea for patients with cancer.

But this part is an additional worry for active cancer at least:

quoted said:
Our findings indicate a non-canonical role for GSH in supporting tumours by acting as a reservoir of amino acids.

So gluta is a food source for breast cancer and probably other cancers too.

An article on the study has a similar warning for taurine (which is a food source for leukemia at least):

https://www.biocompare.com/Life-Science-News/624653-Glutathione-Study-Reveals-How-Cancer-Exploits-Antioxidants/

quoted said:
The findings fit into a broader re-evaluation of how antioxidants interact with cancer. Harris pointed out that substances commonly viewed as benign or beneficial can be “hijacked” by cancer cells. For example, colleague Jeevisha Bajaj recently reported that taurine, another antioxidant found in foods, supplements, and energy drinks, can drive leukemia growth. Harris emphasized that these results do not mean people should avoid antioxidant-rich whole foods; rather, he cautioned against high-dose, unregulated antioxidant supplements, particularly glutathione, which “can present risks.”

Certainly gives pause, at least if one has known genetic risks for cancer. But cancer is very complicated, so to say "gluta feeds breast cancer" or "taurine feeds leukemia" would be an overstatement, like saying "sugar feeds cancer." And of course, low gluta levels are associated with diseases of aging, like Parkinson's, COPD. liver disease, Alzheimer’s, macular degeneration, and cardiovascular disease.

Related discussions on Reddit:

quoted said:
PSA for those supplementing with glutathione, new study shows potential link to tumor growth
by
u/callthesomnambulance in
covidlonghaulers
View: https://www.reddit.com/r/covidlonghaulers/comments/1rz8ttf/psa_for_those_supplementing_with_glutathione_new/

View: https://www.reddit.com/r/EverythingScience/comments/1mu8or4/glutathione_mitochondrial_antioxidant_found_to/

Click to expand...
 
Thanks for the info and a great explanation about some of the specifics about these studies. I always try to take these with a grain of salt and better understand how they could be oversimplified or exaggerated in their findings (namely the amount administered in the experiments seems highly unlikely to be used in humans). But it's always good to understand the risks associated with any supplements.
 
Oral NAC supplementation is more common for raising gluta levels, and is often seen as a more effective option anyway for the long-term compared to gluta injections.

Since oral NAC doesn't spike gluta levels like gluta injections, oral NAC may be less risky in general long-term. But higher doses of NAC can cause an increase in hematocrit, which is not good for those already on TRT. Also, regarding NAC:

Gemini said:
Many focus solely on NAC, but supplementing with glycine (or collagen peptides) can sometimes allow for lower doses of NAC to be more effective by removing the other secondary bottleneck in synthesis.
 
Cancer cells are opportunistic and can feed off of many nutrients. Should you supplement with it if you have active cancer or a history of cancer? No. But, you'll get those aminos in your diet anyway. If you're healthy, supplementing with it is a non-issue.
 
DunningKruger said:
If you're healthy, supplementing with it is a non-issue.

About one in three people will get some form of cancer in their lifetime. So for the cancer researchers, there is always some concern, even with milk raising IGF-1. But yeah, there are bigger things to worry about, like occupational exposure to carcinogens, long-term use of HGH, etc.
 
Calm Logic said:
Oral NAC supplementation is more common for raising gluta levels, and is often seen as a more effective option anyway for the long-term compared to gluta injections.

Since oral NAC doesn't spike gluta levels like gluta injections, oral NAC may be less risky in general long-term. But higher doses of NAC can cause an increase in hematocrit, which is not good for those already on TRT. Also, regarding NAC:
Sorry but thats not correct. This isnt a question of spiking gluta levels and NAC is as good a source of cysteine as any. In fact in the article it explicitly states that NAC rescued the cancer cells just as well. The whole article points out that GSH is a reservoir of cysteine which was artificially restricted to halt tumour growth. Cysteine is a conditionally essential aa, meaning it may be in short supply during cellular growth stages like cancer.

All in all this whole experiment is founded on the effects of GSH found in tumour microenvironment. That is, in teh extracellular environment of an active tumour that was artificially transplanted in mice.

Under normal conditions, GSH is an essential part of a healthy human. It combats oxidative stress, detoxification, liver health, etc. Supplementation has even shown to be prohealth.

TLDR: if you have cancer, GSH can help it by providing cysteine. If you dont have an active cancer, its by far a beneficial molecule.
 
A keyword in the title of the paper is extracellular: "Catabolism of extracellular glutathione supplies cysteine to support tumours"

Oral NAC is for supporting existing intracellular manufacturing. But an injection of gluta bypasses the biological brakes to some degree with extracellular flooding, as with the skin whitening effects in long-term, high-dose South Korean use. So hopefully the injections have more pros than cons or are more for acute, short-term use.

Similarly:

Gemini said:
While the paper shows that tumors can scavenge cysteine from NAC just as easily as from GSH in a controlled environment, the real-world distinction lies in the regulatory gatekeeping of the body.

Oral NAC is processed by the liver and utilized through rate-limited enzymatic pathways , ensuring that cysteine is distributed according to cellular demand. In contrast, injections create an immediate systemic spike that saturates the interstitial fluid , providing an unregulated "free-for-all" of nutrients that tumors are specifically primed to intercept.

NAC: Promotes metabolic resilience by letting the cell stay in control.

GSH Injections: Bypasses cellular signaling, creating a high-energy extracellular "pantry" that favors the opportunistic metabolism of a tumor.

While glutathione is the "master antioxidant," high levels in the extracellular environment can occasionally act as a pro-oxidant. In the blood, high concentrations of GSH can react with "free" copper or iron ions . This reaction can actually generate superoxide radicals, causing temporary oxidative stress to the lining of your blood vessels—the exact opposite of the intended goal.
 
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