NAC (cysteine) Increases Melanoma Spread

haidut

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Another point for Peat and his articles on how antioxidants can be pro-tumorigenic. The free radicals generated through high metabolism is what keeps some cancers in check. NAC (cysteine) blocks the effects of those free radicals. In addition, NAC also suppresses the thyroid so that may be another mechanism of action.

Antioxidants can increase melanoma metastasis in mice
http://medicalxpress.com/news/2015-10-p ... cells.html

"...A man-made antioxidant appears to accelerate the spread of skin cancer in mice, raising questions about its safety in humans, researchers say. The antioxidant, N-acetylcysteine, is used to relieve mucus production in patients with chronic obstructive pulmonary disease (COPD), said study senior author Martin Bergo, a professor at the University of Gothenburg in Sweden. It also is used as a supplement by people who believe that the antioxidant can help reduce exercise-related muscle damage, burn fat and prevent fatigue, Bergo added. But water laced with N-acetylcysteine appeared to speed up the spread of melanoma, the potentially deadly skin cancer, in lab mice, researchers found. The antioxidant had no effect on the number and size of tumors, but it enhanced the migration and invasion of these tumors to other parts of the body, the research team reported Oct. 7 in the journal Science Translational Medicine. N-acetylcysteine was linked to a doubling of the number of lymph-node tumors in mice who drank the laced water, compared to untreated animals, according to the findings. Previously, the same research team reported that certain antioxidants can spur lung tumor growth in mice. Antioxidants are believed to protect healthy cells from damage caused by unstable molecules called "free radicals," according to the U.S. National Institutes of Health (NIH). However, Bergo believes that antioxidants like N-acetylcysteine also protect cancer cells from free radicals that might otherwise slow their growth or keep them from spreading to other parts of the body."
 
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weird, I swear reading online that if you lack glutathione and have problem detoxifying in your liver you should try NAC
Didn't you experiment with NAC + Glycine combo before in one of your other posts?

What's your view on NAC then? Friend or not ?

PS: I was thinking of experimenting with NAC again but now that this study you posted gave me second thoughts
 

LucH

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knockinondoors said:
post 103563 I was thinking of experimenting with NAC again but now that this study you posted gave me second thoughts
NAC is as other antioxydants when cancer is present: Don't take any antioxydant because it neutralizes your defense system.
LucH
 
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CoolTweetPete

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So it is still an ok idea to take NAC here and there? I have a large 250 ct bottle that i'm only 1/4 of the way through.

Dave Asprey the "Bulletproof Exec" says to to take NAC w/ Vitamin C when drinking alcohol in order to support glutathione production. Being that I am an occasional heavy drinker, I listened to his advice on this for a long time. :oops:
 

Agent207

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What a coincidence that this morning I read about this news... but keep in mind they warns against vitamin E too...

"The researchers also performed follow-up lab tests on human melanoma cells, using N-acetylcysteine and vitamin E. Both antioxidants produced similar results in the human skin cancer cells, increasing their ability to migrate and invade other cells"

http://medicalxpress.com/news/2015-10-popular-antioxidant-skin-cancer-cells.html
 

haidut

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knockinondoors said:
post 103563 weird, I swear reading online that if you lack glutathione and have problem detoxifying in your liver you should try NAC
Didn't you experiment with NAC + Glycine combo before in one of your other posts?

What's your view on NAC then? Friend or not ?

PS: I was thinking of experimenting with NAC again but now that this study you posted gave me second thoughts

I did it as an experiment to see if it will raise glutathione. It was a 10 day experiment and I have not taken NAC since. NAC is probably only useful in acute liver failure caused by acetaminophen.
 
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Waynish

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It was just brought up in another thread on breaking biofilms (in upper GI cases)... Anymore thoughts on safety for this? Also: recommended dosage, effective supplement combinations, and timing?
 

High_Prob

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Pilot study demonstrating metabolic and anti-proliferative effects of in vivo anti-oxidant supplementation with N-Acetylcysteine in Breast Cancer. - PubMed - NCBI

Pilot study demonstrating metabolic and anti-proliferative effects of in vivo anti-oxidant supplementation with N-Acetylcysteine in Breast Cancer.
Monti D1, Sotgia F2, Whitaker-Menezes D3, Tuluc M4, Birbe R5, Berger A6, Lazar M6, Cotzia P7, Draganova-Tacheva R4, Lin Z3, Domingo-Vidal M3, Newberg A1, Lisanti MP2, Martinez-Outschoorn U8.
Author information

Abstract
BACKGROUND:
High oxidative stress as defined by hydroxyl and peroxyl activity is often found in the stroma of human breast cancers. Oxidative stress induces stromal catabolism, which promotes cancer aggressiveness. Stromal cells exposed to oxidative stress release catabolites such as lactate, which are up-taken by cancer cells to support mitochondrial oxidative phosphorylation. The transfer of catabolites between stromal and cancer cells leads to metabolic heterogeneity between these cells and increased cancer cell proliferation and reduced apoptosis in preclinical models. N-Acetylcysteine (NAC) is an antioxidant that reduces oxidative stress and reverses stromal catabolism and stromal-carcinoma cell metabolic heterogeneity, resulting in reduced proliferation and increased apoptosis of cancer cells in experimental models of breast cancer. The purpose of this clinical trial was to determine if NAC could reduce markers of stromal-cancer metabolic heterogeneity and markers of cancer cell aggressiveness in human breast cancer.

METHODS:
Subjects with newly diagnosed stage 0 and I breast cancer who were not going to receive neoadjuvant therapy prior to surgical resection were treated with NAC before definitive surgery to assess intra-tumoral metabolic markers. NAC was administered once a week intravenously at a dose of 150 mg/kg and 600 mg twice daily orally on the days not receiving intravenous NAC. Histochemistry for the stromal metabolic markers monocarboxylate transporter 4 (MCT4) and caveolin-1 (CAV1) and the Ki67 proliferation assay and TUNEL apoptosis assay in carcinoma cells were performed in pre- and post-NAC specimens.

RESULTS:
The range of days on NAC was 14-27 and the mean was 19 days. Post-treatment biopsies showed significant decrease in stromal MCT4 and reduced Ki67 in carcinoma cells. NAC did not significantly change stromal CAV1 and carcinoma TUNEL staining. NAC was well tolerated.

CONCLUSIONS:
NAC as a single agent reduces MCT4 stromal expression, which is a marker of glycolysis in breast cancer with reduced carcinoma cell proliferation. This study suggests that modulating metabolism in the tumor microenvironment has the potential to impact breast cancer proliferation.

Copyright © 2017 Elsevier Inc. All rights reserved.




Decongestant revealed as 'highly effective' in starving cancer cells

Decongestant revealed as 'highly effective' in starving cancer cells

Cancer researchers seeking non-toxic alternatives to harmful chemotherapy are reporting a highly significant result for a humble cold remedy.

N-Acetyl cysteine -- or NAC -- is routinely used as a dietary supplement and as a decongestant given to children to ward off a cold.

Now, clinical trials in the US indicate the cheap, over-the-counter drug, is a first rate inhibitor of the tumour stroma, a cell compartment which is fundamental to the spread of cancer.

The results, published in Seminars in Oncology, confirm a long-held theory that cancer cells are being sustained and strengthened by the presence of MCT4, a protein which 'brings them' energy, in the form of lactate, from neighbouring cells.

Patients taking high dosages of NAC saw their levels of the 'transporter' protein fall by more than 80%, drastically reducing the ability of the cancer cells to feed off neighbouring cells.

Professor Federica Sotgia, of the Biomedical Research Centre at the University of Salford, UK, explained: "In cell cultures in the laboratory, we had seen a near complete reduction in MCT4, but to achieve such a substantial result in breast cancer patients is extremely exciting indeed."

The team, which includes Professor Michael Lisanti, of the University of Salford and US-based Ubaldo Martinez-Outschoorn, MD, conducted a 'window trial' on 12 patients awaiting surgery for breast cancer at The Sidney Kimmel Cancer Center (Thomas Jefferson University), in Philadelphia.

Patients were given maximum daily dosages of the over-the-counter drug for three weeks between diagnosis and surgery. Tumour tissue biopsies were then taken before and during surgery and key biomarkers, including MCT4 and K167, were measured post-surgery.

K167 levels fell by 25% and MCT4 levels were reduced by approximately 80%.

"High levels of stromal MCT4 are extremely worrying, as they are linked to aggressive cancer behaviour and poor overall survival, so this is very encouraging result," explained Professor Lisanti.

"Our idea was to repurpose an inexpensive FDA-approved drug, to examine if its antioxidant properties could target the feeding behaviour of cancer cells. To be able to inhibit MCT4 protein expression, in a non-toxic way, is huge step forward."
 
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Hmm. Yet isn’t one of the greatest reasons for avoiding pufa to prevent LPO / free radicals. Would free radicals ever be particularly high in a healthy life-long low PUFA diet? Glutathione levels are much lower in 30+ age range, and melanoma is much higher in this range... I understand that if one already has melanoma - NAC could be dangerous, however it very well may be preventative if you do not already have melanoma. Aspirin may also have a similar dichotomy with melanoma.
 

Amazoniac

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I've been wondering about this supplement after thinking about the consequences of low cysteid content of casein. There isn't much against it in Raj's articles other than cysteine suppression of metabolism but from massive amounts released when muscle is catabolized and using @Glassy studies as reference.

This is one of them:


The body must prevent cysteine from circulating freely:


This could be concerning, but I wasn't able to find it anywhere:

Ray Peat
"Adding cystine to the diet (cysteine, the reduced form of cystine, is a thyroid antagonist) also increases the tumor incidence.[58]"

[58] Tannenbaum, A., and H. Silverstone, "Effects of varying proportion of protein in the diet," Cancer Res. 9, 162, 1949.​

Positive effect:

Diabetes, scleroderma, oils and hormones
"A. Lazarow, "Protective effect of glutathione and cysteine against alloxan diabetes in the rat," Proc. Soc. Exp. Biol. & Med. 61, 441-447, 1946. [While certain doses of cysteine, glutathione, and thioglycolic acid completely prevented alloxan diabetes, it was interesting that all of the rats receiving ascorbic acid became diabetic. To me, this argues for the free radical cause of diabetes, rather than just the sulfhydryl oxidation. Lazarow suggested that succinic dehydrogenase, and various other sulfhydryl enzymes, including those involved in fatty acid oxidation, might be involved.]"​

Apparently NAC is so effective as an antioxidant that you have to be careful to not have too much antioxidation, they compared it with a vitamin E analog there. It's from the original post:

"NAC administration increased the number of lymph node metastases and the proportion of tumor cells in each metastasis but had no impact on the number and size of primary tumors. A potential explanation for this result is that tumor cells that have left the primary tumor experience oxidative stress that limits their ability to migrate, invade, and form metastases, and NAC helps them overcome this limitation."

"NAC and Trolox have distinct chemical and physical properties. NAC is a hydrophilic precursor of cysteine and GSH (24); Trolox is a soluble analog of vitamin E, a lipophilic peroxyl radical scavenger (25). NAC and Trolox nevertheless produced markedly similar biochemical and phenotypic effects on human melanoma cells, and the effects of both antioxidants were blocked by an inhibitor of GSH synthesis. The latter result was expected in the case of NAC but less evident in the case of Trolox. Trolox could potentially boost GSH concentrations by scavenging ROS that would otherwise convert GSH to GSSG or by interacting with enzymes in glutathione pathways (26, 27). Although the similar effects of NAC and Trolox suggest a common mechanism of increased GSH synthesis and RHOA activation, we cannot rule out the possibility that distinct mechanisms underlie their effects."

"[A] limitation of this study is that we do not yet know whether Trolox or vitamin E would increase metastasis in vivo, although it would not be far-fetched to hypothesize that they would. In a previous study, NAC and Trolox produced similar effects on human lung cancer cell proliferation, and NAC and vitamin E produced similar transcriptional profiles in mouse lung tumors and highly overlapping effects on tumor growth and survival (7)."

"Previous studies have raised the possibility that antioxidants might inhibit migration and invasion of melanoma cells and other cancer cells in culture (12–14), and others showed that antioxidants reduce tumor burden in mice with ultraviolet (UV)–induced skin cancer (28, 29). Although our results conflict with these studies, we studied different antioxidants, cell lines, and mouse models. These factors likely contribute to conflicting results of ROS studies in cancer. Indeed, one of the studies on UV-induced skin cancer also showed that a different antioxidant increases, rather than reduces, skin tumor burden (28). Another factor that clearly affects the outcome of antioxidant-cancer studies is whether they are designed to evaluate effects on tumor initiation or tumor progression (30–32). Here, we evaluated the impact of NAC supplementation on the progression of malignant melanoma, and our finding of increased metastasis suggests that cancer patients should use antioxidant supplements with caution."​

I think it's better the control this balance through oxidants manipulation instead of antioxidants starvation.

@Obi-wan
 

Obi-wan

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As @haidut has mentioned its better to keep the redox in a oxidative state vs a reductive state
 
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Dave Clark

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Does Ray think eggs are okay, because I have read that the average egg has about 500 mg of L-cysteine?
 

Vinero

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How dangerous is NAC anyway? I have to take NAC because it helps my asthma. I am also taking other amino acids like Glycine, Taurine, Leucine, Isoleucine, and Phenylalanine. All of those amino acids are Peaty and work in an opposite direction to cancer. I actually like NAC, it makes me feel very "clean" after taking it the first time. I don't think I am increasing my chances of developing cancer when taking 1 supplement that is pro-cancer vs 10 supplements that are anti-cancer like the amino acids I mentioned and also caffeine, aspirin, b-vitamins etc.
 

LCohen

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How dangerous is NAC anyway? I have to take NAC because it helps my asthma. I am also taking other amino acids like Glycine, Taurine, Leucine, Isoleucine, and Phenylalanine. All of those amino acids are Peaty and work in an opposite direction to cancer. I actually like NAC, it makes me feel very "clean" after taking it the first time. I don't think I am increasing my chances of developing cancer when taking 1 supplement that is pro-cancer vs 10 supplements that are anti-cancer like the amino acids I mentioned and also caffeine, aspirin, b-vitamins etc.

It's not dangerous. It has tons of anti-oxidant, anti-inflammatory, anti-fibrotic, pro-metabolic properties. This is just a
controversial study.
 
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How dangerous is NAC anyway? I have to take NAC because it helps my asthma. I am also taking other amino acids like Glycine, Taurine, Leucine, Isoleucine, and Phenylalanine. All of those amino acids are Peaty and work in an opposite direction to cancer. I actually like NAC, it makes me feel very "clean" after taking it the first time. I don't think I am increasing my chances of developing cancer when taking 1 supplement that is pro-cancer vs 10 supplements that are anti-cancer like the amino acids I mentioned and also caffeine, aspirin, b-vitamins etc.

I c
I've been wondering about this supplement after thinking about the consequences of low cysteid content of casein. There isn't much against it in Raj's articles other than cysteine suppression of metabolism but from massive amounts released when muscle is catabolized and using @Glassy studies as reference.

This is one of them:


The body must prevent cysteine from circulating freely:


This could be concerning, but I wasn't able to find it anywhere:

Ray Peat
"Adding cystine to the diet (cysteine, the reduced form of cystine, is a thyroid antagonist) also increases the tumor incidence.[58]"

[58] Tannenbaum, A., and H. Silverstone, "Effects of varying proportion of protein in the diet," Cancer Res. 9, 162, 1949.​

Positive effect:

Diabetes, scleroderma, oils and hormones
"A. Lazarow, "Protective effect of glutathione and cysteine against alloxan diabetes in the rat," Proc. Soc. Exp. Biol. & Med. 61, 441-447, 1946. [While certain doses of cysteine, glutathione, and thioglycolic acid completely prevented alloxan diabetes, it was interesting that all of the rats receiving ascorbic acid became diabetic. To me, this argues for the free radical cause of diabetes, rather than just the sulfhydryl oxidation. Lazarow suggested that succinic dehydrogenase, and various other sulfhydryl enzymes, including those involved in fatty acid oxidation, might be involved.]"​

Apparently NAC is so effective as an antioxidant that you have to be careful to not have too much antioxidation, they compared it with a vitamin E analog there. It's from the original post:

"NAC administration increased the number of lymph node metastases and the proportion of tumor cells in each metastasis but had no impact on the number and size of primary tumors. A potential explanation for this result is that tumor cells that have left the primary tumor experience oxidative stress that limits their ability to migrate, invade, and form metastases, and NAC helps them overcome this limitation."

"NAC and Trolox have distinct chemical and physical properties. NAC is a hydrophilic precursor of cysteine and GSH (24); Trolox is a soluble analog of vitamin E, a lipophilic peroxyl radical scavenger (25). NAC and Trolox nevertheless produced markedly similar biochemical and phenotypic effects on human melanoma cells, and the effects of both antioxidants were blocked by an inhibitor of GSH synthesis. The latter result was expected in the case of NAC but less evident in the case of Trolox. Trolox could potentially boost GSH concentrations by scavenging ROS that would otherwise convert GSH to GSSG or by interacting with enzymes in glutathione pathways (26, 27). Although the similar effects of NAC and Trolox suggest a common mechanism of increased GSH synthesis and RHOA activation, we cannot rule out the possibility that distinct mechanisms underlie their effects."

"[A] limitation of this study is that we do not yet know whether Trolox or vitamin E would increase metastasis in vivo, although it would not be far-fetched to hypothesize that they would. In a previous study, NAC and Trolox produced similar effects on human lung cancer cell proliferation, and NAC and vitamin E produced similar transcriptional profiles in mouse lung tumors and highly overlapping effects on tumor growth and survival (7)."

"Previous studies have raised the possibility that antioxidants might inhibit migration and invasion of melanoma cells and other cancer cells in culture (12–14), and others showed that antioxidants reduce tumor burden in mice with ultraviolet (UV)–induced skin cancer (28, 29). Although our results conflict with these studies, we studied different antioxidants, cell lines, and mouse models. These factors likely contribute to conflicting results of ROS studies in cancer. Indeed, one of the studies on UV-induced skin cancer also showed that a different antioxidant increases, rather than reduces, skin tumor burden (28). Another factor that clearly affects the outcome of antioxidant-cancer studies is whether they are designed to evaluate effects on tumor initiation or tumor progression (30–32). Here, we evaluated the impact of NAC supplementation on the progression of malignant melanoma, and our finding of increased metastasis suggests that cancer patients should use antioxidant supplements with caution."​

I think it's better the control this balance through oxidants manipulation instead of antioxidants starvation.

@Obi-wan

I'm inclined to agree with the statement at the end. Healthy sufficient levels of oxidants like sunlight, quinones and pro thyroid substances with adequate antioxidants to take care of nasty oxidation byproducts.

What kind of antioxidants would be good? I've done the vitamin c and e's, might give NAC a try just to see what it feels like.
 

Amazoniac

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I c


I'm inclined to agree with the statement at the end. Healthy sufficient levels of oxidants like sunlight, quinones and pro thyroid substances with adequate antioxidants to take care of nasty oxidation byproducts.

What kind of antioxidants would be good? I've done the vitamin c and e's, might give NAC a try just to see what it feels like.
Oxidative stress and antioxidant strategies in dermatology
Some of those, but for them to function you'll need other vitamins and minerals as well that weren't mentioned.
 

Dave Clark

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Jun 2, 2017
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I take notice the use of NAC in psychiatry in a lot of publications. Apparently, NAC has the ability to recycle neurotransmitters, not sure what that means except better brain function. This benefit is reported by many people who use it.
 
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