NAC (cysteine) Increases Melanoma Spread

[Amazoniac]

- Impact of Supplementary Amino Acids, Micronutrients, and Overall Diet on Glutathione Homeostasis

Glutathione (GSH) is a critical endogenous antioxidant found in all eukaryotic cells. Higher GSH concentrations protect against cellular damage, tissue degeneration, and disease progression in various models, so there is considerable interest in developing interventions that augment GSH biosynthesis. Oral GSH supplementation is not the most efficient option due to the enzymatic degradation of ingested GSH within the intestine by γ-glutamyltransferase, but supplementation of its component amino acids—cysteine, glycine, and glutamate—enhances tissue GSH synthesis. Furthermore, supplementation with some non-precursor amino acids and micronutrients appears to influence the redox status of GSH and related antioxidants, such as vitamins C and E, lowering systemic oxidative stress and slowing the rate of tissue deterioration. In this review, the effects of oral supplementation of amino acids and micronutrients on GSH metabolism are evaluated. And since specific dietary patterns and diets are being prescribed as first-line therapeutics for conditions such as hypertension and diabetes, the impact of overall diets on GSH homeostasis is also assessed.

 

[Amazoniac]

- Glycine and N‐acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial

 

[orangeUglad]

This isn't good news to the many people high dosing this stuff right now

 

[Dr. B]

This isn't good news to the many people high dosing this stuff right now

quercetin is another one some are megadosing due to some of the covid protocols. they use quercetin, nac, zinc, vitamin c and d.

- Glycine and N‐acetylcysteine (GlyNAC) supplementation in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, insulin resistance, endothelial dysfunction, genotoxicity, muscle strength, and cognition: Results of a pilot clinical trial

doesnt the body synthesize taurine from vitamin b6 as well as cysteine? so supplementing taurine should 'spare' both, which could create an excess of both cysteine and b6 in people who have adequate intake from diet? ive never gotten good effects from taurine, it just causes good relaxation and anti anxiety/pro fatigue effect, it slows digestion significantly
there are many people supplementing taurine, b6, and even both together.
i wonder the same on creatine, it has very similar effects to supplementing choline bitartrate for me, so id imagine supplementing it will increase your methionine, arginine, glycine and choline. on a high protein or high milk diet, you dont really want more of any of those things besides glycine.
i dont remember all the nutrients in glutathione, is it glycine, glutamine and cysteine? someone said cysteine is usually the missing link for most people so NAC boosts glutathione because it provides more cysteine as raw material... is NAC really just like supplementing cysteine or are there unique benefits to it not present in regular cysteine

 

[Amazoniac]

doesnt the body synthesize taurine from vitamin b6 as well as cysteine? so supplementing taurine should 'spare' both, which could create an excess of both cysteine and b6 in people who have adequate intake from diet? ive never gotten good effects from taurine, it just causes good relaxation and anti anxiety/pro fatigue effect, it slows digestion significantly
there are many people supplementing taurine, b6, and even both together.
i wonder the same on creatine, it has very similar effects to supplementing choline bitartrate for me, so id imagine supplementing it will increase your methionine, arginine, glycine and choline. on a high protein or high milk diet, you dont really want more of any of those things besides glycine.
i dont remember all the nutrients in glutathione, is it glycine, glutamine and cysteine? someone said cysteine is usually the missing link for most people so NAC boosts glutathione because it provides more cysteine as raw material... is NAC really just like supplementing cysteine or are there unique benefits to it not present in regular cysteine

I think that you can find information in the previous link, here and below:

- Dietary Glycine Is Rate-Limiting for Glutathione Synthesis and May Have Broad Potential for Health Protection

 

[sladerunner69]

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."

It's remarkable how two studies can contradict each other so perfectly.

 

[TeslaFan]

NAC should be taken with Glycine, in equal amounts at least, or with more Glycine. I have personally found this combo to work well for Glutathione replenishing. I never had a long term good experience with NAC only. As it was mentioned on this forum, Glycine is a limiting factor in Glutathione synthesis, and when Glycine is present, NAC will be used up properly.

 

[Ben.]

What about supplementing S-Acetylglutathion instead?

 

[Amazoniac]

What about supplementing S-Acetylglutathion instead?

If what's preventing glutathione from being synthesized is a lack cystermine, it's probable that the person is also running low on bulline [Tau] and foulate [SO4(2−)], making it preferable to favor the supplementation of the substrates, hoping that the body controls their fate best.

- Impact of Supplementary Amino Acids, Micronutrients, and Overall Diet on Glutathione Homeostasis

"Cysteine is a necessary metabolic precursor for taurine synthesis, so it has been postulated that taurine supplementation would spare cysteine for eventual incorporation into GSH [104]. In research studies on this topic, animals were supplemented with taurine intraperitoneally [104], via drinking water [105,106,107,108,109,110], or intragastric intubation [111]. When investigators supplemented diabetic rats with taurine, lens GSSG and GSSG/GSH ratio levels decreased while GSH levels were not affected [112]. In rabbits on a high-cholesterol diet, taurine failed to affect hepatic GSH levels [113]. However, taurine supplementation normalized GSH and GSSG levels in iron-overloaded mice [110] and increased renal and hepatic GSH levels in rats with hypothyroidism [109].

Effects of taurine on the enzymes GPx and GR have been evaluated in both rodent and human studies. Taurine supplementation recovered hepatic GR activity in diabetic rats [114], whereas hepatic GPx levels remained unaltered by taurine supplementation in type I and type II diabetic mice [105]. However, when young adults were orally supplemented with taurine (50 mg/kg for 2 weeks) after performing eccentric exercise, RBC GPx levels were elevated [115].

Overall, these results point to a limited impact of taurine on GSH, implying that other amino acid or micronutrient supplements may be a more effective option at targeting and raising GSH concentrations."​

 

[Dr. B]

If what's preventing glutathione from being synthesized is a lack cystermine, it's probable that the person is also running low on bulline [Tau] and foulate [SO4(2−)], making it preferable to favor the supplementation of the substrates, hoping that the body controls their fate best.

"Cysteine is a necessary metabolic precursor for taurine synthesis, so it has been postulated that taurine supplementation would spare cysteine for eventual incorporation into GSH [104]. In research studies on this topic, animals were supplemented with taurine intraperitoneally [104], via drinking water [105,106,107,108,109,110], or intragastric intubation [111]. When investigators supplemented diabetic rats with taurine, lens GSSG and GSSG/GSH ratio levels decreased while GSH levels were not affected [112]. In rabbits on a high-cholesterol diet, taurine failed to affect hepatic GSH levels [113]. However, taurine supplementation normalized GSH and GSSG levels in iron-overloaded mice [110] and increased renal and hepatic GSH levels in rats with hypothyroidism [109].​

​

Effects of taurine on the enzymes GPx and GR have been evaluated in both rodent and human studies. Taurine supplementation recovered hepatic GR activity in diabetic rats [114], whereas hepatic GPx levels remained unaltered by taurine supplementation in type I and type II diabetic mice [105]. However, when young adults were orally supplemented with taurine (50 mg/kg for 2 weeks) after performing eccentric exercise, RBC GPx levels were elevated [115].​

​

Overall, these results point to a limited impact of taurine on GSH, implying that other amino acid or micronutrient supplements may be a more effective option at targeting and raising GSH concentrations."​

Lol! Mr. Botox!

I dont remember posting that article/link before but it seems familiar!

can you post more about folate's involvement in glutathione synthesis, also is NAC only valuable for glutathione because its of its cysteine content or is there something unique in NAC beyond its simple cysteine content!

 

[Amazoniac]

Lol! Mr. Botox!

I dont remember posting that article/link before but it seems familiar!

can you post more about folate's involvement in glutathione synthesis, also is NAC only valuable for glutathione because its of its cysteine content or is there something unique in NAC beyond its simple cysteine content!

It was recommended on the previous post.

The acetyl component makes it unique..

- N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why​

..but a great deal of the dose is modified already in the gut. We know that it's utilized because they tag the sulfur in cysteine and track it.

What I can comment about folate is that it can't do much without enough sulfur because it's not adding any into the system, you either trap this sulfur to resynthesize methionine (futile) or transfer it to produce glutathione. In the case of glycine, endogenous synthesis would require that folate is available (manz, 2015).

- Serine hydroxymethyltransferase | Proteopedia​

 

[Jon2547]

I'm the canary in the coal mine so to speak. I have tried NAC a few times in the past and have noticed within 30 minutes of taking it a very uneasy feeling. heart racing, etc. I would say that this is a every once in a while supplement, not to be taken every day! Only use when absolutely needed. Otherwise look to address health from a holistic perspective.

 

[Amazoniac]

- Egg white consumption increases GSH and lowers oxidative damage in 110-week-old geriatric mice hearts

The number of geriatrics with an advanced age is rising worldwide, with attendant cardiovascular disorders, characterized by elevated oxidative stress. Such oxidative stress is accelerated by an age-related loss of critical antioxidants like glutathione (GSH) and dietary solutions to combat this loss does not exist. While egg white is rich in sulphur amino acids (AAs), precursors for GSH biosynthesis, whether they can increase sulphur AA in vivo and augment GSH in the aged myocardium remain unclear. We hypothesized that egg white consumption increases GSH and reduces oxidative damage and inflammation in the geriatric heart. To this end, 101-102 week-old mice were given a AIN 76A diet supplemented with either 9% w/w egg white powder or casein for 8 weeks. Subsequent analysis revealed that egg white increased serum sulphur AA and cardiac GSH, while reducing the cysteine carrying transporter SNAT-2 and elevating glutamine transporter ASCT2 in the heart. Increased GSH was accompanied by elevated expression of GSH biosynthesis enzyme glutathione synthase as well as mitochondrial antioxidants like superoxide dismutase 2 and glutathione peroxidase 1 in egg white-fed hearts. These hearts also demonstrated lower oxidative damage of lipids (4-hydroxynonenal) and proteins [nitrotyrosine] with elevated anti-inflammatory IL-10 gene expression. These data demonstrate that even at the end of lifespan, egg whites remain effective in promoting serum sulphur AAs and preserve cardiac GSH with potent anti-oxidant and mild anti-inflammatory effects in the geriatric myocardium. We conclude that egg white intake may be an effective dietary strategy to attenuate oxidative damage in the senescent heart.

 

[ddjd]

So does glycine reduce most of the negative effects of NAC??

 

[Dave Clark]

Not that I really wanted to, but I started using NAC at night before bed to see if it would help with night time allergies, i.e. mouth breathing, stuffy nose, etc. I had never tried it at bedtime, thinking it may disturb my sleep, but to my surprise, my nights have been remarkably better, waking up with little to no allergy symptoms. I also use glycine, theanine, inositol, zinc, magnesium, aspirin {sometimes}, so that may help a bit, but I have used them before without the NAC and did not have this success. So, it is hard for me now to jump on the band wagon and be a NAC hater. Honestly, I really did not expect any good results. I have played with NAC for probably close to 20 years, but always took it during the day with no palpable benefits. Now, I am going to try stopping it, and see if the benefits go away, if they do, then I know it was working.

 

[Dr. B]

Not that I really wanted to, but I started using NAC at night before bed to see if it would help with night time allergies, i.e. mouth breathing, stuffy nose, etc. I had never tried it at bedtime, thinking it may disturb my sleep, but to my surprise, my nights have been remarkably better, waking up with little to no allergy symptoms. I also use glycine, theanine, inositol, zinc, magnesium, aspirin {sometimes}, so that may help a bit, but I have used them before without the NAC and did not have this success. So, it is hard for me now to jump on the band wagon and be a NAC hater. Honestly, I really did not expect any good results. I have played with NAC for probably close to 20 years, but always took it during the day with no palpable benefits. Now, I am going to try stopping it, and see if the benefits go away, if they do, then I know it was working.

I thought it was known to be useful for allergies or stuffy nose etc because it has some sort of drying effect of mucus? But apparently that same mechanism makes it dangerous for stomach lining as well? When i used to use a multivitamin that had it added, it would create a lot more boogers than usual.

 

[Dave Clark]

I thought it was known to be useful for allergies or stuffy nose etc because it has some sort of drying effect of mucus? But apparently that same mechanism makes it dangerous for stomach lining as well? When i used to use a multivitamin that had it added, it would create a lot more boogers than usual.

It is useful too break up mucus because it breaks the di-sulfide bonds in the mucus, allowing it to thin out, hence more easily flowing to be removed.
I would like to see studies on the stomach assumption, I have the feeling that dose plays a big part in that assertion. My stomach has felt better since using NAC. It may have drawbacks, but then everything does, so if something mitigates a problem that nets worse outcomes, the harm is less than the cure, if there is even a harm.

 

[ecstatichamster]

I think Dr. Peat had a jaundiced eye on cysteine, and perhaps wrongly.

 

[ecstatichamster]

Not that I really wanted to, but I started using NAC at night before bed to see if it would help with night time allergies, i.e. mouth breathing, stuffy nose, etc. I had never tried it at bedtime, thinking it may disturb my sleep, but to my surprise, my nights have been remarkably better, waking up with little to no allergy symptoms. I also use glycine, theanine, inositol, zinc, magnesium, aspirin {sometimes}, so that may help a bit, but I have used them before without the NAC and did not have this success. So, it is hard for me now to jump on the band wagon and be a NAC hater. Honestly, I really did not expect any good results. I have played with NAC for probably close to 20 years, but always took it during the day with no palpable benefits. Now, I am going to try stopping it, and see if the benefits go away, if they do, then I know it was working.

NAC seems, when combined with collagen/glycine, to be amazing. Let us know how your experiment progresses.

For men, NAC has I think kept me healthy, that is, not sick. I still have allergies.

 

[Dave Clark]

NAC seems, when combined with collagen/glycine, to be amazing. Let us know how your experiment progresses.

For men, NAC has I think kept me healthy, that is, not sick. I still have allergies.

Also thinking of trialing the NACET, since the dose to be used is one tenth of a normal NAC dose. I need to research it more, but perhaps because of its high bioavailability and ability to use less, it could potentially have less side effects {if one does experience any], or negative repercussions scientifically speaking that are often attached to NAC.
Off topic, but, regarding allergies, etc., when I started doing hydrogen inhalation with my Brown's gas machine my allergies have improved at least 75 %, and I noticed it the very first time I did a session. I am a skeptical person regarding different modalities, since I have tried many in the past 30 or 40 years, so when something has a palpable effect that is lasting, I become a believer. If you are wondering why I don't use the H2 before bed like I am doing with the NAC, it is mostly because I am not sure if that is going to energize me through out the night and mess up my sleep. But, I might give it a go someday, and if it works without causing sleep disruptions, then I may back off the NAC a bit, we'll see.