176 replies to this topic

[SearchingForAnswers]

I'd like to know this also. Taking 600mg per night, had no idea it might not be safe.

[timar]

The human equivalent doses that caused PAH in lab animals are astronomical - more than 10 g a day. There is no indication that doses up to 1200 mg, which have been employed in many RCTs with human subjects can cause PAH.

 

However, unless you have a specific health issue, I would not recomment to routinely take more than 200 mg daily. NAC is a very powerful glutathione precursor and has been shown to interfere with the hormetic effects of exercise. It's probably not a good idea to megadose on any antioxidant.

 

Personally, I take 600 mg NAC daily for a week a few times a year, primarily to detox heavy metals.

Edited by timar, 28 February 2015 - 07:32 PM.

[FunkOdyssey]

NAC is a powerful mucolytic drug that can break down mucosal barriers throughout the body.  Personally, I would be more concerned about that than the risk of PAH.  I would not recommend it for long-term use unless you have a serious condition and see substantial benefit from it.

[timar]

NAC is a powerful mucolytic drug that can break down mucosal barriers throughout the body.  Personally, I would be more concerned about that than the risk of PAH.  I would not recommend it for long-term use unless you have a serious condition and see substantial benefit from it.

Actually it is available as a mycolitic drug in Germany and other European countries. As such is is subject to drug laws and reporting of adverse effects here. This is a translation from the leaflet (ACC Akkut, 600 mg effervescent tablets):

 

4.1.a General disorders and administration site

4.1.a.1 Occasionally
Headache, fever, allergic reactions (itching, hives, skin rash, shortness of breath, skin and mucosal swelling, tachycardia and blood pressure lowering).
4.1.a.2 Very rarely: anaphylactic reactions including shock
Not known: fluid retention in the face.
4.1.b Ear and labyrinth disorders
Uncommon: ringing in the ears (tinnitus).
4.1.c Respiratory, thoracic and mediastinal disorders
Rare: dyspnoea, bronchospasm - predominantly in patients with bronchial hyperreactivity in bronchial asthma.
4.1.d Diseases of the gastrointestinal tract
4.1.d.1 Occasionally
Oral mucositis, abdominal pain, nausea, vomiting, heartburn and diarrhea.
4.1.d.2 Rarely
Digestive disorders.
4.1.d.3 Very rarely
The occurrence of bleeding associated with the administration of acetylcysteine, partly in the context of hypersensitivity reactions.
Very rarely has been reported on the occurrence of severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis in temporal association with the use of acetylcysteine. In most of these cases reported at least one other drug was administered concomitantly, which may have increased the relevant effects on the mucous membrane.

 

The last entry sounds worrysome, but don't forget that the definition of "very rarely" is "less than 1 out of 10,000 patients, including single case reports". It's a pretty short list of adverse effects for any registered drug. But still, there are reported adverse effects.

Edited by timar, 01 March 2015 - 08:02 AM.

[ta5]

As mentioned above, there's evidence that NAC blunts repair and recovery from exercise.

 

Does anyone know how long after you take NAC that it continues to blunt the effects of exercise? Could you take NAC in the morning, and work out in the evening without blunting repair and recovery much?

[cuprous]

I don't think there's another "base" supplement (it's an amino acid) that has more perceived uncertainty around it than NAC.  I've yet to see epidemiological evidence of any dangers other than possible PAH from either acute dosage or long-term supplementation.  The negative studies that people sometimes reference are almost always irrelevant -- bathing nematodes in ultra-high NAC solutions or cell-line studies using similarly outlandish concentrations.

 

On the other hand the positive effects of NAC in real, walking-around humans are astounding.  Slashing homocysteine levels in the blood, dramatically reducing incidence of flu (your immune system uses a lot of glutathione), raising GSH levels in blood of the elderly to that of youth, and on.  Pretty amazing stuff.  In the flu study they gave 1,200mg daily for six months to the elderly and reported it was "well tolerated."

 

And yet it is somehow often regarded with suspicion on this forum even though it is one of the more studied supplements out there.

 

Personally I take 600mg/day a few times a week.  If I'm going out drinking I'll pop a few.  Hangover - tremendously reduced.

[Dolph]

Personally, I take 600 mg NAC daily for a week a few times a year, primarily to detox heavy metals.

 

Never heard about that. Any links to point me and other to sources of more information?

[timar]

Never heard about that. Any links to point me and other to sources of more information?

 

NAC is a thiol and hence has chelating properties - not as much as dithiols such as DMSA and DTPA but it doesn't come with their drawbacks either. Glutathione and related thiols are the body's own physiological chelating agents, with a double action: besides selectively chelating some organic metals and precipitating their catabolism though the Oat1 pathway, they also alleviate the oxidative stress caused by heavy metal toxicity. I think an occasional course of NAC may be a good preventive measure against chronic background-level exposure to heavy metals such as methylmercury from fish.

 

Some studies in chronological order:

 

http://www.ncbi.nlm....pubmed/24959775

http://www.ncbi.nlm....pubmed/24941299

http://www.ncbi.nlm....pubmed/24579807

http://www.ncbi.nlm....pubmed/24485406

http://www.ncbi.nlm....pubmed/24421152

http://www.ncbi.nlm....pubmed/23731375

http://www.ncbi.nlm....pubmed/22820874

http://www.ncbi.nlm....pubmed/22420031

http://www.ncbi.nlm....pubmed/22416658

http://www.ncbi.nlm....pubmed/21421124

http://www.ncbi.nlm....pubmed/20688495

http://www.ncbi.nlm....pubmed/20401649

http://www.ncbi.nlm....pubmed/17429056

http://www.ncbi.nlm....pubmed/12426113

http://www.ncbi.nlm....pubmed/12237339

http://www.ncbi.nlm....pubmed/12117417

http://www.ncbi.nlm..../pubmed/9577247

http://www.ncbi.nlm..../pubmed/9520359

 

Environ Health Perspect. 1998 May;106(5):267-71.
N-acetylcysteine as an antidote in methylmercury poisoning.
Ballatori N1, Lieberman MW, Wang W.

Abstract

Methylmercury is a ubiquitous environmental pollutant and potent neurotoxin. Treatment of methylmercury poisoning relies almost exclusively on the use of chelating agents to accelerate excretion of the metal. The present study demonstrates that oral administration of N-acetylcysteine (NAC), a widely available and largely nontoxic amino acid derivative, produces a profound acceleration of urinary methylmercury excretion in mice. Mice that received NAC in the drinking water (10 mg/ml) starting at 48 hr after methylmercury administration excreted from 47 to 54% of the 203Hg in urine over the subsequent 48 hr, as compared to 4-10% excretion in control animals. When NAC-containing water was given from the time of methylmercury administration, it was even more effective at enhancing urinary methylmercury excretion and at lowering tissue mercury levels. In contrast, excretion of inorganic mercury was not affected by oral NAC administration. The ability of NAC to enhance methylmercury excretion when given orally, its relatively low toxicity, and is wide availability in the clinical setting indicate that it may be an ideal therapeutic agent for use in methylmercury poisoning.

→ source (external link)

Edited by timar, 04 March 2015 - 12:00 AM.

[lemon_]

more?

[ironfistx]

The latest study about antioxidants is terrifying. Scientists think they may boost cancer cells to spread faster.

Since the term "antioxidants" made the leap from the realm of biochemistry labs and into the public consciousness in the  1990s, Americans have come to believe that more is better when it comes to consuming the substance that comes in things like acai berries, green tea and leafy veggies.

A provocative new study published Wednesday in the journal Nature raises important questions about that assumption.

Antioxidants — which include vitamins C and E and beta-carotene, and are contained in thousands of foods — are thought to protect cells from damage by acting as defenders against something called "free radicals" which the body produces as a part of metabolism or that can enter through the environment.

That's all great for normal cells. But what researchers at the University of Texas Southwestern Medical Center found is that antioxidants can work their magic on cancerous cells, too — turbo-charging the process by which they grow and spread.

Researcher Sean Morrison and his colleagues conducted experiments on mice that had been transplanted with skin cancer cells (melanoma) from human patients. They gave nothing to one group. To the other they gave doses of N-acetylcysteine (NAC) which is a common antioxidant that's used in nutritional and bodybuilding supplements and has been used as a treatment for patients with HIV/AIDS and in some children with certain genetic disorders.

The results were alarming: Those in the second group had markedly higher levels of cancer cells in their blood, grew more tumors and the tumors were larger and more widespread than in the first.

"What we're starting to learn is that there can be bad cells from cancer that appear to benefit more from antioxidants than normal cells," he said in an interview.

 

Morrison, director of the Children’s Medical Center Research Institute at UT Southwestern, explained that it has to do with something called oxidative stress.

Scientists have known for a while now that cancer metastasis — especially when it involves spreading a great distance to another part of the body — is a very inefficient process and that many cells die along the way. This is likely due to oxidative stress, which is an inability by the body to counteract the harmful effect of free radicals. When antioxidants supplements are given, the paper hypothesizes, they may give new life to those cancerous cells that are on the edge of dying.

Morrison said that previous studies have shown that the progression of metastasis of human melanoma cells in mice is predictive of their metastasis in humans, which raises concerns about the use of dietary life to those cancerous cells that are on the edge of dying. Scientists have known for a while now that cancer metastasis — especially when it involves spreading a great distance to another part of the body — is a very inefficient process and that many cells die along the way. This is likely due to oxidative stress, which is an inability by the body to counteract the harmful effect of free radicals. When antioxidants supplements are given, the paper hypothesizes, they may give new antioxidants by patients with cancer.

Moreover, melanoma may not be the only type of cancer to be affected this way.

A similar study conducted at Vanderbilt University and published in PLoS One in 2012 involving mice with prostate cancer also showed that antioxidants appeared to increase the proliferation of cells in the pre-cancerous lesions. And another one in rodents with lung cancer published in Science Translational Medicine in 2014 found that normal doses of vitamin E and smaller doses of acetylcysteine, an antioxidant supplement, appeared to lead to a three-fold increase in the number of tumors and caused them to be more aggressive. As a result, the mice given antioxidants died twice as fast the ones in the control group. The reaction appeared be dose dependent with larger doses leading to a more severe reaction.

Morrison said that further study needs to be done to confirm the findings and that cancer patients should still consume antioxidants as part of a healthy diet.

But, he added, "personally, from the results we've seen, I would avoid supplementing my diet with large amounts of antioxidants if I had cancer."

Over the past 20 years, numerous studies were launched to ascertain the effect of antioxidants on other conditions ranging from heart disease to memory loss. Early results have mostly been mixed, but that hasn't stopped food companies from hyping their disease-fighting abilities.

 

Underlining mine.

 

Original https://www.washingt...study-suggests/

Edited by ironfistx, 11 July 2016 - 01:29 AM.

[thedevinroy]

Note to self: avoid cysteine-based supplements when having cancer.

On the other hand, some antioxidants like quercetin are extremely toxic to cancer. NAC is gentle and endogenous, but uncommon plant based compounds are more of a curve ball.


Sent from my iPhone using Tapatalk

[niner]

Yeah, conventional antioxidants aren't a good combination with cancer cells. Mitochondrial antioxidants, on the other hand, suppress metastasis. See the paper by Porporato et al. (Use forum search for details.)

[Dorian Grey]

Or, we can have our cake and eat it too with IP6.  Powerful antioxidant action with cancer inhibition as a "side effect".   

 

http://www.anaturalh...ol_mono_7.3.pdf

 

Mops up free/unbound iron (the ultimate pro-oxidant), while staving cancer cells of the iron they need to grow and multiply.  

 

Looks like we have a winner folks!  

[normalizing]

i read a lot about IP6, havent seen it as supplement. any guidance?

 

also someone can try to configure what was the problem with NAC when i took it in fasting state. it caused me severe mental confusion, fatigue, general malaise and anxiety. it was that one time that it scared me and i dropped it all together and havent used it since. i still cannot figure out what was its mechanism in fasting state that was so different in lets say taking it with food...

[Dorian Grey]

All IP6 comes from the same (one) company in Japan (Tsuno Foods / Wakayama), so branding doesn't matter much.  

 

Jarrow has the best deal I've seen @ less than a dime per cap, available at iherb, swanson, and several other outlets.  

 

http://www.jarrow.co..._Hexaphosphate)

[Skyguy2005]

Not surprising, NAC feels pretty rough to me. Vs. E.g. niacin willow bark or Ginkgo are good
NAC can also inhibit autophagy
In my opinion there's a LOT to be said for trusting in herbs. And related things like aspirin

[Kinesis]

This is not really so new.  Twenty years ago Michael Murray wrote in Encyclopedia of Nutritional Supplements, 1996, p 63, that high dose N-acetylcysteine in studies "actually increased oxidative damage by acting as a pro-oxidant".  Medical uses include aiding bronchial secretions and as an antidote for liver toxicity due to acetaminophen overdose.  I generally only take NAC when taking acetaminophen, and then only with vitamin C.

[Ambrosia]

what's the latest verdict on NAC? anyone well versed with the latest NAC research on it's safety?

 

There is a massive list of benefits being discovered on NAC but i wonder if it's risky.

[capob]

Cancer eats a lot of things more preferentially than normal cells. 

 

 

For instance, glucose uptake preference by overexpressing preferential insulin receptor

[Insulin receptor isoform A favors tumor progression in human hepatocellular carcinoma by increasing stem/progenitor cell features.](https://www.ncbi.nlm...pubmed/30849481)

- `Hepatocellular carcinoma (HCC) is one of the most common and deadly neoplasms. Insulin receptor (IR) exists in two isoforms, IR-A and IR-B, the latter being predominantly expressed in normal adult hepatocytes while IR-A is overexpressed in HCC to the detriment of IR-B ....  IR-A overexpression promoted gene programs related to stemness, inflammation and cell movement`

- cancer cells express outcompeting insulin receptors, seemingly causing a preferential (over normal cells) uptake of glucose.  Good reason to burn fat.

 

For this particular issue with cystein, here is the mechanism:

 

https://www.ncbi.nlm...les/PMC4388159/

`GGT in tumors is expressed over the entire cell membrane and provides tumors with access to additional cysteine and cystine from reduced and oxidized glutathione in the blood and interstitial fluid. Cysteine is rate-limiting for glutathione synthesis in cells under oxidative stress.`

 

 

That doesn't mean you should starve yourself of those things.  Excuse the speculation, but if you want to kill cancer, ketosis with senolytics is the most generally applicable, and if you are bulky, fasting as the avenue.

[cocoonman]

NAC also seems to be increasing the activity of the HPA axis. https://www.ncbi.nlm.../PMC5457771/  

There is some evidence that it may be helpful in bipolar disorder, but avoid it if you have unipolar depression.

 

[Heyguy]

Bump

[brosci]

I was thinking about tacking on a weekend dose of NAC to offer some liver support for a polyphenol-rich lifestyle. I figure with my ketogenic diet, exercise, fasting, curcumin intake, etc, that my liver has to deal with a lot of crap.

 

In reading about NAC, I came across some concerns over "microbleeding" (increased stroke risk?) and amyloid plaques / blood-brain barrier breakdown.

 

"It remains to be seen whether in humans chronic NAC intake may increase amyloid load in the aging human brain and dementia."

https://www.ncbi.nlm...pubmed/24898644

 

As my main goal is to supplement for cognitive / cardiovascular health, I'm not sure if this would be a wise addition to my stack. (Would S-Acetyl-Glutathione make more sense or something else?) What's the latest thought on NAC?

[xEva]

 
NAC is known to break disulfide bonds, which may be a great thing when dealing with thick mucous discharge, but the same mucolytic activity may also be detrimental, at least in some cases.  After all, mucus is secreted for protection from both, irritating agents and pathogens. A user noticed this in another thread:
 

about acetylcysteine... be careful I tried and now my mouth(including my tongue) is shedding skin... lmao caustic stuff

so make sure it is very diluted.. mouthwash'd for 2 minutes with some in water and it didn't hurt, some irritation, so did not expect my skin to die off, but it did... seems fine now

This makes me sure now that my intense stomach problems solved by a 5 month course of omeprazole was from... acetylcysteine and possibly phenibut. definitely wrecked my stomach lining for a while: gastritis, extreme bloating, always "full", nausea, sweating, shaking...etc.

 

But maybe it depends on the dosage -? I discovered how unpleasant concentrated NAC can be when I tested its use as a mouthwash (people were saying it was a great biofilm disruptor for dental plaque -- not a good idea!). It left inside of my mouth feeling sorta 'stripped' (very unpleasant). This makes me wonder what it does to the stomach mucosa when the capsule dissolves sitting in one spot -? It's probably better taken with lotsa food, no?

 

I too would like to hear more opinions on this.

Edited by xEva, 25 May 2019 - 02:29 AM.

[GABAergic]

they have sustained release NAC now. i would think IF NAC causes problems as mentioned, the quick release which is only hour long is the better choice but not the sustained release which claims it can work for a whole day. i tasted one of those NAC caps and they were like acid, because of the sulfur. that could be a reason for digestion issues FOR SOME but not ALL.

im pretty certain people sensitive to NAC might be sensitive to anything containing sulfur, like garlic. garlic is known to cause severe digestive issues, epesecially if taken on empty stomach (as i have found out painfully enough). as Eva says, maybe its best with food. interestingly enough, the label says on empty stomach... hmm

anyway, im more interested in any science against NAC than just personal experiences. the guy Eva quotes could have had stomach issues from dozens of things. including the most common additive in pills, titanium dioxide, which just recently has been show to cause severe gut ssue. although its in so many products EVERYONE uses https://www.frontier...2019.00057/full and since i had NAC with this crap in there, now i wouldnt even know at this point

[brosci]

 
NAC is known to break disulfide bonds, which may be a great thing when dealing with thick mucous discharge, but the same mucolytic activity may also be detrimental, at least in some cases.  After all, mucus is secreted for protection from both, irritating agents and pathogens.

 

Would S-Acetyl-Glutathione or liposomal GSH get around this issue while promoting similar liver health boosts?

[xEva]

Would S-Acetyl-Glutathione or liposomal GSH get around this issue while promoting similar liver health boosts?

 

Sounds like you're more informed on the topic than most of us here. Care to enlighten us?

[Dorian Grey]

I used to take NAC, but got spooked by the pulmonary hypertension issue.  Looked around and it seems like S-Adenosylmethionine (SAM-e) was my best alternative.  

 

https://academic.oup...5/1151S/4824259

 

For liver health, PPC (polyenylphosphatidylcholine) is also remarkably good.  The only substance I've seen that was 100% effective 100% of the time at preventing alcoholic liver damage in primates.  

 

https://www.ncbi.nlm.../pubmed/8276177

 

The reference to dilinoleoylphosphatidylcholine in the paper indicates it was PPC lecithin used in the study, and the polyunsaturated fraction was the effective component.  

 

Apparently PPC even works against carbon tetrachoride poisoning:

 

https://www.scienced...168827897803613

 

Interestingly, the only thing PPC can't protect the liver from seems to be excess iron:

 

https://www.ncbi.nlm...pubmed/10698372

 

For liver health, keep ferritin out of triple digits (under 100)!  

[GABAergic]

polyenylphosphatidylcholine is marketed as PhosChol on amazon and its insanely pricey with real bad reviews. im surprised. dont you think phosphatidyl choline will work just as good? its widely available and cheaper

Edited by GABAergic, 27 May 2019 - 02:39 AM.

[Dorian Grey]

The negative reviews on amazon appear to be due to leakage of one or more capsules.  The third party suppliers aren't storing it properly (59 F-86 F / 15 C-30 C).  Nutrasal moves the most product, & I haven't had a problem with PhosChol I've gotten from them over the years.  If you factor out the one star reviews due to leaking capsules, most of the other reviews are quite positive.  

 

The dilinoleoylphosphatidylcholine (DLPC) component of polyenylphosphatidylcholine (PPC) is stated as the fraction associated with the remarkable liver protection in the studies I linked to above.  PPC is around 50% DLPC, regular lecithin around 5%.  

 

PhosChol ain't cheap, but one cap a day will keep your liver happy under normal circumstances; 2/day if you tipple/alcohol frequently.  If you keep your ferritin under 100, & don't drink regularly, plain Lecithin is probably fine, & far cheaper.   

Edited by Dorian Grey, 27 May 2019 - 03:52 AM.

[GABAergic]

but in comparison to NAC or TUDCA or plain phosphatidyl choline, wouldnt those work just as well?