NAC toxicity

[asecin]

i wonder if i should be worried using it after finding this info:


Researchers at the University of Virginia reported in 2007 study using very large doses in a mouse model that acetylcysteine, which is found in many bodybuilding supplements, could potentially cause damage to the heart and lungs.[23] They found that acetylcysteine was metabolized to S-nitroso-N-acetylcysteine (SNOAC), which increased blood pressure in the lungs and right ventricle of the heart (pulmonary artery hypertension) in mice treated with acetylcysteine. The effect was similar to that observed following a 3-week exposure to an oxygen-deprived environment (chronic hypoxia). The authors also found that SNOAC induced a hypoxia-like response in the expression of several important genes both in vitro and in vivo.
The implications of these findings for long-term treatment with acetylcysteine have not yet been investigated. The dose used by Palmer and colleagues was dramatically higher than that used in humans;[23] nonetheless, effects on normal control of respiration (the hypoxic ventilatory response) have been observed previously in human subjects at more moderate doses.[24]


anyone can either confirm or neglect this ? 8)

i wanna hear mainly from people who have been using NAC themselves for extended period of time for any serious side effects they have noticed.

 

[atara]

I'm surprised there's no mention of S-nitroso-N-acetylcysteine as a metabolic byproduct of NAC in humans -- it should be relatively easy to test for. However, even this nasty sounding metabolite isn't all bad:

http://www.ncbi.nlm.nih.gov/pubmed/16609997

It is certainly possible (and I'd say likely, at least at some dosage levels) that N-acetylcysteine exhibits some sort of chronic toxicity in man, but the study in rats is not enough to confirm this. For example, safrole is carcinogenic in rats but not in humans, IIRC. Most things are toxic at some level, even otherwise benign things like LSD.

 

[asecin]

I'm surprised there's no mention of S-nitroso-N-acetylcysteine as a metabolic byproduct of NAC in humans -- it should be relatively easy to test for. However, even this nasty sounding metabolite isn't all bad:

http://www.ncbi.nlm.nih.gov/pubmed/16609997

It is certainly possible (and I'd say likely, at least at some dosage levels) that N-acetylcysteine exhibits some sort of chronic toxicity in man, but the study in rats is not enough to confirm this. For example, safrole is carcinogenic in rats but not in humans, IIRC. Most things are toxic at some level, even otherwise benign things like LSD.

ill never fully understand why people rely so heavily on rat testing to determine human factors. seriously, safrole is only exclusion ? there are tons. i remember some others, have to find proper infos tho. point is, still humans complete trust the rat model for every chemical testing to this day.
ridiculous.

 

[asecin]

no responses i see.

is this forum for drug users to know how to make drugs and poison themselves or is it about mature general discussion on various chemicals, that have way more importance than your stupid average teen drugs for abuse chemistry ?

if not, please direct me to such forum k tnx.

 

[chaos_destroy]

ill never fully understand why people rely so heavily on rat testing to determine human factors. seriously, safrole is only exclusion ? there are tons. i remember some others, have to find proper infos tho. point is, still humans complete trust the rat model for every chemical testing to this day.
ridiculous.

I guess its because its kind of frowned upon to inject high doses of things into people and then cut them up to look at the effect it had on their organs. You can volunteer if you want but i might pass on that. Rats and monkeys are the only real viable option in many cases and rats are a lot cheaper and easier to work with than monkeys.

 

[asecin]

chaos, thats off topic tho. i mean, i need help with main topic. it has been here for days and i thought this part of the forum was full of people educated in those popular supplements, why not give me good reliable information ? its ridiculous i have to rely on google's bullshit. its mostly filled with so much info, it becomes a pain in the ass to sort it out.

 

[reformer]

OP is not ADD, its ADHD

no responses i see.

is this forum for drug users to know how to make drugs and poison themselves or is it about mature general discussion on various chemicals, that have way more importance than your stupid average teen drugs for abuse chemistry ?

if not, please direct me to such forum k tnx.

c i need help with main topic. it has been here for days and i thought this part of the forum was full of people educated in those popular supplements, why not give me good reliable information ? its ridiculous i have to rely on google's bullshit. its mostly filled with so much info, it becomes a pain in the ass to sort it out.

OK. First off, this isn't Alot of Discussion by Dicks, nor is it Advanced Demands about Drugs.

Its "Advanced Drug *Discussion*".

1) Your OP, and your followups are demanding information, but you provide absolutely zero intellectual contribution other than posting a single UNSOURCED reference that could be readily refuted by 10 more from a pubmed database in 10 minutes.

2) Don't post an experimental abstract, with no reference to original source, with the internal numbered references redacted, and try to raise a false, phantom issue on an unproven issue... THEN demand attention and repeatedly bump your own thread by saying everyone else is immature because they refuse to rise to your unintellectual foray into the ADD forum. Not Winning.

In fact, it's a complex issue, and you probably wouldn't understand the first thing about nitrogen oxide signalling, nitrosothiol chemistry or hypoxic gene induction and tissue remodeling. So don't ask for what you can't take.

Please, prove me wrong. Do your best to reorient this thread back on topic with a lively premise based on your own contribution to the discussion and not a demand or an insult against fellow forum members. Tell us what you know, what you hypothesize and then ask a question.

If your thread hangs for days with no response, it doesn't mean no one can answer, it means it's ambiguous, or just lame.

 

[MeDieViL]

Meh, no case reports of this occuring in humans, knowing how widespreak nac is being used, i wouldnt worry about this shit.

 

[JBrandon]

That was such a beautiful smackdown by reformer. Thank you.

 

[asecin]

OK. First off, this isn't Alot of Discussion by Dicks, nor is it Advanced Demands about Drugs.

Its "Advanced Drug *Discussion*".

1) Your OP, and your followups are demanding information, but you provide absolutely zero intellectual contribution other than posting a single UNSOURCED reference that could be readily refuted by 10 more from a pubmed database in 10 minutes.

ok, your challenge then. you are bluffing. provide 10 sources to refute me. and no, im not vicious. i dont need 10 mins, you can take few days if you like

8)



In fact, it's a complex issue, and you probably wouldn't understand the first thing about nitrogen oxide signalling, nitrosothiol chemistry or hypoxic gene induction and tissue remodeling. So don't ask for what you can't take.


try me. you are accusing now. well done. challanging yourself, challanging me too. causing stir. please do provide as much as you know. your intellectual addition to this thread will inspire me and many others.

Please, prove me wrong. Do your best to reorient this thread back on topic with a lively premise based on your own contribution to the discussion and not a demand or an insult against fellow forum members. Tell us what you know, what you hypothesize and then ask a question.

i know so little, compared to you im futile. reason why i made this thread is TO LEARN MORE BECAUSE I CANNOT OTHERWISE. you assume a lot and expect a lot from people here. as if, i have to know enough to compare and compete with you. reason i post this is, simply lack of data.

If your thread hangs for days with no response, it doesn't mean no one can answer, it means it's ambiguous, or just lame.

i read lots of threads here and most the times what happens to be ignored are too complicated threads for discussion. lack of comercial interest and so on. not everyone is into the same thing i suppose. either way, this thread, i believe based on vast experience here on the forum, is vital to me and others in the long run.

The massage you have entered is too short ? uh... i have done it wrong way i guess by answering it in your own quotes. bah.

 

[asecin]

there, found some good source to pick on that reformer troll

http://www.ncbi.nlm.nih.gov/pubmed/17786245

 

[reformer]

Please learn what ADD is supposed to be about

there, found some good source to pick on that reformer troll

http://www.ncbi.nlm.nih.gov/pubmed/17786245

What's sad is that you sat around, emasculated by my prior post, for a week or more while trying to find a clickable link that would restore your manhood.

What's even more sad is that you still don't get the point of ADD. It's not about dropping a pubmed link and then running for cover, it's about raising topical issues and then providing insights and asking intellegent questions.

The saddest thing of all though is how you can't even gauge the worth and validity of the very publication you trotted out. Do you forget your own words? You do realize you quoted a animal study, right?

ill never fully understand why people rely so heavily on rat testing to determine human factors.

point is, still humans complete trust the rat model for every chemical testing to this day.
ridiculous.

So, your only proof is of the same sort which you despise. Conflicted much?

Please don't even get me started on how 1) You're acting quite trollish yourself with your bumping and insults; 2) NAC is NOT a fucking psychoactive RC, and has no bearing in ADD on BL. Go post in some bodybuilding forum somewhere with the rest of the folks who give a rat's ass about NAC.

BTW- I actually got an advanced degree from a world reknowned university on this exact same topic of nitrosothiols and nitrogen oxides, so I find it quite comical that you quote back to me work that I am very familair with. Coincidence, or cosmic justice?

Finally, so that other forum members have more to do than read flames and blames in this back and forth between my witticisms and your deadly-dull dearth of information or intelligence, I will go ahead and analyze for you the abstract you posted.

1) The main point is one that has been been increasingly acknowledged in the field, e.g. nitric oxide (NO), a vasodilator, isn't transported as such, but is rather shuffled about as the nitrosothiol derivative.

2) Further, the authors propose that their work "challenges conventional views of oxygen sensing and of NO signaling". The traditional mechanism of NO signaling, NO binding to a metal containing enzyme, is not addressed by these authors and in fact they cannot rule out conventional mechanisms in their work, as they didn't try to inhibit the conventional mechanisms with a guanylate cyclase inhibitor. Thier work is not as novel as you might naively suppose. The eNOS knockout mouse model doesn't show anything convincing, except that NO-thiol derivatives (SNOs) are at play.

3) The authors say: "The plasma NAC level at this dose was similar to the target peak level in the human study of the hypoxia-mimetic effects of NAC, though the dose per weight was approximately 40-fold higher and the exposure continuous. Asecin, did you mss this part? The study attempted to find a new, artificial MODEL of pulmonary hypertension... they are not saying that reasonable supplementation in humans is bad. To suggest otherwise isn't only naive, it's just plain wrong. Please recall your own words ont he subject of animal studies as models.

What is the take-home message from this thread?

Asecin, please figure out how to post in ADD. You have much to learn, before you are worthy it would seem.

Also, doses of NAC taken to abrogate liver toxicity for various reasons (NAC is the treatment of choice for tylenol poisoning for example), should not be avoided based on the current research. Reasonable (<1 g NAC/day) have no reason to cause concern.

 

[23536]

(damn asecin chill)

acetylcysteine is a miracle supplement for me. I take hepatotoxic drugs at times--chronically at times--and when I don't co-administer NALC I begin to feel like I ate a big chunk of Chernobyl graphite. The NALC reverses this profound feeling of un-wellness within a couple of days. I dose it at 600 mg po tid (Vitamin Shoppe brand).

My post would be more helpful with blood work. Unfortunately I haven't followed through with it. Sorry.

I do think they have to find the offending metabolite in humans, or monitor pulmonary artery pressure in a controlled setting. Or O2 sats or something. My own blood pressure is unremarkable (currently 119/67 with a heart rate of 60).

 

[23536]

Just found this:

Toxicology Rounds: Lessons from the Courtroom: N-Acetylcysteine Overdose

http://journals.lww.com/em-news/Ful...gy_Rounds__Lessons_from_the_Courtroom_.9.aspx

full text. Very interesting. Apparently only IV NAC can be a serious risk.

 

[raybeez]

There have been over 250 clinical trials using NAC in humans. A search for "n-acetylcysteine clinical trial" on pubmed returns 823 publications. The majority of trials examine NAC as mucolytic, an anti-oxidant in various diseases, or as a protective agent against drug induced hepatoxicity or neprotoxicity (APAP, chemotherapy drugs, etc).

A scan of the literature reveals that typical doses used in anti-oxidant/mucolytic clinical trials range from 0.7 to 3.0 grams/day (orally or inhaled) over a span of 12-52 weeks, in patients as young as 2 years old. There are multiple trials establishing the safety of NAC at these doses over this period of time, and adverse effects are nearly non-existent (example). The worst thing I came across was increased bronchial secretions when taken by young children as an aerosol, and there are certainly no mention of toxic cardiopulmonary. events as reported in that rat study.

Doses of NAC studied as a hepa/nephro protective agent range from 3-6g/day for 3-12 weeks. Similarly no real adverse events have been reported, although conclusions on cardiopulmonary toxicity (such as arterial hypertension) at these doses should be limited, as such toxicity may take longer periods of time to manifest.

 

[malaparte]

Acetylcysteine is actually used in Germany a mucolytic medcine.
Lower doses(200/300mg) are OTC,higher are prescription only.
It is used for years and considered safe also for children from the age of 2 upwards.
Biggest warning is to not combine with something which supresses the cough reflex
(i.e. codeine),because then the solved mucus doesnt get transported out of the lungs.

 

[atrollappears]

Biggest warning is to not combine with something which supresses the cough reflex
(i.e. codeine),because then the solved mucus doesnt get transported out of the lungs.

You must be much smarter over there considering one of the best selling cold products in America (robitussin DM) is exactly that. I've always wondered why.

 

[nuke]

I have consumed pounds of NAC and as far as I can tell I am fine.

 

[Amu]

Same here, I take 4+ grams NAC daily, wonderful supplement

 

[golden1]

Can't say I notice anything bad @ 600-1200mg /day, been about 2weeks. I notice it reduces ... hm how to put it, like this general mental agitation that makes it hard to focus or feel comfortable at times.

I'm dependant on benzos, so the feeling may not be relate-able as I'm guessing its a side effect of being slightly under dose/tapering/and a side effect of w/d