Is N-acetylcysteine (NAC) Safe?


Researchers at the University of Virginia Health System have discovered troubling side effects of N-acetylcysteine (NAC), a common antioxidant used in nutritional and bodybuilding supplements.

NAC can form a red blood cell-derived molecule called nitrosothiol that fools your body into thinking there’s an oxygen shortage, which can lead to pulmonary arterial hypertension (PAH).

PAH is a serious condition, where the arteries in the lungs narrow, increasing the blood pressure in your lungs, causing the right side of your heart to swell.

Lead researcher Dr. Ben Gaston, noted that this is an entirely new understanding of how oxygen is sensed by the body. As it turns out, your body responds to the nitrosothiols, which are created when a decreased amount of oxygen is carried by red blood cells – not to the amount of oxygen dissolved in the blood.

So far, studies have only been performed on mice. The next step is to determine the threshold at which the antioxidant becomes detrimental to heart and lung function in humans.

Journal of Clinical Investigation September, 2007; 117(9):2592-601 tool=pubmed&pubmedid=17786245

NO transfer reactions between protein and peptide cysteines have been proposed to represent regulated signaling processes. We used the pharmaceutical antioxidant N-acetylcysteine (NAC) as a bait reactant to measure NO transfer reactions in blood and to study the vascular effects of these reactions in vivo.

NAC was converted to S-nitroso-N-acetylcysteine (SNOAC), decreasing erythrocytic S-nitrosothiol content, both during whole-blood deoxygenation ex vivo and during a 3-week protocol in which mice received high-dose NAC in vivo.

Strikingly, the NAC-treated mice developed pulmonary arterial hypertension (PAH) that mimicked the effects of chronic hypoxia. Moreover, systemic SNOAC administration recapitulated effects of both NAC and hypoxia. eNOS-deficient mice were protected from the effects of NAC but not SNOAC, suggesting that conversion of NAC to SNOAC was necessary for the development of PAH.

These data reveal an unanticipated adverse effect of chronic NAC administration and introduce a new animal model of PAH. Moreover, evidence that conversion of NAC to SNOAC during blood deoxygenation is necessary for the development of PAH in this model challenges conventional views of oxygen sensing and of NO signaling.

I had some thought on buying NAC but I only planned on taking in a .25 gram dose. It seems that this also has another offsetting effect: from what I was able to find out taking this requires that you take 3x as much vitamin C since is can become an oxidant.

It’s benefits seem to outweigh the risks…for now. I still think my money would be best spent elsewhere.


You’re right about the vitamin c thing.

At first, I rather panicked when I read those studies because I’ve been taking NAC for years (not separately, but it’s in my multi vitamin).

However, then I discovered that this study

  1. was performed on mice with much higher levels of NAC than humans would take as a supplement.

  2. involved giving NAC intravenously - yet oral NAC is metabolised in the gut wall and liver that would lead to rather different metabolic pathways.

  3. There has not been a single case report of a human developing pulmonary arterial hypertension as a result of NAC supplementation.

I guess it could be safe then. Do you think this would be an excellent addition to any detox stack since it helps to take out mercury? I currently take AKG to remove ammonia and this seems like a good addition to AKG, what do you think?

freedomfighter -

try eating more cilantro to remove mercury - is used in japan as a medicine for this very thing. much safer too. also look up chlorella for heavy metal detoxing.

[quote]lil_azn wrote:
freedomfighter -

try eating more cilantro to remove mercury - is used in japan as a medicine for this very thing. much safer too. also look up chlorella for heavy metal detoxing. [/quote]

Alright, I’ll use that instead just to play it safe, in case NAC turns out to be a lot less safe then we think.