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
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.