Verdict on NAC: Is it safe? (Study inside from 2007 saying otherwise)

I have been taking 600mg 2x/day for ear related problems.

Here is the study I saw posted on longecity:

A type of antioxidant may not be as safe as once thought
By University of Virginia Health System
Sep 4, 2007 - 9:01:29 PM


Charlottesville, Va., Sept. 4, 2007 - Certain preparations taken to enhance athletic performance or stave off disease contain an anti-oxidant that could cause harm. According to new research at the University of Virginia Health System, N-acetylcysteine (NAC), an anti-oxidant commonly used in nutritional and body-building supplements, can form a red blood cell-derived molecule that makes blood vessels think they are not getting enough oxygen. This leads to pulmonary arterial hypertension (PAH), a serious condition characterized by high blood pressure in the arteries that carry blood to the lungs. The results appear in the September issue of the Journal of Clinical Investigation.

“NAC fools the body into thinking that it has an oxygen shortage,” said Dr. Ben Gaston, UVa Children’s Hospital pediatrician and researcher who led the study. “We found that an NAC product formed by red blood cells, know as a nitrosothiol, bypasses the normal regulation of oxygen sensing. It tells the arteries in the lung to ‘remodel’; they become narrow, increasing the blood pressure in the lungs and causing the right side of the heart to swell.”

Gaston notes that this is an entirely new understanding of the way oxygen is sensed by the body. The body responds to nitrosothiols, which are made when a decreased amount of oxygen is being carried by red blood cells; the response is not to the amount of oxygen dissolved in blood. He says that this pathway was designed much more elegantly than anyone had previously imagined. “We were really surprised”, he said.

The research team administered both NAC and nitrosothiols to mice for three weeks. The NAC was converted by red blood cells into the nitrosothiol, S-nitroso-N-acetylcysteine (SNOAC). The normal mice that received NAC and SNOAC developed PAH. Mice missing an enzyme known as endothelial nitric oxide synthase did not convert NAC to SNOAC, and were protected from the adverse effects of NAC, but not SNOAC. This suggests that NAC must be converted to SNOAC to cause PAH.

Could regular use of NAC produce the same effects in humans" The next step is to determine a threshold past which antioxidant use becomes detrimental to heart or lung function, according to Dr. Lisa Palmer, co-researcher of the study.

“The more we understand about complexities in humans, the more we need to be aware of chemical reactions in the body,” said Palmer.

According to Gaston and Palmer, NAC is being tested in clinical trials for patients with cystic fibrosis as well as other conditions; and clinical trials with nitrosothiols are being planned. These results, Palmer says, should motivate researchers to check their patients for PAH.

The results also open up a range of possibilities in treating PAH. Palmer added that the signaling process could be restorative and healing if they figured out how to keep NAC from fooling the body.

“From here we could devise new ways for sensing hypoxia or we could in theory modify signaling to treat PAH,” Palmer said.

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Thanks for any feedback in advance!

sizzlinghairs - On several occasions I was hit with this question.

Here is the short answer: The respiratory system of mice cannot be extrapolated to humans. For that reason, NAC is good for humans, but not so good for mice.

Thanks for the feedback on that study. But I have seen others that cast NAC in a negative light as well (pardon the long post). The second study is the most concerning and definitely wondering your feedback on that as it was done in humans:

http://www.ncbi.nlm....les/PMC3913600/


Long-Time Treatment by Low-Dose N-Acetyl-L-Cysteine Enhances Proinflammatory Cytokine Expressions in LPS-Stimulated Macrophages

Abstract

N-acetyl-L-cysteine is known to act as a reactive oxygen species scavenger and used in clinical applications. Previous reports have shown that high-dose N-acetyl-L-cysteine treatment inhibits the expression of proinflammatory cytokines in activated macrophages. Here, we have found that long-time N-acetyl-L-cysteine treatment at low-concentration increases phosphorylation of extracellular signal-regulated kinase 1/2 and AKT, which are essential for the induction of proinflammatory cytokines including interleukin 1β and interleukin 6 in lipopolysaccharide-stimulated RAW264.7 cells. Furthermore, long-time N-acetyl-L-cysteine treatment decreases expressions of protein phosphatases, catalytic subunit of protein phosphatase-2A and dual specificity phosphatase 1. On the other hand, we have found that short-time N-acetyl-L-cysteine treatment at low dose increases p53 expression, which inhibits expressions of proinflammatory cytokines. These observations suggest that long-time low-dose N-acetyl-L-cysteine treatment increases expressions of proinflammatory cytokines through enhancement of kinase phosphorylation.

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And then this study that shows NAC interrupts the muscle rebuilding process in humans:

http://www.ncbi.nlm.nih.gov/pubmed/23719546

Thiol-based antioxidant supplementation alters human skeletal muscle signaling and attenuates its inflammatory response and recovery after intense eccentric exercise.
Michailidis Y1, Karagounis LG, Terzis G, Jamurtas AZ, Spengos K, Tsoukas D, Chatzinikolaou A, Mandalidis D, Stefanetti RJ, Papassotiriou I, Athanasopoulos S, Hawley JA, Russell AP, Fatouros IG.
Author information
Abstract
BACKGROUND:

The major thiol-disulfide couple of reduced glutathione (GSH) and oxidized glutathione is a key regulator of major transcriptional pathways regulating aseptic inflammation and recovery of skeletal muscle after aseptic injury. Antioxidant supplementation may hamper exercise-induced cellular adaptations.
OBJECTIVE:

The objective was to examine how thiol-based antioxidant supplementation affects skeletal muscle's performance and redox-sensitive signaling during the inflammatory and repair phases associated with exercise-induced microtrauma.
DESIGN:

In a double-blind, crossover design, 10 men received placebo or N-acetylcysteine (NAC; 20 mg · kg(-1) · d(-1)) after muscle-damaging exercise (300 eccentric contractions). In each trial, muscle performance was measured at baseline, after exercise, 2 h after exercise, and daily for 8 consecutive days. Muscle biopsy samples from vastus lateralis and blood samples were collected before exercise and 2 h, 2 d, and 8 d after exercise.
RESULTS:

NAC attenuated the elevation of inflammatory markers of muscle damage (creatine kinase activity, C-reactive protein, proinflammatory cytokines), nuclear factor κB phosphorylation, and the decrease in strength during the first 2 d of recovery. NAC also blunted the increase in phosphorylation of protein kinase B, mammalian target of rapamycin, p70 ribosomal S6 kinase, ribosomal protein S6, and mitogen activated protein kinase p38 at 2 and 8 d after exercise. NAC also abolished the increase in myogenic determination factor and reduced tumor necrosis factor-α 8 d after exercise. Performance was completely recovered only in the placebo group.
CONCLUSION:

Although thiol-based antioxidant supplementation enhances GSH availability in skeletal muscle, it disrupts the skeletal muscle inflammatory response and repair capability, potentially because of a blunted activation of redox-sensitive signaling pathways. This trial was registered at clinicaltrials.gov as NCT01778309.