Summary: NAC - N-acetylcysteine - has been shown to reduce the severity of influenza, cystic fibrosis and COPD. It is available as a supplement. In view of the potential benefit it is worth consideration as a prophylactic measure against coronavirus respiratory illness. Reported adverse effects have been rare and not serious, however, interested parties should review what has been written about them below.
Usefulness of NAC
N-acetylcysteine is a modified form of the amino acid cysteine. NAC is FDA approved for use as IV treatment of liver failure due to acetaminophen poisoning, under the brand name Acetadote. NAC is a precursor for the biosynthesis of glutathione (GSH):
GSH protects cells by neutralising (i.e., reducing) reactive oxygen species.... Glutathione is also employed for the detoxification of methylglyoxal and formaldehyde, toxic metabolites produced under oxidative stress.
From an article entitled: Nutraceuticals have potential for boosting the type 1 interferon response to RNA viruses including influenza and coronavirus, NAC reduces the frequency of influenza symptoms:
Glutathione production can also be promoted by administration of N-acetylcysteine (NAC), which has been shown to be protective in rodents infected with influenza.16., 17., 18. In a little-noticed 6-month controlled clinical study enrolling 262 primarily elderly subjects, those receiving 600 mg NAC twice daily, as opposed to those receiving placebo, experienced significantly fewer influenza-like episodes and days of bed confinement.19 Although the rate of seroconversion to influenza A was comparable in the two groups – indicating that they were exposed at the same frequency – only 25% of the virus-infected subjects in the NAC group developed symptoms, as contrasted to 79% of those of placebo. (Given the carnage that influenza wreaks among the elderly, it is most regrettable that no effort has been made to replicate this study, conducted over 20 years ago.) The particular utility of NAC in the elderly might reflect the fact that plasma cysteine levels and cellular glutathione levels tend to decline with advancing age.20"
COPD [Chronic obstructive pulmonary disease] patients treated with NAC had fewer exacerbations:
we noted 497 acute exacerbations in 482 patients in the N-acetylcysteine group who received at least one dose and had at least one assessment visit ...and 641 acute exacerbations in 482 patients in the placebo group (... risk ratio 0·78, ... p=0·0011).
Meta-analysis of use of NAC in COPD:
A meta-analysis of randomized controlled trials retrieved from PubMed and Medline databases (12 trials; 2691 patients). High-dose [relative ratio (RR) = 0.90...P = 0.041] and low-dose (RR = 0.83... P = 0.043) NAC reduced COPD exacerbation prevalence. Long-term (≥6 months), but not short-term, NAC reduced exacerbation prevalence (RR = 0.85...P = 0.024).
NAC has been reported to be useful in two studies of cystic fibrosis patients:
Results: Lung function (FEV1and FEF25–75%) remained stable or increased slightly in the NAC group but decreased in the placebo group
High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis:
N-acetylcysteine, given orally in high doses (0.6 to 1.0 g three times daily, for 4 weeks). ... Consistently, neutrophil burden in CF airways was decreased upon treatment (P = 0.003), as was the number of airway neutrophils actively releasing elastase-rich granules (P = 0.005)...positive treatment effects ... included decreased sputum IL-8 levels (P = 0.032).
Safety:
There are reports of anaphylactoid reactions when NAC has been used at very high dosage for liver toxicity - 150mg per kilogram loading dose. This would amount to 7.5 g for a 50 kg / 110 pound person, or more for someone heavier. We are interested in the safety of NAC when used at less than 1/10 that dosage dosage, 600 mg, 2-3 times a day. Here is a safety review of studies of patients taking moderate dosages of NAC for prevention of ototoxicity:
A total of 5014 patients received a median of 1200 mg (IQR 600–1800) of NAC per day over a median of 24 weeks (IQR 12–54), and 4974 patients served as a control group. .... No deaths were reported as being attributable to NAC administration. There was no difference in the risk of overall withdrawal ... in the NAC compared with the control group. Furthermore, there was no increased risk of withdrawal attributable to NAC... when comparing NAC with placebo or control group ...The most commonly reported side effects were abdominal pain, nausea, and vomiting and diarrhoea. The risk of abdominal pain (pooled RR 1.4 ...), nausea and vomiting (pooled RR 2.0 ...), diarrhoea (pooled RR 1.8...) and arthralgia [joint pain] (pooled RR 2.2 ...) were all significantly increased in patients receiving NAC compared with placebo. However, the pooled risk differences for all these side effects were relatively small, ranging from 1.6% for diarrhoea to 6.1% nausea. The risks of headache, rash, dizziness, cramps and drowsiness were not significantly increased
Here are the results of a meta-analysis of NAC safety used in moderate dosage for pulmonary fibrosis:
However, the present meta-analysis identified no significant difference in the incidence of adverse effects between NAC therapy and the control treatments. Furthermore, the present analysis revealed that NAC therapy did not increase the mortality of IPF patients
Here is a safety readout for NAC at a daily dosage of 2.7 g in cystic fibrosis patients:
We found no evidence of PH [pulmonary hypertension] upon high-dose oral NAC treatment over 24 weeks, which supports the safe, long-term use of this drug in CF.
Some animal studies have found potential adverse effects
Here is a study showing NAC caused pulmonary arterial hypertension (PAH) in an animal model. PAH is a serious and unusual condition. When there was a rash of cases of PAH caused by a diet pill it was rapidly tracked down to the source. NAC is a common supplement. If it were causing PAH in humans it seems likely it would have been noticed. Poor exercise tolerance is a symptom of PAH. I personally have been taking NAC for years and have excellent exercise tolerance. Moreover the study of cystic fibrosis cited above found no evidence of this occurring in humans.
Another study found NAC induced development of cancer in an animal model. Apparently this was a result of NAC being an antioxidant, preventing DNA damage, and down regulating the p53 gene as a result. This concern applies to any antioxidant, such as vitamin E which was also found to have the same effect. For what is worth, folate supplementation is even worse - it has been demonstrated to increase cancer incidence in humans. I wrote about that here - Folate Supplementation Carcinogenic.
These animal model results have not been reported in humans. However, each person should consider all factors pro and con and make their own decision as to whether NAC supplementation is appropriate.
Availability, Quality
NAC is available over-the-counter as a supplement at Amazon and other suppliers of supplements such as Swanson and Vitacost. Subscription site Consumerlab has tested 11 different brands of NAC — all contained the amount stated on the label and none was noted to have contamination.
Conclusion
NAC is useful for reducing the severity of diverse respiratory conditions, although it has yet to be proven effective against coronavirus. After weighing the potential risks and benefits it is worth consideration as a prophylactic treatment in view of the possibility of contracting coronavirus illness.
Crossposted at: healthunlocked.com/...