Research and Reference

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It is well established that N-Acetyl-Cysteine (NAC) or cysteine is a precursor to glutathione (GSH) 1-3 . However, it
is important to note that NAC is also a precursor to hydrogen sulfide 1, 4, 5 , inorganic sulfate 6 , taurine 7, 8 , Coenzyme
A 9 and albumin 10 . It is, therefore, clear that NAC has many physiological functions, apart from being an
antioxidant precursor to GSH.
During chronic illness there is a rapid depletion of sulfur amino acids due to oxidative stress or inflammation-
induced proteolysis 4 , therefore amino acid replenishment becomes critical during illness 6 . NAC supplementation
has been demonstrated to successfully replenish sulfur amino acid levels 4 . There exist a direct correlation
between GSH and inorganic sulfate levels. Any dietary excess of the sulfur amino acids cysteine and methionine are
stored in the form of GSH in the liver. Low GSH levels indicate that the levels of inorganic sulfate will be low too.
Inorganic sulfate is the substrate for sulfation and, therefore, detoxification of many endogenous steroid hormones,
catecholamines, cholesterol, cresols, phenols and bile salts 29-31, apart from exogenous drugs, toxins and
xenobiotics 11, 12 . Inorganic sulfate is also the substrate for sulfation of glycosaminoglycans 13 , which play a very
important role in the glycocalyx of the extracellular matrix. It is the degree and position of the sulfate groups that
determine biological function. Sulfated glycosaminoglycans are playing a major role in barrier function and pathogen
evasion, immune and inflammation modulation, coagulation and mechanotransduction 14-18 .
Various research studies confirm that NAC modulates the immune system, inhibits viral binding and suppresses
replication 19 , plus reduces inflammation 1, 4, 20, 21 . Furthermore, NAC has antibiofilm 19 and antioxidant properties 4, 22, 23 ,
apart from its clinical benefits such as in cough and dry eyes, and as mucolytic 21, 24 . Research studies in the elderly
found that NAC treatment significantly reduced the frequency of influenza and the severity and duration of most of
the symptoms 25-27 . It has been demonstrated that NAC inhibits NF-κB and replication of influenza viruses in human
lung epithelial cells 1, 26, 28 .
NAC protects the lungs of smokers, by attenuating inflammation and lung airspace enlargement 1 . Various
neurological studies demonstrated the beneficial role of NAC in recovery facilitation after cerebral ischemia and traumatic brain injury, as well as in the treatment of cerebrovascular vasospasm after subarachnoid haemorrhage 2 . NAC supplementation improved brain functional connectivity and cognitive performance in psychosis,
as a significant improvement in working memory 29, 30 .
It was found that NAC potentiates the vasodilator and antiaggregatory effects of NO, which proof to be valuable in
the context of acute heart failure, myocardial ischemia and infarction 1 . NAC supplementation also improved renal
oxygenation in acute kidney injury in a rat model by decreasing free radicals 31 and increasing inorganic sulfate levels.
Administration of NAC also resulted in the proliferation of lymphocytes and inhibited the downstream activities post
TNFɑ receptor activation and gene expression of TNFɑ and IL-6, while under oxidative stress 25 . It was demonstrated
that an infusion of NAC attenuated hyperglycaemia induced reduction of the endothelial glycocalyx volume, which
was associated with impairment of flow-mediated vascular dilation and activation of the coagulation system 32 .
NAC's potential therapeutic benefits, therefore, include replenishing intracellular GSH and inorganic sulfate levels,
scavenging ROS radicals extracellularly, as well as suppressing cytokines and establishing T cell protection, thus
mitigating inflammation, coagulation, and tissue injury 1, 25, 27 during viral infection and other chronic disease
processes.

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