N-Acetyl-Cysteine (NAC): A Powerful Health Aid

N-Acetyl-Cysteine (NAC) is the precursor (raw material) for the body to make glutathione (GSH). Glutathione is essential to protect your cells and is the most powerful antioxidant in your body. NAC has been used for several decades in clinical medicine as a mucolytic agent (clears up mucus), for respiratory infections and for the treatment of disorders associated with GSH deficiency.

N-Acetyl-Cysteine (NAC) is a supplement form of the amino acid cysteine and is not a drug.

Health benefits of NAC

• Inhibition of inflammation
• Nonantibiotic compound that exerts antimicrobial properties
• Anticarcinogenic and antimutagenic effects against certain types of cancer
• Improves oral and dental health
• Helps replenish glutathione levels in the lungs and reduces inflammation in the bronchial tubes and lung tissue
• Plays an important role in the body’s detoxification process
• Helps to prevent side effects of drugs, drug overdose and environmental toxins
• Can assist with rehabilitation and withdrawal therapy for drug addiction
• Hospital emergency departments regularly give intravenous (IV) NAC to people with an acetaminophen overdose to prevent kidney and liver failure/damage
• Has applications for many types of liver diseases

Therapeutic effects

N-Acetyl-Cysteine (NAC) possesses therapeutic effects over a wide range of disorders. These disorders include cystic fibrosis, acetaminophen poisoning, chronic obstructive pulmonary disease, chronic bronchitis, doxorubicin-induced cardiotoxicity, human immunodeficiency virus infection, heavy metal toxicity, and psychiatric/neurological disorders [1].

NAC is a cysteine pro-drug and glutathione (GSH) precursor that helps scavenge free radicals and bind metal ions into complexes [1]. Because NAC possesses anti-inflammatory activity via inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and modulation of proinflammatory cytokine synthesis [2], it has been used for modulating oxidative stress and inflammation-related diseases [3].

Antioxidants are effective in reducing the cumulative effects of oxidative stress caused by free radicals which are continually attacking the body. N-Acetyl-Cysteine is a direct antioxidant that interacts with the electrophilic groups of free radicals through its free thiol side-chain.  NAC reacts with the hydroxyl radical (·OH), nitrogen dioxide (·NO2), and carbon trioxide ion (CO3·−), and therefore detoxifies Reactive Oxygen Species (ROS) produced by white blood cells (leukocytes) [15]. NAC chelates transition metal ions such as Cu2+ and Fe3+, as well as heavy metal ions such as cadmium (Cd2+), mercury (Hg2+), and lead (Pb2+), through its thiol sidechain to produce complexes. This is called chelation and increases the removal of these toxic metal ions from the body [17].

Although NAC is not an antibiotic, it possesses antimicrobial properties and breaks down biofilms of medically relevant pathogens [4]. This makes NAC a potential candidate for managing oral diseases, especially gum disease.

NAC was shown to inactive Staphylococcus epidermidis biofilm formation in 1997 [47],  and many studies have demonstrated the efficacy of NAC in reducing biofilm formation induced by a broad array of medically significant microorganisms. One of those studies evaluated the antibacterial and biofilm eradication potential of NAC on Enterococcus faecalis [48], one of the most important bacterial pathogens responsible for chronic root canal infections [49]. This study showed that NAC was effective against both the planktonic and biofilm forms of E. faecalis. A more recent study reported that NAC has potent antibacterial effects against multiple planktonic endodontic pathogens (Actinomyces naeslundii, Lactobacillus salivarius, Streptococcus mutans, and E. faecalis) and effectively inhibits biofilm formation by all the monospecies and multispecies bacteria [50]. The biofilm disrupting activity of NAC is significantly better than that of calcium hydroxide or 2% chlorhexidine.

N-Acetyl-Cysteine has a long-established safety record in adults and children; the drug has been approved by the US Food and Drug Administration since 1963. The adverse effects experienced with the use of NAC are somewhat dependent on the route of administration. The clinical effects of NAC have been investigated in a phase I clinical study of 26 volunteers with a 6-month oral administration of NAC. The major reported side effects were gastrointestinal symptoms including intestinal gas, diarrhea, nausea, and fatigue with the highest nontoxic dose being 800 mg/m2/day [81]. In another clinical trial, oral administration of NAC at doses up to 8000 mg/day was reported to cause no significant adverse reactions in patients infected with the human immunodeficiency virus [82].

Absorption of NAC

Considering the poor oral absorption of dietary glutathione (GSH), orally administered NAC has been found to be more efficient than direct GSH administration and is as effective as intravenously administered NAC [83]. Compared with cysteine, the acetyl moiety of NAC reduces the reactivity of the thiol functionality, rendering NAC less toxic and less susceptible to oxidation to disulfide and easier for absorption and distribution [84]. N-Acetyl-Cysteine is rapidly and almost completely absorbed after oral administration in both animals and humans; only 3% of radioactive-labelled NAC is excreted in the feces [85]. Thus, NAC is a better source of cysteine compared with intravenous administration of cysteine.

Oral administration of NAC is preferred despite some clinical situations where other drug delivery routes are required.

Summary

The past decade has witnessed an explosion of data regarding the multifaceted biological activities of NAC, including antioxidant, anti-inflammatory, antimicrobial, and anticarcinogenic activities. The oral cavity is susceptible to oxidative stress from environmental factors which induce inflammation, and even initiate cancer. The actions of NAC and its ability to circumvent the mechanisms of disease progression make it a potential therapeutic agent for intervention in dental and oral disorders.

You may also be interested in this article: https://psychscenehub.com/video/application-of-n-acetylcysteine-nac-from-addiction-to-autism/

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