Prior to its approval for use as a mucolytic drug, N-acetylcystine was known as the potent-smelling ingredient in garlic that made it good at addressing mucous-smothered infections (1). The chemical is made of the amino acid cystine which is a sulphur rich amino acid. When you open up a bottle of NAC, there is no mistaking that it is somehow related to the allicin family as the sulphur rich smell is too overpowering to miss. Nonetheless, NAC supplements are usually simple synthetics that contain a single ingredient precursor to cysteine.
Why Not Take The Natural Path?
If NAC was a simple chemical compound picked out from the long list of functional compounds found in garlic, why not just take garlic and skip the chemical? The truth is, NAC, though incredible in functional profile, is very poorly absorbed. Considering the amount that naturally occurs in garlic along with the poor oral absorbability of NAC, one would have to take a very large amount of garlic to be able to obtain only a small portion of NAC (2). Taking very large amount of garlic many not be a suitable option for everyone. Thus, keeping in mind the high safety profile of NAC, it was established that a synthetic exact equivalent is of better therapeutic value (1).
The Pharmaceutical Therapeutic Value
Intravenous NAC shines as an emergency use pharmaceutical in the realm of acetaminophen toxicity (3). Better known under the brand name Tylenol, acetaminophen is a potent hepatotoxic in doses of more than 150mg/Kg body weight (4). It damages liver tissue because of the lack of availability of adequate enough amounts of glutathione to clear the toxic metabolites of acetaminophen. Glutathione is the body's anti-oxidizing detox chemical and is significantly important for healthy tissue synthesis, immune health and liver function (5).
The Glutathione Conundrum
If the main reason why NAC is so great is because of its glutathione enhancement effects, why not just supplement with glutathione? Glutathione is a highly reactive anti-oxidant that has even poorer oral availability than NAC (6). Most Glutathione supplements have to come in a significantly more expensive liposomal preparation for them to have minimal therapeutic availability. Though glutathione supplements have their place in the naturopathic world it is more affordable to supplement with NAC. Additionally, though very important for healthy lung function, research does not show as significant of a mucolytic effect to glutathione, if any (7).
Why Is It Important To Be Antioxidant Mucolytic?
Glutathione is a pivotal antioxidant and detox molecule that is functional in many major organs including the lung, liver and kidney. On the other hand, NAC supports glutathione levels facilitating detox, but has a couple of extra advantages including the fact that it counts as a two-in-one for respiratory illness (8). NAC facilitates the breakdown of mucous and protects the surrounding tissue from the pro-oxidizing agents that the body naturally makes in the process of immune defence. Immune defence results in the formation of highly reactive "bleach" like chemicals that are meant to neutralize invaders. As the pro-oxidizing mechanism can sometimes be triggered by a high pathogen load, those chemicals end up stuck inside of the mucous matrix irritating surrounding tissues (9). NAC facilitates the clearance with mucous and enhances glutathione to remove as many reactive oxygen species as possible, preventing further organ damage and facilitating repair (10).
How Safe Is Too Safe?
According to research NAC has a very wide therapeutic window. There is one recorded case of mortality of a suicide patient who suffered complication with the use of an IV infusion of 150mg/Kg/30min (11) (dose of standard use for Acute Respiratory Distress) (12). IV NAC availability is 100% while oral NAC bioavailability is 9.1% (2). Keeping the previous numbers in mind, most supplements come at a dose of 500 mg-1000 mg. After case evaluation, most naturopaths find themselves not needing to advice more than the 1000 mg for therapeutic effect. Individual cases may benefit form higher doses as a healthcare practitioner evaluates.
NAC is a supplement with a unique therapeutic profile that may help individuals heal faster from a variety of conditions including respiratory illness, acute colds and flus and even allergic reactions. Some significantly difficult to deal with, chronic conditions like COPD, emphysema and cystic fibrosis may highly benefit from a medically evaluated high dose of NAC. Other uses of NAC as a whole body detox, liver support, after toxin exposure and as a hormone detoxifying agent may also be helpful upon medical evaluation.
NAC Commonly Recommended with:
Dewi, A. D. R., Kusnadi, J., & Shih, W. L. (2017). Comparison of the main bioactive compounds and antioxidant activity from garlic water-soluble and garlic oil. KnE Life Sciences, 20-34.
Olsson, B., Johansson, M., Gabrielsson, J., & Bolme, P. (1988). Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. European journal of clinical pharmacology, 34(1), 77-82.
Smilkstein, M. J., Bronstein, A. C., Linden, C., Augenstein, W. L., Kulig, K. W., & Rumack, B. H. (1991). Acetaminophen overdose: a 48-hour intravenous N-acetylcysteine treatment protocol. Annals of emergency medicine, 20(10), 1058-1063.
Tenenbein, M. (2004). Acetaminophen: the 150 mg/kg myth. Journal of Toxicology: Clinical Toxicology, 42(2), 145-148.
Mitchell, J. R., Jollow, D. J., Potter, W. Z., Gillette, J. R., & Brodie, B. B. (1973). Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. Journal of Pharmacology and Experimental Therapeutics, 187(1), 211-217.
Byeon, J. C., Lee, S. E., Kim, T. H., Ahn, J. B., Kim, D. H., Choi, J. S., & Park, J. S. (2019). Design of novel proliposome formulation for antioxidant peptide, glutathione with enhanced oral bioavailability and stability. Drug delivery, 26(1), 216-225.
Konrad, F., Schoenberg, M. H., Wiedmann, H., Kilian, J., & Georgieff, M. (1995). The application of n-acetylcysteine as an antioxidant and mucolytic in mechanical ventilation in intensive care patients. A prospective, randomized, placebo-controlled, double-blind study. Der Anaesthesist, 44(9), 651-658.
Dodd, S., Dean, O., Copolov, D. L., Malhi, G. S., & Berk, M. (2008). N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility. Expert opinion on biological therapy, 8(12), 1955-1962.
Faith, M., Sukumaran, A., Pulimood, A. B., & Jacob, M. (2008). How reliable an indicator of inflammation is myeloperoxidase activity?. Clinica Chimica Acta, 396(1-2), 23-25.
Sucu, N., Cinel, I., Unlu, A., Aytacoglu, B., Tamer, L., Kocak, Z., ... & Oral, U. (2004). N-acetylcysteine for preventing pump-induced oxidoinflammatory response during cardiopulmonary bypass. Surgery today, 34(3), 237-242.
Smilkstein, M. J., Knapp, G. L., Kulig, K. W., & Rumack, B. H. (1988). Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. New England Journal of Medicine, 319(24), 1557-1562.
Jepsen, S. O. R. E. N., Herlevsen, P., Knudsen, P. R. E. B. E. N., Bud, M. I., & Klausen, N. O. (1992). Antioxidant treatment with N-acetylcysteine during adult respiratory distress syndrome: a prospective, randomized, placebo-controlled study. Critical care medicine, 20(7), 918-923.