N-acetyl-cysteine 101

Highlight

• N-acetyl-cysteine (NAC) is the supplemental form of the amino acid cysteine. It acts as the precursor for cysteine production in our body.
• NAC is commonly used in medical settings to treat painkiller overdose (paracetamol) & to break down thick mucus.
• Glutathione is one of the most powerful antioxidants in human’s body. NAC initiates the production of cysteine, which in turn promotes glutathione production in our body.
• NAC is able to alleviate health complications associated with obesity such as insulin resistance, lipid accumulations, and cell damages from oxidative stress.
• NAC treatment can be combined with other drugs or natural products to enhance its efficacy and effects.
• NAC protects the brain and nervous system by regulating some of the key neurotransmitter systems & by increasing the production of antioxidants in the brain.
•  NAC possesses the ability to protect humans from heart injuries and diseases. Though, clinical studies done were mainly on animals and tissues.
• NAC intake is generally safe for a wide group of population.
• Very little to no side effects have been reported since its administration for human consumption.
• Consult your doctor & dietitian before taking it to make sure no health issues occur.
• Avoid taking NAC with nitroglycerin and/or activated charcoal.
• If you have asthma, gastric hemorrhage, and/or liver diseases, consult your doctor prior to taking NAC.

1. Introduction

Chances are you have heard about N-acetyl-cysteine (NAC) somewhere that it triggers you to look it up online. A quick search might direct you to several NAC supplements suggestions that you can buy. They can be found in your local drugstore and pharmacies too. So what does it actually do? And do you need to consider consuming it for health improvement? 

2. What is NAC

Traditionally, N-acetyl-cysteine (NAC) is a commonly prescribed drug used in a clinical setting to treat painkiller overdoses and to thin the mucus in patients with pulmonary issues. The World Health Organization (WHO) recognises NAC as a relevant medication needed in a basic healthcare system. In the clinical and research settings, NAC is also quite a popular molecule as it is widely used in various research.³ 

On a molecular level, NAC acts as the precursor for one of the amino acids in our body, cysteine. Which means it is the starter molecule needed for cysteine production & release. Cysteine is needed for many purposes in our body especially for the production of glutathione.

3. NAC functions

I. Replenishes glutathione ¹

Glutathione is one of the most powerful antioxidants in the human body. However, its production in our body is limited by a few factors. One of them is the level of cysteine available. If cysteine storage is low, only so much glutathione can be produced.

This is where NAC comes to support this process by initiating the release of cysteine. As enough cysteine becomes available, our body can then start to generate glutathione as it needs.

Our body’s requirement of glutathione changes in different situations and health conditions. It increases when we get sick, get exposed to pollutants, and when we are undergoing a stressful situation.

NAC’s efficiency in replenishing glutathione’s level in our blood plasma has been shown in several studies. Oral supplementation of NAC resulted in a higher plasma glutathione level compared to when subjects were to take oral supplementation of Glutathione and L-cysteine.^4,5

II. Improves complications associated with obesity ²

NAC has also been shown to reduce health complications linked to obesity including insulin resistance, fat cell accumulations, and damages caused by the oxidative stress & inflammation in fat cells.

It is believed that one of the ways NAC works is by suppressing the proteins & markers that cause fat cells accumulation. On top of that, it is also able to regulate the proteins involved in the insulin signaling pathway, hence increasing insulin sensitivity and improving insulin resistance.

These effects were best seen when NAC treatment is paired or combined with other obesity-related drugs or natural products such as curcumin, EGCG, and amentoflavone. The best result from this treatment is observed when NAC is combined with the polyphenol in green tea called EGCG. In addition to that, when NAC is taken together with resveratrol found in red grapes and red wine, fibroblast growth factor 2 is suppressed, therefore inhibiting the production of free radicals.

III. Nerves and brain protections ³

In the brain, NAC has the ability to penetrate the blood-brain barrier (BBB) efficiently, increasing the glutathione level in the brain. Once inside a cell, NAC can quickly initiate the release of cysteine. As a glutathione precursor, cysteine’s presence then allows glutathione to be synthesized. With the increase of glutathione in the brain, free radicals such as ROS will be scavenged at a higher rate, thus reducing oxidative damages in the brain.

In the brain and nervous system, NAC poses an important role in modulating a number of key neurotransmitter systems. Neurotransmitters are chemical messengers that transport & transmit signals from a neuron to other target cells all over our body. Many neuropsychiatric conditions such as addiction & schizophrenia can evolve when the system that controls neurotransmitters in the brain gets disrupted. Neuron damages & degenerations that were associated with this disordered system can also be prevented and reduced with NAC treatment. 

NAC also preserves the mitochondria in the brain and helps to prevent memory loss as people age. It prevents the death of dopaminergic neurons (the main source of dopamine in our brain), which is shown in Parkinson’s disease patients.

IV. Protection from heart diseases ⁴

Due to its ability to promote the production of the antioxidant glutathione, NAC also exhibits protective properties on the heart. This is mainly by increasing the antioxidant activities in that organ to fight oxidative stress caused by free radicals. It was also reported that NAC has the ability to decrease the activation of a factor that induces heart muscle injury and reduces the cell death in heart cells.

Bear in mind several of the past studies in this area were done in animals and cell tissues. More clinical studies on humans need to be established to confirm these beneficial effects of NAC on the human heart.

4. Do you need to take NAC?

Just like taking any health supplements, the necessity may vary depending on an individual’s needs. With the potency and the efficacy of NAC, it is believed that many people can benefit from taking it. There’s also very limited cases of side effects reported from taking NAC supplements which makes it safe to take for the general public.

Consider taking NAC if you are someone who:

• Often get sick and need support with your immune system.
• Have tried other antioxidants or multivitamins and find them not helping much with your health concerns.
• Are looking to improve your overall energy level.
• Are exposed to pollutants (UV light, smoke, vehicle exhausts, etc.) and stressful situations on a daily basis.
• Do not eat enough servings of vegetables and fruits on a daily basis.

5. Precautions⁶

There aren’t many drugs or food items that may interact with NAC upon consumption. However, interactions have been shown when it is taken together with activated charcoal and/or nitroglycerin.

• Nitroglycerin/isosorbide dinitrate – dilate blood vessels, increase blood flow. NAC increases nitroglycerin’s effects. May cause side effects – headache, dizziness, lightheadedness.
• Activated charcoal – binds to medications in the stomach & prevents meds absorption. Taking charcoal with NAC may decrease NAC’s effectiveness.

NAC has also been reported to interact with these health conditions:

• Asthma
• Gastric hemorrhage
• Hepatic encephalopathy

Regardless of your current health conditions, please consult your doctor & dietitian before deciding on taking any supplements. This is to ensure no adverse effects or complications to occur in case of any health issues.

Most importantly, be sure to only take a supplement from a brand that is authorised and registered under the Ministry of Health of Malaysia (MOH/KKM) or any food and drugs regulatory bodies in your region.

References

1. Ezeriņa, D., Takano, Y., Hanaoka, K., Urano, Y., & Dick, T. P. (2018). N-Acetyl Cysteine Functions as a Fast-Acting Antioxidant by Triggering Intracellular H2S and Sulfane Sulfur Production. Cell Chemical Biology, 25(4). https://doi.org/10.1016/j.chembiol.2018.01.011

2. Dludla, P. V., Mazibuko-Mbeje, S. E., Nyambuya, T. M., Mxinwa, V., Tiano, L., Marcheggiani, F., Cirilli, I., Louw, J., & Nkambule, B. B. (2019). The beneficial effects of N-acetyl cysteine (NAC) against obesity associated complications: A systematic review of pre-clinical studies. Pharmacological Research, 146, 104332. https://doi.org/10.1016/j.phrs.2019.104332

3. Tardiolo, G., Bramanti, P., & Mazzon, E. (2018). Overview on the Effects of N-Acetylcysteine in Neurodegenerative Diseases. Molecules, 23(12), 3305. https://doi.org/10.3390/molecules23123305

4. Burgunder, J. M., Varriale, A., & Lauterburg, B. H. (1989). Effect of N-acetylcysteine on plasma cysteine and glutathione following paracetamol administration. European Journal of Clinical Pharmacology, 36(2), 127–131. https://doi.org/10.1007/bf00609183

5. 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. https://doi.org/10.1517/14728220802517901

6. Drugs.com. (n.d.). NAC Interactions – Drugs.com Interactions Checker. Drugs.com. https://www.drugs.com/drug-interactions/acetylcysteine,nac.html.