N-acetylcysteine (NAC) is more than just an expectorant

When we do our research we find that n-acetylcysteine (NAC) is one of the best supplements you can take if your goal is to increase the production of GSH.

If you’ve been around supplements for a while, you’ve no doubt heard of glutathione (GSH), which we call the body’s main antioxidant.

We say Glutathione is the king of antioxidants because it is one of the most abundant and powerful antioxidants in the body, but the best thing about this compound is that the body produces glutathione on its own.

As part of a natural antioxidant defense system. GSH levels are a key factor in overall health. It is extremely difficult to conduct controlled longevity studies in humans, but studies of simple organisms go without saying.

For example, studies of saccharomyces cerevisiae (also known as brewer’s yeast) consistently show that organisms with higher GSH levels live much longer than those with lower GSH levels. In humans, GSH depletion has been linked to the development of serious diseases such as dementia, diabetes, and obesity.

Supplement GSH Precursor (NAC)

Low bioavailability of target molecules is a common problem in supplement science. The best way to solve this problem is usually to take a precursor of the molecule.

Often, their bioavailability is much higher than the target molecule itself.

Fortunately for GSH, this is definitely a viable solution. Studies consistently show that supplementation with GSH precursors, such as cysteine and glycine, can greatly help people with GSH depletion return to normal levels.

Studies on N-acetylcysteine

Once you understand the role of GSH in the body, it’s easy to understand that your health largely depends on keeping the production of GSH at an appropriate level.

Similarly, it is the most powerful and ubiquitous antioxidant in the body, which means it is used in almost all metabolic processes.

Uncontrolled oxidative stress has been linked to rapid aging and the development of major diseases, including cancer, cardiovascular disease, respiratory disease, rheumatoid arthritis, kidney disease, and sexual dysfunction.

There is a two-way relationship between oxidative stress and inflammation. Oxidative stress makes inflammation worse, and inflammation makes oxidative stress worse.

Since chronic systemic inflammation damages basically every tissue in the body, the potentially catastrophic consequences of GSH depletion are obvious.

This, of course, is also the key mechanism behind the link between GSH depletion and metabolic and neurological disorders that we discussed in the introduction.

If you think NAC is too good to be true when you read the following studies, remember that we are dealing with a mechanism that is very fundamental to human health and performance – the management of oxidative stress and inflammation.

This goes a long way to explaining NAC’s extraordinary potential to improve human health.

NAC can improve liver function and detoxification

Let’s first understand why most people seem to be interested in supplementing with NAC – its impact on liver health.

More specifically, interest in NAC has surged in recent years due to the popularity of the fact that NAC can help the body control alcohol toxicity.

It is believed that NAC can promote recovery after drinking while preventing or reducing the intensity of hangovers. This claim is based on animal studies showing that NAC reduces oxidative stress, thereby preventing some of the damaging effects caused by alcohol.

In one study, rats given NAC and alcohol had lower levels of liver enzymes than rats given alcohol alone. Reduced levels of liver enzymes are good because damaged or inflamed liver cells tend to leak their contents into the bloodstream, including these enzymes.

Lower levels of liver enzymes mean less damage and inflammation in liver tissue.

In one particularly interesting study, researchers took a group of mice that showed a preference for alcohol consumption (basically, alcoholic mice) and gave them NAC supplements. When given any amount of alcohol, mice treated with NAC spontaneously drank 65 percent less than mice not supplemented with NAC.

Because of this effect, some researchers have actually proposed that NAC should be used to treat or control alcohol use disorders in humans.

So how exactly does NAC protect the liver from toxic damage? You guessed it – by restoring glutathione levels in liver cells.

In fact, NAC is so effective at protecting the liver from toxins that it’s actually the first-line drug for treating acetaminophen poisoning.

Can NAC fight hangovers? Its effect on acetaldehyde dehydrogenase (ALDH) enzyme

NAC’s ability to strengthen the body’s resistance to the harmful effects of alcohol abuse is partly due to its action on acetaldehyde dehydrogenase (ALDH), an enzyme responsible for detoxifying aldehydes produced when the body metabolizes alcohol.

These aldehyde metabolites are extremely toxic and the sooner they are eliminated, the better.

The good news is that at least one animal study has shown that NAC can significantly up-regulate ALDH activity.

There’s certainly not much research on the topic, so it’s hard to draw firm conclusions right now. But given the positive effects of NAC on overall liver health and function, we wouldn’t be at all surprised to see significant upregulation of ALDH and ADH (alcohol dehydrogenase, the enzyme that converts alcohol into aldehydes).

Neurological benefits of NAC

Because of its ability to promote GSH production, NAC can exert some significant neuroprotective effects.

On the one hand, it helps balance glutamate activity in the brain by providing cysteine, which helps trigger negative feedback on the amount of free glutamate released by neurons.

Excessive glutamate activity can cause neurons to fire uncontrollingly, a condition called excitotoxicity, which is essentially a low-grade neuroinflammation.

Because glutamate-induced excitotoxicity can damage brain tissue and impair cognitive function, it is thought to be a contributing factor to serious mental illness.

According to a meta-analysis and randomized, double-blind, placebo-controlled study, NAC has been shown to improve OCD symptoms.

An animal study suggests that NAC treatment can reverse some of the neurological changes associated with schizophrenia.

It turns out that NAC’s ability to spontaneously reduce alcohol use may also apply to other drugs. A study of 18 – to 21-year-old people of all genders found that after four weeks of NAC supplementation, participants’ daily marijuana use decreased from 15.9 at the start of the study to 11.9 by week four.

That is, by supplementing with NAC alone, cannabis use was reduced by about 25 percent.

To sum up, what is the theme behind it? NAC appears to help stabilize brain function by upregulating GSH. This makes it potentially useful for treating a range of neurological conditions that have traditionally been seen as intractable – as a 2013 editorial advocating for more NAC research noted.

The respiratory benefits of NAC

Another body system affected by GSH production is the respiratory system. Consumption of GSH is associated with the development of respiratory diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis, and cystic fibrosis.

A 2016 meta-analysis of NAC literature concluded that the compound has been shown to significantly improve COPD symptoms, which is not surprising.

A similar study in 2000 found that NAC also improves symptoms of bronchitis, in part because its up-regulation of GSH can actually dilute mucus produced by the respiratory tract.

Of course, NAC has proven its golden worth over the past few years, with incredible results in fighting more “modern” respiratory diseases.

The progrowth effect of NAC

Most of us have probably heard by now that oxidative stress can also seriously damage fertility – for both people of all genders.

One particularly interesting study that investigated the effect of NAC on this was conducted in men with varicocele.

Varicocele is a disease of varicose veins in the testicles that causes blood to return and a buildup of toxins in the testicular tissue. In some cases, varicocele can negatively affect fertility and testosterone production.

The men in the study first had their varicocele surgically corrected and were then randomly assigned to either the NAC group or a placebo group so the researchers could track the impact of each treatment on their fertility.

By the end of the three-month study period, the men who took 450 mg of NAC daily had significantly better sperm quality than those who took a placebo.

In another study, men with varicocele were randomly divided into four groups: those who took 500 milligrams of NAC daily, those who took 200 micrograms of selenium daily, those who took a placebo, and the final group was those who took both 500 milligrams of NAC and 200 micrograms of selenium.

Although sperm quality in the combined NAC and selenium group improved most significantly by the end of the treatment period, the group taking just 450 mg of NAC also saw significant improvements.

Studies have shown that NAC can inhibit the adhesion of endothelial cells to neutrophils and improve the secretion function of prostate.

NAC activates proteolytic enzymes to promote semen liquefaction.

There is also evidence that NAC can improve fertility by improving symptom severity in women with polycystic ovary syndrome (PCOS).

Antidiabetic effect of NAC

Inflammation and oxidative stress also play an important role in the development of insulin resistance, metabolic syndrome, and type 2 diabetes (T2D).

As we mentioned in the introduction, GSH depletion is a feature of metabolic dysfunction and is persistent in patients with severe T2D.

Although NAC does not seem to improve symptoms in people with existing type 2 diabetes, animal studies suggest that it can help prevent the onset of diabetes by normalizing blood sugar and reducing inflammation.

Cardioprotective effect of NAC

Studies have also shown that NAC increases the body’s production of nitric oxide (NO), a gaseous molecule produced by artery cells that causes vasodilation, or the dilation of blood vessels, which improves blood circulation and leads to a drop in blood pressure and resting heart rate.

Since reduced NO activity is a feature of cardiovascular disease (CVD), this may help prevent or improve the symptoms of CVD.

NAC boosts immunity

NAC has been shown to help improve the function of the body’s immune system and has been very useful over the past few years.
According to one study, NAC can “fine-tune” the immune response independently of its antioxidant effects.

According to the authors of the study, the GSH produced by NAC supplements not only fights oxidative stress, but also plays an important signaling role for the immune system.

This may be related to the molecular sulfur abundant in NAC regulating immune function through H2S signaling pathway.

Pharmacological effects of acetylcysteine

The antioxidant effect

NAC, as a thiol compound, can react directly with both free radical and non-free radical oxidants, and its reaction rate to oxidants is significantly higher than that of endogenous antioxidants.

Because the molecule contains sulfhydryl group (-SH), it can capture unpaired electrons, remove oxygen free radicals (ROS), and reduce the two bonds in biological macromolecules (-S-S-) through the oxidation of its own -SH, which plays an antagonistic role in oxidation.

Hepatoprotective effect

NAC can dilate blood vessels, improve blood perfusion in the liver, correct tissue hypoxia, ischemia, prevent liver cell necrosis, and protect the liver.

NAC can also improve the mitochondrial autophagy function of hepatocytes induced by free fatty acids in the mitochondrial tricarboxylic acid cycle, and alleviate the symptoms of hepatocyte inflammation.

Promote the synthesis of intracellular glutathione

Glutathione is an important substance in cells. NAC enters the cell, deacetylates and biosynthesizes GSH in the cell, thereby increasing the content of GSH in the cell.

NAC can also convert oxidized glutathione to reduced glutathione, promote its antioxidant capacity, and achieve the purpose of preventing cell damage.

Protective nucleic acid molecule

NAC can protect the body by repairing DNA damage, inhibiting genotoxicity and cell transformation.

It also inhibits the direct mutagenicity of reactive oxygen species (ROS) and DNA breakage caused by peroxide.

immunomodulation

NAC has a strong antioxidant and increase the level of T cell CD4, so it has the effect of improving immunity.

Apoptosis regulation

NAC has the effect of anti-peroxide damage, which increases the content of SOD and glutathione, reduces the oxidative stress reaction, and thus inhibits the level of apoptosis.

Inhibit inflammation

The function of NAC is to capture electrons directly through the active group in the molecule and inhibit the formation of superoxide anion. The indirect reason is that the blocking of intracellular reactive oxygen species (ROS) leads to the activation of stress active enzymes and the overexpression of vulvae inflammation.

NAC improves gut health

Chronic inflammation underlies many intestinal diseases, including intestinal permeability or leaky gut, which is one of three factors that must be present for autoimmune diseases such as Hashimoto’s to occur.

Intestinal leakage involves damage to the lining of the body’s intestines and causes tight connection failure, which allows materials such as bacteria and food particles that are not intended to pass through the intestinal wall to pass through.

Studies have shown that NAC improves intestinal tissue damage by generating signals to tighten connections within the intestinal wall, just as it does when the gut leaks. This, in turn, patched the “leak” of intestinal leakage.

When the intestinal tissue damage heals and the intestinal leak is reversed, many people may even be able to relieve their Hashimoto!

NAC can also promote gut health by helping gut bacteria detoxify and break down biofilms. Biofilms are collections of microorganisms that grow on the surface of living organisms and often house intestinal pathogens, which in turn can cause infections.

Many biofilms are becoming resistant to many clinical antimicrobial treatments and host immune responses, so researchers are looking for new substances to combat these resistant biofilms.

A 2014 study investigated the effectiveness of NAC in preventing biofilm formation as well as destroying existing biofilms.

The study found that in combination with different antibiotics, NAC can significantly penetrate the deepest layers of bacterial biofilms, which are increasingly resistant to classical antimicrobial treatments.

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