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How Does N-Acetyl-L-Cysteine Work?

The main mechanism of action of N-Acetyl-L-Cysteine is by being a substrate of glutathione synthesis, the master antioxidant in the human body. (1) Glutathione is so crucial for the body that its levels are often used as the predictor of disease and longevity of life. (2) It is this vital because it works within the cell, making its actions beneficial at the basic cellular level. By replenishing and maintaining intracellular levels of glutathione, N-Acetyl-L-Cysteine is thus extremely important for supporting the function of cells in the whole human body.

So, how exactly does N-Acetyl-L-Cysteine increase the levels of glutathione?

N-Acetyl-L-Cysteine provides cysteine, which then enters the red blood cells to sustain glutathione synthesis and metabolism.  (3) Cysteine is usually short in supply in the cells, hence the need for supplementation.

You may be wondering whether it would be more beneficial to supplement with glutathione instead of N-Acetyl-L-Cysteine. Unfortunately, some studies state that glutathione is not appreciably absorbed from the gastrointestinal tract. Also, in the supplement form it may not cross the blood-brain barrier as well as N-Acetyl-L-Cysteine. (4) Therefore, N-Acetyl-L-Cysteine is the best supplement to consider. However, using the two of them at the same time produces better results as they synergize each other’s actions.

The Benefits of N-Acetyl-L-Cysteine

2.1 Reduces Free Radicals & Oxidative Stress

As mentioned above, the most well-known benefit of N-Acetyl-L-Cysteine is the increment of glutathione levels. Glutathione is a tripeptide (three amino-acid molecule) with many roles, but it is the hat of “mother of all antioxidants” that is the most talked about. It is a powerful free radical scavenger and detoxifying agent that protects cells from oxidative damage and the downstream effects associated with oxidative stress. (5) Glutathione is often depleted in high performing individuals (both physical and psychological) due to their high oxidative loads.

For instance, for mentally engaged persons like entrepreneurs, students, and professionals, mental stress and environmental toxins are sources of free radical exposure. In athletes, sustained increased exercise intensity leads to chronic overconsumption of oxygen, which consequently causes the production of free radicals. The creation of these reactive oxygen species originates from mitochondria, in capillaries and a burst of inflammatory cells from muscle damage. (6)

In all these individuals, accumulation of free radicals causes damage to the DNA as well as cellular molecules and lipids. The results are a cognitive decline, premature aging, and deterioration of the immune system. N-Acetyl-L-Cysteine although a minor antioxidant by itself, revives glutathione levels, preventing and reversing this damage.

By combating oxidative stress, N-Acetyl-L-Cysteine also supports immune system function. Just like most other antioxidants, it shields the immune cells and encourages production of white blood cells (WBC). (7) WBCs are the key players in attacking infections.

As an antioxidant, N-Acetyl-L-Cysteine also plays a role in detoxification. Treatment of acute liver toxicity showcases the powerful actions of N-Acetyl-L-Cysteine in dealing with toxins in the body. Taking N-Acetyl-L-Cysteine supports the liver in clearing harmful toxins and regaining its normal function. Reducing the total body toxin levels may help turn back the hand of time, not just by rejuvenating the cells but also by reversing the skin aging process.

2.2 Neuroprotective Effects

N-Acetyl-L-Cysteine readily crosses the blood-brain barrier (BBB), (8) where it protects the brain in several ways; as a precursor of glutathione, by reducing inflammation, modulating glutamate levels and boosting the levels of dopamine.

The presence and actions of glutathione are felt in all organs, including the brain. Though many brain neurons can survive a rise in reactive oxygen species, there are specific parts that are more vulnerable. Because of that selective vulnerability, these neurons are usually the first to manifest cognitive degeneration. (9) Mental processes get slower and thought clarity becomes a problem. The good thing about glutathione is that once it crosses, the BBB, it goes to all regions of the brain where it neutralizes the free radicals.

Glutamate is a powerful excitatory neurotransmitter that is critical for sending signals in the brain and throughout the peripheral nervous system, but if it is too much, it can be toxic to neurons. Abnormally high concentrations are related to overexcitation of nerve cells which causes profound collapse of mitochondrial membranes, triggering neuronal damage or even death. (10) N-Acetyl-L-Cysteine regulates the amount of glutamate in the brain, maintaining it at safe and healthy levels. (11)

N-Acetyl-L-Cysteine also controls dopamine release and the sensitivity of its receptors. (12) Dopamine not only regulates the brain’s reward and pleasure centers but also modulates plasticity of the brain, specifically the striatum, cortex, and hippocampus regions. (13) Dopamine is also known to protect neurons from glutamate excitotoxicity by preventing the onset of calcium accumulation in mitochondria, which is what contributes to necrosis of neurons. (14)

N-Acetyl-L-Cysteine reduces inflammation in the brain by altering pro-inflammatory cytokines such as tumor necrosis factor and interleukins. (15) Although these cytokines are helpful in cell survival, if they are chronically elevated they increase the likelihood of neurodegeneration. Other than reducing the levels of pro-inflammatory cytokines, N-Acetyl-L-Cysteine also improves healing of cells in mild traumatic brain injury. (16)

2.3 Reduces Symptoms of ADHD

Attention-Deficit/Hyperactive Disorder (ADHD) is a brain disorder that mainly affects children, but adults too can have it. In fact, business moguls Sir Richard Branson, Ikea founder Ingvar Kamprad and JetBlue founder David Neeleman have one thing in common, ADHD.

Although people with ADHD have higher entrepreneur intentions, some of the traits do not always correlate with success in institutional settings like schools and corporate environments. ADHD makes a person easily wander off tasks, lack persistence, and have trouble sustaining focus. Hyperactivity is also marked by constant movement, excessive fidgeting, tapping and talking, which may play against someone since they are almost always interpreted as nervousness. It also makes someone make hasty decisions that are not well thought out.

N-Acetyl-L-Cysteine helps with ADHD by activating behavior control centers in the brain, resulting to better focus, controlled activity levels, and improved attention span. (17) Combining N-Acetyl-L-Cysteine with vitamins C, B6, and folate makes its action on ADHD even better. (18) The good news with N-Acetyl-L-Cysteine is that when it is compared to other prescription drugs, it has minimal side effects and does not mask symptoms.

Suggested Dosage, Synergies & Administration N-Acetyl-L-Cysteine

N-Acetyl-L-Cysteine can be taken orally, by inhalation as a mist or intravenously. As a dietary supplement, it is commonly available as a powder, tablet or capsule. Usual supplement doses of N-Acetyl-L-Cysteine as a general cognitive wellness agent range from 500 to 600mg daily. Other users have safely used doses up to 2 to 3 grams still with desirable effects. Although N-Acetyl-L-Cysteine is generally safe within the recommended ranges, very high doses (more than 7 grams) are toxic to human cells.

Being a dopaminergic stimulating supplement, N-Acetyl-L-Cysteine can be combined with choline boosters to synergize cognitive gains. The most common combination is that of N-Acetyl-L-Cysteine and glutathione. They both increase each other’s bioavailability and hence multiply their total effect. (19) On the other hand, N-Acetyl-L-Cysteine should not be taken together with ACE inhibitors, antihypertensives, activated charcoal or anticoagulants. The general rule is that if you are on any long-term medication, you should first consult your doctor before introducing any supplement.

Common side effects of N-Acetyl-L-Cysteine include nausea, vomiting, diarrhea, headaches, dizziness, and a dry mouth. As with all other nootropic supplements, the best way to avoid or lower the gravity of side effects is to start with the least effective dosage.

History and Origin of N-Acetyl-L-Cysteine

N-Acetyl-L-Cysteine was initially patented in 1960, but it was until 1968 when it was licensed for use. (20) Scientific institutions have done thorough research, and there are thousands of publications and hundreds of human clinical trials. As a result, N-Acetyl-L-Cysteine is on the World Health Organization’s (WHO) list of the most effective and safe drugs used both therapeutically and nutritionally.

Currently, N-Acetyl-L-Cysteine is licensed both as a dietary supplement and as a drug for treating paracetamol (acetaminophen) overdose, loosening mucus in people with cystic fibrosis and chronic obstructive pulmonary disease.

Final Thoughts on N-Acetyl-L-Cysteine

N-Acetyl-L-Cysteine, a slightly modified version of L-cysteine, has been used for decades to combat damage from free radicals and as a detoxifying agent. The nootropics community adores it for its ability to prevent oxidative stress in the brain, rejuvenate neuronal connections and to suppress neurological inflammation. All these actions sum up to better cognition, potentiation of short and long-term memory and better mental focus. Below is a summary of N-Acetyl-L-Cysteine:

It is highly valued for its ability to upregulate glutathione levels. Glutathione is a master antioxidant and detoxifier found in every cell of the body. N-Acetyl-L-Cysteine increases these levels by providing cysteine, which is essential for synthesis and metabolism of glutathione.By supporting glutathione levels, it neutralizes free radicals and combats the effects of oxidative stress damage. In this way, it also prevents cognitive decline, premature aging, helps the liver in detoxification and boosts the function of the immune system.In emergency medicine, N-Acetyl-L-Cysteine is also used for treating acetaminophen toxicity.N-Acetyl-L-Cysteine protects neurons by preventing glutamate neurotoxicity, regulating dopamine release and modulating inflammatory agents in the brain.It also activates behavior control centers in the brain, to reduce the symptoms of Attention-Deficit/Hyperactive Disorder (ADHD).Effective doses of N-Acetyl-L-Cysteine range between 500 to 600mg daily. Higher doses may cause adverse effects or even liver toxicity.For synergistic effects, N-Acetyl-L-Cysteine can be combined with choline boosters, glutathione or multivitamins, especially vitamin C.Side effects though rare, include headaches, nausea, vomiting and a dry mouth. These side effects are less likely to be noticed with low doses.