A Comparison of NAC and NACET

Cysteine is a semi-essential amino acid. It’s considered semi-essential because your body can produce it from other amino acids, namely methionine and serine. It becomes essential only when the dietary intake of methionine and serine is low. Cysteine is found in most high-protein foods, such as chicken, turkey, yogurt, cheese, eggs, sunflower seeds and legumes.

N-acetyl cysteine (NAC) and NACET are supplement forms of cysteine. Consuming adequate cysteine and NAC or NACET are important for a variety of health reasons — including replenishing the most powerful antioxidant in your body, glutathione. These amino acids also help with chronic respiratory conditions, fertility and brain health. But which of the two supplements are the most effective? The following information shows us how beneficial NAC is believed to be and how NACET (a form of NAC) takes it to the next level.

N-acetyl-cysteine, N-acetylcysteine, N-acetyl cysteine, and N-acetyl-L-cysteine are all designations for the same compound, which is abbreviated as NAC. NAC is a precursor to the amino acid cysteine, which ultimately plays two key metabolic roles. The first being through its metabolic contribution to glutathione production, cysteine participates in the general antioxidant activities of the body. 

Along with two other amino acids — glutamine and glycine — NAC is needed to make and replenish glutathione. Glutathione is one of the body’s most important antioxidants which helps neutralize free radicals that can damage cells and tissues in your body. It’s essential for immune health and fighting cellular damage. Some researchers believe it may even contribute to longevity. Its antioxidant properties are also important for combatting numerous other ailments caused by oxidative stress, such as heart disease, infertility and some psychiatric conditions.

NAC plays an important role in your body’s detoxification process. It can help prevent side effects of drugs and environmental toxins. In fact, doctors regularly give intravenous (IV) NAC to people with an acetaminophen overdose to prevent or reduce kidney and liver damage. NAC also has applications for other liver diseases due to its antioxidant and anti-inflammatory benefits.

NAC can relieve symptoms of respiratory conditions by acting as an antioxidant and expectorant, loosening mucus in your air passageways. As an antioxidant, NAC helps replenish Glutathione levels in your lungs and reduces inflammation in your bronchial tubes and lung tissue.

People with chronic obstructive pulmonary disease (COPD) experience long-term oxidative damage and inflammation of lung tissue, which causes airways to constrict — leading to shortness of breath and coughing. NAC supplements have been used to improve COPD symptoms, exacerbations and lung decline 

Those with chronic bronchitis can also benefit from NAC. Bronchitis occurs when the mucous membranes in your lungs’ bronchial passageways become inflamed, swell and shut off airways to your lungs. By thinning mucus in your bronchial tubes and boosting glutathione levels, NAC may help decrease the severity and frequency of wheezing, coughing and respiratory attacks 

In addition to relieving COPD and bronchitis, NAC may improve other lung and respiratory tract conditions like cystic fibrosis, asthma and pulmonary fibrosis, as well as symptoms of nasal and sinus congestion due to allergies or infections.

Many male infertility issues increase when antioxidant levels are insufficient to combat free radical formation in your reproductive system. The oxidative stress can cause cell death and reduced fertility. In some cases, NAC has been shown to improve male fertility.

One condition that contributes to male infertility is varicocele — when veins inside the scrotum become enlarged due to free radical damage. Surgery is the primary treatment.

In one study, 35 men with varicocele were given 600 mg of NAC per day for three months post-surgery. The combination of surgery and NAC supplement improved semen integrity and partner pregnancy rate by 22% compared to the control group (27Trusted Source).

Another study in 468 men with infertility found that supplementing with 600 mg of NAC and 200 mcg of selenium for 26 weeks improved semen quality (28Trusted Source). Researchers suggested that this combined supplement should be considered as a treatment option for male infertility.

In addition, NAC may improve fertility in women with polycystic ovary syndrome (PCOS) by inducing or augmenting the ovulation cycle (29Trusted Source). 

Some other things that NAC is being tested for are the ability to stabilize blood sugar by decreasing inflammation in fat cells and thereby improving insulin resistance.

NAC may reduce heart attacks by reducing oxidative damage to heart tissue which often leads to heart disease, causing strokes, heart attacks and other serious conditions. It has also been shown to increase nitric oxide production, which helps veins dilate and improves blood flow. This expedites blood transit back to your heart and can lower your risk of heart attacks.

NAC and glutathione also boost immune health. Research on certain diseases associated with NAC and glutathione deficiency suggests that immune function might be improved — and potentially restored — by supplementing with NAC (36Trusted Source).

This factor has been studied most in people with human immunodeficiency virus (HIV). In two studies, supplementing with NAC resulted in a significant increase in immune function — with an almost complete restoration of natural killer cells (36Trusted Source, 37Trusted Source, 38Trusted Source). High levels of NAC in your body may also suppress HIV-1 reproduction (39Trusted Source).

A test-tube study indicated that in other immune-compromised situations, such as the flu, NAC may hamper the virus’s ability to replicate. This could potentially reduce the symptoms and lifespan of the illness (40Trusted Source). Similarly, other test-tube studies have linked NAC to Cancer cell death and blocked cancer cell replication (41Trusted Source, 42Trusted Source).

Through NAC’s role as a modulator of the glutamatergic system (glutamatergic agent is a chemical that directly modulates the excitatory amino acid glutamate/aspartate system in the body or brain), cysteine influences the reward-reinforcement pathway by helping to regulate the levels of glutamate (the most important neuro transmitter in the brain). Glutamate is required for normal brain action, excess glutamate paired with glutathione depletion can cause brain damage. This may contribute to mental health conditions, such as bipolar disorder, schizophrenia, obsessive-compulsive disorder (OCD) and addictive behavior 

For people with bipolar disease and depression, NAC may help decrease symptoms and improve your overall ability to function. What’s more, research suggests that it may play a role in treating moderate to severe OCD. NAC supplements can also help decrease withdrawal symptoms and prevent relapse in cocaine addicts and may help with marijuana and nicotine cravings. 

The brain neurotransmitter glutamate is also involved in a broad range of learning, behavior and memory actions, while the antioxidant glutathione helps reduce oxidative damage to brain cells associated with aging. 

The neurological disorder Alzheimer’s disease slows down a person’s learning and memory capacity. Animal studies suggest that NAC may slow the loss of cognitive ability in people with Alzheimer’s. 

Another brain condition, Parkinson’s disease, is characterized by the deterioration of cells that generate the neurotransmitter dopamine. Both oxidative damage to cells and a decrease in antioxidant ability contribute to this disease.

NAC supplements appear to improve both dopamine function and disease symptoms such as tremors. While NAC may improve brain health, more human research is needed to make strong conclusions.

NAC has low bioavailability as an oral supplement, meaning that it’s not well absorbed. The accepted daily supplement recommendation is 600–1,800 mg of NAC (44Trusted Source, 45Trusted Source). NAC can be administered as an IV or taken orally, as an aerosol spray or in liquid or powder form.

However, recent large clinical trials failed to confirm the supposed beneficial effects of N-acetylcysteine (NAC) in preventing oxidative stress-related diseases. This may be due to its low bioavailability. 

There are many new derivatives of NAC that may be more effective. These derivatives also have many biological properties and aid in maintaining proper biological functions. Some of these derivatives include: N- acetyl-L-cysteine amide, N-acetyl-L-cysteine methyl ester, N-acetyl-L-cysteine ethyl ester, N-acetyl-L-cysteine propyl ester, and N-acetyl-L-cysteine isopropyl ester. 

 NAC Ester (NACET) is the simplest cysteine derivative of NAC. By the esterification of the carboxyl group of NACs to produce N-acetylcysteine ethyl ester (NACET) it drastically increased the lipophilicity (the ability to dissolve in fats, oils, and lipids) of NAC, thus greatly improving its pharmacokinetics (the movement of drugs within the body). In other words, NACET has much higher bioavailability (around 60%) than NAC.

One study shows that NACET is able to rapidly enter cells and is trapped to produce NAC and cysteine. NACET is found in the cells of different tissues, including brain as it is able to cross the blood-brain barrier. Some research indicates NAC also crosses the blood brain barrier (BBB), but it only does so in slight amounts, and is only absorbed approximately 3-6% orally. NACET is more like 60% + absorbed, and goes intracellular instead of outside the cells, as well as penetrating the brain more.

It was found that NACET is rapidly absorbed in rats after oral administration but reaches very low concentrations in plasma. This is due to a unique feature of NACET: it rapidly enters the cells where it is trapped being transformed into NAC and cysteine. After oral treatment, NACET (but not NAC) was able to increase significantly the glutathione content of most tissues examined, brain included, and to protect from Acetaminophen (Tylenol) intoxication in the rat. NACET has also the unique feature to accumulate in human erythrocytes where it behaves as a potent protector against hydroperoxide-induced oxidative damage. 

 NACET also provides a variety of protective antioxidant effects. NACET may be taken orally and helps increase glutathione. It can accumulate in human erythrocytes (red blood cells that transport oxygen and carbon dioxide to and from the tissues). NACET may also behave as a potent protector against hydroperoxide induced oxidative damage. Note that NACET, because of its much better bioavailability has major advantages over NAC so therapeutic use will likely include other things that NAC has not been shown effective against. From the studies it looks like anything NAC can do NACET does even better.

Buildup of free radicals and oxidation in the body are key reason for many diseases and mental disorders. The inability for our bodies to remove these toxins comes from genetics (poor methylation), poor food, stress, and environmental toxins. NAC and its uses are evolving thanks to science. The esterification of NAC to NACET seems to have opened the door way for a much more efficient way for the body to use it as a way to help us to regain physical and mental health.