What is NAC and how can it benefit your health?

NAC (N-acetyl cysteine) helps replenish glutathione – which is an antioxidant that rapidly depletes during times of oxidative stress. NAC may help with fertility, brain health, heart health, and long-term respiratory conditions (such as Asthma or COPD), and reduce the risk of developing certain cancers. In medicine, NAC has been used as an antidote to acetaminophen overdose since the 1960s and to treat those with acute liver failure.

Any condition that causes inflammation, increased generation of free radicals, or depletes glutathione directly could potentially benefit from NAC supplementation. Glutathione deficiency may be recognizable through nonspecific symptoms such as premature aging, reduced immune function, fatigue, or an overall decrease in health.

Antioxidant effects

NAC is one of the most widely used antioxidants in clinical studies, although the exact way it works remains poorly understood. Some believe its main antioxidant benefits are due to it being a precursor to the semi-essential amino acid cysteine, increasing its levels to ensure the production of glutathione by the liver.

Antioxidants neutralize free radicals and reduce oxidative stress. Research has shown oxidative stress is associated with many health conditions including diabetes, cancer, cardiovascular disease, infertility, and liver and kidney disease.

Respiratory disease

NAC has historically been used as a treatment option for conditions characterized by problems with mucus clearance from the lungs, such as COPD, bronchitis, and intubated or post-operative patients. It works by hydrolyzing disulfide bonds in mucus proteins which decrease mucus viscosity and allow it to be more easily coughed up.

Research has shown an improvement in response to steroids, general well-being, a reduction in exacerbations, and other improved outcomes in people with COPD with orally administered NAC (dosages of at least 600mg/day).
Studies have also shown supplemental NAC to be a valuable and inexpensive add-on treatment to decrease chronic inflammation and improve lung function in people with cystic fibrosis.

Liver and kidney support

NAC is a cysteine prodrug and glutathione precursor that can bind heavy metals, scavenge free radicals and reduce disulfide bonds in proteins. The antioxidant effects of NAC and glutathione reduce oxidative stress in the liver and kidneys. NAC is widely used for acetaminophen poisoning but has also been shown to improve liver function in people with non-alcoholic liver disease and other acute liver conditions.

Acetaminophen poisoning

NAC is used medically as an antidote to acetaminophen poisoning because it restores levels of glutathione in the liver which is rapidly depleted as the liver tries to breakdown acetaminophen into its metabolite N-acetyl-benzoquinone imine (NAPQI). Detoxification of NAPQI requires high concentrations of glutathione.

NAC is usually given as soon as possible for acetaminophen overdosages higher than 150mg/kg, for lower overdosages in the presence of liver disease, or if other criteria are met. Early administration reduces the severity of liver damage.

Other conditions

Beneficial effects have also been reported for NAC for:

• Acute pancreatitis
• Cancer prevention
• Diabetes and insulin resistance
• Endothelial cells for protecting against fine hazardous particles and smoke
• Helicobacter pylori
• High dose irradiation
• Hypertension and cardioprotection including during cardiopulmonary bypass
• Infertility
• Inflammation or infection at alleviating symptoms and healing and strengthening the immune response
• Lung transplantation: protects from the effects of cigarette smoke and other toxins
• Neuroprotection including use in Alzheimer's disease to counteract deficits in learning and memory and hearing loss
• Skin photoaging.

Does NAC help with COVID-19?

People with severe COVID-19 have increased levels of free radicals and often present with glutathione depletion, which can precipitate a cytokine storm. NAC also possesses anti-inflammatory activity and immune-modulating characteristics in addition to its antioxidant activity.

Research has shown that supplementation with NAC was associated with significantly lower mortality in people with severe COVID-19 than with no supplementation. It is thought NAC administration may suppress replication of the SARS-CoV-2 virus and improve outcomes if administered promptly. In combination with antiviral agents, it may also reduce hospital admission and mechanical ventilation rates.

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How does NAC work?

NAC is converted to cysteine in the body and then converted again to glutathione. Cysteine is considered a semi-essential or conditional amino acid because its production depends on levels of two other amino acids, serine and methionine. If body levels of these two amino acids are low, then levels of cysteine will be low and dietary supplementation with cysteine (or its precursor, NAC) essential. Without cysteine, our bodies cannot make glutathione, and levels of this important antioxidant become depleted, which can compromise the immune response and cause oxidative damage to important organs and tissues.

Are there any side effects of NAC?

NAC has a wide safety margin and generally a low risk of side effects.

Only a small subset of patients administered oral NAC report side effects such as nausea, vomiting, and heartburn, and dosages of up to 8000 mg/day are considered safe. Data from trials indicate that when cysteine is delivered in a non-toxic form (ie, as NAC), side effects are negligible.

What foods contain NAC?

NAC is not found in food, but cysteine is. Cysteine is a sulfur-containing amino acid that is essential for the production of glutathione. Foods with high levels of cysteine include:

• Broccoli
• Brussel sprouts
• Cabbage
• Dates
• Egg yolks
• Garlic
• Ginseng
• Legumes, such as chickpeas and lentils
• Meat, such as beef, chicken, duck, or pork
• Milk and dairy products
• Onion
• Red bell peppers
• Seafood, such as hake, monkfish, or tuna
• Soy and soy products (eg, tofu, tempeh)
• Sunflower seeds
• Wheat germ
• Yeast.

What is the relationship between glutathione and NAC?

NAC is converted in the body to cysteine which is then used with two other amino acids, glycine, and glutamic acid to make glutathione.

NAC is the supplemental form of cysteine that is less toxic and more easily absorbed.

Why is glutathione important?

Research has shown that the presence of glutathione prevents cell damage by free radicals due to oxidative stress. Free radicals are unstable oxygen-containing molecules that are made by the body during normal metabolic processes. In most circumstances, the body can make enough antioxidants to neutralize these free radicals. Oxidative stress happens when there are too many free radicals circulating in the body for the number of antioxidants present.

Long-term oxidative stress has been shown to contribute to many health conditions, including diabetes, cancer, and heart disease.

Glutathione is naturally made by our liver and consists of three different amino acids – cysteine, glutamine, and glycine.

If I take NAC do I need to take glutathione as well?

NAC appears a much more effective way of increasing glutathione levels in the body than taking glutathione itself. Glutathione is poorly absorbed and may be broken down by enzymes in the stomach. Taking glutathione long-term as a supplement has also been associated with lower zinc levels

In contrast, few side effects have been reported with NAC compared with glutathione.

Why are NAC supplements better than cysteine supplements?

Because NAC contains an acetyl group, it is less reactive than cysteine. This makes it less susceptible to oxidation, less toxic, more soluble in water, and more easily absorbed. Once ingested orally, NAC is readily absorbed through the stomach and intestine and sent to the liver where it is almost entirely converted to cysteine. Overall NAC is a better source of cysteine than cysteine itself given by injection. The majority of cysteine is converted by the liver into glutathione.