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N-Acetyl cysteine

Cysteine is an amino acid that contains sulphur. It's used by our bodies as a building block for many vital things. Cysteine must come from food since our bodies cannot produce it. A synthetic version of cysteine, called NAC, is often used as a supplement because it is more readily absorbed and breaks down into cysteine in the body.

  • Cysteine is very liver-protective and great for drinkers.
  • Cysteine is used in the synthesis of glutathione in the liver. Glutathione is a key scavenging antioxidant within cells.
  • Cysteine is important for making some collagens. Keratin is rich in cysteine, and has the ability to self-assemble into fibres. So it's found in the hair and nails.

Why is glutathione important?

Glutathione is central to recovery from exercise, it makes you feel good and helps prevent both infectious diseases and chronic degenerative diseases. Glutathione protects your vision, boosts your immune system, helps turn carbohydrates into energy, and prevents the buildup of oxidised fats that may contribute to atherosclerosis. A healthy adult has about 10g of glutathione circulating in the body tissues. Synthesis of glutathione depends upon the cells ATP, which is the molecule that provides cellular energy. Glutathione levels are linked to low energy and lethargy. This is why exercise is so beneficial for your overall health as it boosts your glutathione levels. Three amino acids come together to form glutathione.

  1. Glutamic acid is found in food. In the body it turns into glutamate, it's quite abundant in meats, fish and dairy.
  2. Cysteine comes from food, or from NAC. It can also be converted from another amino acid called methionine.
    (These two combine to form gamma glutamyl-cysteine).
  3. This combines with glycine to form glutathione.

The optimal thing to do is to take an NAC supplement plus a glycine supplement (this is called GLYNAC). It gives your body the best foundation to make glutathione. You should not take a glutathione supplement because it will switch off natural production.

Boosting glutathione levels with NAC makes liver cells more able to protect themselves from ongoing damage. Your liver can often take a beating due to fatty accumulation, infections, drug damage, alcohol excess, or autoimmune inflammation. Glutathione is an important antioxidant with important functions in the body, such as making DNA, supporting the immune system, supporting the function of specific enzymes, helping certain organ functions, and more.

Modified from Chris Masterjohn, PhD. Step 1 is the rate determining step and it is favoured when the body needs more glutathione. Cysteine and Methionine are the only 2 sulphur containing amino acids.

NAC for drinkers.

NAC boosts the production of glutathione. Taking at least 200mg of NAC, 30 minutes before you drink can help lessen the effects of alcohol. NAC is thought to work even better when combined with vitamin B1. NAC is so good for the liver, that Doctors administer NAC to patients who have taken a paracetamol (Tylenol) overdose or have alcohol poisoning. NAC can also help people with the urge to drink to excess.

NAC and addiction.

NAC has long been used to treat liver issues; however, in recent years, researchers have begun to tap its potential for treating substance use and psychiatric disorders. NAC is thought to upregulate the glutamate transporter, GLT-1, that removes excess glutamate from the nucleus. Glutamate is the primary excitatory neurotransmitter in the central nervous system, which plays an important role in many aspects of normal brain function. Accumulation of glutamate in the cells will induce excitotoxicity which is considered to be a major mechanism of cell death in brain ischemia, which is not enough blood to the brain.

GlyNAC and longevity.

Glycine combined with NAC is the best way to boost glutathione and can make you live longer. Aging is associated with glutathione deficiencies and increased levels of oxidative stress. A recent study looked at the performance of the GlyNAC supplement for longevity. This was an animal study that saw a 24% increase in the lifespan of mice. This incredible increase in longevity was attributed to the increase and maintenance in glutathione. Glutathione levels drop as you get older, so it's important to maintain good levels.

But what about human longevity studies? We can't wait around for people to die to prove longevity, but we can look at the biomarkers that are associated with aging. Elevated oxidative stress and mitochondrial dysfunction are identified as key contributors to aging. In a small 16 week 2022 study, it was found that these 2 biomarkers were greatly improved with GlyNAC supplementation, due to the restoration of glutathione levels. Blood pressure and waist size were also lowered. GlyNAC has already been studied for the treatment of HIV.

GlyNAC is going to be the next big thing in terms of supplementation. But a quick assessment of several GlyNAC capsule supplements showed very low doses, (as low as 500mg of glycine and 300mg of NAC). The best thing to do is:-

  • Buy a 1kg glycine supplement in loose powder form. A healthy dose would be 3g before your first meal, because glycine blunts the blood sugar response,  and 3g before bed, because glycine is great for winding down to a night of deep sleep. Glycine tastes sweet, so you can even add a teaspoon to your daytime coffee! A 1kg bag should last around 6 months.
  • Buy NAC in loose powder form, but you must store it properly. You could get some 1000mg capsules if it's more convenient. Take 1.5-2g a day, ideally split into two doses. It's good to take 1g of NAC before drinking alcohol. After taking NAC, its maximum plasma concentration occurs approximately between 1 and 2 hours. NAC is more expensive than Glycine, but you will consume less. See the current prices in the description of this video.

Food sources of Cysteine and glycine.

  • Choose the foods that are high in cysteine, such as pork, beef, liver, turkey, chicken, oily fish, shellfish (such as clams), lentils, eggs, yogurts, milk, and hard cheeses.
  • Choose the foods that are high in glycine, such as red meat, turkey, chicken, pork, oily fish and nuts (almonds, pistachios, cashews walnuts and macadamia).
  • Raw whey protein that is undenatured, contains the highest levels of the full range of naturally occurring glutathione building blocks. Quality whey provides all the key amino acids for glutathione production, cysteine, glycine and glutamate, and contains a unique cysteine residue, glutamylcysteine, that is highly bioactive converting to glutathione. Whey is considered a fast protein, because it is rapidly digested in as little as an hour, Casein is a slow protein that is digested over several hours. TRY TO GET NATIVE WHEY PROTEIN MADE BY THE COUNTER-FLOW METHOD. Native whey protein is a protein extracted directly from milk. It has a neutral taste and a higher nutritional value than traditional whey proteins.

NAC storage and shelf life.

NAC contains sulphur, which has unpleasant smelly breakdown products. In a study of NAC capsules, storing NAC at high temperatures and high humidity will cause some degradation of the NAC (30-40% over 420 days). In cool and dry storage conditions, the breakdown was negligible at 2%. Bulk powder NAC and capsules should therefore be stored in a cool dry place. If you buy a bulk powder NAC, it's best to store the whole bag and its contents inside a sealable Tupperware container.

N-Acetyl Cysteine Ethyl Ester, NACET

NAC can be chemically changed, esterified, into a far more bioavailable version called NACET. Studies have shown that NACET is the most efficient molecule for increasing the intracellular levels of glutathione. This is because NACET is lipophilic, fat-loving, and can freely cross plasma membranes. Inside the cell, it is de-esterified back to NAC, which is trapped in the cell and slowly transformed into cysteine. You can look for A NACET supplement which is often way more expensive than normal NAC. Manufacturers claim that 50mg of NACET is equivalent to 1000mg of NAC, but that would assume a 20x bioavailability which seems a bit overstated.

Don't take paracetamol, Tylenol.

Paracetamol is one of the most common causes of poisoning worldwide.  It's deadly because of the depletion of glutathione and liver tissue damage.

  • Worldwide sales of acetaminophen were ten billion dollars in 2022.
  • 50 million Americans take Paracetamol each week. This results in 10,000 hospital visits and 500 deaths per year.
  • Around 200 million packs of paracetamol are sold without a prescription in the UK every year.
  • One in four people frequently exceeds the maximum daily dose of 4,000mg).
  • Paracetamol consumes the glutathione precursor, glutamyl-cysteinyl-glycine.
  • Don't give children paracetamol-containing medicines such as Calpol.
  • Paracetamol damage is often irreversible, but doctors often give patients NAC in an attempt to restore glutathione levels.

In conclusion.

  • NAC is an important building block the body's most critical cellular antioxidant, glutathione.
  • NAC protects the liver and is especially helpful to drinkers.
  • NAC in combination with glycine helps to increase longevity and lower the signs of aging.

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  • https://pubmed.ncbi.nlm.nih.gov/28641538/
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993450/
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1868496/
  • https://academic.oup.com/biomedgerontology/advance-article-abstract/doi/10.1093/gerona/glac135/6668639 (GlyNAC)
  • https://onlinelibrary.wiley.com/doi/abs/10.1002/j.2055-2335.2008.tb00843.x  (NAC storage)
  • https://www.sciencedirect.com/science/article/abs/pii/S0891584918311055  NACET