Supplementing with Glycine and NAC: reduce oxidative stress, increase mitochondrial function

Mitochondrial dysfunction and elevated oxidative stress are part of the root cause of aging.

  • With poor mitochondrial function, cells can’t perform at an optimal level, leading to an increase in ROS (reactive oxygen species).
  • Oxidative stress, due to an increase in ROS, increases the risk of cognitive decline, inflammation, heart disease, and insulin resistance.

So how do young cells fight oxidative stress and keep mitochondrial function in tip-top shape? Glutathione.

Glutathione is an antioxidant produced in your cells to combat excess ROS (reactive oxygen species). It is the body’s first line of defense against oxidative stress.

As we age, we produce less glutathione, and glutathione is used up more rapidly to combat oxidative stress.[ref][ref]

Increasing glutathione:

When trying to mitigate the negative effects of aging, the question is: How can we increase the production of glutathione? 

Glycine, cysteine, and glutamate are the amino acids that your cells need to synthesize glutathione. The limiting factor in producing enough glutathione seems to be the amino acids glycine and cysteine. Glutamate is plentiful.[ref]

Research shows that low levels of glycine and cysteine in older adults lead to a decrease in the production of glutathione.[ref][ref]

Production of glutathione is a multistep process, and glycine and cysteine are needed in different steps of the synthesis. Low levels of either amino acid are enough to decrease glutathione levels, thus supplementing with both glycine and cysteine together is needed to reliably increase glutathione and decrease oxidative stress.[ref]  Studies using only glycine or only cysteine are not all that impressive when it comes to stopping the diseases of aging.

Research studies on cysteine plus glycine in aging:

Supplemental cysteine and glycine have now been shown in several studies to raise glutathione levels and reduce oxidative stress in older adults. Studies show:

  • Supplementing with glycine and cysteine increased glutathione by 94.6% in elderly adults, bringing their glutathione levels back in line with younger people within two weeks.[ref]
  • A long-term study looked at the effects of supplementing with glycine and cysteine in older adults (age 70+) for 6 months. The study participants took 1.33 mmol/kg/day of glycine and 0.81 mmol/kg/day, provided as N‐acetylcysteine [NAC]. The results showed that the supplements corrected the baseline deficiency. It also improved inflammation, insulin resistance, cognition, strength, walking speed, and exercise capacity.[ref]
  • In older adults with HIV, supplementing with cysteine and glycine for 2-weeks corrected their glutathione deficiency. This also improved mitochondrial function.[ref]
  • Glycine plus cysteine also increased heart function and decreased inflammatory markers in old mice.[ref]

A new (May 2023) study on glycine plus n-acetylcysteine in really old mice showed that it could reverse cognitive decline. The study went further in elucidating the mechanisms causing age-related cognitive decline, with the results putting mitochondrial dysfunction and oxidative stress at the root.[ref]

How much?  

A couple of the studies in older individuals used the following:[ref][ref]

  • 1.33 mmol/kg/day glycine –> about 6g/day for a 130 lb person, divided into two doses
  • 0.81 mmol/kg/day of n-acetyl cysteine –> about 8g/day for a 130 lb person, divided into two doses

Note: The dose seems really high for N-acetyl cysteine, but the clinical trial with this dose did run for 6 months. Glycine intake from food is normally in the 2-3 g/day range for a normal diet.

Where do I get it?

Disclaimer: I’m not a doctor…If you have questions about supplements and whether they are right for you, definitely talk with your own doctor. N-acetyl cysteine may interact with medications such as nitroglycerine. It can also lower blood pressure in some people, which could be a problem if you are already on a blood pressure medication.

The studies are using large doses of glycine and n-acetyl cysteine…Your best bet for supplementing may be to buy the powder in bulk. Amazon carries NAC in powder and capsules. sells powdered NAC, and is another good source. You can also get both NAC and glycine in capsules, but that would be a lot of capsules to take in a day.

Glycine is available in bulk powder on Amazon. It is also available from BulkSupplements and PureBulk.

Don’t want to supplement with glycine? Try incorporating gelatin or collagen into your daily routine. For example, Zint collagen contains 4.5g of glycine per 12g serving (scoop included). You can add it to coffee, smoothies, or soup.

Another good source of glycine is bone broth. The glycine content is going to vary a bit, depending on how you make your bone broth. You could always add a little more gelatin or collagen to your broth if needed.[ref]

Foods high in cysteine include pork, beef, chicken, and tuna. But you would need to eat a whole lot to get to a level that is similar to supplemental n-acetyl cysteine. For example, a 6oz steak contains 587 mg of cysteine.

Exercise boosts glutathione a little, but not as significantly as the supplemental glycine plus cysteine. The supplement studies (above) showed a ~95% increase in glutathione. Compare this to a study showing that  40 minutes of aerobic exercise, 6 days a week, increased glutathione levels by about 25%.[ref]

Personally, I like to supplement with things initially in order to isolate the variables and see what the effect is at a known dose. Supplementing long-term, though, can get expensive and I often lose motivation. At that point, I branch out and try incorporating foods or lifestyle changes.  For example, after trying supplemental NAC and glycine for a while, I may switch to bone broth, collagen, and beef, along with exercise. And then cut back on the supplements to see what happens.