What is glutathione?

Often referred to as the “master” antioxidant because of its capacity to enhance the utilization and recycling of other antioxidants, glutathione (GSH) is a small protein found in virtually all cells. Its primary functions within the body include supporting the immune system, providing antioxidant protection, and removing toxins.^1,2 The glutathione molecule is made up of three amino acids: cysteine, glycine, and glutamate. These amino acids act as glutathione “precursors,” and effectively increase the body’s production of glutathione. One of the most studied glutathione precursors is cysteine.

What is cysteine?

Cysteine is abundant in many foods, particularly foods high in sulfur or protein, such as eggs, soybeans, lentils, chicken, turkey, and fish.^3,4 Given that the body can make cysteine from the amino acid methionine, it is technically a non-essential amino acid.⁵ However, there are times when the body may not be able to keep up with cysteine production. For instance, people that have high blood sugar or high blood pressure levels may need more cysteine to help maintain healthy levels of glutathione—thus cysteine is also considered a semi-essential or conditionally essential amino acid.⁶

What is N-acetylcysteine (NAC)?

N-acetylcysteine (NAC) is a derivative of the amino acid cysteine.⁷ When consumed, NAC gets absorbed in the gastrointestinal tract, sent to the liver, and converted to cysteine.⁸ The liver uses cysteine to produce glutathione, which then enters the bloodstream and gets distributed throughout the body.⁹

What causes glutathione levels to become depleted?

Health factors such as aging, infection, poor nutrition, excessive exercise, alcohol use, exposure to toxins, genetic defects, and high blood sugar levels may lead to an unhealthy glutathione status.^10,11 Fortunately, some of these factors are “modifiable,” meaning that making healthy lifestyle choices can support healthier glutathione levels.^12,13 Conversely, older adults, people with certain medical conditions, and athletes that train extensively may need additional glutathione support to maintain adequate levels.¹⁴

Considering all of the factors that may cause glutathione to become depleted, this article is here to help you learn about the research-based benefits associated with having adequate body-stores of glutathione.

The benefits of glutathione and NAC 

1. Supports the immune system

The body’s immune cells require high amounts of glutathione to function optimally.¹⁵ In a six-month trial analyzing the effects of glutathione (GSH) supplementation on immune system function, those who supplemented with GSH had higher blood levels of glutathione and greater natural killer cell activity than individuals taking a placebo¹⁶ This is significant, given that natural killer cells play an important role in neutralizing infections. 

Immune function declines with age, which may be due to falling glutathione levels¹⁷ Notably, a 2008 study comparing the immune functions of postmenopausal and younger women found that, after supplementing with NAC for 4 months, the older women’s immune responses more closely matched those of the younger women.¹⁸ Additionally, glutathione levels increased in the white blood cells of postmenopausal women taking NAC. These results suggest that positive changes in immune activity are related to having adequate glutathione levels.

2. May help reduce oxidative stress

Oxidative stress occurs when an imbalance exists between free radicals and antioxidants in the body, and can lead to a variety of health problems.¹⁹ A 2018 study found that athletes with low glutathione levels who supplemented with NAC for one month experienced increased glutathione blood levels, reduced oxidative stress, and restored exercise performance.¹⁴

Somewhat similarly, a 2011 study found that in those with high blood sugar levels, supplementing with NAC and glycine for two weeks resulted in higher glutathione levels and lower levels of oxidative stress.²⁰ This research demonstrates how important it is for our cells to maintain adequate levels of glutathione. 

3. Supports male fertility

Research finds that problems with male fertility increase when excessive oxidative stress is present in the reproductive system.²¹ Several trials have evaluated the effects of NAC supplementation on male fertility and oxidative stress.^22,23 A 2019 study found that men with fertility problems who supplemented daily with NAC for three months experienced healthier sperm function, higher sperm counts, more favorable hormone levels, and reduced levels of oxidative stress.²³ Based on this research, it appears that NAC is a powerful antioxidant that supports male fertility. 

4. Increases magnesium levels

Evidence suggests that having insufficient glutathione may impair magnesium levels.²⁴ For example, those with high blood pressure or high blood sugar tend to also suffer from low levels of glutathione and magnesium.²⁵ In a study evaluating the effects of glutathione on magnesium levels in subjects with and without blood pressure problems, results showed that glutathione administration increased magnesium levels.²⁴ Because magnesium is a vitally important mineral that supports numerous body functions—including blood pressure regulation—ensuring sufficient body stores of glutathione can also help maintain healthy magnesium levels.

5. Regenerates antioxidants  

Glutathione helps regenerate antioxidants such as vitamins C and E.² Conversely, having low levels of antioxidants may result in oxidative stress and glutathione depletion.²⁶ A 2015 study showed that compared to individuals with adequate vitamin C intake, those with a low intake of vitamin C had depleted levels of glutathione and high levels of oxidative stress.²⁷ This research suggests that vitamin C and glutathione have a synergistic relationship—meaning that glutathione restores vitamin C and vitamin C helps maintain glutathione.

6. Removes toxins  

Glutathione plays an important role in the detoxification of various compounds in the body.²⁸ For instance, its mercury-binding ability helps carry this toxic metal to the urine for elimination.²⁹ Due to rising pollution levels, glutathione is necessary to neutralize the exposures that all of us face daily. If external sources of toxins weren’t enough, the body also creates its own “internal toxins,” which glutathione also helps remove.³⁰

7. May support healthy liver function 

Poor liver function is a common problem that can be exacerbated by a lack of antioxidants, including glutathione.³¹ Glutathione has a long history of being used to support liver health. A 2017 study explored the effects of four months of oral glutathione supplementation on those with liver problems.³² The results showed that supplementation with glutathione had positive effects on certain markers of liver health. 

8. May provide brain-supportive properties  

Research suggests that glutathione regulates glutamate, a vital neurotransmitter responsible for communication between nerve cells in the brain.³³ Some people with specific mood problems may have suboptimal glutamate activity, which can impact the health of nerve cells.³⁴ Preliminary studies suggest that the glutathione precursor known as NAC may support healthy brain-glutamate levels.³⁵

A 2020 analysis of several studies reported that, among those experiencing mood problems with repetitive thoughts, those who supplemented with NAC had fewer instances of repetitive thoughts and behaviors, as compared to the placebo group.³⁶ More research is needed to determine if NAC’s brain and mood-supportive properties may be due to its ability to help maintain healthy glutamate levels. 

9. Supports cellular health by reducing homocysteine levels

Homocysteine is an important sulfur-containing amino acid produced by the body that supports several body functions.³⁷ However, excessive production of homocysteine may lead to cardiovascular health problems.³⁸ A review of studies conducted in 2015 found that men supplementing with NAC for 4 weeks had greater reductions in blood homocysteine levels than a placebo group.³⁹ In addition, the men supplementing with NAC experienced healthy changes in blood pressure whereas the placebo group did not. These results suggest that NAC may promote healthier homocysteine and blood pressure levels.

10.  May support respiratory health

The lungs are subjected to high amounts of oxidative stress, which means this organ needs particularly high amounts of glutathione.⁴⁰ For those with lung problems, maintaining adequate glutathione levels is especially essential.⁴¹ A 2015 analysis of several studies reported that among those with lung problems, subjects that received NAC supplements had fewer lung exacerbations as compared to the placebo group.⁴²

Conclusion

To review, maintaining adequate glutathione levels helps optimize antioxidant levels, maintain immune and respiratory health, support brain and liver health, and increase the body’s capacity to remove toxins. Glutathione also plays a vital role in male fertility, maintaining adequate magnesium levels, and may help support healthier homocysteine and blood pressure levels. 

Given glutathione’s importance, the fact that infections, aging, and common medical conditions can deplete glutathione levels mean many of us stand to benefit from supplementing with glutathione or NAC.