The human body is a metabolic powerhouse in which thousands of chemical reactions are used to facilitate metabolic processes. The balance between redox reactions in this system are crucial for overall health, and life itself. Redox reactions consist of the interplay between antioxidants and free radicals. While the production of free radicals as a result of various metabolic functions is a prerequisite for those reactions to proceed to fruition, an accumulation or excess of free radicals can be damaging to tissues and organs. To balance these out and bring the body into homeostasis, humans have developed an intricate and effective system of antioxidants. Antioxidants serve to quench free radicals, thus ensuring that they are effectively escorted out of the body or neutralized to the extent that they don’t cause detrimental effects.

The most important of the antioxidant systems in the body is the glutathione system. Glutathione – often referred to as the body’s master antioxidant – is critical to human health. In fact, its importance is illustrated by the fact that it is broadly distributed in cells throughout the body and is present in very high concentrations relative to other nutrients. Estimates suggest that glutathione is present in concentrations of 5 millimolar in most cells, which is about the same concentration as glucose, potassium and cholesterol. Given how metabolically intensive the process of producing glutathione is, the fact that the body maintains such high levels illustrates how glutathione benefits overall health.

Glutathione is key to several important metabolic processes in the body. It plays a critical role in the neutralization of various free radicals, including singlet oxygen, hydroxyl, and superoxide radicals, as it goes back and forth between oxidized and reduced states. It serves as a cofactor for various enzymes and participates in the regeneration of other antioxidants, including vitamins C and E. It also facilitates detoxification reactions in the body by neutralizing free radicals produced during Phase I liver metabolism, and conjugates the metabolic byproducts produced during Phase II liver metabolism, escorting them out of the body. In addition, glutathione is vital for mitochondrial function in cells and supports the integrity and stability of mitochondrial DNA, which is important for cellular health.

Not to be overlooked is its key role in immune function and protection of lung tissue from oxidative stress and damage. Glutathione is essentially present in the lining of the lungs and protects the mucosa from damage, making it necessary for supporting the health of the lungs against immune challenges as well as in conditions where lung function is compromised (such as in asthma and other conditions). For these reasons, supporting glutathione production and overall levels in the body is crucial for overall health.

What Is the Difference Between NAC and Glutathione?

We all know that raising levels of glutathione is necessary to support health in so many areas. However, there are multiple ways to do this from a supplementation perspective. Two of the most common are supplementing with glutathione itself or supplementing with the amino acid N-acetyl cysteine (NAC). Both approaches can allow you to experience glutathione benefits.

What is the difference between each approach? Well, glutathione is a tripeptide, meaning the molecule itself consists of three amino acids (cysteine, glycine, and glutamic acid). It is the combination of the three amino acids that makes the molecule function in its role in the body’s antioxidant defenses.

NAC, on the other hand, is a form of the sulfur-containing amino acid cysteine. As a donor to body’s overall pool of cysteine, NAC provides a key building block for the production of glutathione. Research has found that supplementing with NAC is an effective way of increasing the body’s total level of glutathione and it has further been found to be effective for supporting detoxification and lung health. NAC benefits also include reducing mucus in the lungs and sinuses. NAC is also a preferentially absorbed form of cysteine, so it is likely superior to supplementing with the amino acid cysteine itself, which can have stability issues. Given NAC’s superior absorption versus cysteine, it’s easy to see why NAC supplements are key to supporting glutathione production.

Glutathione supplements are obviously another key way to raise glutathione levels. Here, you are supplementing with the preformed molecule glutathione, and its production is not dependent on cysteine from NAC being synthesized into glutathione in the body. In the past, there has been concern that preformed glutathione is not well absorbed through the digestive tract; however, recent studies have found that glutathione can indeed be absorbed through oral supplementation, and that it increases the body’s stores of glutathione.

In other words, both approaches effectively work to support the body’s levels of glutathione. Whether you are using NAC or glutathione supplements, the result is essentially the same.

Can NAC and Glutathione Be Taken Together?

The question may arise of whether both a NAC supplement and glutathione supplement can be used at the same time. In most cases, the answer is yes. The body has its own way of regulating what nutrients it needs and can utilize and what nutrients need to be stored for future use or excreted out of the system. In this way, if you are supplementing with glutathione and NAC together, if the body has the precursor amino acids on board in sufficient supply, it won’t need to utilize the cysteine coming from NAC. Since the body tightly controls the levels of precursors used for various molecules, and both NAC and glutathione have a high level of safety, supplementing with both together will not cause harm. In this scenario, cysteine can be diverted to be used for other key processes in the body when glutathione levels are sufficiently high.

Does Taking in the Morning, or at Night Matter?

Whether you take a glutathione supplement or NAC supplement in the morning or night, the most important thing is to take them. Time of day doesn’t have a significant impact on how effective these products are. Feel free to experiment with different times of day if you want to evaluate whether one regimen works better for you than another; however, the important thing with both NAC and glutathione is to ensure you are taking them regularly, day in and day out. This is the only way they will work as intended to raise stores of glutathione, the master antioxidant for the body.

References

• Pizzorno J. Glutathione!. Integr Med (Encinitas). 2014;13(1):8-12.
• Schwalfenberg GK. N-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks). J Nutr Metab. 2021;2021:9949453. Published 2021 Jun 9.