Navigating Glutathione Supplementation: When to use the Whole molecule vs Precursors

Glutathione is a tripeptide, known as the master antioxidant, and is often used as a therapeutic agent in integrative health. The level of glutathione in the body has a direct relationship with the amount of oxidative stress a person experiences and is actually the marker through which oxidative stress is measured.

Glutathione is a regulatory molecule that maintains redox balance, ensures detoxification pathways run efficiently and enhances immune function. Due to the regulatory effects of glutathione, suboptimal levels are a risk factor for, but not limited to, the onset and progression of cancer as a whole, neurodegenerative disease, cardiovascular disease, autoimmune conditions, liver and eye conditions and respiratory pathologies. This makes levels of cellular glutathione an important biomarker for various pathologies and an indication of the trajectory of an individual’s health if no intervention is put in place.

Restoring glutathione levels is a critical part of any healing protocol that aims to provide long-term results. With this in mind, glutathione optimization is a potent health promotion and disease prevention strategy. How we as practitioners work to increase levels in our clients and patients depends on several factors. Generally, there are 4 avenues we can take to clinically increase levels.

- Reduce overall free radical load, chemical exposure and inflammation

- Improve glutathione recycling capacity

- Supply the body with precursors and sulfur-based compounds

- Supplement with glutathione

Considerations for Increasing Glutathione

When designing protocols, the basics of glutathione biochemistry is helpful to choose the most efficacious method through which you will help your clients/patients increase their levels.

Glutathione is a molecule made up of glutamic acid, glycine and cysteine. Cysteine is thought to be the rate limiting factor in glutathione synthesis, however new research is making the argument that glycine supplementation is more efficacious than cysteine. For this reason, we often recommend NAC and increased protein intake to supply the building blocks for endogenous synthesis of glutathione.

There are two enzymes, GCL and GS, that are required for glutamic acid, glycine and cysteine to form glutathione. When the amount of either enzyme is insufficient, or their functions are blocked the ability to synthesize glutathione decreases substantially.

The other way through which the body maintains glutathione homeostasis is by recycling glutathione though another enzyme.

In order to have a consistent level of glutathione that is required for health, both endogenous production and recycling must be present. When one pathway is dominant and the complementary relationship between these two is compromised, levels of glutathione cannot be sustained.

When Precursors Might Not Be Enough

1. In the presence of heavy metals, such as mercury as they can block the pathway of GS- which is responsible for adding glycine to complete the synthesis of the glutathione molecule

2. In those who consume alcohol regularly, as alcohol inhibits an important step in methylation that enables cysteine to become available for glutathione synthesis

3. Those with poor methylation often need the whole glutathione molecule as methylation is important for cysteine regulation

4. Clients with excessive oxidative stress or free radical exposure as this blocks the Nrf2 pathway that controls both GCL and GS. When this pathway is compromised, glutathione synthesis is downregulated

5. If someone has a SNP (which is determined through genetic testing), that impacts the ability to synthesize glutathione

When Glutathione Supplementation is Contraindicated

Glutathione supplementation isn’t always beneficial. In our previous blog, Clinical Pearls: Foundations of Glutathione Supplementation, we dive into common adverse reactions that can be seen with glutathione. You can check it out here.

Those who have been dealing with unmanaged chronic infections, those who are in the infancy of their treatment plans or those with long-term mold exposure for example, might not be able to tolerate the whole molecule.

The exception to this is if glutathione is administered in a clinical setting with the appropriate mitigation interventions such as other IVs and therapies that help to re-establish strong baseline physiology.

If using glutathione supplements with compromised individuals, it is a good idea to start with low doses and monitor symptoms. This is where the precursor molecules are valuable along with utilizing other interventions such as enzymes to increase protein digestion along with complementary supplements such as vitamin C.


Glutathione supplementation is tricky, as there is an intermediate stage where precursors will not be sufficient and likely make symptoms worse, but where we also see adverse reactions when supplementing with the whole molecule.

In this case, we can either refer to a clinic that has the knowledge and means to offer the supportive therapies or slowly build glutathione stores by modifying diet and lifestyle until their baseline can tolerate either precursors or direct supplementation.

For more information outlining considerations for how to supplement glutathione in this population head to our other blog!

Glutathione is an essential pillar for enhancing health and managing chronic illness. Optimizing glutathione levels is an indispensable element in efficacious health prevention plans, and would be beneficial to incorporate into public health as well as traditional medical education as its implications are vast. The deeper we get into the physiological effects of glutathione the more we understand the need to start interventions early with our clients and patients. The more we understand the biochemistry of glutathione and how it interfaces with the methylation cycle, among many other facets of physiology we can create targeted plans that optimize levels in our patients/clients in a way that yields the most benefit and faster trajectory of healing. Stay tuned for the 3rd blog in our glutathione series that looks at lifestyle and nutrition interventions to preserve glutathione from a preventative health standpoint.

Author: Lisa Kowalyk, Co-Founder Fiore health



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