There is a lot of recent buzz around the term “methylation” in the health-conscious community. The buzz is well deserved, as this process is happening in almost every cell in the body, all the time, and contributes to a long list of physiological processes necessary for our health. On top of all this, we have the power to control the efficiency (or inefficiency) of methylation with the type of nutrition we take in from food and supplements. 

Methylation and glutathione are often discussed in conjunction because the methylation cycle is directly joined with the transsulfuration pathway. Transsulfuration is how the body makes its master antioxidant: glutathione. 

Unfortunately, if your body is not methylating efficiently, due to a genetic mutation in the MTHFR gene, disease, chronic stress, or nutritional deficiency, you are likely not only lacking L-methylfolate, but also L-glutathione. A simplified explanation is that some of the homocysteine produced during methylation reactions is used to make cysteine, which is then combined with two other amino acids (glutamate and glycine) to form glutathione [1]. 

Why Worry About Glutathione Levels?

L-Glutathione, sometimes referred to as GSH, is a sulfur-containing tripeptide that is an important part of the body’s antioxidant defense system. It is a “tripeptide” as it is made up of three amino acids: glutamine (the body’s most abundant amino acid), glycine (the smallest amino acid), and cysteine (a sulfur-bearing amino acid). Glutathione is in every cell of the body, including the blood. It has strong antioxidant properties as it directly neutralizes free radicals, reduces inflammation, and contributes to the effect of other antioxidants like vitamin C, E, and lipoic acid [2]. Glutathione’s sulfur groups aid in detoxification by adhering to toxins and heavy metals before carrying them out of the body.

Another function of glutathione is to protect vitamin B-12 from reacting with toxins [3]. When B-12 reacts with toxins, it cannot perform its metabolic tasks. One of its primary roles is being a precursor for a reaction that takes place at the junction of the methylation cycle and the folate cycle. If this reaction slows down due to a lack of active B-12, as a result of glutathione deficiency, it affects both these cycles. Therefore, low glutathione levels can contribute to the inefficiency of methylation, creating a vicious cycle and furthering depleting one’s glutathione levels.

Glutathione plays important roles in intracellular redox balance, cellular defense, nutrient metabolism, and regulation of cellular events (including gene expression, DNA and protein synthesis, cell proliferation and apoptosis, signal transduction, cytokine production, and immune response, and protein glutathionylation) throughout the body [4,5]. Glutathione is found to be most concentrated, respectively, in the liver, spleen, kidneys, eye lenses, erythrocytes, and leukocytes [6]. Glutathione deficiency has been linked to a number of disease states in these tissues and cell types [6]. In specific relation to the immune system, glutathione deficiency is known to impair macrophage and T-cell function [7]. Because serious glutathione depletion can occur under conditions of trauma and stress, maintenance of adequate glutathione levels may enhance immunocompetence and thus improve your ability to recover from illness or physical stress [7].

What Can I Do To Restore My Glutathione Levels?

Optimal amounts of L-glutathione are necessary for the proper function of the immune system, and to help the liver to detoxify chemicals. Reduced L-glutathione is the most active form of the nutrient. Until recently, the bioavailability of orally supplemented L-glutathione was heavily debated, however, oral dosages of Setria® glutathione, specifically, have been shown to increase glutathione levels within the body stores of healthy adults [4]. 

Metabolic Maintenance offers Setria® Reduced L-Glutathione in a 100 mg capsule dose that can be taken conveniently at the frequency and time of day recommended by your trusted healthcare professional. If you are taking L-methylfolate supplements to counterbalance the effects of a gene mutation, or have an otherwise compromised methylation/folate cycle, please speak to your doctor about the benefits of adding glutathione to your nutritional regimen.



  1. Mcevoy, Michael. “GLUTATHIONE & DETOXIFICATION: THE METHYLATION CONNECTION.” Metabolic Healing. July 24, 2014
  2. Corey, Michelle. “Methylation: Why It Matters For Your Immunity, Inflammation & More”. MBG Food. Accessed April 24, 2019.
  3. Watson, William P., Tony Munter, and Bernard T. Golding. “A new role for glutathione: protection of vitamin B12 from depletion by xenobiotics.” Chemical research in toxicology 17.12 (2004): 1562-1567.
  4. Wu, Guoyao, et al. “Glutathione metabolism and its implications for health.” The Journal of nutrition 134.3 (2004): 489-492.
  5. Deneke, SUSAN M., and BARRY L. Fanburg. “Regulation of cellular glutathione.” American Journal of Physiology-Lung Cellular and Molecular Physiology 257.4 (1989): L163-L173.