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Glutathione (GSH) is an important antioxidant and is capable of preventing damage to important cellular components caused by reactive oxygen species (often elevated in patients with chronic fatigue syndrome) such as free radicals, peroxides, lipid peroxides and heavy metals. The weight of evidence suggests that lowered levels of glutathione may suppress immune responses. The below quote, from a review paper demonstrate the importance of optimal glutathione levels in CFS:

Glutathione-, selenium-, and glutathione-dependent enzymes are all involved in antiviral defenses

Low GSH levels and chronic and latent viral infections are frequently seen in patients with chronic fatigue syndrome. In fact rather than the common concept that a viral infection causing CFS, it may be a depletion of glutathione levels has led to the reactivation of a latent virus!

GSH also modulates NF-κB-instigated signalling

NF-kB is involved in initiating the inflammatory response, inflammation often seen in patients with chronic fatigue syndrome.

The optimum function and indeed the very survival of mitochondria are wholly dependent on the coordinated activity of glutathione

As I have discussed in other articles, mitochondrial dysfunction is often seen in patients with chronic fatigue syndrome (see our article on mitochondrial dysfunction here).

GSH depletion impairs mitochondrial function and ATP production by inhibiting complex I of the electron transport chain. Since GSH biosynthesis is an energy dependent process, mitochondrial dysfunction significantly depletes GSH production thereby further exacerbating oxidative damage which further impairs electron transport chain activity. Hence, glutathione depletion is almost certainly a major contributing factor to the progressive nature of mitochondrial diseases.

The above quote highlights the vicious cycle we can get in – low glutathione levels impairs energy production, and energy is required for glutathione production!

Supporting Glutathione Status

Logan and Wong reported an improvement in disability levels in patients with CFS following supplementation with glutathione or N-acetyl cysteine.

Treatments targeting the GSH system in depression and CFS further underscore the important role of GSH and related enzymes in the pathophysiology of these neuroimmune disorders. Coenzyme Q10, in a concentration dependent manner, prevents stress-induced decreases in glutathione peroxidise and GSH.

It will also be important to consider what may be ‘draining the body’ of its glutathione.

We can support the production of glutathione via:

  • Ensuring adequate nutrient intake (and thus providing the building blocks which are cysteine, gluatmic acid and glycine)
  • Supporting the trans-sulfaration pathway, which is the pathway leading to glutathione production (a vitamin B6, magnesium, molybdenum, iron and vitamin B2  dependent pathway) but we also want to consider the rate at which glutathione is being utilised.

Th2 Dominant

In my article ‘CFS: A Th2 Dominant State‘, we discussed how research suggests that in a large subset of CFS patients, there is immune imbalance. The shift to the Th2 immune response is a known effect of both elevated cortisol and of depleted glutathione – again making the individual more susceptible to infections.

Other nutrients such as zinc and selenium, as well as hormones such as progesterone, have an impact on the Th1/Th2 balance.

Nrf-2 & Chronic Fatigue Syndrome

Nrf-2 is critical for the activation of the cellular glutathione system and maintaining the redox state

Curcumin, ECGC from green tea, resveratrol, and sulforphane are just some of the nutrients that have been shown to activate Nrf2. For more information on Nrf2 see our previous article entitled ‘Antioxidants or Phytochemicals‘ (click here).


Glutathione depletion is an important aspect of the pathogenesis of chronic fatigue syndrome, at least a subset of patients. It may also be the underlying cause of some of the most frequent findings in the CFS literature such as viral infections, mitochondrial dysfunction, a dysregulated immune system, heavy metal poisoning such as mercury, autoimmune thyroid disease (or other autoimmune mechanisms) .

At Conquering Fatigue Successfully we assess levels of GSH, oxidative stress and Co Q 10 in our clients to help formulate personalised protocols.

Glutathione repletion is likely only going to part of an overall treatment programme but it is important none the less!

There is a great summary of information here.