Glutathione (GSH) deficiency

Glutathione (GSH) is a primary antioxidant synthesized within the body to provide defense mechanism against bacteria, viruses, toxic metabolism byproducts, heavy metal toxicity and toxic poisoning. The highest density of glutathione is found in the liver, where most of the blood detoxification occurs. Of all the most powerful antioxidants such as vitamin C, grape-seed and blueberry extracts, and lycopene, glutathione is the strongest.

The glutathione production can be affected by the following factors

  • Chronic illness(es), stress
  • Unhealthy lifestyle such as an imbalance nutrition, smoking, alcohol, caffeine, etc.
  • Drug treatments such as antibiotics, antidepressants, pain relievers
  • Unintentional malnutrition
  • Physical or psychological trauma
  • Aging (the GSH production is markedly decreased by 12% each decade after age 25)
  • Glutathione synthetase deficiency [srs]
  • Type and frequency of infectious diseases experienced during the lifetime
  • Genetic predisposition in absence of specific genes which leads to a more rapid depletion of glutathione with age

Free radicals and other oxidative agents by increase of oxidative stress can deplete GSH very rapidly. The homeostatic glutathione redox cycle is mediated to keeps GSH levels sufficient on as needed basis. However, the amounts of glutathione deriving  from foods nutrients are limited, less that 200 mg per day, therefore the oxidative impact on glutathione production can outpace its synthesis.

When glutathione capacity is depleted, the immune system function becomes compromised. The inefficiency of detoxification pathways and poorly controlled viral and bacterial activities imposes a toxic burden many functions of the body, including the digestive function. When digestion is affected, less nutrients are available for glutathione production, depleting the stores of glutathione, which eventually leads to illnesses.

Low glutathione levels are implicated in conditions where increased oxidative stress require more aggressive detoxification capacity. These include but not limited to chemical and infectious toxicities, cancers, liver diseases, gastrointestinal illnesses, Parkinson’s and  Alzheimer’s diseases, asthma, chronic obstructive pulmonary disease, radiation poisoning, strenuous physical stress, aging, chronic psychological stress, systemic inflammatory conditions such as rheumatoid arthritis, lupus, chronic fatigue syndrome ME / CFS and others. Schizophrenia and bipolar disorder are also associated with systemic glutathione deficiency.

Restoring the glutathione levels

Correcting the glutathione deficiency can be very beneficial to restore the body’s overall health. Research suggests that when taken orally, glutathione is not absorbed very well in the gastrointestinal tract. The most optimal way to naturally increase the glutathione production is via adjustments in the diet and daily 20-minute cardio exercise.

Foods rich in sulphur-containing amino acids can help boost glutathione levels

  • Bone broth is very rich in glycine, which is one of the primary amino acids required for glutathione synthesis. Properly prepared bone broth significantly boosts glutathione levels.
  • Asparagus
  • Broccoli and broccoli sprouts
  • Avocado
  • Spinach, Kale
  • Cabbage
  • Collards
  • Raw eggs
  • Garlic
  • Onions
  • Unprocessed meats

Supplements, can also help increasing the levels of glutathione when used along with an appropriate diet. Nevertheless, glutathione supporting supplements should not be used long term (recommended 3-6 months) as the body’s own GSH production may decrease via a negative feedback inhibition. The supplements should also be gradually discontinued to avoid a rebound effect.

If you experience significant symptoms that could be related to toxicity, such as neurological symptoms, insomnia and discomfort in the liver area, increasing of glutathione with supplements can produce side effects due to a rapid detoxification, stressing the detox pathways even further. In this case, with side effects from taking NAC, the initial dosage should be as low as 50mg per day, and gradually increased over a few weeks period to 200-500mg per day. If side effects persist, the supplements will need to serve a limited function in glutathione support while the nutrients beneficial to its production should come from foods.

The major amino acids used in biosynthesis of glutathione are glutamic acid, cysteine and glycine. Co-factors are vitamin C, D [srs], E, B1, B2, B6, B12, Folate (5-MTHF, 5-Methyltetrahydrofolate), Selenium and Zinc.

  • One of the following can be used to directly increase the levels of glutathione
    • N-Acetyl-Cysteine (NAC) is synthesized from L-Cysteine and acts as a precursor of glutathione. The sustained NAC is a better option. L-glutamine has been also been shown to enhance glutathione saturation when taken with N-Acetyl-Cysteine. Note, NAC increases zinc excretion, so supplementing with zinc and copper in 8:1 ratio is recommended. Vitamin C should also be taken with NAC to prevent the cysteine  conversion to cystine, which can promote kidney or bladder stones
    • S-adenosylmethionine (SAMe)
  • Alpha Lipoic Acid increases intracellular glutathione and helps recycle vitamin D and E [srs]
  • Milk Thistle (Silymarin) increases concentrations of glutathione in the liver by about 30%
  • Turmeric (Curcumin) increases activity of glutathione S-transferase
  • Selenium (mineral) is required for regulation of glutathione peroxidase enzyme activity
  • Melatonin has capacity to stimulate glutathione peroxidase enzyme in brain [srs]

Glutathione is a tightly regulated and is limited in its production by negative feedback inhibition of its own synthesis through the gamma glutamylcysteine synthetase enzyme, which greatly minimizing any possibility of overdosage.