Glutathione is considered the most powerful endogenous antioxidant with a wide variety of functions in the body. It consists of three amino acids: cysteine, glutamic acid and glycine. The body breaks this tripeptide apart before absorption, but the rate limiting (most valuable) amino acid for the purpose of making glutathione is cysteine. Unlike vitamin C, which has an antioxidant role outside the cell, glutathione acts inside cells to directly to eliminate free radicals throughout the cytoplasm and inside the mitochondria. Clinical applications include detoxification, cardiovascular disease, neurological injury, liver protection, immune support and cancer. It most recently has gained attention due to its anti-aging applications. Due to its powerful and multifaceted effects both scientists and doctors are often trying to boost levels in the body with a variety of supplements and foods.
There are only a few ways to increase levels in the body:
1) Oral supplementation of glutathione
2) Oral supplementation with glutathione precursors
3) Regular physical exercise (not high intensity)
4) Intravenous (IV) glutathione
Recently, some companies have created glutathione formulations that are claiming good absorption but the evidence is limited. Some recent data shows that liposomal (putting a substance in a fat soluble sphere to improve absorption) is better absorbed than N-Acetyl-L-Cysteine. More research is needed to confirm these results. The other problem with glutathione supplements is that it is very unstable and quickly breaks down outside the body. That is why our cells (especially in the liver) are always producing it. Oral and IV preparations (i.e. liposomal) are also very expensive compare to precursors. Another emerging consideration that is now being researched heavily is that some people have a number of genetic alterations (AKA polymorphisims) that can reduce the conversation and transport of glutathione. All these points still suggest that the most research based and cost-effective method to boost glutathione is to use glutathione precursors.
N-Acetyl-L-Cysteine (NAC) is an amino acid that acts as an antioxidant and is a precursor to glutathione. Numerous studies have show NAC powerfully enhances glutathione levels and protects the liver from toxic damage. NAC is also more bioavailable and 6 times as cost-effective as glutathione. It also has a number of unique clinical benefits including the reduction of homocystine (cardioprotection), reducing viral infections and as a mucolytic. New evidence suggests that NAC has immune balancing (to impact viral replication and balance autoimmunity) effects independent of glutathione.
Another powerful glutathione booster is whey protein. Whey protein is unique because it contains a protein complex called alpha-lactalbumin, which is rich in the amino acid cysteine. While vegan proteins are a favorite choice for detoxification they do increase glutathione to the same degree as whey and may be a better option if the patient is not sensitive to dairy.
Milk thistle contains a class of plant compounds called flavonoids of which silymarin and silybin are the best studied. These compounds exert a substantial effect on protecting the liver from damage as well as enhancing detoxification processes. This hepatoprotective effect is supported but a number of clinical studies have found that Milk thistle can increase liver, pancreas and blood levels of glutathione.
Selenium an important nutrient that is needed for the production of glutathione peroxidase a key enzyme in the activation of glutathione. Its role is so vital that deficient levels may impair detoxification function and increase cancer risk.
I would also consider supporting antioxidants such as R+ lipoic to recharge glutathione from the oxidized to the reduced form. My favorite formulations for glutathione support are NAC or NAC + R lipoic acid sustained release. While I prefer the non-sustained release form to spike plasma levels and have a greater therapeutic effect the sustained release version offers an option if the patient is not willing to take NAC/lipoic 3-4 times daily. Both of these formulations are better absorbed on an empty stomach. AOR’s whey protein has been specifically formulated to reduce the allergenic component but maintaining at least 20% alpha-lactalbumin and 28% more lactoferrin than other whey proteins.
Lastly, AOR’s liver support is often overlooked for products with a greater number of ingredients but it offers therapeutic doses of lipoic acid, NAC, chanca piedra, milk thistle, and broccoli seed extract. This combination makes it a premier detoxification, glutathione boosting and anti-viral (especially hepatitis) formula. Increasing glutathione production is one of the best ‘bang for your buck” strategies since there isn’t a more powerful substance that has so many different actions in every part of the body.
NAC, whey protein, milk thistle and selenium remain the most effective supplements and should be considered with the majority of diseases.
Had you ever heard of this important antioxidant before? What results have you noticed? Leave a comment or question in the section below!
Morris D, Guerra C, Khurasany M, Guilford F, Saviola B, Huang Y et al (2013) Glutathione supplementation improves macrophage functions in HIV. J Interferon Cytokine Res 33(5):270–279
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Atkuri KR et al. N-Acetylcysteine--a safe antidote for cysteine/glutathione deficiency. Curr Opin Pharmacol. 2007 Aug;7(4):355-9. Epub 2007 Jun 29.
Micke P et al. Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients. Eur J Clin Invest. 2001 Feb;31(2):171-8.