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A 5-minute Guide To Glutathione: Why It’s Important For Immune Function

By Dr. Michael Murray

In this article:


One of the most important compounds that every cell in your body produces is glutathione

‌‌‌‌What is Glutathione?

Glutathione is a small protein molecule composed of the amino acids glutamate, cysteine, and glycine. 

‌‌‌‌What Does Glutathione Do?

Glutathione helps protect our cells from damage as well as aids in detoxifying harmful compounds. 

Over the course of 100 years of research, more than 100,000 scientific papers have established maintaining cellular glutathione levels as one of the most important keys in maintaining proper cellular function, immune health, and slowing the aging process. 

‌‌‌‌5 Benefits of Glutathione

  1. It is an antioxidant. Glutathione is the cell’s major antioxidant to protect the cell from damage. It is also critical to the recycling and proper utilization of other antioxidants such as vitamins C and E.
  2. It has immune system effects. Glutathione protects immune cells from damage while also exerting some direct antiviral effects. It is also critical in modulating balance within the immune system. It boosts functions when the immune system is underactive and brings it back into balance when it is overactive.
  3. It has mitochondrial effects. Glutathione plays a critical role in the function of mitochondria (the energy-producing compartments in cells). 
  4. It is critical to cellular function. Glutathione is required for the manufacture of many cellular proteins, the synthesis and repair of DNA, the activation and regulation of cellular enzymes involved in overall cell function, and the proper action of vitamin D3.
  5. It is a detoxifying compound. Glutathione is the body's most effective detoxifying agent. Glutathione binds undesirable toxins, pollutants, chemicals, heavy metals, and drug metabolites and excretes them through the urine or the gut.

‌‌‌‌What Happens When Glutathione Levels in the Body are Low?

Glutathione levels tend to drop as we age, as well as when we are exposed to toxins, drugs, environmental pollution, and any other compound that causes oxidative damage. Even something as simple as taking acetaminophen (e.g., Tylenol) can cause glutathione levels to plummet. Low levels of glutathione are linked to accelerated aging and almost every chronic disease, especially those associated with aging like cognitive decline, type 2 diabetes, and many forms of chronic disease.1,2

Being older is a well-recognized risk factor for severe illness, complications, and death from a variety of causes including viral infections. Lower glutathione levels make cells more susceptible to oxidative damage. Low glutathione levels can also impair the immune system as well as the protective barriers in the respiratory and gastrointestinal tract. 

The same impairments exist in these conditions:

  • Chronic kidney disease
  • COPD (chronic obstructive pulmonary disease)
  • Immunocompromised state (weakened immune system) from solid organ transplant
  • Obesity (body mass index [BMI] of 30 or higher)
  • Serious heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies
  • Sickle cell disease
  • Type 2 diabetes mellitus

‌‌‌‌What Role Does Glutathione Play in Immune Function?

During this time of increased focus on immune health, it is important to understand how important glutathione is in protecting against infections. What the research is quite clear on is that higher cellular levels of glutathione are associated with a person having the proper response to viral infections.3 This effect is due to glutathione protecting immune cells from damage as well as enhancing immune functions that are critical to protecting against viruses.4 Glutathione has also shown direct effects in blocking the replication of various viruses at different stages of its life cycle.5 These antiviral properties of glutathione are thought to help prevent increased viral loads and the subsequent massive release of inflammatory cells into the lungs seen with certain viral illnesses. 

‌‌‌‌What Dietary Factors and Supplements Boost Glutathione Levels?

Diet can help raise glutathione levels, but only to a limited extent. The human body, mainly the liver, makes about 8,000 to 10,000 mg of glutathione daily. To put this amount into perspective, a healthy diet rich in fresh fruit and vegetables may provide about 150 mg of preformed glutathione per day. That said, the cell strives to hang on to glutathione so the cumulative effects of higher dietary glutathione intake are certainly an important goal. Asparagus, avocado, and walnuts are particularly rich dietary sources of glutathione. 

The most popular supplemental approaches to boost glutathione levels involve taking either glutathione or N-acetylcysteine. Prior to recent studies, there was some controversy with glutathione as a dietary supplement because it was thought that glutathione may not be absorbed when taken orally. One early study is often cited to show a lack of absorption. In the study, a single dose of 3,000 mg of glutathione failed to increase glutathione levels in the blood. However, it turns out there is another reason.7 Researchers were looking for free glutathione levels and because glutathione is so valuable it is quickly bound to transport proteins to carry to cells8 causing it to not show up as free glutathione in the blood. 

‌‌‌‌Can Glutathione Supplements Be Absorbed Orally? 

The first study showing significant oral absorption in humans with reduced glutathione (GSH) was conducted at Kyoto University in 2014.9 The study was different because it looked not only at free, unbound glutathione in the blood, but also the level of glutathione bound to protein. The results showed that while there was no significant difference in free glutathione levels, the level of glutathione bound to protein increased significantly after glutathione supplementation. This study was groundbreaking because it explained the shortcomings of previous absorption studies.

The next study, conducted at Penn State University in 2015, showed again quite clearly that glutathione is absorbed orally and increases the tissue concentration of glutathione.10 A total of 54 healthy, non-smoking adults were randomized to placebo or oral glutathione at a dosage of 250 mg or 1,000 mg per day for 6 months. The results showed that glutathione levels increased significantly from baseline in whole blood and red blood cells at 3 months and 6 months at both dosages. After 6 months, taking 250 mg glutathione per day increased glutathione levels by 17% in whole blood and by 29% in red blood cells. Taking 1,000 mg glutathione per day increased glutathione levels by 31% in whole blood and by 35% in red blood cells. Even more impressive was that glutathione levels the cells that line the inner cheek increased by 250% in those taking 1,000 mg of glutathione per day.

Lastly, a study in animals in 2018 showed that glutathione is directly absorbed in the intestine, is then transported in the blood bound to proteins, and is finally delivered to the liver where it is then utilized in cellular protection and detoxification reactions.11 

‌‌‌‌What is NAC and How Does it Boost Glutathione?

N-acetylcysteine (NAC) is a form of the amino acid, cysteine – the key amino acid of glutathione. Taking NAC as a dietary supplement to boost tissue levels of glutathione. NAC supplementation can boost glutathione levels and is especially helpful in protecting the lungs and respiratory tract, and gastrointestinal tract from damage.14-17 NAC is also the treatment of choice in the treatment of acetaminophen (Tylenol®, paracetamol) toxicity. Acetaminophen is metabolized to toxic compounds that deplete liver glutathione stores and subsequently damage the liver. At high enough levels or coupled with alcohol ingestion this depletion of glutathione by acetaminophen can be fatal.

NAC is also a mucus modifying agent. It has been used orally with great success as well as in hospitals through breathing tubes to help people dealing with inefficient or thick mucus in acute and chronic lung conditions such as emphysema, bronchitis, chronic asthma, and cystic fibrosis. 

NAC can help to reduce the viscosity of bronchial secretions. NAC has also been found to improve the ability of cilia in the respiratory tract to clear mucus, increasing the clearance rate by 35%. As a result of these effects, NAC improves bronchial and lung function, reduces cough, and improves oxygen saturation in the blood when the respiratory tract is being challenged. 

For protection and boosting glutathione levels in the lungs, the dosage is generally 500 to 1,000 mg daily. For use in reducing mucus thickness, the typical dosage is 200 to 400 mg three to four times daily.17-19

‌‌‌‌Which is Better? Glutathione or NAC?

In answering this question, it is important to state that both forms have shown clinical benefits, and choosing one over the other is a bit like splitting hairs. The advantage of glutathione is that it is the preformed, active compound. The advantage of NAC is that it may be a more effective mucolytic and a better choice when the respiratory tract mucus is thick and sticky.

References:

  1. Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol. Aspects Med. 2009;30, 1−12. 
  2. Dwivedi D, Megha K, Mishra R, Mandal PK. Glutathione in Brain: Overview of Its Conformations, Functions, Biochemical Characteristics, Quantitation and Potential Therapeutic Role in Brain Disorders. Neurochem Res. 2020;45(7):1461-1480.
  3. Dröge W, Breitkreutz R. Glutathione and immune function. Proc Nutr Soc. 2000;59(4):595-600.
  4. Fraternale A, Brundu S, Magnani M. Glutathione and glutathione derivatives in immunotherapy. Biol Chem. 2017;398(2):261-275.
  5. Fraternale A, Paoletti MF, Casabianca A, et al. Antiviral and immunomodulatory properties of new pro-glutathione (GSH) molecules. Curr Med Chem. 2006;13(15):1749-1755.
  6. Jones DP, Coates RJ, Flagg EW, et al. Glutathione in foods listed in the National Cancer Institutes Health Habits and History Food Frequency Questionnaire. Nutr Cancer 1995;17:57-75.
  7. Witschi A, Reddy S, Stofer B, Lauterburg BH. The systemic availability of oral glutathione. Eur J Clin Pharmacol 1992;43(6):667-9.
  8. Kovacs-Nolan J, Rupa P, Matsui T, et al. In vitro and ex vivo uptake of glutathione (GSH) across the intestinal epithelium and fate of oral GSH after in vivo supplementation. J Agric Food Chem. 2014;62(39):9499-9506.
  9. Park EY, Shimura N, Konishi T, et al. Increase in the protein-bound form of glutathione in human blood after the oral administration of glutathione. J Agric Food Chem. 2014;62(26):6183-6189.
  10. Richie JP Jr, Nichenametla S, Neidig W, et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr. 2015;54(2):251-263.
  11. Yamada H, Ono S, Wada S, et al. Statuses of food-derived glutathione in intestine, blood, and liver of rat. NPJ Sci Food. 2018;2:3. Published 2018 Feb 6. doi:10.1038/s41538-018-0011-y.
  12. Sacco R, Eggenhoffner R, Giacomelli L. Glutathione in the treatment of liver diseases: insights from clinical practice. Minerva Gastroenterol Dietol. 2016;62(4):316-324.
  13. Kessoku T, Sumida Y, Imajo K, et al. Efficacy of Glutathione for the Treatment of Non-Alcoholic Fatty Liver Disease: An Open-Label, Multicenter, Prospective Study. J Hepatology 2016;64(2):S500.
  14. Šalamon Š, Kramar B, Marolt TP, Poljšak B, Milisav I. Medical and Dietary Uses of N-Acetylcysteine. Antioxidants (Basel). 2019;8(5):111.
  15. Pei Y, Liu H, Yang Y, et al. Biological Activities and Potential Oral Applications of N-Acetylcysteine: Progress and Prospects. Oxid Med Cell Longev. 2018;2018:2835787.
  16. Elbini Dhouib I, Jallouli M, Annabi A, Gharbi N, Elfazaa S, Lasram MM. A minireview on N-acetylcysteine: An old drug with new approaches. Life Sci. 2016;151:359-363. doi:10.1016/j.lfs.2016.03.00.
  17. Santus P, Corsico A, Solidoro P, Braido F, Di Marco F, Scichilone N. Oxidative stress and respiratory system: pharmacological and clinical reappraisal of N-acetylcysteine. COPD. 2014 Dec;11(6):705-1.
  18. Stey C, Steurer J, Bachmann S, Medici TC, Tramer MR. The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Eur Respir J 2000;16(2):253-62.
  19. Grandjean EM, Berthet P, Ruffmann R, Leuenberger P. Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials. Clin Ther 2000;22(2):209-21.

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