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A Closer Look at the Benefits of Glutathione Supplementation

benefits of glutathione

Over the last few years, glutathione supplements have been appearing on store shelves and health food websites, raising questions among patients and clinicians alike about the potential benefits of glutathione supplementation. Whenever a hot new supplement like glutathione hits the market, it is important to consider the rigorous research behind the use of the compound for health purposes before jumping on the bandwagon. For glutathione, a relative abundance of in vitro research provides a strong foundation of information about the compound’s broad role in improving human health, and several recent studies have supported the effectiveness of taking it in supplemental form. While there is still a relative lack of large-scale clinical studies on the benefits of glutathione for treating specific health problems, early studies suggest that it may aid in the prevention and/or management of a wide variety of serious conditions, ranging from neurological diseases to aging skin.

The Basics of Glutathione: Structure and Physiological Activities

Glutathione is a low-molecular-weight, water-soluble tripeptide consisting of three amino acids: glycine, cysteine, and glutamic acid. It exists in two forms: the reduced form (GSH) and the oxidized form (GSSG), and the ratio between these two forms determines the cell’s redox status—that is, its capacity for antioxidation. Although many patients may not have heard about glutathione until recently, it is actually one of the most abundant compounds in cells; under normal conditions, the concentration of glutathione is comparable to that of glucose, potassium, and cholesterol, a fact that highlights its importance in supporting healthy cell function.

Over the last few decades, in vitro research on glutathione has indicated that it plays a variety of critical roles in cellular function, primarily through its activities as an antioxidant. Glutathione directly neutralizes several different types of free radicals that cause cellular and tissue damage, including singlet oxygen radicals, hydroxyl radicals, and superoxide radicals. It also plays a detoxifying role in the body by neutralizing the free radicals that are produced during the first phase of liver metabolism. Importantly, these antioxidant activities do not just occur in the cytosol; they are also crucial to the functioning of mitochondria (organelles involved primarily in cell energy generation) and the protection of mitochondrial DNA from damage. This key connection between glutathione and mitochondrial function is significant because of the importance of the mitochondria in cellular longevity and metabolism—two crucial aspects of health maintenance.

It is important to note, however, that the antioxidant activities of glutathione go beyond its direct function as an antioxidant. The compound also serves as an essential cofactor for several antioxidant enzymes, which means that its presence is necessary for these enzymes to carry out their own antioxidant activities. In addition, glutathione is a necessary component of the regeneration pathways for two other major antioxidants: ascorbate (vitamin C) and tocopherol (vitamin A).

Glutathione is also involved in detoxification processes. For instance, in the second phase of liver metabolism, glutathione is required for the conjugation of toxic intermediates, rendering them water-soluble enough for excretion by the kidneys. Another detoxifying activity of glutathione is the removal of mercury from cells throughout the body, including neurons in the brain. There is also evidence from in vitro studies that glutathione may aid in detoxification processes after overexposure to toxic chemicals like paraquat, iron, and hydrogen peroxide.

Finally, glutathione has been implicated as a possible regulator of cell proliferation and apoptosis, suggesting that the compound may have significant anticarcinogenic effects. As early as the mid-1990’s, scientists recognized that glutathione had anticancer properties, and in vitro research highlighted some of the molecular mechanisms through which this role may be mediated. Specifically, glutathione impacts the expression levels of p53, a protein with connections to multiple cancer-related cell-signaling pathways. It is also associated with the inhibition of tumor angiogenesis. Based on these observations, glutathione is now considered a promising all-natural candidate for cancer prevention and/or treatment.

The Effectiveness of Glutathione Supplementation

Clearly, there is a wide range of benefits of glutathione for individual cells the body as a whole. However, as with any compound, patients and practitioners must recognize that taking a supplement may not necessarily have clinically relevant benefits. Excitingly, with glutathione, the early evidence suggests that taking glutathione in supplemental form can have a positive effect on overall patient health.

Most notably, in 2015, a group of researchers from Penn State University conducted a randomized, double-blinded, placebo-controlled trial to determine whether oral glutathione supplementation actually increased glutathione stores in patients’ cells. The sample included 54 healthy adults who received either a placebo, a daily supplement of 250mg of glutathione, or a daily supplement of 1000mg of glutathione. The researchers reported statistically significant increases in glutathione stores in both of the glutathione treatment groups after the six-month-long study period. This study served as the first-ever demonstration that daily supplementation can lead to higher stores of glutathione in the body. Importantly, the researchers also observed multiple improvements in immune function, including a twofold increase in natural killer cell cytotoxicity in patients who took the higher dose of glutathione, which indicates that supplementation can have clinically significant effects that directly impact patient health outcomes.

When it comes to the effectiveness of glutathione supplementation, the naturally low bioavailability of the compound has remained an important concern for both researchers and supplement developers who are interested in the potential health benefits of glutathione supplementation for patients. With recent improvements in delivery system technology, researchers have successfully developed innovative systems that have significantly enhanced the absorption of oral glutathione supplements. By choosing a supplement that has been optimized for bioavailability, patients can maximize the impact of glutathione supplementation on their cellular stores of the compound.

Opportunities for Future Research on the Benefits of Glutathione

Because of the well-documented antioxidant, detoxifying, and other cell regulatory activities of glutathione, there is growing interest within the research community to explore the effectiveness of the compound as a supplement for the management and treatment of specific health conditions, as well as the supplement’s potential as a promoter of general wellness. Here are a few of the most promising findings:

  • Glutathione supplementation may offer benefits for patients with Parkinson’s disease.
  • There are multiple ways in which glutathione may fight cognitive impairment.
  • By improving immune cell function, the compound may help promote immune health.
  • The anti-aging effects of glutathione have been demonstrated through multiple studies on skin health.
  • Sports science researchers have recently been looking to ways in which glutathione supplementation may help reduce muscle fatigue.
  • For patients with certain stomach problems, glutathione may help protect the integrity of the gastrointestinal tract.
  • In some cancer cases, glutathione may help increase the susceptibility of tumors to treatments like chemotherapy.
  • Glutathione may help improve some of the behavioral and physiological symptoms associated with autism spectrum disorder.

As researchers continue to call for more comprehensive clinical trials on the potential health benefits of glutathione, patients and practitioners more fully discover how to harness the wide-ranging activities of this unique compound to improve health outcomes. Even now, it is possible to take advantage of the existing research to explore the possible benefits of glutathione supplementation for individual patients, which can increase the body of anecdotal evidence and motivate more glutathione research in the future.

Foundational Medicine Review offers analysis on cutting-edge research relating to a wide range of nutritional supplements, including glutathione. Join our mailing list today to learn more about the most innovative strategies for treating neurological, gastrointestinal, and other relevant health conditions.

Works Cited

Allen J, Bradley RD. 2011. Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. Journal of Alternative and Complementary Medicine. 17(9):827-33. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162377/

Aoi W, Ogaya Y, Takami M, Konishi T, Sauchi Y, et al.  2015. Glutathione supplementation suppresses muscle fatigue induced by prolonged exercise via improved aerobic metabolism. Journal of the International Society of Sports Nutrition. 12:7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4328900/

Chan AC. 1993. Partners in defense, vitamin E and vitamin C. Canadian Journal of Physiology and Pharmacology. 71(9):725-31. https://www.ncbi.nlm.nih.gov/pubmed/8313238

Droge W, Breitkreutz R. 2000. Glutathione and immune function. The Proceedings of the Nutrition Society. 59(4):595-600. https://www.ncbi.nlm.nih.gov/pubmed/11115795

Mari M, Morales A, Colell A, Garcia-Ruiz C, Fernandez-Checa JC. 2009. Mitochondrial glutathione, a key survival antioxidant. Antioxidants and Redox Signaling. 11(11):2685-2700. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821140/

Meng Q, Velalar CN, Ruan R. 2008. Regulating the age-related oxidative damage, mitochondrial integrity, and antioxidative enzyme activity in Fischer 344 rats by supplementation of the antioxidant epigallocatechin-3-gallate. Rejuvenation Research. 11(3):649-60. https://www.ncbi.nlm.nih.gov/pubmed/18593283

Pizzorno J. 2014. Glutathione! Integrative medicine: A clinician’s journal. 13(1):8-12. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4684116/

Richie JP, Nichenametla S, Neidig W, Calcagnotto A, Haley JS, et al. 2015. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. European Journal of Nutrition. 54(2):251-63. https://www.ncbi.nlm.nih.gov/pubmed/24791752

Schmitt B, Vicenzi M, Garrel C, Denis FM. 2015. Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study. Redox Biology 6:198-205. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536296/

Schwartz JL, Shklar G. 1996. Glutathione inhibits experimental oral carcinogenesis, p53 expression, and angiogenesis. Nutrition and Cancer. 26(2):229-36. https://www.ncbi.nlm.nih.gov/pubmed/8875560

Singh S, Khan AR, Gupta AK. 2012. Role of glutathione in cancer pathophysiology and therapeutic interventions. Journal of Experimental Therapeutics and Oncology. 9(4):303-16. https://www.ncbi.nlm.nih.gov/pubmed/22545423

Traverso N, Ricciarelli R, Nitti M, Marengo B, Furfaro AL, et al. 2013. Role of glutathione in cancer progression and chemoresistance. Oxidative Medicine and Cellular Longevity. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3673338/

Uchida H, Nakajima Y, Ohtake K, Ito J, Morita M, Kamimura A, Kobayashi J. 2017. Protective effects of oral glutathione on fasting-induced intestinal atrophy through oxidative stress. World Journal of Gastroenterology. 23(36):6650-64. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643286/

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