Function and application of glutathione


Structure and physiological function of glutathione

1. Structure of glutathione

Glutathione (γ-L-glutamyl-L-cysteinyl-glycine) is a tripeptide composed of L-glutamic acid, L-cysteine, and glycine. It is a bioactive non-protein mercaptan compound that is widely found in living organisms.

In animal and plant cells, Glutathione mainly exists in two forms: reduced GSH and oxidized glutathione (GSSG), of which active GSH accounts for about 90%. GSSG can be reduced to GSH by Glutathione Reductase (GR). And consume NADPH;

In addition to GSSG, GSH can also form other mixed disulfide mercaptan compounds such as GS-COA, GS-CYS, etc.

Figure shows the molecular structure of glutathione (GSH)
Figure shows the molecular structure of GSH

The chemical structure of glutathione determines its structural stability.

Glycine residues can protect glutathione from gamma-glutamyl Cyclotransferase (gamma-GCT).

The gamma-peptide bond between glutamate and cysteine prevents GSH from being hydrolyzed by many polypeptidases.

Diagram of glutathione REDOX cycle
Diagram of glutathione REDOX cycle

Note: Reduced glutathione GSH is oxidized to glutathione disulfide (GSSG), which is reduced to GSH in the presence of NADPH by GSH reductase.

Glutathione peroxidase converts hydrogen peroxide (H2O2) to water (H2O).

2. Metabolism of glutathione in vivo

Metabolism of glutathione in animals and plants is accomplished through the gamma-glutamyl cycle.

Overview of gamma-glutamyl cycle
Overview of gamma-glutamyl cycle

Applications of glutathione in various fields

The main characteristics of glutathione molecular structure are its free sulfhydryl group and strong ability to supply electron or protic hydrogen, and it can be used as a water-phase antioxidant and antioxidant cofactor to protect DNA, proteins and other biomolecules against oxidative damage.

The structural characteristics of GSH determine that it plays an important physiological function in living organisms, and is widely used in medicine, food and cosmetics industries.

Four application areas of glutathione and their functions
Four application areas of glutathione and their functions

1. Application of glutathione in food

Glutathione has been widely used in various fields of food processing, and it is mainly used to inhibit Browning, prolong food storage period, and increase food flavor.

(1) Application in livestock and poultry meat and seafood:

Adding glutathione to meat and seafood can effectively inhibit the decomposition of nucleic acid, enhance flavor, and extend the shelf life of food.

(2) Application in wine: Glutathione has a protective effect on the aroma components of wine, which is conducive to extending the storage period of kiwi wine. GSH plays an important role in wine making and ripening, such as the reduction of Browning due to its antioxidant properties, the optimization of flavor, etc.

(3) Application in condiment: Glutathione and L-glutamate sodium, cystine and xylose mixed heating, can produce a unique beef flavor; And GSH and flavor nucleotides such as inosine, guanylic acid and sodium glutamate after mixing, will form a strong meat flavor, can be used as flavoring agents and flavor agents in a variety of food processing.

(4) Application in vegetable and fruit foods: In the processing of vegetable and fruit foods, adding an appropriate amount of GSH can effectively prevent Browning, and maintain the original attractive color, flavor and nutritional value.

(5) Application in flour products: During the processing of flour products, adding an appropriate amount of glutathione can not only effectively improve the rheological properties of dough, control the strength and viscosity of dough, but also shorten the kneading time and drying time of flour products; In noodle processing, GSH also acts as an inhibitor of tyrohydrase, preventing undesirable color changes.

(6) Application in dairy products and fermented foods: the appropriate addition of GSH in dairy products can enhance its pleasant flavor and effectively improve the quality of dairy products; Adding glutathione to yogurt production can play a role in stabilizing quality.

2. Application of glutathione in the field of whitening

The color of the skin depends on the ratio of two different types of melanin in the skin, namely the dark brown eumelanin and the yellow-red phaeomelanin. Glutamine acts as a skin whitening agent by inhibiting tyrosinase, which helps in the formation of melanin.

It also converts eumelanin to fusomelanin, which causes the skin to turn white. Glutathione Manufacturer

It has become a popular skin whitening agent, and even dermatologists use it to treat melasma and other facial melanosis.

Glutathione for whitening is ingested in many forms, including topical lotions, oral and injectable.

When used consistently over a period of time, topical preparations show considerable improvement in skin tone. Both tablet and solution versions of oral formulations are available. The FDA considers the sublingual method to be safe because it is easier to obtain and requires less amount.

The amount required is 20-40 mg/kg (i.e., 1 g to 2 g, given in two doses), and significant results are evident in as little as three months.

Glutathione can be used alone, or in combination with ascorbic acid, vitamin E, tranexamic acid, and other ingredients.

Synthesis mechanism of fusomelanin in skin
Synthesis mechanism of fusomelanin in skin

3. Application of glutathione in the medical field

In view of the multiple roles of glutathione in cell physiology, clinical studies to alter GSH homeostasis have also received attention.

The list of conditions associated with impaired GSH homeostasis continues to grow and reflects the importance and diversity of glutathione cell function.

The most well-known include neurodegenerative diseases (particularly Parkinson’s and Alzheimer’s diseases), lung diseases (chronic obstructive pulmonary disease, asthma and acute respiratory distress syndrome), cystic fibrosis, immune diseases (HIV, autoimmune diseases), cardiovascular diseases (hypertension, myocardial infarction, cholesterol oxidation), And age-related oxygen-related diseases (such as cataracts, macular degeneration, hearing impairment, and glaucoma), as well as the aging process itself. Although sufficient GSH is an important defense against many carcinogens, several cancer types have been shown to have elevated glutathione levels, making them more resistant to apoptosis and chemotherapy/radiotherapy.

Although therapies that enhance GSH synthesis, such as n-acetylcysteine, may prevent chemotherapy-related toxicity, it may also be necessary to restrict its intake during treatment of specific cancer cell lines.

Glutathione plays a key role in healthy and tumor cells
Glutathione plays a key role in healthy and tumor cells

In the liver, GSH plays a particularly important role as an antioxidant. In the treatment of viral liver disease, reduced glutathione can enhance the detoxification function of the liver through transmethylation and transpropylamino reaction, and promote bile metabolism, thereby protecting liver cells.

treatment of drug-induced liver disease, GSH can effectively reduce the side effects of drugs and protect the liver.

In the treatment of alcoholic liver disease, glutathione can accelerate free radical excretion, reduce liver cell damage, restore liver detoxification function, and promote liver function recovery.

Oxidative stress is a pathophysiological marker of metabolic liver disease, and GSH is used in the treatment of NAFLD as well as other types of liver disease.

4. Dietary supplements and anti-aging

Under Section 201(s) of the Federal Food, Drug, and Cosmetic Act issued by the US Food and Drug Administration (US-FDA), glutathione-based oral dietary supplements are generally not restricted in the United States.

Since free radicals play an important role in the development of age-related diseases, GSH is considered an effective anti-aging drug due to its outstanding antioxidant properties.

Maintaining optimal GSH levels in different tissues is considered an important strategy for preventing oxidative stress-related diseases. GSH produces a number of metabolites that can enter the Krebs cycle to produce energy for the body, and it is also an important part of the glutathione-ascorbic acid cycle.

GSH supplements and their alternatives can be obtained in a variety of ways, such as: percutaneous, intramuscular, sublingual, oral, or by inhalation.


  • [1] Kaplowitz N, Aw T Y, Ookhtens M. The regulation of hepatic glutathione. Annu Rev Pharmacol Toxicol, 1985, 25(1): 715.
  • [2] Carmel Harel O, Storz G. Roles of the glutathione and thioredox independent reduction systems in the Escherichia coli and Saccharomyces cerevisiae responses to oxidative stress. Annu RevMicrobiol, 2000, 54(1): 439-461.
  • [3] Penninckx M J. An overview on glutathione in Saccharomyces versus non-conventional yeasts. FEMS Yeast Res, 2002, 2 (3): 295-305.
  • [4] Meister A, TateS S. Glutathione and relatedγ-glutamyl compounds: biosynthesis and utilization. Annu Rev Biochem, 1976,45(1): 559-604.
  • [5] Meister A, Anderson M E. Glutathione. Annu Rev Biochem, 1983, 52(1): 711-760.
  • [6] Meister A, Tate S S. Glutathione and Related γ-Glutamyl compounds: Biosynthesis and Utilization. Annu Rev Biochem, 1976, 45(1): 559-604.
  • [7] Hara K Y, Kiriyama K, Inagaki A, Et Al. Improvement of glutathione production by metabolic engineering the sulfate assimilation Pathway of Saccharomyces Cerevisiae. Appl Microb Biot, 2012, 94(5): 1313-1319.
  • [8] Paul N. Brennan, John F. Dillon, Elliot B. Tapper, Gamma-Glutamyl Transferase (γ-GT) – an old dog with new tricks? Liver International, 2022, 42(1): i-iii, 1-261.
  • [9] Jones D P. Redefining Oxidative Stress. Antioxid Redox Signal, 2006, 8(9-10): 1865-1879.
  • [10] Santos L O, Silva P G P, Lemos Junior W J F, de Oliveira V S, Anschau A, Glutathione production by Saccharomyces cerevisiae: current state and perspectives, Applied Microbiology and Biotechnology, 2022, 106: 1879–1894.
  • [11] Miao Qi-Qing. The physiological function of GSH and its application prospect in food processing. Science and Technology Wind, 2010(8): 247.
  • [12] Lv Fei, Shen Kejing, Wei Qianqian, et al. Effects of combined treatment with exogenous glutathione, CO and O3 on storage quality of chilled beef. Chinese Journal of Food Science, 2018, 18(3): 188-195.
  • [13] Shen Kejing. Study on preservation and quality control technology of chilled beef. Hangzhou: Theses of Zhejiang University of Technology, 2015: 1-103. (in Chinese)
  • [14] Qi Yi-man, CHENG Zhi-Gen, Fan Ming-tao. Effect of GSH addition on aroma components of stored kiwi wine. Food Industry Science and Technology, 2017, 38(8): 183-188.
  • [15] Webber, V.; Dutra, S.V.; Spinelli, F.R.; Marcon, Â.R.; Carnieli, G.J.; Vanderlinde, R. Effect of glutathione addition in sparkling wine. Food Chem. 2014, 159, 391–398.
  • [16] Vaimakis, V.; Roussis, I.G. Must oxygenation together with glutathione addition in the oxidation of white wine. Food Chem. 1996, 57, 419–422.
  • [17] Kritzinger, E.C.; Bauer, F.F.; du Toit, W.J. Role of Glutathione in Winemaking: A Review. J. Agric. Food Chem. 2013, 61, 269–277.
  • [18] Zhou Xiuqin. A special amino acid derivative – GSH. Fermentation Technology Bulletin, 2007(2): 50-51.
  • [19] Jiang Jie, Shan Lifeng. Production of glutathione and its application in food industry. Chinese Condiments, 2009, 34(2): 40-44. (in Chinese)
  • [20] Wu S, Preparation of canned apple juice using GSH as an enzymatic and non‐enzymatic browning inhibitor. Journal of Food Processing and Preservation, 2017, 41(1), , DOI: 10.1111/jfpp.12750.
  • [21] Zhang Jin, Liang Shuyan, Wang Manjun, et al. Study on anti-browning effect of ascorbic acid and glutathione compound antioxidant on fresh-cut apple. Agricultural Products Processing, 2019(21): 57-60, 63.
  • [22] Li Shuang, Shen Yaling, Lei Zhaozu. New functional food factor-Glutathione. Proceedings of the Sino-Japanese Symposium on New Food Technology in 2000. Beijing: China Agricultural University Press, 2000: 141-145. (in Chinese)
  • [23] Verheyen, C.; Albrecht, A.; Herrmann, J.; Strobl, M.; Jekle, M.; Becker, T. The contribution of glutathione to the destabilizing effect of yeast on wheat dough. Food Chem. 2015, 173, 243–249.
  • [24] The combination of glutamine transaminase and GSH can improve the rheological properties of yogurt. Dairy Industry of China, 2011(7): 55-55.
  • [25] Sidharth S, Deepashree D, Rashmi. Glutathione as a skin whitening agent: Facts, myths, evidence and controversies. IJDVL.2016, 82: 262-72.
  • [26] Dickinson DA, Forman HJ. Glutathione in defense and signaling: Lessons from a small thiol. Ann N Y Acad Sci. 2002; 973: 488-504.
  • [27] Watanabe F, Hashizume E, Chan GP, Kamimura A. Skin-whitening and skin- condition-improving effects of topical oxidized GSH: a double- blind and placebo-controlled clinical trial in healthy women. Clin Cosmet Investig Dermatol. 2014, 7: 267-74.
  • [28] Sonthalia S, Jha AK, Lallas A, Jain G, Jakhar D. Glutathione for skin lightening: a regnant myth or evidence-based verity? Dermatol Pract Concept. 2018, 8(1): 15- 21.
  • [29]
  • [30] Potterf SB, Virador V, Wakamatsu K, Furumura M, Santis C, Ito S, et al. Cysteine transport in melanosomes from murine melanocytes. Pigment Cell Res. 1999, 12: 4-12.
  • [31] Mahmood M N, The Effectiveness of Glutathione on Skin Lightening: A Review, International Journal of Medical Sciences, 2022, 5(2): 5-16.
  • [32] Gasmi A, Nasreen A, Larysa Lenchyk L, et al, An Update on Glutathione’s Biosynthesis, Metabolism, Functions, and Medicinal Purposes, Current Medicinal Chemistry, Pub Date: 2023-11-06 , DOI: 10.2174/0109298673251025230919105818
  • [33] Kennedy L, Sandhu J K, Harper M-E, Cuperlovic-Culf M, Role of Glutathione in Cancer: From Mechanisms to Therapies, Biomolecules 2020, 10, 1429.
  • [34] Kennedy L, Sandhu J K, Harper M-E, Cuperlovic-Culf M, Role of Glutathione in Cancer: From Mechanisms to Therapies, Biomolecules 2020, 10, 1429.
  • [35] Lu Xiaobi. Clinical observation of reduced glutathione in the treatment of chronic viral hepatitis complicated with alcoholic liver injury. Journal of Clinical Rational Drug Use, 2019, 12(5): 15-16,20.
  • [36] Gao Jinhua. To investigate the clinical effect of reduced glutathione in the treatment of drug-induced liver injury. Straits Pharmacy,2018, 30(2): 99-100.
  • [37] Wei Jianming. Effect of reduced glutathione combined with salvia miltiorrhiza injection on hepatic fibrosis indexes in alcoholic liver disease. Modern Diagnosis and Therapy, 2019, 30(4): 608-610.
  • [38] Cichoż-Lach H, Michalak A. Oxidative stress as a crucial factor in liver diseases. World J Gastroenterol. 2014, 20: 8082–91.
  • [39] Massa P, Coccia G, et al. Reduced gluthatione in alcoholic hepatophaty. Giornale Ital Ricerche Clin Ter. 1993, 14: 87–92.
  • [40] Irie M, Sohda T, Anan A, Fukunaga A, Takata K, Tanaka T, et al. Reduced glutathione suppresses oxidative stress in nonalcoholic fatty liver disease. Eur J Hepatogastroenterol. 2016, 6: 13–8.
  • [41] Homma, T.; Fujii, J. Application of GSH as anti- oxidative and anti-aging drugs. Curr. Drug Metab., 2015, 16(7), 560-571.
  • [42] Liguori, I.; Russo, G.; Curcio, F.; Bulli, G.; Aran, L.; Della- Morte, D.; Gargiulo, G.; Testa, G.; Cacciatore, F.; Bona- duce, D.; Abete, P. Oxidative stress, aging, and diseases. Clin. Interv. Aging, 2018, 13, 757-772.