Glutathione: A Powerful Antioxidant for Improved Health

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Glutathione is a champion free radical scavenger.

Often referred to as the “master antioxidant,” gamma-glutamyl-cysteinyl-glycine (glutathione) has gained fame among healthcare practitioners and consumers for reducing oxidative stress and toxicity in cells. Unlike most antioxidants, glutathione is unique in that it is produced by our bodies in the liver. However — as we age, acquire illness, or practice poor dietary and lifestyle habits, our glutathione levels become depleted as the body’s ability to produce glutathione decreases. Can we protect our health by boosting glutathione levels? 

Mounting scientific research shows just how powerfully glutathione protects against oxidative damage — demonstrating itself as a strong detoxifier of the cells, liver, kidneys, and brain, as well as a sturdy defender against aging, inflammation and fatigue. Before diving into evidence, let’s review the basics of glutathione.

What is Glutathione?

Glutathione is a tripeptide composed of three amino acids — glutamate, cysteine, and glycine. As a champion free radical scavenger, it assists in metabolizing nutrients, regulating gene expressions, and protecting against an array of age-related and pathogenic diseases such as Alzheimer’s, Parkinson’s, arthritis, liver toxicity, diabetes, heart attack, and stroke.

As mentioned, our bodies produce glutathione naturally, but we can also boost our antioxidant levels — either directly with glutathione, or indirectly with glutathione precursors.

Here are a few available options: 

  • Oral supplementation with bioavailable liposomal, reduced, or S-acetyl glutathione forms 
  • intravenous (IV) glutathione supplementation
  • Reducing toxin exposure
  • Supplementing with liver detoxifying compounds — milk thistle, N-acetyl cysteine (NAC), superoxide dismutase (SOD), and undenatured whey protein
The fastest way to increase glutathione levels in through IV.
    The fastest way to increase glutathione levels is through IV administration, but most people won’t have regular access to this method for general health improvement. Therefore, supplementing directly with an absorbable form of oral glutathione and incorporating a glutathione-boosting lifestyle and diet is the most practical way to experience a health boost. 

    Past controversies have argued that oral glutathione supplements were not bioactive, rendering most oral supplements useless. However, that debate was extinguished in a landmark 2015 publication in the European Journal of Nutrition. During a six-month randomized, placebo-controlled trial, oral glutathione supplementation significantly increased available body stores by as much as 31% in whole blood and 250% in buccal (cheek) cells. 

    What else can we glean from scientific research supporting this master antioxidant’s power? Let’s take a look at the top healing properties of glutathione.

    Top 4 Health Benefits of Glutathione

    1. Boosts Energy Production 

    Mitochondria, the powerhouses of our cells, play a crucial role in cellular and metabolic health — two major components that contribute to optimal energy levels. Through a number of chemical reactions, mitochondria break down glucose into energy (fuel) known as adenosine triphosphate (ATP). When free radicals damage our cells, the ability of the mitochondria to convert glucose into fuel is hindered — leading to a decrease in energy production and metabolism. On the extreme end of the spectrum, we see this in ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome). While the cause of ME/CFS has not yet been proven, extensive free radical generation may be involved in the disease process. But for healthy individuals, increasing our glutathione levels helps detoxify the cells — combatting daily fatigue-inducing free radical damage. 

    2. Enhances Immunity

    Oxidative stress increases as we age, lowering immunity and increasing the risk of developing chronic diseases. Glutathione mitigates this by decreasing oxidation and boosting natural killer cytotoxicity — doubling natural killer (NK) cells — according to the previously mentioned study. Another trial found glutathione to be supportive of immunity by its ability to modulate NK and T-cells responsible as front-line defenders, protecting against microbial infections. One more compelling way glutathione supports immunity is by triggering upregulation of sirtuin, our longevity genes — particularly SIRT1. A review in Free Radical Biology and Medicine suggested that upregulating sirtuins opens the door to future prospects of healthy aging, delaying the onset of oxidative-related disease.

    3. Supports Detoxification

    With the level of environmental and food-based toxicity rising globally, our livers and other detoxification organs are vulnerable to overload. Typically, any toxins — food additives, alcohol, drugs, and allergens — entering the body are first sent to the liver, where they get processed and circulated to the kidneys or intestines for elimination. Other organs in charge of detoxification and elimination are the skin, lungs, and lymphatic system. With concentrations 10 times higher in the liver, glutathione plays a huge role in phase II and phase III detoxification — the process of metabolizing molecules for removal from the body by activating the Nrf2 protein. 

    It is a complex process, but ultimately, glutathione not only binds to toxins before they can bind to and damage cells, but it transforms toxins into a water-soluble form for further filtering and easy excretion through the urinary system. Our livers are responsible for so many bodily functions — metabolism, bile production, digestion, hormone and cholesterol processing, blood filtering, and more. Therefore, supporting liver health should be a priority for everyone. 

    4. Protects the Brain 

    Glutathione may help protect the brain from oxidative stress.

    Where inflammation can greatly impair important body systems, such as the nervous and circulatory system, glutathione’s antioxidant power may repair inflammatory cellular damage in the brain. In an aging brain, oxidative stress is a major contributing factor to chronic inflammation, leading to cognitive impairment, memory issues, or more serious manifestations like Parkinson’s and Alzheimer’s disease. Cell-based studies have unveiled glutathione as a worthy opponent against Parkinson’s by protecting dopamine neurons in the pars compacta — a section in the midbrain associated with hearing, vision, and motor control — from free radical damage. 

    Glutathione’s ability to combat oxidation plays a central role in preventing Alzheimer’s as well. While more human trials are needed to further explore this topic, one study showed depleted levels of glutathione in the hippocampus of generally healthy elderly persons, resulting in mild cognitive impairment, a precursor to the advanced impairment seen in Alzheimer’s disease. An observational study is forthcoming to determine how glutathione supplements may delay the progression of Alzheimer’s.

    What to Look for in an Oral Glutathione Supplement

    With glutathione found in virtually every cell in the body, there are not many body functions that aren't enhanced by adequate glutathione levels. If you are thinking of adding this master antioxidant to your regimen, consider the following to make sure you are investing in a quality glutathione supplement.

    Dosage: 250-1000 mg of supplemental glutathione have been reported to significantly boost glutathione levels in blood and cells.

    Forms and Bioavailability: When you invest in a supplement, you want it to make sure your body can actually utilize it. Here are four forms of supplemental oral glutathione that will ensure you are receiving the most benefit:

    • Reduced Glutathione The term “reduced” does not mean you’ll receive less glutathione. An enzyme called glutathione reductase is what turns glutathione back into its antioxidant state upon being oxidized in the body. Ensuring you have a non-oxidized (reduced) form of oral glutathione will give you the most antioxidant benefit of glutathione in its active form.

    • S-acetyl glutathioneThis highly bioavailable glutathione variant crosses the membrane of mitochondria and is the most absorbable when compared against other options. S-acetyl glutathione can also cross the blood-brain barrier, providing direct support to the brain.

    • Liposomal glutathioneA direct, side-by-side comparison between liposomal and non-liposomal glutathione hasn’t been conducted, but studies show liposomal forms boost glutathione levels in as early as one week. The liposomal form offers rapid uptake and fast cellular delivery and is up to 100 times more potent than non-liposomal forms — a great alternative if you don’t like to swallow pills.

    • Acid-Resistant CapsuleWhen purchasing a capsule form, check for stomach acid-resistant capsules that protect the glutathione from becoming destabilized by stomach acid. 

    Contraindications: If you are pregnant or lactating, or if you commonly experience abdominal cramps, allergic reactions, or any respiratory restrictions, check with your doctor before adding glutathione to your daily regimen. 

    The Takeaway

    Glutathione is a master antioxidant found in almost all cells in the body and is responsible for regulating oxidative stress, inflammation, and detoxification — supporting overall immunity and longevity. Along with a balanced diet and healthy lifestyle, incorporating a bioactive form of oral glutathione is the most effective way to boost your glutathione levels.

    Show references

    Anderson MF, Nilsson M, Sims NR. Glutathione monoethylester prevents mitochondrial glutathione depletion during focal cerebral ischemia. Neurochem Int. 2004;44(3):153-159. doi:10.1016/s0197-0186(03)00133-5

    Bains VK, Bains R. The antioxidant master glutathione and periodontal health. Dent Res J (Isfahan). 2015;12(5):389-405. doi:10.4103/1735-3327.166169

    Cascella R, Evangelisti E, Zampagni M, et al. S-linolenoyl glutathione intake extends life-span and stress resistance via Sir-2.1 upregulation in Caenorhabditis elegans. Free Radic Biol Med. 2014;73:127-135. doi:10.1016/j.freeradbiomed.2014.05.004 

    Cook, S. Oral Availability of Glutathione. Natural Medicine Journal. 2017.  Available at: https://www.naturalmedicinejournal.com/sites/default/files/glutathione_final_digital.pdf

    Deepika Shukla, Pravat K. Mandal, Lars Ersland, Eli Renate Grüner, Manjari Tripathi, Partha Raghunathan, Ankita Sharma, G.R. Chaithya, Khushboo Punjabi, Christopher Splaine. A Multi-Center Study on Human Brain Glutathione Conformation using Magnetic Resonance Spectroscopy. Journal of Alzheimer's Disease, 2018; 1. doi:10.3233/JAD-180648

    Dentico P, Volpe A, Buongiorno R, et al. Il glutatione nella terapia delle epatopatie croniche steatosiche [Glutathione in the treatment of chronic fatty liver diseases] . Recenti Prog Med. 1995;86(7-8):290-293.

    Erden-Inal M, Sunal E, Kanbak G. Age-related changes in the glutathione redox system. Cell Biochem Funct. 2002;20(1):61-66. doi:10.1002/cbf.937

    Finegold SM, Molitoris D, Song Y, et al. Gastrointestinal microflora studies in late-onset autism. Clin Infect Dis. 2002;35(Suppl 1):S6-S16. doi:10.1086/341914

    Kennedy G, Spence VA, McLaren M, Hill A, Underwood C, Belch JJ (September 2005). Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms. Free Radic. Biol. Med. 39 (5): 584–9. doi:10.1016/j.freeradbiomed.2005.04.020

    Kromidas L, Trombetta LD, Jamall IS. The protective effects of glutathione against methylmercury cytotoxicity. Toxicol Lett. 1990;51(1):67-80. doi:10.1016/0378-4274(90)90226-c

    Marí M, Morales A, Colell A, García-Ruiz C, Fernández-Checa JC. Mitochondrial glutathione, a key survival antioxidant. Antioxid Redox Signal. 2009;11(11):2685-2700. doi:10.1089/ARS.2009.2695

    Morris D, Khurasany M, Nguyen T, et al. Glutathione and infection. Biochim Biophys Acta. 2013;1830(5):3329-3349. doi:10.1016/j.bbagen.2012.10.012

    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. doi:10.1007/s00394-014-0706-z

    Shimizu H, Kiyohara Y, Kato I, et al. Relationship between plasma glutathione levels and cardiovascular disease in a defined population: the Hisayama study. Stroke. 2004;35(9):2072-2077. doi:10.1161/01.STR.0000138022.86509.2d

    Sinha R, Sinha I, Calcagnotto A, et al. Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. Eur J Clin Nutr. 2018;72(1):105-111. doi:10.1038/ejcn.2017.132

    Smeyne M, Smeyne RJ. Glutathione metabolism and Parkinson's disease. Free Radic Biol Med. 2013;62:13-25. doi:10.1016/j.freeradbiomed.2013.05.001

    Weschawalit S, Thongthip S, Phutrakool P, Asawanonda P. Glutathione and its antiaging and antimelanogenic effects. Clin Cosmet Investig Dermatol. 2017;10:147-153. Published 2017 Apr 27. doi:10.2147/CCID.S128339

    Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr. 2004;134(3):489-492. doi:10.1093/jn/134.3.489

    Yeh MY, Burnham EL, Moss M, Brown LA. Non-invasive evaluation of pulmonary glutathione in the exhaled breath condensate of otherwise healthy alcoholics. Respir Med. 2008;102(2):248-255. doi:10.1016/j.rmed.2007.09.005

    Zeevalk, G.D., Bernard, L.P. & Guilford, F.T. Liposomal-Glutathione Provides Maintenance of Intracellular Glutathione and Neuroprotection in Mesencephalic Neuronal Cells. Neurochem Res 35, 1575–1587 (2010). doi:10.1007/s11064-010-0217-0

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