Glutathione

Glutathione may support a range of conditions where endogenous levels are depleted due to high oxidative stress, systemic inflammation, or immune dysregulation. In addition, it plays an independent role in liver detoxification by aiding the elimination of harmful substances. Glutathione may help with the following:

• Alzheimer’s Disease and Parkinson’s Disease
• Suboptimal immune function
• Cardiovascular Disease
• Chronic Fatigue Syndrome
• COPD and Asthma
• Hyperpigmentation & Overall Skin Health
• Depression and anxiety disorders
• Diabetes
• Inflammatory Bowel Disease
• Liver Disease/Liver Detoxification of Harmful Chemicals
• Multiple Sclerosis
• Neuropathy
• Rheumatoid Arthritis
• Periodontal disease
• Hallmarks of Aging
• Schizophrenia/Bipolar Disorders
• Post-workout recovery

Potential side effects

• Injections may cause site reactions such as pain, redness, and stinging.
• Oral forms may cause transient gastrointestinal discomfort
• Excessive glutathione supplementation may impair immune signaling.

Precautions

• Individuals with pre-existing kidney disease should avoid high dose glutathione.
• Avoid in pregnant or breastfeeding individuals due to a lack of appropriate data.
• Glutathione may exert a limited effect in patients already on a medication regimen that harnesses anti-inflammatory pathways.

Glutathione (GSH) functions primarily as a potent intracellular antioxidant, neutralizing free radicals and reactive oxygen species (ROS) through its sulfur-containing thiol group. GSH is converted to its oxidized form (GSSG) by donating its electrons to neutralize free radicals. By donating electrons, it helps stabilize these reactive molecules and may protect against oxidative damage to cells. It also plays a key role in detoxification by binding to toxins, rendering them less harmful, and making them more water-soluble and easier for the body to excrete. Additionally, glutathione supports immune function by aiding in the activation and regulation of immune cells, contributing to a balanced immune response. It helps maintain cellular integrity by modulating oxidative stress, assisting in protein repair, and influencing inflammatory pathways—ultimately promoting overall cellular homeostasis.

Can glutathione impact mitochondrial health?

Mitochondria is a cellular organelle often referred to the "powerhouse" of the cell, regulating a range of functions from energy generation, metabolism and cell survival. Enhancing mitochondrial function is the wellspring of efforts to optimize physical fitness and longevity at the cellular level. Glutathione plays an important role in the theory of aging that cumulative oxidative stress in mitochondria may determine lifespan. Glutathione stabilizes the inner mitochondrial membrane, squelches reactive oxygen species (ROS) generated by mitochondrial respiration, and maintains mitochondrial DNA fidelity to profoundly influence mitochondrial function and cell survival.¹⁰

What is the role of glutathione in the aging process?

Glutathione levels are believed to rapidly decline after the age of 45. The body has to contend with increased oxidative stress, weakening immune, and more DNA repair demands as we age. Randomized clinical studies in rodents and older adults indicate that glutathione acts in concert with the independent actions to two key precursors, glycine and and cysteine, to improve an array of biomarkers associated with the hallmarks of aging. Biomarkers for endothelial function, insulin sensitivity, intracellular signaling, maintaining DNA integrity , inflammation, metabolic flexibility, mitophagy (recycling old and damaged mitochondria) and cellular senescence (also called "zombie cells" as these cells have lost proper function, harm nearby cells and do not die off) are all improved. To expound further on the previous question, most of these biomarkers are modulated by glutathione and its precursors at the mitochondrial level. These improved biomarkers correspond with endpoints such as improved gait and body composition.^11,12

IMPORTANT INFORMATION ABOUT COMPOUNDED MEDICATIONS

This medication has been compounded (custom-prepared) by a pharmacy. Compounded medications are specially prepared for individual patient needs based on a valid prescription and, as such, are not reviewed or approved by the U.S. Food and Drug Administration (FDA) for safety or efficacy. These statements have not been evaluated by the FDA.

This compounded preparation:

• Has not been approved by the FDA
• Has not undergone FDA review for safety, effectiveness, or quality
• Is prepared specifically for you based on your prescriber's order
• Individual outcomes may vary

Dosing is determined by the prescribing provider based on patient-specific factors. Always follow your healthcare provider's instructions. Compounded medications are not subject to FDA approval and lack the same safety and efficacy data as FDA-approved commercial medications. This medication should be prescribed and monitored by a licensed healthcare professional familiar with the condition being addressed and the specific applications of the medication.

1. Eshkevari, Ladan, et al. “Efficacy of addition of the anti-inflammatory, IV glutathione to standard ketamine IV therapy in major depressive disorder.” Psychiatry Research 337 (2024): 115949.
2. Bell CJM, Mehta M, Mirza L, Young AH, Beck K. Glutathione alterations in depression: a meta-analysis and systematic review of proton magnetic resonance spectroscopy studies. Psychopharmacology (Berl). 2024 Dec 21. doi: 10.1007/s00213-024-06735-1. Epub ahead of print. PMID:39708105.
3. Bounous, G., and J. Molson. “Competition for glutathione precursors between the immune system and the skeletal muscle: pathogenesis of chronic fatigue syndrome.” Medical hypotheses 53.4 (1999): 347-349.
4. Dean OM, van den Buuse M, Bush AI, Copolov DL, Ng F, Dodd S, Berk M. A role for glutathione in the pathophysiology of bipolar disorder and schizophrenia? Animal models and relevance to clinical practice. Curr Med Chem. 2009;16(23):2965-76. doi: 10.2174/092986709788803060. PMID: 19689277.
5. Fitzpatrick AM, Jones DP, Brown LA. Glutathione redox control of asthma: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal. 2012 Jul 15;17(2):375-408. doi: 10.1089/ars.2011.4198. Epub 2012 Mar 9. PMID: 22304503; PMCID: PMC3353819.
6. Kaplowitz N. The importance and regulation of hepatic glutathione. Yale J Biol Med. 1981 Nov-Dec;54(6):497-502. PMID: 7342494; PMCID:PMC2596047.
7. Ueno, Yuki, et al. “Dietary glutathione protects rats from diabetic nephropathy and neuropathy.” The Journal of nutrition 132.5 (2002): 897-900.
8. Bravenboer B, Kappelle AC, Hamers FP, van Buren T, Erkelens DW, Gispen WH. Potential use of glutathione for the prevention and treatment of diabetic neuropathy in the streptozotocin-induced diabetic rat. Diabetologia. 1992 Sep;35(9):813-7. doi: 10.1007/BF00399926. PMID: 1397775.
9. Tredici G, Cavaletti G, Petruccioli MG, Fabbrica D, Tedeschi M, Venturino P. Low-dose glutathione administration in the prevention of cisplatin-induced peripheral neuropathy in rats. Neurotoxicology. 1994 Fall;15
10. Lushchak VI. Glutathione homeostasis and functions: potential targets for medical interventions. J Amino Acids. 2012;2012:736837. doi:10.1155/2012/736837
11. Kumar P, Liu C, Suliburk J, Hsu JW, Muthupillai R, Jahoor F, Minard CG, Taffet GE, Sekhar RV. Supplementing glycine and N-acetylcysteine (GlyNAC) in older adults improves glutathione deficiency, oxidative stress, mitochondrial dysfunction, inflammation, physical function, and aging hallmarks: a randomized clinical trial. The Journals of Gerontology: Series A. 2023 Jan 1;78(1):75-89.
12. Kumar P, Osahon OW, Sekhar RV. GlyNAC (glycine and N-acetylcysteine) supplementation in mice increases length of life by correcting glutathione deficiency, oxidative stress, mitochondrial dysfunction, abnormalities in mitophagy and nutrient sensing, and genomic damage. Nutrients. 2022 Mar 7;14(5):1114.