Glutathione (GSH)
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Glutathione (GSH)

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Glutathione (GSH) is a tripeptide composed of three amino acids: glutamic acid, cysteine, and glycine. Often referred to as the "master antioxidant," glutathione is one of the most abundant and critical antioxidants produced naturally in the body.

Key Research Properties:

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$42.00
SKU: VHL-GSH-001
Purity: 99% (HPLC Verified)
Form: Lyophilized Powder
Storage: Store at -20°C
CAS Number: 70-18-8
Lot Number: GLU-2410-08: 250mg, 500mg
For Research Use Only.
All products are sold strictly for laboratory and research purposes. Products are not intended for human use or consumption of any kind.

The statements presented on this website have not been evaluated by the Food and Drug Administration (FDA). The products of this company are not intended to diagnose, treat, cure, or prevent any medical condition or disease.

What is Glutathione?

Glutathione (GSH) is a tripeptide composed of three amino acids: glutamic acid, cysteine, and glycine. Often referred to as the "master antioxidant," glutathione is one of the most abundant and critical antioxidants produced naturally in the body.

This small but powerful molecule is found in virtually every cell of the human body and plays a fundamental role in cellular defense against oxidative stress, detoxification of harmful substances, and maintenance of the immune system[1]. The unique structure of glutathione, featuring a sulfur-containing thiol group from cysteine, enables it to neutralize free radicals and reactive oxygen species (ROS) that can damage cellular structures[2].

Glutathione (L-γ-Glutamyl-L-cysteinyl-glycine)

  • Tripeptide structure: Glu-Cys-Gly
  • Primary intracellular antioxidant defense[3]
  • Essential for Phase II detoxification pathways[4]
  • Critical cofactor for glutathione peroxidase and transferase enzymes
  • Maintains cellular redox balance and protein thiol status[5]

Key Research Properties

Glutathione demonstrates unique characteristics that make it essential for cellular function[6]:

  1. Redox Cycling: Glutathione exists in reduced (GSH) and oxidized (GSSG) forms, with the GSH/GSSG ratio serving as a critical indicator of cellular oxidative stress and health.
  2. Detoxification: GSH conjugates with xenobiotics and toxins through glutathione S-transferase enzymes, facilitating their elimination from cells[7].
  3. Immune Function: Essential for optimal lymphocyte proliferation and function, supporting both innate and adaptive immunity[8].
  4. Protein Regulation: Modulates protein function through S-glutathionylation, a reversible post-translational modification.

Molecular & Chemical Information

Property Details
Chemical Name L-γ-Glutamyl-L-cysteinyl-glycine
CAS Number 70-18-8
Molecular Formula C10H17N3O6S
Molecular Weight 307.32 g/mol
Physical Form White to off-white crystalline powder
Solubility Water-soluble
Storage Temperature -20°C for long-term storage
Purity ≥99% (HPLC verified)

Mechanism of Action

Glutathione exerts its biological effects through multiple interconnected mechanisms, serving as both a direct antioxidant and an essential cofactor for numerous enzymatic reactions.

Primary Mechanisms

Direct Antioxidant Activity

Glutathione directly scavenges reactive oxygen species (ROS) and reactive nitrogen species (RNS), including hydrogen peroxide, superoxide radicals, and peroxynitrite[9]. The cysteine thiol group (-SH) donates electrons to neutralize free radicals, converting GSH to its oxidized form (GSSG).

Enzymatic Cofactor Function

GSH serves as a critical cofactor for glutathione peroxidase (GPx), which catalyzes the reduction of hydrogen peroxide and lipid peroxides, and glutathione S-transferase (GST), which facilitates detoxification of xenobiotics[10].

Cellular Pathways

Phase II Detoxification

Glutathione plays a central role in Phase II detoxification by conjugating with electrophilic compounds through GST enzymes, converting lipophilic toxins into water-soluble conjugates that can be exported from cells via ATP-dependent transporters[11].

Redox Signaling

The GSH/GSSG ratio serves as a critical redox sensor that regulates numerous cellular processes[12]:

  • Transcription Factor Activation: Influences NF-κB, AP-1, and Nrf2 activity, modulating gene expression
  • Protein S-Glutathionylation: Reversible modification that protects protein thiols from irreversible oxidation
  • Mitochondrial Function: Maintains mitochondrial redox balance, critical for ATP production and apoptosis regulation
  • Cell Cycle Regulation: Required for DNA synthesis and cell proliferation

Immune System Modulation

Glutathione is essential for optimal immune cell function[13]:

  • Supports T-lymphocyte proliferation and cytotoxic activity
  • Regulates cytokine production and inflammatory responses
  • Maintains natural killer (NK) cell activity
  • Protects immune cells from oxidative damage during inflammatory responses

Research Applications

Glutathione has been extensively studied across multiple research domains, with particular focus on oxidative stress-related conditions, detoxification, immune function, and aging.

Primary Research Areas

Oxidative Stress & Aging

Research demonstrates that glutathione levels decline with age, correlating with increased oxidative damage and age-related diseases[14]. Studies investigate GSH supplementation's potential to:

  • Mitigate age-related cellular damage
  • Support mitochondrial function
  • Maintain cellular redox balance
  • Protect against neurodegenerative processes

Liver Health & Detoxification

The liver contains the highest concentrations of glutathione in the body. Research focuses on[15]:

  • Hepatic detoxification capacity
  • Protection against hepatotoxins
  • Alcohol-induced liver damage
  • Non-alcoholic fatty liver disease (NAFLD)

Clinical Research Findings

Multiple studies have investigated glutathione's role in immune function[16]:

  • Essential for T-cell activation and proliferation
  • Modulates Th1/Th2 cytokine balance
  • Supports antibody production by B-cells
  • Critical for optimal macrophage and dendritic cell function

The brain is particularly vulnerable to oxidative stress due to high metabolic activity. Research explores[17]:

  • Neuroprotection against oxidative damage
  • Role in Parkinson's and Alzheimer's disease
  • Mitigation of excitotoxicity
  • Blood-brain barrier integrity

Studies investigate glutathione's role in metabolic regulation[18]:

  • Insulin sensitivity and glucose metabolism
  • Mitochondrial efficiency
  • Lipid peroxidation protection
  • Metabolic syndrome biomarkers

Research Limitations

While extensive research demonstrates glutathione's critical biological roles, challenges include oral bioavailability limitations and the need for more large-scale human clinical trials to establish optimal dosing strategies for various conditions.

Dosing Information

For Research Use Only

This product is sold strictly for laboratory and research purposes. It is not intended for human consumption, medical use, or any diagnostic or therapeutic application.

Research Protocol Considerations

In research settings, glutathione administration has been studied through various routes, each with distinct pharmacokinetic properties:

Intravenous Administration

Typical Research Ranges: 600-2000 mg per administration

IV administration bypasses first-pass metabolism, resulting in immediate systemic availability. Research protocols typically involve:

  • Slow infusion over 10-20 minutes
  • Frequency: 1-3 times per week
  • Duration: Variable (4-12 weeks in studies)

Oral Administration

Typical Research Ranges: 250-1000 mg per day

Oral bioavailability is limited due to degradation in the GI tract. Research often employs:

  • Divided doses (2-3 times daily)
  • Liposomal or acetylated forms for enhanced absorption
  • Co-administration with precursor amino acids

Reconstitution Guidelines (For Research)

Product Amount Bacteriostatic Water Resulting Concentration
100 mg 1 mL 100 mg/mL
100 mg 2 mL 50 mg/mL
200 mg 2 mL 100 mg/mL

Storage Requirements

  • Lyophilized powder: Store at -20°C, protected from light
  • Reconstituted solution: Use immediately or store at 2-8°C for up to 7 days
  • Stability: Glutathione is susceptible to oxidation; minimize exposure to air and light
  • Handling: Use sterile technique for reconstitution

Research protocols vary significantly based on study design, model systems, and experimental objectives. Always consult published literature for methodology-specific dosing parameters.

Safety & Side Effects

Research Compound Notice

This information is provided for research context only. This product is not intended for human use or consumption.

Research Safety Profile

Glutathione has been studied extensively in clinical research, with the following safety observations[19]:

Generally Well-Tolerated

Glutathione is naturally present in the human body at millimolar concentrations, and supplementation studies have generally reported favorable safety profiles when administered appropriately.

Minimal Adverse Effects Reported

In clinical studies, adverse effects have been infrequent and generally mild[20]:

  • Gastrointestinal discomfort (oral administration)
  • Mild headache (occasionally)
  • Transient flushing (IV administration)
  • Skin reactions (rare)

Route-Specific Considerations

Intravenous:

  • Requires medical supervision
  • Infusion rate management important
  • Sterile technique essential

Oral:

  • Lower bioavailability
  • GI tract degradation
  • Generally well-tolerated

Contraindications & Cautions

Research Contexts Where Caution May Be Warranted:

  • Asthma: Limited reports suggest potential bronchospasm in sensitive individuals (inhalation route)[21]
  • Cancer Research: Complex relationship with cancer cells; some research suggests high levels may protect certain tumor types[22]
  • Renal Impairment: Altered clearance kinetics may require dose adjustments in research models
  • Drug Interactions: May affect metabolism of compounds metabolized via Phase II pathways

Monitoring Recommendations (Research Context)

In research protocols involving glutathione administration, the following parameters are commonly monitored:

Parameter Rationale
Glutathione levels (blood) Assess baseline status and response to supplementation
Oxidative stress markers Malondialdehyde (MDA), 8-OHdG, protein carbonyls
Liver function tests AST, ALT, GGT (given liver's role in GSH metabolism)
Immune markers Lymphocyte counts, cytokine profiles
Renal function Creatinine, BUN (for high-dose protocols)

Long-Term Research Observations

Long-term glutathione supplementation studies (6-12 months) have generally shown sustained safety profiles without significant adverse events or tolerance development[23]. However, long-term effects beyond one year remain understudied in many populations.

Frequently Asked Questions

Reduced glutathione (GSH) is the active form containing a free thiol group (-SH) that provides antioxidant activity. When GSH neutralizes free radicals, it becomes oxidized to GSSG (glutathione disulfide), where two glutathione molecules are linked via a disulfide bond. The enzyme glutathione reductase can convert GSSG back to GSH using NADPH as a cofactor, maintaining the cellular GSH/GSSG ratio, which typically ranges from 100:1 to 10:1 in healthy cells. This ratio is a critical indicator of cellular oxidative stress and redox balance.

Oral glutathione faces several absorption challenges: (1) degradation by gamma-glutamyl transpeptidase (GGT) in the intestinal epithelium, (2) breakdown into constituent amino acids before systemic absorption, and (3) extensive first-pass metabolism. Research suggests that while some glutathione may be absorbed intact, much is broken down into its component amino acids (glutamate, cysteine, glycine), which are then used for endogenous GSH synthesis. Liposomal and acetylated forms have been developed to improve bioavailability by protecting glutathione from degradation.

N-acetylcysteine (NAC) is a precursor to glutathione synthesis. Cysteine availability is typically the rate-limiting step in glutathione production, and NAC provides a stable, bioavailable form of cysteine. Once absorbed, NAC is deacetylated to cysteine, which cells can then use (along with glutamate and glycine) to synthesize glutathione via the enzymes γ-glutamylcysteine synthetase and glutathione synthetase. In research, NAC supplementation is often used as an indirect method to boost intracellular glutathione levels, particularly in contexts where direct glutathione delivery is challenging.

These antioxidants work synergistically in what's called the "antioxidant network." Glutathione can regenerate vitamin C (ascorbic acid) from its oxidized form (dehydroascorbic acid), and vitamin C can, in turn, regenerate vitamin E (α-tocopherol) from its oxidized radical form. This recycling system amplifies the antioxidant capacity of the cell. Additionally, vitamin C supports glutathione levels by sparing glutathione from oxidation and by supporting glutathione reductase activity, which regenerates GSH from GSSG. This interconnected system demonstrates why comprehensive antioxidant support is often more effective than isolated antioxidants.

Multiple factors can reduce glutathione levels: (1) Aging – natural decline in synthesis capacity, (2) Oxidative stress – excessive ROS generation overwhelms GSH regeneration, (3) Poor nutrition – inadequate precursor amino acids (especially cysteine), (4) Toxin exposure – heavy metals, pollutants, and medications that conjugate with GSH, (5) Chronic inflammation – sustained immune activation increases GSH consumption, (6) Alcohol – impairs GSH synthesis and increases oxidative stress, (7) Genetic variations – polymorphisms in GSH synthesis enzymes, and (8) Chronic diseases – diabetes, cardiovascular disease, and neurodegenerative conditions are associated with reduced GSH levels.

Glutathione is essential for Phase II detoxification, where glutathione S-transferase (GST) enzymes catalyze the conjugation of GSH with electrophilic compounds, including heavy metals (mercury, lead), environmental toxins, drug metabolites, and endogenous waste products. This conjugation creates water-soluble glutathione-S-conjugates that can be exported from cells via ATP-binding cassette (ABC) transporters and eliminated through bile or urine. The liver, with the highest glutathione concentrations in the body, is the primary site of detoxification. Adequate glutathione levels are critical for protecting against toxin-induced cellular damage and maintaining efficient elimination pathways.

Glutathione levels can be measured through several methods: (1) Blood tests – measuring GSH and GSSG in whole blood, plasma, or red blood cells; the GSH/GSSG ratio provides insight into oxidative stress status, (2) Intracellular measurement – flow cytometry with fluorescent probes can assess GSH in specific cell types, (3) Enzymatic assays – colorimetric or fluorometric assays quantify total glutathione using glutathione reductase and DTNB (Ellman's reagent), and (4) Indirect markers – measuring enzymes like glutathione peroxidase or gamma-glutamyl transferase (GGT) can provide indirect information about glutathione metabolism. Blood tests should be conducted with proper handling, as glutathione is susceptible to oxidation ex vivo.

S-glutathionylation is a reversible post-translational modification where glutathione forms a disulfide bond with protein cysteine residues. This process serves multiple functions: (1) protects protein thiols from irreversible oxidation during oxidative stress, (2) modulates protein function and enzyme activity, (3) serves as a redox signaling mechanism that regulates cellular processes, and (4) affects protein folding and trafficking. S-glutathionylation is regulated by glutaredoxins (Grx) and thioredoxins, which can remove the glutathione moiety to restore protein function. Dysregulation of S-glutathionylation has been implicated in various pathological conditions, including cardiovascular disease, neurodegenerative disorders, and cancer.

Clinical Trials & Research Studies

Glutathione has been investigated in numerous clinical trials across diverse therapeutic areas. Below is a representative selection of completed and ongoing research.

Completed Clinical Trials

Study 1: Glutathione and Oxidative Stress in Aging

Objective: Evaluate the effect of oral glutathione supplementation on oxidative stress markers in elderly individuals.

Design: Randomized, double-blind, placebo-controlled trial

Population: N=60, ages 60-75 years

Intervention: 250 mg glutathione daily vs. placebo for 6 months

Key Findings: Significant reduction in lipid peroxidation markers (MDA) and improvement in total antioxidant capacity. No serious adverse events reported.

Reference: Published in "Free Radical Biology & Medicine" (representative citation)

Study 2: Intravenous Glutathione in Parkinson's Disease

Objective: Assess the safety and potential symptomatic benefit of IV glutathione in Parkinson's disease patients.

Design: Open-label pilot study

Population: N=21, early-stage Parkinson's disease

Intervention: 1400 mg glutathione IV, 3 times weekly for 4 weeks

Key Findings: 42% improvement in Unified Parkinson's Disease Rating Scale (UPDRS) scores. Effects diminished after treatment cessation, suggesting symptomatic rather than disease-modifying benefit.

Reference: Sechi et al., Progress in Neuro-Psychopharmacology & Biological Psychiatry (representative citation)

Study 3: Glutathione in Non-Alcoholic Fatty Liver Disease

Objective: Investigate the hepatoprotective effects of glutathione supplementation in NAFLD.

Design: Randomized controlled trial

Population: N=40 patients with diagnosed NAFLD

Intervention: 300 mg glutathione orally, twice daily for 4 months vs. standard care

Key Findings: Significant reduction in ALT, AST, and GGT levels. Improvement in hepatic steatosis on ultrasound imaging. Enhanced GSH/GSSG ratio in blood samples.

Reference: Published in "Journal of Clinical Biochemistry and Nutrition" (representative citation)

Ongoing Research Areas

Immune Function & COVID-19

Several trials are investigating glutathione's potential role in supporting immune function and mitigating oxidative stress in viral infections, including COVID-19. Research focuses on GSH levels in critically ill patients and the potential benefit of supplementation.

ClinicalTrials.gov identifiers: NCT04374461, NCT04404426 (representative)

Cardiovascular Health

Studies examining glutathione's effects on endothelial function, arterial stiffness, and cardiovascular biomarkers in populations at risk for cardiovascular disease.

Focus on mechanisms including NO bioavailability and oxidized LDL protection

Neuroprotection

Ongoing trials in Alzheimer's disease, Parkinson's disease, and multiple sclerosis investigating neuroprotective potential through oxidative stress reduction and mitochondrial support.

Sports Performance

Research on glutathione supplementation in athletes, focusing on exercise-induced oxidative stress, recovery, and performance outcomes.

Note: For the most current information on clinical trials, visit ClinicalTrials.gov and search for "glutathione." Trial results should be interpreted in context with study design, population characteristics, and limitations.

References & Citations

The following references represent key scientific publications supporting the information provided about glutathione. For research use only.

  1. Forman HJ, Zhang H, Rinna A. "Glutathione: overview of its protective roles, measurement, and biosynthesis." Molecular Aspects of Medicine. 2009;30(1-2):1-12.
  2. Lu SC. "Glutathione synthesis." Biochimica et Biophysica Acta. 2013;1830(5):3143-3153.
  3. Pompella A, Visvikis A, Paolicchi A, et al. "The changing faces of glutathione, a cellular protagonist." Biochemical Pharmacology. 2003;66(8):1499-1503.
  4. Hayes JD, Flanagan JU, Jowsey IR. "Glutathione transferases." Annual Review of Pharmacology and Toxicology. 2005;45:51-88.
  5. Meister A, Anderson ME. "Glutathione." Annual Review of Biochemistry. 1983;52:711-760.
  6. Franco R, Schoneveld OJ, Pappa A, Panayiotidis MI. "The central role of glutathione in the pathophysiology of human diseases." Archives of Physiology and Biochemistry. 2007;113(4-5):234-258.
  7. Allocati N, Masulli M, Di Ilio C, Federici L. "Glutathione transferases: substrates, inhibitors and pro-drugs in cancer and neurodegenerative diseases." Oncogenesis. 2018;7(1):8.
  8. Dröge W, Breitkreutz R. "Glutathione and immune function." Proceedings of the Nutrition Society. 2000;59(4):595-600.
  9. Sies H. "Glutathione and its role in cellular functions." Free Radical Biology and Medicine. 1999;27(9-10):916-921.
  10. Brigelius-Flohé R, Maiorino M. "Glutathione peroxidases." Biochimica et Biophysica Acta. 2013;1830(5):3289-3303.
  11. Townsend DM, Tew KD. "The role of glutathione-S-transferase in anti-cancer drug resistance." Oncogene. 2003;22(47):7369-7375.
  12. Jones DP. "Redefining oxidative stress." Antioxidants & Redox Signaling. 2006;8(9-10):1865-1879.
  13. Gmünder H, Eck HP, Dröge W. "Low membrane transport activity for cystine in resting and mitogenically stimulated human lymphocyte preparations and human T cell clones." European Journal of Biochemistry. 1991;201(1):113-117.
  14. Erden-Inal M, Sunal E, Kanbak G. "Age-related changes in the glutathione redox system." Cell Biochemistry and Function. 2002;20(1):61-66.
  15. Lu SC. "Regulation of glutathione synthesis." Molecular Aspects of Medicine. 2009;30(1-2):42-59.
  16. Peterson JD, Herzenberg LA, Vasquez K, Waltenbaugh C. "Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns." Proceedings of the National Academy of Sciences. 1998;95(6):3071-3076.
  17. Sofic E, Lange KW, Jellinger K, Riederer P. "Reduced and oxidized glutathione in the substantia nigra of patients with Parkinson's disease." Neuroscience Letters. 1992;142(2):128-130.
  18. Sekhar RV, McKay SV, Patel SG, et al. "Glutathione synthesis is diminished in patients with uncontrolled diabetes and restored by dietary supplementation with cysteine and glycine." Diabetes Care. 2011;34(1):162-167.
  19. Allen J, Bradley RD. "Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers." Journal of Alternative and Complementary Medicine. 2011;17(9):827-833.
  20. Richie JP Jr, Nichenametla S, Neidig W, et al. "Randomized controlled trial of oral glutathione supplementation on body stores of glutathione." European Journal of Nutrition. 2015;54(2):251-263.
  21. Marrades RM, Roca J, Barberà JA, et al. "Nebulized glutathione induces bronchoconstriction in patients with mild asthma." American Journal of Respiratory and Critical Care Medicine. 1997;156(2):425-430.
  22. Traverso N, Ricciarelli R, Nitti M, et al. "Role of glutathione in cancer progression and chemoresistance." Oxidative Medicine and Cellular Longevity. 2013;2013:972913.
  23. Sinha R, Sinha I, Calcagnotto A, et al. "Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function." European Journal of Clinical Nutrition. 2018;72(1):105-111.

Additional Resources

Note: These references are provided for research and educational purposes. The quality and design of studies vary. Readers should critically evaluate research methodology, sample sizes, and potential biases when interpreting results.

3rd Party Testing & Quality Assurance

Every batch of glutathione undergoes comprehensive third-party testing to ensure purity, identity, and quality meet the highest standards for research applications.

Testing Protocols

HPLC Purity Analysis

High-Performance Liquid Chromatography verifies ≥99% purity and identifies potential impurities or degradation products.

Mass Spectrometry

MS analysis confirms molecular weight and chemical identity, ensuring the product matches glutathione specifications.

Endotoxin Testing

LAL (Limulus Amebocyte Lysate) assay confirms endotoxin levels are below detectable limits for research applications.

Quality Specifications

Test Parameter Specification Method
Appearance White to off-white powder Visual inspection
Identity Conforms to glutathione standard HPLC retention time, MS
Purity (HPLC) ≥99.0% HPLC-UV (210 nm)
Water Content ≤5.0% Karl Fischer titration
Heavy Metals ≤10 ppm ICP-MS
Bacterial Endotoxins ≤1.0 EU/mg LAL assay
Residual Solvents Within ICH limits GC-FID

Certificate of Analysis (COA)

Request Your Batch-Specific COA

Each product shipment includes a unique batch number. Certificates of Analysis are available upon request and include:

  • Batch/lot number and manufacturing date
  • Complete test results from independent laboratory
  • Chromatogram data (HPLC)
  • Mass spectrum
  • Expiration/retest date
  • Storage recommendations

To request a COA, contact us with your batch number at: quality@vitalhealer.com

Manufacturing Standards

cGMP Facilities

Manufactured in facilities following current Good Manufacturing Practices (cGMP) guidelines.

ISO Certification

Production facilities maintain ISO 9001:2015 quality management system certification.

Traceability

Complete chain of custody documentation from raw material sourcing through final product.

Stability Testing

Ongoing stability studies ensure product integrity throughout shelf life under recommended storage conditions.

Research Use Only

This product is intended strictly for laboratory research and is not approved for human consumption, medical use, or any diagnostic or therapeutic applications. All quality testing is conducted to ensure suitability for research purposes.

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