Research Dossier on Glutathione

(Antioxidant Peptide)

Classification & Molecular Identity

Amino acid sequence, molecular weight, structural motifs

Glutathione (GSH) is a tripeptide composed of L-glutamate, L-cysteine, and glycine with a non-proteogenic γ-peptide bond (γ-glutamyl linkage) between the γ-carboxyl of glutamate and the amino group of cysteine; cysteine and glycine are connected through a conventional peptide bond. The reduced thiol on cysteine confers nucleophilicity and redox activity; the oxidized form is glutathione disulfide (GSSG). Typical cellular concentrations approach millimolarlevels, and the GSH:GSSG ratio serves as a widely used index of intracellular redox status. PMC+1

• Empirical identity: L-γ-Glu-L-Cys-Gly (reduced, GSH).

• Structural features: γ-peptide bond (protease-resistant), central thiol (redox active), small highly polar tripeptide scaffold. PMC

Discovery history (lab, year, species)

Work dating back to the mid-20th century placed GSH at the center of the γ-glutamyl cycle (later broadened to a “glutathione cycle”), integrating biosynthesis, extracellular breakdown, and salvage pathways. Foundational contributions include Meister’s mechanistic delineation of synthesis and turnover (1970s–1980s) and modern updates that refine or challenge aspects of the original model. PubMed+2ScienceDirect+2

Endogenous vs synthetic origin

GSH is endogenous and ubiquitous in aerobic life. It is synthesized in nearly all mammalian cells via two ATP-dependent cytosolic steps and distributed to subcellular compartments and extracellular spaces (e.g., bile, alveolar fluid). Synthetic GSH for laboratory use is produced by standard peptide synthesis or fermentation routes. PubMed+1

Homologs, analogs, derivatives

• GSSG (oxidized dimer) and glutathione conjugates (GS-X) formed enzymatically (e.g., by GSTs) or non-enzymatically with electrophiles. PubMed

• Pro-drugs/derivatives (e.g., GSH esters, N-modified analogs) designed to alter uptake/pharmacokinetics; recent N-methylated GSH derivatives in rodents show extended half-life and higher oral bioavailability (preclinical). Translation to humans: Not established. MDPI

• Related thiol buffers: cysteine/cystine pools; thioredoxin system (parallel redox network).

Historical Development & Research Trajectory

Key milestones in discovery and study

• 1970s–1990s: Biochemical formalization of the γ-glutamyl cycle and identification of glutathione’s roles in xenobiotic conjugation, peroxide detoxification, and disulfide chemistry. ScienceDirect+1

• 2000s: Consolidation of GSH as a master redox hub; advances in GSH synthesis regulation (GCL/GSS), transport, and compartmentalization. PubMed+1

• 2010s–2020s: Expansion into systems biology (GSH-responsive gene networks, ferroptosis resistance via cystine import), and clinical interest in restoring GSH pools; controlled human trials begin to quantify body-store responses to oral GSH. PubMed+1

Paradigm shifts and controversies

1. Beyond the γ-glutamyl cycle: Updated models emphasize a broader “glutathione cycle” that integrates compartment-specific pools and transporter families, revising earlier assumptions about amino-acid transport coupling. IUBMB Journal

2. Transport complexity: Multiple ABC transporters (MRPs/ABCCs) and selected OATPs export GSH and GS-conjugates; system x_c^− (SLC7A11/xCT) imports cystine for de novo synthesis, tightly linking cystine supply to GSH homeostasis. PubMed+2PubMed+2

3. Clinical translation gap: Despite overwhelming basic science, dose-exposure-response relationships and indication-specific outcomes in humans remain uneven and context-dependent (see Human Clinical Evidence). Frontiers

Evolution of scientific interest

GSH research moved from biochemical detoxication to an integrative redox and signaling hub spanning immunity, metabolism, cell death (ferroptosis), and aging, with enhanced focus on cystine transport, glutathione-dependent enzymes, and genetics of redox regulation. Wiley Online Library+1

Mechanisms of Action

Primary and secondary interactions

• Redox buffer & thiol chemistry: GSH maintains protein thiols in the reduced state, participates in S-glutathionylation, and neutralizes reactive species via glutathione peroxidases (GPX), which use GSH to reduce H₂O₂ and organic hydroperoxides, generating GSSG that is recycled by glutathione reductase (GSR) using NADPH. Frontiers+2PMC+2

• Conjugation/detoxication: Glutathione S-transferases (GSTs) catalyze nucleophilic addition of GSH to electrophiles (xenobiotics, lipid peroxidation products), producing GS-conjugates destined for export and further metabolism (mercapturic acid pathway). PubMed+1

• Metal/quinone buffering: GSH can reduce or conjugate redox-active species, mitigating oxidative cycling (context-specific). Direct receptor interactions: Not established (GSH acts enzymatically and chemically rather than via a single receptor).

Intracellular signaling pathways

• GPX-dependent peroxide control limits H₂O₂-mediated signal transduction (e.g., MAPK, ASK1) and oxidative damage. Nature

• GSH:GSSG ratio influences protein S-glutathionylation, modulating enzyme activities and transcription factors; GSR and the pentose-phosphate pathway (NADPH supply) maintain reducing capacity. PMC

• Ferroptosis resistance depends on cystine import (system x_c^−) and GSH-dependent GPX4 activity; limiting cystine or GSH favors lipid peroxidation and ferroptotic death in many models. (Mechanistic evidence robust in vitro/in vivo models; clinical translation is evolving.) Nature+1

CNS vs peripheral effects

• Peripheral: Major roles in liver (xenobiotic metabolism), erythrocytes (oxidant defense), lung/bile (extracellular pools), immune cells, and across highly oxidative tissues. MDPI

• CNS: GSH is present in brain; transport across the blood–brain barrier is limited—brain GSH homeostasis depends on local synthesis and precursor transport rather than bulk GSH uptake. (Quantitative human BBB GSH transport: Not established; inferred from transporter and enzymology literature.) PMC

Hormonal, metabolic, immune interactions

• Immune function: GSH modulates redox-sensitive immune signaling and antigen presentation; de novo synthesis (GCL/GSS; cystine import) is crucial in T-cell differentiation and macrophage function in multiple models. eLife+1

• Metabolism: Links to NADPH status (PPP) and amino-acid availability (cysteine often rate-limiting). Nature

Evidence grading (A–C)

• A (replicated, foundational): Biochemistry of GSH synthesis (GCL/GSS); GPX/GSR cycles; GST-mediatedconjugation; MRP/OATP export of GSH/GS-X; x_c^−-dependent cystine supply; functional roles in oxidative stress detoxication. PubMed+5PubMed+5PubMed+5

• B (translational/clinical): Controlled human trials demonstrate increases in body GSH stores with chronic oral GSH; disease-specific outcomes vary (see RCTs). PubMed

• C (hypothesis/early): Novel bioavailable derivatives and targeted ferroptosis modulation in human indications remain investigational. MDPI

Pharmacokinetics & Stability

ADME profile

• Absorption: Oral bioavailability of native GSH has been debated; a 6-month randomized, double-blind, placebo-controlled trial showed dose-dependent increases in body compartment stores with 250 mg or 1,000 mg day⁻¹ (investigational doses used in study Richie 2015; NCT01044277). PubMed+1

• Distribution: After intravenous (IV) infusion, plasma total GSH rises markedly but clears rapidly; in a classic human PK study with 2 g·m⁻² IV GSH the apparent half-life was ~14 min (investigational dose used in study Aebi 1991). PubMed+1

• Metabolism: GSH is degraded extracellularly by γ-glutamyltransferase (GGT) to cysteinyl-glycine and γ-glutamyl amino acids; aminopeptidases then liberate cysteine and glycine, enabling salvage for de novo synthesis (γ-glutamyl cycle). PMC

• Excretion: GS-conjugates are exported (mainly MRPs/ABCC) and processed to mercapturic acids for renal/biliary elimination; GSSG is exported under oxidative load. PubMed+1

Plasma half-life & degradation pathways

• IV native GSH: short plasma t½ (~14 ± 9 min) with rapid thiol exchange and metabolism; rises in plasma cysteine accompany infusion (human PK). PubMed

• Oral: systemic appearance of intact GSH is limited; increases in body compartment stores over months imply contributions from intestinal handling, tissue salvage, and enhanced synthesis from liberated amino-acid precursors. Absolute oral bioavailability (humans): Not established. PubMed

Stability in vitro & in vivo

• In vitro/ex vivo: GSH is labile in biological samples; pre-analytical handling (temperature, derivatization with N-ethylmaleimide) is critical to prevent artifactual oxidation/degradation and to obtain reliable GSH/GSSG ratios. PMC

• Storage effects: Studies indicate poor stability of GSH in plasma at 4 °C, recommending immediate processing or −80 °C storage for accurate quantification. Nature+1

Storage/reconstitution considerations (lab)

Peer-reviewed references emphasize sample-handling constraints rather than vendor-specific vial stability; validated, product-agnostic reconstitution and shelf-life curves for research-grade GSH are Not established. General thiol/peptide practices apply (oxygen/light minimization; cold storage; pH-appropriate buffers).

Preclinical Evidence

Animal and in vitro studies (selected domains)

1) Oxidative-stress detoxication & redox control

• GPX system: GSH serves as the electron donor for GPX isoforms that reduce H₂O₂ and lipid peroxides, with broad protective effects in many tissues. Knockdown/deficiency models underscore GPX-dependent control of H₂O₂ signaling and cell death pathways. Frontiers+1

• GSR/NADPH recycling: Glutathione reductase rapidly reduces GSSG → 2 GSH, sustaining a high GSH:GSSGratio essential for protein thiol homeostasis and redox signaling. PMC

2) Conjugation, detoxication, and transport

• GSTs catalyze conjugation of GSH to electrophiles, including certain anticancer drug metabolites; MRP/ABCCtransporters then export GS-conjugates, GSSG, and S-nitrosoglutathione. This coupling governs xenobiotic clearance and drug resistance in tumors. PubMed+2PubMed+2

3) Cystine import & de novo synthesis

• SLC7A11/xCT system x_c^− imports cystine in exchange for glutamate; intracellular reduction produces cysteine, often the rate-limiting GSH precursor. Genetic and pharmacologic modulation of xCT markedly alters GSH pools, ferroptosis sensitivity, and tumor biology in models. PubMed+2Europe PMC+2

4) γ-Glutamyltransferase (GGT) and extracellular catabolism
GGT, an ectoenzyme on the external leaflet of plasma membranes, hydrolyzes extracellular GSH, enabling cysteine recovery and driving amino-acid transport via the γ-glutamyl cycle. GGT shapes local redox chemistry (e.g., generation of cysteinyl-glycine), with context-dependent antioxidant/pro-oxidant consequences. PMC+1

5) Tissue-specific models

• Liver and kidney: high flux through GSH/GST/MRP pathways supports xenobiotic clearance.

• Immune cells: de novo synthesis—rather than GSSG recycling—dominates control of T-cell ROS and differentiation in certain contexts (mouse models). eLife

• Cancer: Overexpression of GSTs and MRPs links GSH metabolism to chemoresistance; modulating GSH or its enzymes can alter drug responses (preclinical). MDPI

Dose ranges tested (illustrative; investigational)

• In vitro: millimolar GSH is often used to buffer ROS; micromolar ranges for conjugation kinetics and transporter studies, depending on model (investigational concentrations; model-specific).

• In vivo: parenteral GSH challenge studies in animals employ ranges that elevate plasma GSH acutely to probe distribution and metabolism; dosing varies widely with species and endpoints (investigational; heterogeneous).

Comparative efficacy/safety (preclinical)

GSH and pathway enzymes are essential for survival across taxa. Perturbing synthesis (GCL) or cystine import (xCT) reduces GSH, elevates lipid peroxidation, and sensitizes to oxidant injury; excessive GSH conjugation/export contributes to chemotherapy resistance. PubMed+1

Key limitations

• Species differences in transporter expression and redox network wiring.

• Complexity of interpreting “antioxidant effects”—benefit depends on compartment, flux, and redox balancerather than absolute levels.

• Model dependence of xenobiotic outcomes and ferroptosis responses.

Human Clinical Evidence

Summary: Human evidence is strongest for biochemical/biomarker outcomes (raising body GSH stores, shifting redox indices). Large, indication-specific Phase II/III outcomes are limited and heterogeneous.

Randomized, placebo-controlled trials (illustrative)

Oral GSH and body stores

• Design: 6-month randomized, double-blind, placebo-controlled trial in healthy adults (n≈54).

• Arms & amounts: 250 mg·day⁻¹ and 1,000 mg·day⁻¹, oral (investigational doses used in study Richie 2015).

• Outcomes: Dose- and time-dependent increases of GSH in blood compartments (≈30–35 % in erythrocytes/plasma/lymphocytes at 6 months in the high-dose group), reduced oxidized-to-reduced GSH ratio, and washout toward baseline after cessation. Trial registered as NCT01044277. Clinical endpoints: exploratory immune markers only. PubMed+1

Skin-related RCTs (cosmetic outcomes; context)

• Oral GSH 500 mg·day⁻¹ for 4 weeks has been examined for melanin index changes in small RCTs; findings suggest modest effects but are cosmetic, not therapeutic, and outcomes are context-specific. (investigational dose used in study Arjinpathana 2010/2012; see also later registry entries). Generalizability to other indications: Not established. PubMed+2Europe PMC+2

Intravenous GSH pharmacokinetics

• Design: Single-arm human PK with 2 g·m⁻² IV GSH.

• Outcomes: Plasma total GSH increased from ~18 to ~823 µmol·L⁻¹; volume of distribution ~176 mL·kg⁻¹ and t½ ~14 min; plasma cysteine rose markedly, indicating rapid extracellular catabolism and thiol exchange. (investigational dose used in study Aebi 1991). Clinical efficacy endpoints: not assessed. PubMed

Safety signals/adverse events

Across controlled studies above, tolerability was generally acceptable within study scopes; systematic drug-level pharmacovigilance and long-term safety datasets are limited and indication-dependent. Comprehensive human safety profile: Not established. Frontiers

ClinicalTrials.gov identifiers (illustrative)

• NCT01044277 — randomized oral GSH body-store study (completed; biomarker-focused). ClinicalTrials.gov

• Additional registry entries address topical/cosmetic contexts; disease-directed late-phase trials of native GSHremain limited as of September 26, 2025.

Comparative Context

Related peptides/thiol systems

• Thioredoxin/Peroxiredoxins: parallel peroxidatic systems using NADPH; differ in substrate specificity and signaling roles.

• Cysteine/cystine pools and system x_c^−: upstream determinants of de novo GSH synthesis. Nature

Advantages (research perspective)

• Endogenous, universal redox buffer with well-defined enzymatic network (GCL/GSS/GPX/GSR/GST/MRPs).

• Robust preclinical data across tissues; quantitative biochemical readouts (e.g., GSH:GSSG, GS-conjugates). PMC

Disadvantages/constraints

• Short systemic half-life after IV administration; complex oral handling and uncertain absolute bioavailabilityin humans. PubMed

• Context-dependence: Benefits or risks depend on compartment, dose-flux, disease state, and metal/drug interactions; over-simplified “antioxidant” narratives can be misleading. PubMed

Research category placement

• Core endogenous redox metabolite; tool compound for probing oxidant defenses, xenobiotic conjugation, ferroptosis, and transporter biology.

Research Highlights

• Biochemical bedrock: Two-step ATP-dependent de novo synthesis (GCL/GSS), GPX/GSR cycle, GST-mediated conjugation, and MRP-mediated export—replicated across species and tissues. PubMed+3PubMed+3Frontiers+3

• Transport frontiers: xCT (SLC7A11) is pivotal for cystine supply and GSH homeostasis; MRP family handles GSH, GSSG, and GS-conjugates; OATPs participate in selected contexts. PMC+2PubMed+2

• Human biomarker gains: A 6-month randomized trial demonstrated dose-dependent elevations of GSH across compartments with 250/1,000 mg·day⁻¹ oral GSH (investigational doses used in study Richie 2015). PubMed

• Conflicting/uncertain areas: Absolute bioavailability, brain delivery, indication-specific outcomes, and long-term safety remain Not established or heterogeneous across small trials and contexts. Frontiers

Potential Research Applications (no clinical claims; research-use framing)

1. Redox network dissection

   • Map GSH:GSSG dynamics and S-glutathionylation under defined oxidative challenges in primary human cells and organoids; pair with RNA-seq/ATAC-seq to link redox shifts to transcriptional remodeling. PMC

2. Xenobiotic metabolism & transport

   • Examine GST-dependent conjugation kinetics and MRP-mediated export of model electrophiles (drug metabolites, lipid peroxidation products); quantify mercapturic acid formation. PubMed+1

3. Cystine transport & ferroptosis

   • Use xCT perturbation (genetic or pharmacologic) to modulate GSH pools and ferroptosis sensitivity; test combinatorial strategies with ROS generators in cancer cell systems (mechanistic only). Europe PMC

4. Enzyme systems physiology

   • Quantify GPX and GSR flux control coefficients in human cell models; couple to NADPH measurements and PPP flux to probe bottlenecks under metabolic stress. Frontiers+1

5. Extracellular turnover & GGT biology

   • Investigate GGT-dependent GSH breakdown in airway and biliary models and consequences for cysteine salvage and local oxidative chemistry (e.g., cysteinyl-glycine/iron redox). PMC+1

Safety & Toxicology

Preclinical toxicity data

GSH is endogenous; toxicity studies typically focus on pathway perturbations (e.g., inhibition of GCL, disruption of xCT) rather than GSH itself. Nevertheless, GLP-style repeat-dose tox, genotox, reproductive tox, and carcinogenicity packages for exogenous GSH as a drug are limited in the public domain (Not established).

Known/theoretical molecular risks

• Drug interactions via GST/MRP axes: Elevated GSH/GST/MRP activity can lower intracellular exposure to some electrophilic drugs and contribute to chemoresistance (context-dependent). PubMed

• Metal/redox interplay: Altered thiol status can modulate metal redox and S-nitrosothiol pools; directionality depends on compartment and flux. (General mechanistic principle; human risk quantification: Not established.)

Human safety observations

• Controlled human studies (e.g., 6-month oral RCT) reported good tolerability within study confines; long-term drug-level safety, drug–drug interactions, and population-specific risks remain Not established. PubMed

Data gaps

• Absolute human oral bioavailability, organ-specific PK, brain delivery, dose-exposure-response relationships by indication, and long-term safety require rigorous, registered trials.

Limitations & Controversies

• Translation gap: Abundant preclinical evidence contrasts with a limited late-phase clinical evidence base for native GSH across specific diseases. Frontiers

• Analytical pitfalls: Pre-analytical instability of GSH can bias human biomarker studies; rigorous derivatization/temperature control is essential. PMC

• Framework evolution: The classic γ-glutamyl cycle remains informative, but modern views emphasize a broader glutathione cycle, compartmentation, and transporter crosstalk—some earlier assumptions about amino-acid transport coupling have been re-interpreted. IUBMB Journal

Future Directions

• Quantitative human PK/PD of native GSH and next-gen derivatives (e.g., N-modified, esters) with validated metalloproteomic/speciation to track exchange with albumin/thiols and entry into specific tissues. MDPI

• Compartment-resolved redox mapping in humans (e.g., erythrocyte vs lymphocyte vs epithelial) under standardized pre-analytics, linking GSH:GSSG shifts to transcriptomic and proteomic responses. PMC

• Transporter-targeted strategies: Controlled human physiology studies modulating xCT (cystine supply) or MRPactivities (export), to causally connect transporter flux with GSH pools and oxidative biomarkers. PubMed+1

• Ferroptosis/immune interfaces: Define how GSH depletion or restoration shapes lipid peroxidation and immune cell function in vivo (mechanistic endpoints first). eLife

References

Biochemistry, synthesis, enzymology

1. Lu SC. Glutathione synthesis. Biochim Biophys Acta. 2013;1830:3143–3153. PMID: 22995213. PubMed

2. Franklin CC, Dikitect AJ. Structure, function, and post-translational regulation of glutamate cysteine ligase. J Biol Chem. 2009. PMID: 18812186. PubMed

3. Griffith OW. The enzymes of glutathione synthesis. Am J Physiol. 1999. PMID: 10218110. PubMed

4. Lushchak VI. Glutathione homeostasis and functions. Int J Mol Sci. 2012. PMCID: PMC3303626. PMC

Glutathione/γ-glutamyl cycle & updates
5) Meister A. Glutathione, metabolism and function via the γ-glutamyl cycle. Life Sci. 1974. PMID: 4620960. PubMed
6) Bachhawat AK, et al. The glutathione cycle: beyond the γ-glutamyl cycle. IUBMB Life. 2018. doi:10.1002/iub.1756. IUBMB Journal
7) Taniguchi N, et al. From the γ-Glutamyl Cycle to the Glycan Cycle. J Biol Chem. 2009. PMCID: PMC2787308. PMC

Transport & cystine supply
8) Ballatori N, et al. Plasma membrane glutathione transporters (MRPs/OATPs). Toxicol Appl Pharmacol. 2009. PMID: 18786560. PubMed
9) Ballatori N, et al. Role of MRP/CFTR/ABCC and OATP in GSH transport. Toxicol Appl Pharmacol. 2005. PMID: 15845416. PubMed
10) Jedlitschky G, et al. MRP as ATP-dependent export pump for GS-conjugates/GSSG. Proc Natl Acad Sci USA.1996. PMID: 8640791. PubMed
11) Jyotsana N, et al. SLC7A11/xCT in cancer & glutathione synthesis. Trends Cancer. 2022. PMID: 35280777; PMCID: PMC8904967. PubMed+1
12) Parker JL, et al. Molecular basis for redox control by human xCT. Nat Commun. 2021. doi:10.1038/s41467-021-27414-1. Nature

GGT & extracellular metabolism
13) Hanigan MH, Ricketts WA. GGT in redox regulation and the γ-glutamyl cycle. Antioxid Redox Signal. 2014. PMCID: PMC4388159. PMC
14) Whitfield JB. Gamma-glutamyl transferase review. Crit Rev Clin Lab Sci. 2001. PMID: 11563810. PubMed
15) Ndrepepa G. GGT and cardiovascular disease (redox implications). Ann Transl Med. 2016. Annals of Translational Medicine

Enzyme systems & redox
16) Lubos E, et al. Glutathione peroxidase-1 in health & disease. Antioxid Redox Signal. 2011. PMCID: PMC3159114. PMC
17) Handy DE, et al. Role of GPX-1 in health & disease (update). Antioxid Redox Signal. 2022. PMCID: PMC9586416. PMC
18) Pannala VR, et al. GSR catalysis & modeling. PLoS One. 2013. PMCID: PMC3870161. PMC
19) Salinas AE, Wong MG. Glutathione S-transferases—review. Curr Med Chem. 1999. PMID: 10101214. PubMed
20) Allocati N, et al. GSTs: substrates, inhibitors, pro-drugs. Cell Death Dis. 2018. doi:10.1038/s41389-017-0025-3. Nature
21) Potęga A, et al. GSH-mediated conjugation of anticancer drugs. Cancers (Basel). 2022. PMID: 36014491. PubMed

Clinical/PK & human trials
22) Richie JP Jr., et al. Randomized controlled trial of oral GSH on body stores (250 or 1,000 mg·day⁻¹; 6 months).Eur J Nutr. 2015. PMID: 24791752; NCT01044277. PubMed+1
23) Aebi S, et al. High-dose IV glutathione PK in humans (2 g·m⁻²). J Clin Pharm Ther. 1991. PMID: 1907548. PubMed
24) Arjinpathana N, et al. Oral GSH 500 mg·day⁻¹; skin melanin index RCT (cosmetic outcome). J Dermatol Treat.2010/2012. PMID: 20524875. Europe PMC

Analytics & stability
25) McGill MR, et al. Measuring oxidized vs reduced glutathione; pre-analytical considerations. Free Radic Biol Med. 2015. PMCID: PMC4831617. PMC
26) Coden KM, et al. Impact of collection/storage on plasma GSH stability. Transl Psychiatry. 2024. doi:10.1038/s41398-024-03086-5. Nature

Reviews/overviews
27) Liu Y, et al. Emerging regulatory paradigms in GSH metabolism. Adv Cancer Res. 2014. PMCID: PMC4515967. PMC
28) Ikeda Y, et al. Emerging roles of γ-glutamyl peptides (GGT/GCL context). Cells. 2023. PMCID: PMC10741565. PMC
29) Vašková J, et al. Glutathione-related enzymes & proteins. Molecules. 2023. doi:10.3390/molecules28031447. MDPI
30) Hong SY, et al. Pharmacokinetics of GSH & metabolites (preclinical/PK frameworks). Yonsei Med J. 2005. PMCID: PMC2779265. PMC
31) Yin N, et al. N-methylated GSH derivatives improve oral bioavailability (rat PK). Pharmaceutics. 2025. doi:10.3390/pharmaceutics17030385. (Preclinical). MDPI

Notes on investigational amounts (examples):
• 250 mg or 1,000 mg oral daily for 6 months—investigational doses used in study Richie 2015; biomarker outcomes only. PubMed
• 2 g·m⁻² IV infusion—investigational dose used in study Aebi 1991; PK/biochemical outcomes only. PubMed
• 500 mg·day⁻¹ oral for 4 weeks in cosmetic RCT—investigational dose used in study Arjinpathana 2010/2012 (melanin index). Europe PMC

⚠️ Disclaimer This peptide is intended strictly for laboratory research use. It is not FDA-approved or authorized for human use, consumption, or therapeutic application.