Glutathione Research, Specifications & Scientific Information

Glutathione is the endogenous tripeptide gamma-glutamyl-cysteinyl-glycine and the principal intracellular thiol redox buffer. It is not approved by the FDA for any indication; its human trial record by oral and intravenous routes is mixed, and its oral bioavailability has been disputed since 1992.

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Category: Other research peptides

Introduction

Glutathione is a tripeptide that is not really a peptide in the sense the rest of this library uses the word. It has no receptor, carries no signal, and does not act on a pathway. It is a reagent — the cell's principal thiol, present at millimolar concentrations, continuously consumed and continuously regenerated, and the substrate on which a whole family of enzymes depends [1].

One structural detail determines almost everything about it. The bond between its glutamate and its cysteine is a gamma-linkage, formed from the side-chain carboxyl rather than the alpha-carboxyl, and ordinary peptidases do not recognise it. That is why the molecule survives inside cells. It is also why administering it from outside is difficult: degradation requires gamma-glutamyltransferase, an enzyme sitting on the outer face of membranes and abundant in the intestine and liver — exactly the tissues an oral administration passes through first.

The human literature reflects that difficulty rather than resolving it. A 1992 pharmacokinetic study concluded systemic availability was negligible [2]. A 2015 six-month randomised trial reported substantial increases in tissue stores [3]. An intravenous trial in Parkinson's disease found no significant clinical difference from placebo [4]. This page sets out all three and explains why the first two are less contradictory than they look.

What Is Glutathione?

Glutathione is gamma-L-glutamyl-L-cysteinyl-glycine, three residues, 307 daltons, and the most abundant endogenous low-molecular-weight thiol in human cells. It is synthesised inside cells in two ATP-dependent steps rather than absorbed intact, and it is not a dietary essential in the ordinary sense.

Its functional group is the cysteine thiol. Everything the molecule does chemically, it does through that sulphur: reducing peroxides, conjugating electrophiles, maintaining other proteins' thiols in the reduced state.

Two forms matter and both are routinely measured. GSH is the reduced monomer. GSSG is the oxidised dimer, two molecules joined by a disulphide. The ratio between them, rather than the total amount, is what describes a cell's redox state, because glutathione is regenerated from GSSG by glutathione reductase at the expense of NADPH in a continuous cycle [1].

PubChem carries the reduced form under compound identifier 124886, with CAS registry number 70-18-8 and FDA/NCATS UNII code GAN16C9B8O.

It has not been approved by the U.S. Food and Drug Administration for any indication. It is widely sold as an oral dietary supplement — a category in which efficacy is not assessed before marketing — and intravenous preparations are administered outside any approved indication.

Glutathione Specifications

Compound name
Glutathione
Full chemical name
gamma-L-glutamyl-L-cysteinyl-glycine
Aliases
GSH, reduced glutathione, L-glutathione, gamma-Glu-Cys-Gly
Development code
Not publicly characterised
CAS number
70-18-8
PubChem CID
124886
UNII
GAN16C9B8O
Compound type
Endogenous tripeptide, prepared synthetically or by fermentation
Peptide family
Not a signalling peptide family. Glutathione is a thiol tripeptide cofactor of cellular redox metabolism.
Amino acid sequence
gamma-Glu-Cys-Gly
Sequence length
3 residues
Molecular formula
C10H17N3O6S
Molecular weight
307.33 g/mol
Primary target
Not publicly characterised
Secondary targets
Not publicly characterised
Receptor family
Not publicly characterised
Agonist / antagonist status
Not applicable. Glutathione is not a receptor ligand; it is a substrate and cofactor for a family of enzymes and a direct chemical reductant.

Glutathione is a tripeptide with one structural peculiarity that determines almost everything about it: the bond between glutamate and cysteine is a gamma-linkage, formed from the glutamate side-chain carboxyl rather than from its alpha-carboxyl. Ordinary peptidases do not recognise that bond, which is why the molecule survives in the cytosol at millimolar concentrations and why its breakdown requires a dedicated enzyme, gamma-glutamyltransferase, positioned on the outside of cell membranes. The cysteine thiol is the functional group; it is what reacts, and it is also why the molecule oxidises readily to the disulphide-linked dimer GSSG. PubChem carries the reduced form under compound identifier 124886 with CAS registry number 70-18-8 and the FDA/NCATS UNII code GAN16C9B8O. The ratio of the reduced to the oxidised form is the quantity most redox studies actually measure, and a preparation's thiol content, not its mass, is what determines whether it is the intended substance.

Values that a public register does not carry are shown as not publicly characterised rather than estimated. Identifiers are reference values; the certificate of analysis supplied with a laboratory order is the record for a given lot.

How Does Glutathione Work?

Not through a receptor. Glutathione has four distinct chemical roles, and separating them is the clearest way to describe it [1].

As a peroxide reductant. Glutathione peroxidases use it to reduce hydrogen peroxide and lipid hydroperoxides to water and alcohols, oxidising two molecules of GSH to one of GSSG in the process. This is the reaction most often meant when the molecule is called an antioxidant.

As a conjugating nucleophile. Glutathione S-transferases attach it to electrophilic compounds — including many drug metabolites and environmental chemicals — producing conjugates that are exported and excreted. This is a detoxification chemistry, and it consumes the molecule rather than cycling it.

As a protein thiol buffer. Protein cysteines are held in defined oxidation states partly by exchange with the glutathione pool, so the GSH:GSSG ratio propagates into the redox state of many enzymes.

As a regenerator of other antioxidants. It participates in recycling oxidised forms of other cellular reductants.

Two consequences follow for anyone reading claims about it.

Concentration is a flux, not a store. Because GSSG is reduced back to GSH continuously by glutathione reductase, a measured concentration reflects the balance of consumption and regeneration. Raising the number is not the same as improving the process that maintains it.

The gamma linkage cuts both ways. It protects the molecule inside the cell and blocks its route in from outside. This is the mechanistic explanation the 1992 pharmacokinetic study gave for negligible systemic availability [2], and it is why much of the field pursues glutathione status through precursors such as N-acetylcysteine, which enter by ordinary amino acid transport and are built into glutathione intracellularly.

Glutathione Mechanism of Action

The biochemistry above is established textbook enzymology rather than a compound-specific experimental claim, and it is referenced to the standard review of the field [1] rather than to primary assays. No in vitro study was located that adds anything about the molecule beyond what that biochemistry already establishes, and none is invented here.

What is not established is the step between administering glutathione and changing anything inside a cell. The enzymology is certain; the delivery is the open question, and it is addressed in the human section below rather than assumed here.

What Is Glutathione Being Researched For?

  • Oral supplementation and body glutathione stores — whether daily administration raises tissue concentrations, and for how long [2, 3].
  • Parkinson's disease — intravenous administration, in a randomised pilot trial [4].
  • Dermatological administration — intravenous, oral and topical routes reviewed systematically, with the reviews concerned as much with the quality of the evidence as with its direction [6, 5].
  • Gut microbiome composition — after long-term oral supplementation in people with type 2 diabetes [7].
  • Redox biochemistry generally — where the molecule is a measurement and a mechanism rather than an intervention [1].

None of that research is research into, or evidence about, research-grade material supplied for laboratory use.

Human Research on Glutathione

Human clinical research

Results from pharmaceutical clinical trials describe the investigational material and populations used in those studies and should not be interpreted as establishing the effects of research-grade materials offered for laboratory use.

Systemic availability after oral administration, 1992

Design. Seven healthy volunteers, given glutathione at 0.15 mmol/kg — about 3 g — with plasma glutathione, cysteine and glutamate measured over the following 270 minutes [2].

Result. Basal plasma concentrations were 6.2, 8.3 and 54 µmol/L respectively, and none increased significantly after administration. The authors conclude that systemic availability is negligible in humans because of hydrolysis by intestinal and hepatic gamma-glutamyltransferase, that dietary glutathione is not a major determinant of circulating glutathione, and that circulating concentrations cannot be raised to a clinically meaningful extent by a single 3 g oral administration [2].

Limitations and scope. Seven volunteers, one administration, a 270-minute window, and plasma as the only compartment. It is a well-posed pharmacokinetic question with a clear answer, and the answer applies to acute plasma appearance after a single administration — not to anything else.

Six-month supplementation trial, 2015

Population. 54 non-smoking adults [3].

Endpoint and design. A six-month randomised, double-blinded, placebo-controlled trial of oral glutathione at 250 mg or 1,000 mg daily, measuring glutathione in blood, erythrocytes, plasma, lymphocytes and exfoliated buccal mucosal cells, with immune markers as secondary outcomes in a subset [3].

Result. Concentrations rose at 1, 3 and 6 months against baseline at both amounts. At six months in the higher group, mean increases were 30–35% in erythrocytes, plasma and lymphocytes and 260% in buccal cells; in the lower group, 17% in blood and 29% in erythrocytes. Increases were generally related to amount and to duration, and returned to baseline after a one-month washout. The oxidised-to-reduced ratio in whole blood fell at six months in both groups, and natural killer cytotoxicity more than doubled against placebo at three months in the higher group [3].

Limitations. 54 participants, biomarker endpoints rather than clinical outcomes, and a secondary immune finding in a subset. The washout result is important in both directions: it supports the attribution of the increase to the supplement, and it shows the effect does not persist once administration stops.

Why the 1992 and 2015 results are not in conflict

They measured different things. The earlier study asked whether plasma glutathione rises in the hours after one large administration, and found that it does not [2]. The later study asked whether tissue concentrations rise over months of daily administration, and found that they do [3]. A molecule can be poorly available acutely and still shift a slowly turning pool when supplied continuously — plausibly through its constituent amino acids after hydrolysis rather than as the intact tripeptide, which neither study was designed to distinguish. A reader who quotes either paper as the answer to "is oral glutathione absorbed" is quoting an answer to a narrower question than the one asked.

Intravenous administration in Parkinson's disease, 2009

Population and design. 21 participants with Parkinson's disease whose motor symptoms were not adequately controlled by their existing regimen, randomised double-blind to intravenous glutathione 1,400 mg or placebo three times weekly for four weeks, with follow-up beyond [4].

Result. No significant differences in change on the Unified Parkinson's Disease Rating Scale. Activities-of-daily-living plus motor scores improved by a mean 2.8 units more in the glutathione group over the treatment period (p = 0.32), then worsened by a mean 3.5 units more over the following eight weeks (p = 0.54). No safety concerns were identified and there were no withdrawals for adverse events in either group [4].

Limitations. Twenty-one participants, four weeks, described by its authors as a pilot. The authors suggest the possibility of a mild symptomatic effect requiring a larger study; that larger study has not been published, and a suggestion unconfirmed for more than fifteen years should be weighted accordingly.

Dermatological administration and its safety evidence

What the literature says. Intravenous glutathione given for skin lightening has been the subject of repeated critiques on the ground that safety data are inadequate [5], and a 2025 systematic review has assessed the evidence across that application [6].

Why it is reported here. Because it is the context in which most non-oral human exposure to this compound now occurs, and because the published assessment of it is primarily about the absence of adequate evidence rather than about an effect. That is a finding, and it belongs on the page.

Other reported work

Long-term oral supplementation has been examined for effects on gut microbiome composition in people with type 2 diabetes [7].

Current Research Status

Regulatory status (United States)
Not approved as a medicine. Glutathione has not been approved by the U.S. Food and Drug Administration for any indication, and no marketing application for it is on record in the United States. It is widely sold as an oral dietary supplement, a category that involves no premarket approval of efficacy, and intravenous preparations are administered outside any approved indication.
Investigational status
Studied in academic trials by oral and intravenous routes, with mixed results. Oral bioavailability was reported negligible in an early pharmacokinetic study and body-store increases were reported in a later six-month randomised trial; an intravenous trial in Parkinson's disease found no significant difference from placebo on its clinical scale. Dermatological use by intravenous administration has been the subject of repeated safety-evidence critiques.
Highest research phase reached
Randomised double-blind placebo-controlled trials, including a six-month supplementation trial and a pilot intravenous trial. No registrational programme exists.
Approved uses
None
Approval is compound-specific
Yes

Status as of . This block is rendered from maintained fields, not from prose, so it cannot go stale in one place and stay current in another.

Chemical & Molecular Characteristics

Glutathione is a three-residue thiol peptide of molecular formula C10H17N3O6S and average mass 307.33 g/mol, under PubChem compound identifier 124886 and CAS registry number 70-18-8.

The gamma linkage is the defining structural feature. Formed from the glutamate side-chain carboxyl rather than the alpha-carboxyl, it is unrecognised by ordinary peptidases. A preparation in which that bond were an alpha-linkage would have the identical elemental composition and the identical mass, and would be a different substance with a different stability. Mass spectrometry cannot distinguish them; the isomer question requires nuclear magnetic resonance or a chromatographic method validated against an authentic standard. This is the single most consequential analytical point about the molecule.

The thiol is the assay. Content of the reduced form, not total glutathione and certainly not mass, is what determines whether a preparation is what it claims to be. Reduced glutathione oxidises to the disulphide dimer GSSG on exposure to air, in solution, and over time in the solid state. A certificate reporting purity without reporting free thiol content is reporting the wrong number.

GSSG is the characteristic impurity and it is not detected by mass alone. The dimer is 612 daltons where the monomer is 307, so it is readily seen if looked for — but a chromatographic purity figure that integrates both peaks as glutathione-related substance conceals exactly what matters.

No aromatic residue, so no ultraviolet handle. There is no tryptophan, tyrosine or phenylalanine, and absorbance at 280 nm is negligible. Quantification relies on thiol-specific chemistry — Ellman's reagent and its successors — or on chromatographic methods with derivatisation, which is one reason thiol assays rather than ultraviolet purity are the norm for this compound.

Very high polarity, and poor reversed-phase retention. At 307 daltons with three ionisable groups, the molecule is barely retained on conventional C18 columns and can elute near the void volume, where it is difficult to separate from salts and from synthesis-related impurities. Ion-pairing or hydrophilic-interaction chromatography is generally required.

Frequently Asked Questions

What is Glutathione?
A tripeptide, gamma-L-glutamyl-L-cysteinyl-glycine, and the most abundant endogenous low-molecular-weight thiol. It is the principal intracellular redox buffer, present in most cells at millimolar concentrations, and it functions as a substrate and cofactor for the glutathione peroxidases, reductase and S-transferases rather than as a ligand for any receptor [1]. Registers carry it under CAS registry number 70-18-8, PubChem compound identifier 124886 and UNII GAN16C9B8O.
Why is the gamma linkage important?
Because it is what keeps the molecule intact. The bond between glutamate and cysteine is formed from the glutamate side-chain carboxyl, not its alpha-carboxyl, and ordinary peptidases do not cleave it. Degradation instead requires gamma-glutamyltransferase, an enzyme positioned on the outer face of cell membranes and abundant in intestine and liver [1]. That single structural feature explains both the molecule's stability inside cells and the difficulty of delivering it into them from outside.
Is oral Glutathione absorbed?
The literature disagrees, and the disagreement is the most substantive thing on this page. A 1992 pharmacokinetic study in seven healthy volunteers found that after a single 3 g administration, plasma glutathione, cysteine and glutamate did not increase significantly, and concluded that systemic availability in humans is negligible because of hydrolysis by intestinal and hepatic gamma-glutamyltransferase [2]. A 2015 six-month randomised double-blind placebo-controlled trial in 54 adults reported increases in glutathione in blood, erythrocytes, plasma, lymphocytes and buccal cells [3]. The two studies asked different questions — acute plasma appearance after one administration, against tissue stores after six months of daily supplementation — and both results can be correct.
What did the 2015 supplementation trial report?
In 54 non-smoking adults given 250 mg or 1,000 mg daily for six months, glutathione rose 30–35% in erythrocytes, plasma and lymphocytes and 260% in buccal cells in the higher group, and 17% and 29% in blood and erythrocytes in the lower group. Increases were generally related to amount and duration, and returned to baseline after a one-month washout. The oxidised-to-reduced ratio in whole blood fell, and natural killer cytotoxicity more than doubled against placebo at three months in the higher group [3]. The return to baseline after washout is worth noting as much as the increase: it indicates the effect depends on continued administration.
What happened in the Parkinson's disease trial?
It was negative on its clinical measure. Twenty-one participants whose motor symptoms were inadequately controlled received intravenous glutathione 1,400 mg or placebo three times weekly for four weeks. The compound was well tolerated with no withdrawals for adverse events, and there were no significant differences in change on the Unified Parkinson's Disease Rating Scale — a 2.8-unit greater improvement over the treatment period (p = 0.32) followed by a 3.5-unit greater worsening over the subsequent eight weeks (p = 0.54). The authors describe a possible mild symptomatic effect requiring evaluation in a larger study [4]. That larger study has not been published.
Is Glutathione FDA approved?
No. It has not been approved by the U.S. Food and Drug Administration for any indication, and no marketing application for it is on record in the United States. It is widely sold as an oral dietary supplement, a category in which efficacy is not assessed before marketing. Intravenous administration for dermatological purposes has been the subject of repeated critiques on the ground that safety evidence is inadequate [5, 6].
What is the GSH to GSSG ratio?
The proportion of glutathione present in its reduced form against the oxidised disulphide dimer, and it is the quantity most redox studies actually report. Because glutathione is consumed and regenerated continuously by glutathione reductase at the expense of NADPH, a cell's glutathione status is a flux rather than a store, and the ratio describes that state better than total concentration does [1]. The 2015 trial reported a fall in the oxidised-to-reduced ratio in whole blood as its oxidative-stress measure [3].
What else has been studied?
Long-term oral supplementation has been examined for effects on the gut microbiome in people with type 2 diabetes [7], and dermatological administration has been reviewed systematically, with the reviews addressing the quality of the evidence as much as its direction [6, 5]. The wider interest in glutathione status across neurological and metabolic conditions is largely pursued through precursors rather than through the tripeptide itself, for the bioavailability reasons described above.

Scientific References

  1. Forman HJ, Zhang H, Rinna A. Glutathione: overview of its protective roles, measurement, and biosynthesis Molecular aspects of medicine; 2009. PMID 18796312 doi:10.1016/j.mam.2008.08.006
  2. Witschi A, Reddy S, Stofer B, et al.. The systemic availability of oral glutathione European journal of clinical pharmacology; 1992. PMID 1362956 doi:10.1007/BF02284971
  3. 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. PMID 24791752 doi:10.1007/s00394-014-0706-z
  4. Hauser RA, Lyons KE, McClain T, et al.. Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson's disease Movement disorders : official journal of the Movement Disorder Society; 2009. PMID 19230029 doi:10.1002/mds.22401
  5. Davids LM, Van Wyk JC, Khumalo NP. Intravenous glutathione for skin lightening: Inadequate safety data South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde; 2016. PMID 27499402 doi:10.7196/SAMJ.2016.v106i8.10878
  6. Sarkar R, Yadav V, Yadav T, et al.. Glutathione as a skin-lightening agent and in melasma: a systematic review International journal of dermatology; 2025. PMID 39444151 doi:10.1111/ijd.17535
  7. Gaike AH, Kalamkar SD, Gajjar V, et al.. Effect of long-term oral glutathione supplementation on gut microbiome of type 2 diabetic individuals FEMS microbiology letters; 2023. PMID 37935462 doi:10.1093/femsle/fnad116

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Research-Use Information

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