Glutathione: what the studies show, status and safety
Summary
Glutathione is a small molecule that every human cell builds for itself. Its legal standing splits three ways. Japan has licensed it as a prescription medicine since 1967, and Italy licenses an injection for one narrow purpose in cancer care. In the European Union and the United States it is sold as a food supplement, with no medicine approval. As a cosmetic whitening drip it is approved nowhere, and regulators have tied such drips to fever, shock and hospital admissions.
Key findings at a glance
- An approved medicine in two countries, and in neither for cosmetic use. Japan licensed tablets in August and September 1967 [1]. Italy licenses an injection for one purpose only, preventing nerve damage from cisplatin chemotherapy [2].
- No medicine approval in the United States or the European Union. Oral products are sold as supplements. American regulators list the substance in category 1 as at 14 May 2026, meaning they do not currently act against compounding pharmacies that use it [3], [4].
- Not on the American list of risky compounding substances. A full-text search of that list, current as at 22 April 2026, found no entry [5].
- At least 30 people harmed by injections in 2026, and 8 in 2019. All the batches traced back to material sold as supplement grade. Laboratory tests in 2019 found bacterial toxin up to five times the permitted limit, and two Texas pharmacies recalled their product in August 2026 [6], [7], [8], [9].
- It leaves the blood within minutes. After one infusion in 10 healthy volunteers the level fell with a half-life of 14.1 minutes, with a spread of 9.2 minutes [10].
- Three large controlled trials missed their main target. These were injections in Parkinson's disease in 21 people [11], nose drops in the same disease in 45 people [12], and inhalation in cystic fibrosis in 153 people [13].
- One controlled trial came out positive. It enrolled 52 people on oxaliplatin chemotherapy. After eight rounds of treatment, moderate to severe nerve damage affected 2 people on glutathione and 11 on dummy infusions, p = 0.003 [14].
- Skin lightening: a meter reading, not a proven benefit. A 2025 review of the whole field calls the effect moderate and unsustainable, and states that the intravenous route is contraindicated [15].
What it is
Glutathione is a chain of three amino acids: glutamate, cysteine and glycine. Every cell makes its own supply in two energy-driven steps. It keeps enough of it to act as the cell's main chemical buffer against damage by oxygen [16], [17].
One structural detail matters. The link between the first two building blocks is an unusual side-chain bond, so most protein-splitting enzymes cannot cut the molecule. Only one enzyme in the gut and liver, gamma-glutamyl transferase, takes it apart, and that enzyme is the reason swallowed glutathione largely never arrives intact [16], [18].
The medicine came from Japan. Yamanouchi, now part of Astellas, produced the first industrially made reduced glutathione preparation and obtained tablet licences in 1967. The Japanese products are made today by Choseido, which took them over in April 2012 [19].
Quick facts
| Field | Value | Ref |
|---|---|---|
| Name | Glutathione; the reduced form is written GSH, the oxidised pair GSSG | [20] |
| Class | Tripeptide made by the body; antioxidant and enzyme cofactor | [16], [21] |
| Structure | Glutamate-cysteine-glycine, joined at the first step by a side-chain bond | [16], [20] |
| Formula and mass | C10H17N3O6S, 307.33 g/mol | [20] |
| Half-life | 14.1 minutes, spread 9.2, after a single infusion in 10 volunteers | [10] |
| Routes studied | By mouth, under the tongue, into a vein or muscle, inhaled, into the nose, on the skin | [18], [10], [13], [22], [23] |
| Status | Prescription medicine in Japan and Italy; food supplement in the European Union and the United States | [1], [2], [24], [3] |
| Developer | Yamanouchi, Japan; now made by Choseido | [19] |
| ATC group | V03AB32, the group for antidotes | [2], [1] |
| CAS registry number | 70-18-8 | [20] |
| UNII | GAN16C9B8O | [20] |
| PubChem CID | 124886 | [20] |
| ChEBI | CHEBI:16856 | [20] |
| InChIKey | RWSXRVCMGQZWBV-WDSKDSINSA-N | [20] |
How it works
The basic biochemistry is settled textbook material. What remains open is whether adding glutathione from outside changes anything a patient would notice [25].
- It neutralises reactive oxygen. As the partner of the glutathione peroxidase enzymes it converts hydrogen peroxide and damaged fats into harmless products, turning into its oxidised pair in the process. A second enzyme then converts that pair back [16], [21].
- It carries waste out of the cell. With the glutathione S-transferase enzymes it binds reactive chemicals and drugs into compounds the kidney can excrete. This is why the Japanese and Italian licences classify it as an antidote [17], [1], [2].
- The skin effect, if real, may work through pigment chemistry. Laboratory work suggests it may slow the tyrosinase enzyme and shift pigment production from the dark form towards the light form. That has not been demonstrated in a person [26], [27].
- Some of the effect of an injection may not be glutathione at all. After infusion in 10 volunteers, cysteine in the blood rose from 8.9 to 114 micromoles per litre. Total cyst(e)ine fell at the same time. That pattern suggests cells were taking up cysteine released from the molecule [10].
- Reaching the target tissue is possible but not sufficient. Nose drops raised the level measured in the brain, p below 0.001, and inhalation raised it in lung secretions. Neither translated into a clinical benefit [22], [13].
The counter-example that keeps the biochemistry honest is inherited disease. People born unable to make glutathione properly develop haemolytic anaemia, acid in the blood and nerve damage. A genuine shortage matters; it does not follow that a healthy person gains from more [28].
What the trials found
The human evidence is wide but thin. Almost every positive result is a laboratory measurement rather than something a patient would feel, and the three biggest controlled trials all failed on their main question [25].
Whether swallowed glutathione reaches the body
Pharmacokinetic study In seven healthy volunteers, a single large oral dose left the blood levels of glutathione, cysteine and glutamate unchanged over four and a half hours. The authors concluded that gut and liver enzymes destroy it, so a single dose cannot lift the blood level [18].
Randomised controlled trial Daily use over six months tells a different story. Among 54 healthy non-smokers, the higher daily amount raised stores by 30 to 35 per cent in red cells, plasma and lymphocytes. In cheek lining cells the rise reached 260 per cent.
The lower daily amount raised whole blood by 17 per cent and red cells by 29 per cent. Everything returned to baseline after a one-month break [29].
Two separate studies, not a head-to-head comparison. The single dose was measured in 7 healthy volunteers over four and a half hours; the daily use in 54 healthy non-smokers over six months. The top bar covers a reported range of 30 to 35 per cent. Sources [18], [29].
Randomised crossover In 20 people with metabolic syndrome, a form dissolved under the tongue produced higher blood levels than the swallowed form, p = 0.003. In an uncontrolled month-long study in 12 adults, a fat-encapsulated form raised whole blood by 40 per cent. Both studies were run with the makers of the product tested [30], [31].
Skin pigmentation
Randomised controlled trial In 60 medical students in Bangkok, four weeks of oral use lowered the melanin index, a meter reading of skin pigment, at all six measured sites. The difference from dummy treatment reached significance at two of them, the right cheek at p = 0.021 and the sun-exposed left forearm at p = 0.036 [32].
Randomised controlled trial A twelve-week study in 60 healthy women tested both the reduced and the oxidised form against dummy capsules. Pigment readings tended lower under both, and wrinkle depth fell significantly at individual sites. The authors report the pigment results as a trend, not a clear main effect [33].
Randomised controlled trial The clearest single result is topical. Thirty women aged 30 to 50 applied a lotion of the oxidised form to one side of the face for ten weeks. The melanin index there fell below the untreated side, p below 0.001 at week 10 [23].
A later trial in 46 people found the combination of cream plus capsules better than either alone, p below 0.05 [34].
Systematic review The 2025 overview puts these results in order. Five randomised trials and one open study found lower pigment readings with oral use. The stronger topical concentration beat both the weaker one and dummy cream.
For injections the reviewers found a single dummy-controlled study, and its result missed significance. Six of 16 people responded against 3, that is 37.5 against 18.7 per cent, p = 0.054. They call the effect unsustainable and state that the intravenous route is contraindicated [15].
Parkinson's disease
Open case series The whole line of research starts with nine untreated patients in 1996, given infusions for 30 days without blinding or a control group. Disability was reported to fall by 42 per cent, with the effect lasting two to four months after stopping [35].
Randomised controlled trial, negative When that was tested properly in 21 patients, the difference vanished. Over four weeks the combined daily-living and movement score improved by 2.8 points more on glutathione, p = 0.32. It then worsened by 3.5 points more over the next eight weeks, p = 0.54 [11].
Phase 2b trial, negative Nose drops did no better. Forty-five patients were treated for three months. The higher-dose group improved by 4.6 points on the combined score, p = 0.0025, and by 2.2 points on the movement part, p = 0.0485.
Neither dose beat dummy drops, because the dummy group improved as well. One person on the higher dose developed a heart muscle disorder [12]. An earlier safety study in 30 patients found no meaningful difference in side effects [36].
Cystic fibrosis
Phase 2 trial, primary endpoint missed The largest lung trial enrolled 153 people aged 8 and over and ran for six months. Lung function did not differ from dummy treatment, either as a before-and-after change, p = 0.180, or as an area under the curve, p = 0.205. Exacerbations and quality of life were unchanged. Sputum measurements confirmed the substance had reached the lungs and had done nothing measurable there [13].
Randomised trial, primary endpoint missed A twelve-month study in 105 adults and children set a 15 per cent improvement in lung function as its target and did not reach it [37].
Cochrane review The review pooled 924 people from 20 studies, only one of which was judged free of bias. Inhalation probably improves lung function at three months, by 3.50 percentage points, 95 per cent confidence interval 1.38 to 5.62.
At six months the difference had gone, 2.30, interval -0.12 to 4.71. Quality of life barely changed, 0.80, interval -1.63 to 3.23 [38].
A follow-up analysis of the sputum samples offers an explanation and a warning. Where the breakdown enzyme is more active in inflamed airways, inhaled glutathione is destroyed quickly, and the reactions that follow may make the damage worse [39].
Nerve damage during chemotherapy
Randomised controlled trial, positive This is the one result that carries a licence. Among 52 people with advanced bowel cancer receiving oxaliplatin, infusions given before each round reduced nerve damage. After eight rounds, moderate to severe damage affected 2 people against 11, p = 0.003; after twelve rounds, 3 against 8, p = 0.004. Nerve conduction in the calf fell only in the dummy group. Tumour response was unaffected, 26.9 against 23.1 per cent, so the chemotherapy still worked [14].
Randomised, double-blind trial in 52 people with advanced bowel cancer. The difference was unlikely to be chance, p = 0.003. Source [14].
Blood vessel function
Acute physiological studies Two small studies measured vessel behaviour during an infusion rather than any clinical outcome. In 26 people the coronary arteries responded better to acetylcholine [40]. In 17 people with atherosclerosis or its risk factors, leg vessel widening improved, p = 0.003. The signalling molecule cyclic GMP rose from 17.6 to 23.3 picomoles per millilitre, p = 0.006. The effect appeared only where vessel function was already impaired [41].
What is still unknown
- No hard clinical outcome anywhere. Every positive supplement result is a laboratory value or a skin meter reading. No trial has shown an effect on illness, function or survival [25], [29].
- No reliable dose-response relationship. The liposomal study found no difference between its two amounts; the six-month trial did find one. No curve exists for any outcome [31], [29].
- No long-term safety data. The longest study found ran twelve months, and the skin studies ran four to twelve weeks [37], [15].
- No sound trial of the cosmetic drip. The Philippine regulator recorded in 2019 that no clinical trial of injections for skin lightening had been published. Nor was there any published guideline on giving them [42].
- Precursors may work better than the molecule itself. A 2026 review concludes that supplements supplying the building blocks raise human levels more strongly and more consistently than glutathione does [43].
- The trial count is misleading. A register query returned 269 studies. Most of them use glutathione as a marker of oxidative stress or study its enzymes, rather than giving it [44].
Side effects and safety
Safety depends almost entirely on the route. By mouth and on the skin the record is reassuring but short. By injection the record contains fever, shock and hospital admissions, and the cause is usually the product rather than the molecule [7], [15].
- By mouth and on the skin: no serious events reported. Across the pigment and supplement trials, laboratory values stayed normal and nothing serious was recorded. The longest of those studies ran six months [32], [33], [23], [29], [31].
- Inhalation can tighten the airways. In eight people with mild asthma, nebulised glutathione cut lung function by 19 per cent and raised airway resistance by 61 per cent. Salt water gave -1 and +17 per cent, p = 0.03 and p = 0.02. Four coughed and three became breathless, and salbutamol beforehand blocked the reaction [45].
- A brief dip in lung function after inhaling. This was recorded in cystic fibrosis, with the value rising above the pre-treatment level after 14 days [46].
- Contaminated injections cause endotoxin reactions. The American regulator described fever, chills, pain, dizziness, signs of shock and sepsis-like symptoms, some needing admission. All the traced batches were labelled as supplement grade [7], [6].
- A published case of collapse after a cosmetic drip. A previously healthy woman in the United Kingdom developed shock and a temperature above 41 degrees within an hour. Her white cells reached 26 x 10^9 per litre and C-reactive protein 160 mg/l, with procalcitonin 28.8 micrograms/l, ALT 311 IU/l and prothrombin time 26.4 seconds. No infection was found [47].
- Severe skin reactions reported to a regulator. The Philippine authority has recorded reactions from rashes to Stevens-Johnson syndrome and toxic epidermal necrolysis, plus severe abdominal pain. These are spontaneous reports, not proven causes [48], [42].
- Infection risk from the setting, not the substance. The same authority names transmission of HIV and of hepatitis B and C. The risk arises where injections are given by untrained people or in non-sterile rooms [42].
- Side effects from the Japanese label. Stomach pain was recorded in 0.05 per cent. Nausea, vomiting, loss of appetite, chills, rash, injection-site pain and one case of seizure-like cramps each fall at 0.02 to 0.03 per cent [49].
- A theoretical concern about sun protection. If lightening works by shifting pigment towards the lighter form, it also removes some natural protection from ultraviolet light. That is a mechanism-based worry, not an observed finding [50].
- Too much reduction may itself be a problem. The 2026 review names reductive stress as an under-examined risk of supplementation [25].
Why this page lists no doses
Glutathione is a licensed medicine in Japan and Italy, and both licences come with official product information and an approved schedule. Where a medicine is approved, the dose belongs to that label and to the doctor or pharmacist handling it, not to a reference page.
Supplement amounts are a different matter again. They vary from product to product, they are set by manufacturers rather than by any authority, and the amounts used in the trials described above were chosen for those trials. None of them is a recommendation.
For injections there is nothing to describe in any case. No authority anywhere has approved an injection for cosmetic use, and the published record contains no agreed schedule, only warnings [42], [7]. This page therefore gives no amounts, strengths, schedules or instructions, in any direction.
Development and approval status
From a Japanese antidote to an American recall
- 1967Japanese approvalTablets licensed in August and September, on the market from January 1968, refs [1], [19]
- 1984Japanese re-evaluation passedThe regulator confirmed efficacy on 27 September, ref [19]
- 1992Oral availability questionedA single dose leaves blood levels unchanged in 7 volunteers, ref [18]
- 2002The trial behind the Italian licenceNerve damage on oxaliplatin, 52 people, p = 0.003, ref [14]
- 2009Parkinson injections failNo difference from dummy treatment in 21 patients, ref [11]
- 2013Cystic fibrosis trial misses its target153 people, lung function unchanged, ref [13]
- 2017Parkinson nose drops fail45 patients, no advantage over dummy drops, ref [12]
- 2019Two regulators warnAmerican endotoxin cases in June, Philippine advisory on skin lightening in July, refs [6], [42]
- 2026At least 30 harmed, two recallsAmerican reminder in August and two Texas recalls, refs [7], [8], [9]
| Market | Oral supplement | Approved medicine | Cosmetic injection |
|---|---|---|---|
| Japan | Sold | Yes, since 1967 | Not approved |
| Italy | Sold | Yes, one indication | Not approved |
| Philippines | Sold | Yes, cancer care only | Not approved |
| United States | Sold | No | Not approved |
| European Union | Sold | No | Not approved |
| Germany | Sold | No | Not approved |
| United Kingdom | Sold | No | Not approved |
| Australia | Not checked | Not checked | Not approved |
| Canada | Not checked | Not checked | Not approved |
| Switzerland | Not checked | Not checked | Not approved |
The status was checked on 7 September 2026, and three entries deserve a footnote rather than a tick. The Australian, Canadian and Swiss rows were not verified against those regulators' own databases. They are marked as unchecked rather than guessed.
The British row rests on a 2025 case report, which states that cosmetic infusions are used there without approval. It is not a document from the regulator [47].
In the European Union, glutathione is not on the union list of approved novel foods. A full-text search of the consolidated regulation returned no match, while a control search worked [24].
Oral products are nevertheless sold, on the argument that they were eaten in Europe before May 1997. Food eaten before that date falls outside the novel food rules. That argument could not be checked against the Commission's own catalogue, so it is reported here as a claim.
Germany does not license supplements at all. They are notified to the federal office before first sale, and no authority assesses them [51]. One glutathione supplement does have a published German clearance, granted in June 2017 under the mutual recognition route [52].
The same office warns that a product sold as a supplement elsewhere can fall under medicines law in Germany. Import may then be barred [51].
The American position is the most easily misread. Glutathione sits in category 1 of the compounding list, which means it was nominated with enough supporting material and is still being evaluated [3], [4]. That is a temporary decision not to take enforcement action, not an approval.
Its absence from the list of substances that may present significant safety risks is a real finding. It separates glutathione from the research peptides in this register [5].
For the general legal picture see are peptides legal and FDA-approved peptides.
Anti-doping
Glutathione is not named on the 2026 prohibited list, and the catch-all clause does not reach it either. That clause covers substances with no current approval by any government health authority for human therapeutic use. Japan and Italy have approved it, so the condition is not met [53].
This is a genuine difference from the research peptides in this register, which the same clause captures precisely because nobody has approved them. Nothing in the sections on peptide hormones or metabolic modulators touches glutathione either [53].
Two cautions remain. Supplements can be contaminated with banned substances, and under strict liability the athlete carries the responsibility regardless. Section M2.2 of the same list also prohibits intravenous infusions or injections totalling more than 100 ml per 12 hours outside hospital treatment, surgery or clinical diagnostics, whatever is being infused [53]. More context is at peptides banned in sport.
Compared with related peptides
| Substance | What it is | Status | Strongest human evidence found here |
|---|---|---|---|
| Glutathione | Tripeptide made by every cell | Medicine in Japan and Italy; supplement elsewhere | Fewer moderate to severe nerve injuries on oxaliplatin, 52 people, p = 0.003 [14] |
| N-acetylcysteine | Supplies cysteine, the limiting building block | Established medicine for paracetamol poisoning and as a mucolytic | Raised plasma glutathione over seven days in 12 people with HIV [54] |
| Glycine | The third building block | Food and supplement | No trial assessed on this page |
| NAD+ | A coenzyme the body makes, sold as supplement and infusion | No medicine approval for the uses marketed | No study comparing it with glutathione among the sources used here |
The useful comparison is with N-acetylcysteine, because the two are constantly treated as interchangeable. They are not. Glutathione is the finished molecule; N-acetylcysteine delivers the part that runs short, and it is an approved medicine with a defined emergency use [54], [17].
That difference points somewhere awkward for the supplement market. The 2026 review found that precursor-based approaches raise human glutathione more strongly and more consistently than swallowing the tripeptide does [43].
Glycine is the least studied of the three here and is included only because it is the remaining building block. NAD+ shares the marketing story rather than the chemistry, and no study found for this page compares the two.
Common misconceptions
- "Swallowing it and injecting it are the same thing at different strengths." They behave nothing alike. A single oral dose leaves blood levels unchanged, an infusion raises the plasma level from 17.5 to 823 micromoles per litre, which then clears within minutes [18], [10].
- "Glutathione is a proven skin lightener." Small trials do show lower pigment readings by mouth and on the skin. What is missing is durability, a clinical benefit and long-term safety. The 2025 review calls the effect unsustainable and rules out the intravenous route [15], [32].
- "The Japanese licence proves whitening drips are safe." The Japanese label covers defined skin diseases such as melasma, not the lightening of healthy skin. The licensed amount is also many times smaller than cosmetic drips use. Its efficacy figures, such as 59.6 per cent for pigment disorders, come from uncontrolled observation in the 1960s and 1970s [49].
- "The FDA warnings show the substance is dangerous." Both warnings and both recalls concern contamination, not the molecule. Supplement-grade powder carrying bacterial toxin was used to make sterile injections, and the symptoms match toxin exposure [6], [7], [8].
- "Glutathione detoxifies the body." The chemistry is real: it binds reactive compounds so the kidney can remove them, which is why two countries license it as an antidote. The leap from that to detoxifying a healthy person has no controlled trial behind it [17], [1].
- "The body makes it, so more of it must be harmless." Route and product decide. The documented harm came from injections, and a 2026 review names excessive reduction as a risk that has barely been studied [7], [25].
- "Reduced, oxidised and acetylated forms are the same substance." They are three different chemicals, and the topical trial with the clearest result used the oxidised form. Anyone comparing studies has to check which form was given [23], [33], [20].
- "Falling levels with age prove that supplements help." The decline is an observation. The 2026 review concludes that the evidence supports the mechanism and the pharmacokinetics rather than established therapeutic effect [55], [25].
Frequently asked questions
Is glutathione an approved medicine?
In two countries, yes. Japan has licensed tablets, powder and an injection since 1967, for poisoning, liver and skin conditions and pregnancy complications. Italy licenses an injection for a single purpose, preventing nerve damage caused by cisplatin chemotherapy. In the United States, the European Union, Germany and the United Kingdom there is no medicine approval at all, and oral products are sold as food supplements.
Why does this page list no glutathione doses?
Because glutathione is an approved medicine in Japan and Italy, and where a medicine is approved the dose belongs to its official product information and to a doctor or pharmacist. Supplement amounts differ from product to product and are set by manufacturers, not by any authority. The amounts used in trials were chosen for those trials and are not recommendations. Injections for cosmetic use are approved nowhere, so there is no schedule to describe.
Does swallowed glutathione reach the body?
Partly, and only with daily use. A single dose left blood levels unchanged in seven volunteers, because enzymes in the gut and liver break the molecule apart. Six months of daily use in 54 people did raise stores, by 30 to 35 per cent in red cells, plasma and lymphocytes. Everything returned to baseline a month after stopping. Those are laboratory values, not health outcomes.
Does glutathione lighten skin?
Pigment meters read lower, modestly and not lastingly. Several small randomised trials measured that after four to twelve weeks, taken by mouth or applied as a cream. The 2025 systematic review calls the effect moderate and unsustainable. For injections it found one dummy-controlled study whose result missed significance, and it states that the intravenous route is contraindicated.
Are glutathione drips safe?
The published record says no, and the problem is mostly the product. American regulators recorded at least 30 people harmed in 2026 and eight in 2019. All the batches traced back to material sold as supplement grade, and testing found bacterial toxin at up to five times the permitted limit. Two Texas pharmacies recalled their product in August 2026. A British case report describes shock and a temperature above 41 degrees within an hour of a cosmetic infusion.
What did the glutathione trials in Parkinson's disease and cystic fibrosis show?
All three large controlled trials missed their main target. Injections in 21 people with Parkinson's disease produced no difference from dummy treatment. Nose drops in 45 patients raised brain levels but did not beat dummy drops, because that group improved too. Inhalation in 153 people with cystic fibrosis reached the lungs, confirmed in sputum, and changed neither lung function nor exacerbations nor quality of life.
Is glutathione the same as N-acetylcysteine?
No, though they are related. Glutathione is the finished three-part molecule. N-acetylcysteine supplies cysteine, the building block that usually runs short, and it is an approved medicine for paracetamol poisoning and for loosening mucus. A 2026 review concludes that supplying the building blocks raises human glutathione more consistently than swallowing glutathione itself.
Does glutathione detoxify the body?
It has a real detoxifying role inside cells, binding reactive chemicals and drugs into forms the kidney can excrete. That is why Japan and Italy classify it as an antidote and why it decides how much paracetamol the liver can tolerate. The step from that biochemistry to the claim that supplements detoxify a healthy person has no controlled trial behind it.
Is glutathione banned in sport?
It is not named on the 2026 prohibited list, and the catch-all clause for unapproved substances does not apply, because Japan and Italy have approved it as a medicine. That is a real difference from most peptides in this register. Two cautions remain: supplements can be contaminated with banned substances, and the list restricts intravenous infusions in their own right, whatever they contain.
Sources
- Pharmaceuticals and Medical Devices Agency, Japan. Product information for Tathion tablets 50 mg and 100 mg and Tathion powder 20 per cent, active substance glutathione, Japanese Pharmacopoeia. Approval number of the 50 mg tablet 14200AZZ05810000, marketed from January 1968; current manufacturer Choseido Pharmaceutical. Approved indications: drug poisoning, acetonaemic vomiting, metal poisoning, hyperemesis gravidarum and hypertensive disorders of pregnancy. ATC group V03AB32. Retrieved 7 September 2026. https://www.pmda.go.jp/PmdaSearch/bookSearch/01/04987792020781
- Teofarma S.r.l. Riassunto delle Caratteristiche del Prodotto, Tationil 600 mg/4 ml, powder and solvent for solution for injection, marketing authorisation number AIC 026185049, holder Teofarma S.r.l., Valle Salimbene. Section 4.1 gives the single approved indication, prophylaxis of neuropathy following chemotherapy with cisplatin or its analogues. Contraindication: hypersensitivity to the active substance. ATC V03AB32, therapeutic category antidote; authorisation renewed June 2010. Retrieved 7 September 2026. https://www.teofarmasrl.it/wp-content/uploads/2021/01/Tationil_RCP.pdf
- US Food and Drug Administration. Bulk drug substances nominated for use in compounding under section 503A of the FD&C Act, document updated 14 May 2026. Glutathione appears once in the whole document, in 503A category 1, substances under evaluation. Downloaded and searched in full on 7 September 2026. https://www.fda.gov/media/94155/download
- US Food and Drug Administration. Interim policy on compounding using bulk drug substances under section 503A of the FD&C Act, guidance for industry. Defines category 1 as substances nominated with sufficient supporting information, still under evaluation and on no other list, and sets the four conditions of the enforcement policy. Also states that a substance is listed only if it is neither the subject of a USP or NF monograph nor a component of an FDA-approved drug. Retrieved 7 September 2026. https://www.fda.gov/media/174456/download
- US Food and Drug Administration. Certain bulk drug substances for use in compounding that may present significant safety risks. Page content current as of 22 April 2026, full text searched for glutathione on 7 September 2026; no match. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks
- US Food and Drug Administration. FDA highlights concerns with using dietary ingredient glutathione to compound sterile injectables, published 7 June 2019, with a warning to compounders on 1 February 2019. Seven people treated on 9 January 2019 developed nausea, vomiting, dizziness, chills, limb pain and sneezing within minutes, one with a fall in blood pressure and breathlessness requiring admission; a second report concerned an admission for suspected bloodstream infection after treatment on 17 October 2018. Agency laboratory testing found excessive bacterial endotoxin, some results as high as five times the appropriate limit; the powder was labelled Caution: Dietary Supplement. Retrieved 7 September 2026. https://www.fda.gov/drugs/human-drug-compounding/fda-highlights-concerns-using-dietary-ingredient-glutathione-compound-sterile-injectables
- US Food and Drug Administration. FDA reminds compounders not to use dietary supplement grade glutathione for injectables, 27 August 2026. Reports of at least 30 patients with adverse events after intravenous glutathione alone or in combination; a single batch from one source, labelled as dietary supplement grade, common to the pharmacies involved. Reported events: fever, chills, pain, dizziness, signs of shock and sepsis-like symptoms, some resulting in hospitalisation. Retrieved 7 September 2026. https://www.fda.gov/drugs/human-drug-compounding/fda-reminds-compounders-not-use-dietary-supplement-grade-glutathione-injectables
- US Food and Drug Administration, recalls, market withdrawals and safety alerts. Victory Medical Center Pharmacy, Austin, Texas, voluntary nationwide recall to the patient level of certain lots of compounded glutathione multiple-dose vials for elevated bacterial endotoxin, 5 August 2026. The notice states that injectable products with elevated endotoxin levels could cause fevers, hypotension, inflammatory reactions, anaphylactic shock and death. Retrieved 7 September 2026. https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts
- US Food and Drug Administration, recalls, market withdrawals and safety alerts. Optimal Balance Pharmacy, Houston, Texas, voluntary nationwide recall to the patient level of one lot of compounded glutathione for elevated bacterial endotoxin, 19 August 2026. Retrieved 7 September 2026. https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts
- Aebi S, Assereto R, Lauterburg BH (1991). High-dose intravenous glutathione in man: pharmacokinetics and effects on cyst(e)ine in plasma and urine. European Journal of Clinical Investigation 21(1):103-110. PMID 1907548. DOI 10.1111/j.1365-2362.1991.tb01366.x. Ten healthy volunteers; total plasma glutathione rose from 17.5 (SD 13.4) to 823 (SD 326) micromoles per litre, volume of distribution 176 (SD 107) ml/kg, elimination rate constant 0.063 (SD 0.027) per minute, half-life 14.1 (SD 9.2) minutes.
- Hauser RA, Lyons KE, McClain T, Carter S, Perlmutter D (2009). Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson's disease. Movement Disorders 24(7):979-983. PMID 19230029. DOI 10.1002/mds.22401. Registered as NCT01177319. Twenty-one patients, four weeks of infusions three times weekly against salt water, with eight weeks of follow-up.
- Mischley LK, Lau RC, Shankland EG, Wilbur TK, Padowski JM (2017). Phase IIb study of intranasal glutathione in Parkinson's disease. Journal of Parkinson's Disease 7(2):289-299. PMID 28436395. DOI 10.3233/JPD-161040. Forty-five patients at Hoehn and Yahr stages 1 to 3, three months of treatment in three arms with one month of washout; one participant in the higher-dose group developed a cardiomyopathy.
- Griese M, Kappler M, Eismann C, et al., Glutathione Study Group (2013). Inhalation treatment with glutathione in patients with cystic fibrosis: a randomized clinical trial. American Journal of Respiratory and Critical Care Medicine 188(1):83-89. PMID 23631796. DOI 10.1164/rccm.201303-0427OC. Registered as NCT00506688 and EudraCT 2005-003870-88. 153 people aged 8 and over, six months; FEV1 unchanged as a before-and-after difference, p = 0.180, and as area under the curve, p = 0.205, despite confirmed deposition in sputum.
- Cascinu S, Catalano V, Cordella L, Labianca R, Giordani P, Baldelli AM, Beretta GD, Ubiali E, Catalano G (2002). Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial. Journal of Clinical Oncology 20(16):3478-3483. PMID 12177109. DOI 10.1200/JCO.2002.07.061. Fifty-two people; after eight rounds of treatment 9 of 21 assessable participants on glutathione had any neurotoxicity against 15 of 19 on dummy infusions, and grade 2 to 4 neuropathy affected 2 against 11, p = 0.003.
- Sarkar R, Yadav V, Yadav T, P J, Mandal I (2025). Glutathione as a skin-lightening agent and in melasma: a systematic review. International Journal of Dermatology 64(6):992-1004. PMID 39444151. DOI 10.1111/ijd.17535. Assesses evidence level, strength of recommendation and risk of bias across routes; the single placebo-controlled intravenous study gave 6 of 16 against 3, that is 37.5 against 18.7 per cent, p = 0.054. States that intravenous glutathione is contraindicated due to lack of efficacy and side effects, and describes the topical and oral effects as unsustainable.
- Lu SC (2013). Glutathione synthesis. Biochimica et Biophysica Acta 1830(5):3143-3153. PMID 22995213. DOI 10.1016/j.bbagen.2012.09.008. Reference for the two-step cytosolic synthesis, the rate-limiting glutamate-cysteine ligase and its transcriptional control.
- Wu G, Fang YZ, Yang S, Lupton JR, Turner ND (2004). Glutathione metabolism and its implications for health. Journal of Nutrition 134(3):489-492. PMID 14988435. DOI 10.1093/jn/134.3.489. Reference for regulation by enzyme activity, cysteine availability and feedback inhibition, and for cystine, methionine and N-acetylcysteine as cysteine sources.
- Witschi A, Reddy S, Stofer B, Lauterburg BH (1992). The systemic availability of oral glutathione. European Journal of Clinical Pharmacology 43(6):667-669. PMID 1362956. DOI 10.1007/BF02284971. Seven healthy volunteers, single dose, observed over 270 minutes; plasma glutathione, cysteine and glutamate unchanged from baseline values of 6.2, 8.3 and 54 micromoles per litre.
- Interview form for Tathion, Japanese product documentation. Records the first industrially produced reduced glutathione preparation, developed at Yamanouchi Seiyaku, now Astellas; tablet approvals in August and September 1967, market entry January 1968; powder approved 1971 and renamed in 2007; a positive regulatory re-evaluation announced on 27 September 1984; transfer to Choseido Pharmaceutical in April 2012. Retrieved 7 September 2026. https://medical.nihon-generic.co.jp/uploadfiles/medicine/TATHI00_IF.pdf
- PubChem, compound CID 124886 (glutathione). Queried through the PUG-REST interface on 7 September 2026. Formula C10H17N3O6S, molecular weight 307.33 g/mol, InChIKey RWSXRVCMGQZWBV-WDSKDSINSA-N. The synonym list yielded CAS 70-18-8, UNII GAN16C9B8O and CHEBI:16856. https://pubchem.ncbi.nlm.nih.gov/compound/124886
- Forman HJ, Zhang H, Rinna A (2009). Glutathione: overview of its protective roles, measurement, and biosynthesis. Molecular Aspects of Medicine 30(1-2):1-12. PMID 18796312.
- Mischley LK, Conley KE, Shankland EG, Kavanagh TJ, Rosenfeld ME, Duda JE, White CC, Wilbur TK, De La Torre PU, Padowski JM (2016). Central nervous system uptake of intranasal glutathione in Parkinson's disease. npj Parkinson's Disease 2:16002. PMID 28725693. DOI 10.1038/npjparkd.2016.2. Registered as NCT02324426. Fifteen patients, magnetic resonance spectroscopy over about an hour; brain glutathione rose significantly from baseline, p below 0.001.
- Watanabe F, Hashizume E, Chan GP, Kamimura A (2014). Skin-whitening and skin-condition-improving effects of topical oxidized glutathione: a double-blind and placebo-controlled clinical trial in healthy women. Clinical, Cosmetic and Investigational Dermatology 7:267-274. PMID 25378941. DOI 10.2147/CCID.S68424. Thirty women aged 30 to 50, ten weeks, split-face design.
- EUR-Lex. Commission Implementing Regulation (EU) 2017/2470 establishing the Union list of authorised novel foods, consolidated text of 20 February 2025. Full text downloaded and searched on 7 September 2026: no match for glutathione, against 23 matches for the control term astaxanthin. https://eur-lex.europa.eu/eli/reg_impl/2017/2470/2025-02-20/eng
- Carnib BL, Matos ERSB, Lage TM, et al. (2026). Glutathione in redox homeostasis: bridging molecular mechanisms, bioavailability constraints, and translational challenges in systemic therapeutics. Biomedicine and Pharmacotherapy 203:119817. PMID 42585816. DOI 10.1016/j.biopha.2026.119817. PRISMA review of publications from 2004 to 2025, concluding that current findings primarily support the mechanistic and pharmacokinetic relevance of glutathione rather than its established therapeutic efficacy, and naming the potential risk of reductive stress.
- Sonthalia S, Daulatabad D, Sarkar R (2016). Glutathione as a skin whitening agent: facts, myths, evidence and controversies. Indian Journal of Dermatology, Venereology and Leprology. PMID 27088927. Describes direct and indirect inhibition of tyrosinase and a shift from eumelanin to phaeomelanin production as the proposed mechanism.
- Sonthalia S, Jha AK, Lallas A, Jain G, Jakhar D (2018). Glutathione for skin lightening: a regnant myth or evidence-based verity? Dermatology Practical and Conceptual 8(1):15-21. PMID 29445569. DOI 10.5826/dpc.0801a04. States that the clinical evidence for intravenous glutathione is limited to a single study with a dubious design and apparently flawed analysis.
- Ristoff E, Larsson A (2007). Inborn errors in the metabolism of glutathione. Orphanet Journal of Rare Diseases 2:16. PMID 17397529. DOI 10.1186/1750-1172-2-16. Glutathione synthetase deficiency in severe form is associated with haemolytic anaemia, metabolic acidosis, 5-oxoprolinuria, central nervous system damage and recurrent bacterial infections.
- Richie JP Jr, Nichenametla S, Neidig W, Calcagnotto A, Haley JS, Schell TD, Muscat JE (2015). Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. European Journal of Nutrition 54(2):251-263. PMID 24791752. DOI 10.1007/s00394-014-0706-z. 54 healthy non-smokers, six months, two daily amounts against dummy capsules, with a one-month washout.
- Schmitt B, Vicenzi M, Garrel C, Denis FM (2015). Effects of N-acetylcysteine, oral glutathione and a novel sublingual form of glutathione on oxidative stress markers: a comparative crossover study. Redox Biology 6:198-205. PMID 26262996. DOI 10.1016/j.redox.2015.07.012. Twenty people with metabolic syndrome, three 21-day periods. Two of the four authors were employed by the laboratory producing the sublingual preparation tested.
- Sinha R, Sinha I, Calcagnotto A, Trushin N, Haley JS, Schell TD, Richie JP Jr (2018). Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. European Journal of Clinical Nutrition 72(1):105-111. PMID 28853742. DOI 10.1038/ejcn.2017.132. Twelve healthy adults, one month, no control group; funded by the company selling the preparation tested.
- Arjinpathana N, Asawanonda P (2012). Glutathione as an oral whitening agent: a randomized, double-blind, placebo-controlled study. Journal of Dermatological Treatment 23(2):97-102. PMID 20524875. DOI 10.3109/09546631003801619. Sixty healthy medical students in Bangkok, four weeks, melanin index measured at six sites.
- Weschawalit S, Thongthip S, Phutrakool P, Asawanonda P (2017). Glutathione and its antiaging and antimelanogenic effects. Clinical, Cosmetic and Investigational Dermatology 10:147-153. PMID 28490897. DOI 10.2147/CCID.S128339. Sixty healthy women, twelve weeks, three arms testing the reduced form, the oxidised form and dummy capsules.
- Wahab S, Anwar AI, Zainuddin AN, Hutabarat EN, Anwar AA, Kurniadi I (2021). Combination of topical and oral glutathione as a skin-whitening agent: a double-blind randomized controlled clinical trial. International Journal of Dermatology 60(8):1013-1018. PMID 33871071. DOI 10.1111/ijd.15573. Forty-six participants, eight weeks, measured with mexameter and chromameter.
- Sechi G, Deledda MG, Bua G, Satta WM, Deiana GA, Pes GM, Rosati G (1996). Reduced intravenous glutathione in the treatment of early Parkinson's disease. Progress in Neuro-Psychopharmacology and Biological Psychiatry 20(7):1159-1170. PMID 8938817. DOI 10.1016/s0278-5846(96)00103-0. Nine untreated patients, open, uncontrolled, 30 days of infusions.
- Mischley LK, Leverenz JB, Lau RC, Polissar NL, Neradilek MB, Samii A, Standish LJ (2015). A randomized, double-blind phase I/IIa study of intranasal glutathione in Parkinson's disease. Movement Disorders 30(12):1696-1701. PMID 26230671. DOI 10.1002/mds.26351. Thirty patients, three arms, three months; no meaningful difference between groups in reported or observed adverse events.
- Calabrese C, Tosco A, Abete P, et al. (2015). Randomized, single blind, controlled trial of inhaled glutathione vs placebo in patients with cystic fibrosis. Journal of Cystic Fibrosis 14(2):203-210. PMID 25458463. DOI 10.1016/j.jcf.2014.09.014. Registered as NCT01450267. 54 adults and 51 children, twelve months; the predefined target of a 15 per cent improvement in FEV1 was not met.
- Ciofu O, Smith S, Lykkesfeldt J (2019). Antioxidant supplementation for lung disease in cystic fibrosis. Cochrane Database of Systematic Reviews 10:CD007020. PMID 31580490. DOI 10.1002/14651858.CD007020.pub4. Twenty studies, 924 children and adults, only one judged free of bias; the inhaled comparison rests on two studies with 258 people.
- Corti A, Griese M, Hector A, Pompella A (2017). Increasing sputum levels of gamma-glutamyltransferase may identify cystic fibrosis patients who do not benefit from inhaled glutathione. Journal of Cystic Fibrosis 16(3):342-345. PMID 27988297. DOI 10.1016/j.jcf.2016.12.002. Re-analysis of the sputum samples from the 2013 trial; the authors warn that where enzyme activity rises the treatment may even aggravate the damage.
- Kugiyama K, Ohgushi M, Motoyama T, et al. (1998). Intracoronary infusion of reduced glutathione improves endothelial vasomotor response to acetylcholine in human coronary circulation. Circulation 97(23):2299-2301. PMID 9639372. DOI 10.1161/01.cir.97.23.2299. Twenty-six people without significant coronary narrowing; the benefit appeared in the subgroup with at least one cardiovascular risk factor.
- Prasad A, Andrews NP, Padder FA, Husain M, Quyyumi AA (1999). Glutathione reverses endothelial dysfunction and improves nitric oxide bioavailability. Journal of the American College of Cardiology 34(2):507-514. PMID 10440166. DOI 10.1016/s0735-1097(99)00216-8. Seventeen people with atherosclerosis or its risk factors; resistance index fell by 47 and 56 per cent before against 61 and 67 per cent after, p = 0.003, with cyclic GMP rising from 17.6 to 23.3 picomoles per millilitre, p = 0.006.
- Food and Drug Administration Philippines. Advisory No. 2019-182, unsafe use of glutathione as skin lightening agent, 5 July 2019. States that no clinical trials evaluating injectable glutathione for skin lightening have been published, that no guidelines on regimens or duration exist, and that no injectable product is approved for skin lightening; injectable glutathione is approved there only as an adjunct in cisplatin chemotherapy. Names toxic effects on liver, kidney and nervous system, Stevens-Johnson syndrome, kidney stones and dialysis risk when combined with intravenous vitamin C, and transmission of HIV and hepatitis B and C. Retrieved 7 September 2026. https://www.fda.gov.ph/fda-advisory-no-2019-182-unsafe-use-of-glutathione-as-skin-lightening-agent/
- Bradauskiene V, Moscenkova E, Sniepiene G, Kubiliute R, Vaiciulyte L (2026). Glutathione in our diet and its role in the body: from disease prevention to anti-aging. Nutrients 18(10):1640. PMID 42197099. DOI 10.3390/nu18101640. States that precursor-based supplements and compounds activating synthesis pathways show stronger and more consistent increases in human glutathione.
- ClinicalTrials.gov, collective query under the term glutathione, 7 September 2026: 269 studies, of which 100 were examined in detail. Many entries use glutathione as a marker of oxidative stress, study glutathione-dependent enzymes or administer the precursor N-acetylcysteine, so the total must not be read as a count of interventional studies of the substance. https://clinicaltrials.gov/
- Marrades RM, Roca J, Barbera JA, de Jover L, MacNee W, Rodriguez-Roisin R (1997). Nebulized glutathione induces bronchoconstriction in patients with mild asthma. American Journal of Respiratory and Critical Care Medicine 156(2 Pt 1):425-430. PMID 9279219. DOI 10.1164/ajrccm.156.2.9611001. Eight people with mild asthma, randomised double-blind crossover against identical salt water; the solution's osmolarity of 660 mosm/kg and pH of 3.0 did not explain the effect, and the fall in FEV1 correlated inversely with the metabisulphite threshold, pointing to sulphite formation.
- Griese M, Ramakers J, Krasselt A, et al. (2004). Improvement of alveolar glutathione and lung function but not oxidative state in cystic fibrosis. American Journal of Respiratory and Critical Care Medicine 169(7):822-828. PMID 14726422. DOI 10.1164/rccm.200308-1104OC. Intrathoracic deposition of 86.3 per cent of the delivered amount; FEV1 fell briefly straight after inhaling and rose above the pre-treatment value after 14 days, p below 0.001.
- Sharma D, Daram S, Sharma P (2025). Systemic inflammatory response syndrome following high-dose intravenous glutathione-containing revitalising solution in a patient on tirzepatide: a case report. Cureus 17(5):e84736. PMID 40556995. DOI 10.7759/cureus.84736. Previously healthy woman in the United Kingdom; the paper also states that intravenous glutathione products are increasingly used for cosmetic purposes there without regulatory approval or robust safety data.
- Food and Drug Administration Philippines. Advisory No. 2011-004, safety on the off-label use of glutathione solution for injection. States that use as a skin whitener is not approved and warns the public against it, notes inadequate safety documentation for the high amounts used cosmetically, and lists reported reactions ranging from skin rashes to Stevens-Johnson syndrome and toxic epidermal necrolysis, plus severe abdominal pain. Retrieved 7 September 2026. https://www.fda.gov.ph/wp-content/uploads/2022/06/FDA-Advisory-No.-2011-004.pdf
- Pharmaceuticals and Medical Devices Agency, Japan. Product information for Tathion injection 100 mg and 200 mg, data record 3922400D1060, last revised 9 September 2024; prescription-only. Approved indications include drug poisoning, improvement of liver function in chronic liver disease, eczema and dermatitis, Riehl melanosis, melasma and post-inflammatory hyperpigmentation, pregnancy complications, corneal healing and radiotherapy effects. Historical uncontrolled response rates including 59.6 per cent (87 of 146) for pigment disorders, and the adverse event frequencies, were taken from this record and the accompanying interview form. Retrieved 7 September 2026. https://www.pmda.go.jp/PmdaSearch/rdSearch/02/3922400D1060
- Davids LM, van Wyk JC, Khumalo NP (2016). Intravenous glutathione for skin lightening: inadequate safety data. South African Medical Journal 106(8):782-786. PMID 27499402. DOI 10.7196/SAMJ.2016.v106i8.10878. Literature search to 30 September 2015 found no study of intravenous use for skin lightening and none of chronic intravenous use for any indication, and warns that a switch from brown to red melanin may raise the risk of sun-induced skin cancers in previously protected people.
- Bundesamt fuer Verbraucherschutz und Lebensmittelsicherheit, Germany. Information pages on food supplements and novel foods. States that no authorisation is granted for food supplements, that notification under section 5 of the supplements regulation is required before first marketing, and that the office itself makes no legal or health assessment; also that products traded as supplements elsewhere may fall under medicines law in Germany, in which case import may be prohibited. Retrieved 7 September 2026. https://www.bvl.bund.de/
- Bundesamt fuer Verbraucherschutz und Lebensmittelsicherheit, Germany. Announcement of a general ruling under section 54 of the food and feed code for a food supplement containing added reduced L-glutathione, reference BVL 17/01/004, 8 June 2017, now held in the archive of such rulings. Only the existence and date were verified; the content of the document itself was not. Retrieved 7 September 2026. https://www.bvl.bund.de/
- World Anti-Doping Agency, The 2026 Prohibited List. Full text searched for glutathione on 7 September 2026; no match in any section. Section S0 covers any pharmacological substance not addressed elsewhere on the list and with no current approval by any governmental regulatory health authority for human therapeutic use. Section M2.2 prohibits intravenous infusions and/or injections of more than a total of 100 mL per 12-hour period, except those legitimately received in the course of hospital treatments, surgical procedures or clinical diagnostic investigations; both passages were read in the 2026 document on 7 September 2026. https://www.wada-ama.org/en/prohibited-list
- Borges-Santos MD, Moreto F, Pereira PC, Ming-Yu Y, Burini RC (2012). Plasma glutathione of HIV+ patients responded positively and differently to dietary supplementation with cysteine or glutamine. Nutrition 28(7-8):753-756. PMID 22261571. DOI 10.1016/j.nut.2011.10.014. Registered as NCT00910442. Twelve treated HIV-positive people and 20 healthy controls, seven-day crossover with N-acetylcysteine or glutamine.
- Sies H et al. (2023). Glutathione and glutathione-dependent enzymes: from biochemistry to gerontology and successful aging. Ageing Research Reviews 92:102101. PMID 37683986. Recorded from title and metadata only and used here as context for the age-related decline in glutathione levels.
Cite this page
The facts on this page were checked on 7 September 2026, and the registers and regulator documents behind the status table were read that day. Several points are openly unresolved: the Australian, Canadian and Swiss entries were not verified against primary documents, and the European supplement argument rests on a claim that could not be checked.
myPeptides Research & Editing. (2026). Glutathione: what the studies show, status and safety. Version 1.0, 7 September 2026. myPeptides Peptide Register. Retrieved from https://mypep.app/peptides/glutathione
How pages in this register are compiled and graded is described under methodology; the full register is at peptides.
| Version | Date | Change |
|---|---|---|
| 1.0 | 2026-09-07 | Initial publication |
Last verified: 7 September 2026. Next review: on any change to the Japanese or Italian licence, on any further regulatory action concerning injections, or on publication of a controlled trial with a clinical endpoint.