Key papers ✓ 2✗ 1~ 4? 1

• ~ Mixed systematic reviewInt J Dermatol · 2025

  Glutathione as a skin-lightening agent and in melasma: a systematic review.

  No new data5 RCTs pooled

  Systematic review (PubMed, Embase, Cochrane; past 10 years)

  Systematic review of skin-lightening and melasma studies: oral (250-500 mg/day) and topical glutathione gave moderate, localized-to-generalized lightening that faded after stopping; the single placebo-controlled IV study was not significant (37.5% vs 18.7%), and IV use was judged contraindicated.

  Key resultOnly one placebo-controlled IV study: 6/16 (37.5%) vs 3 (18.7%) (p0.054).

  Study details

  Studied

  Studies of glutathione as a skin-lightening agent and in melasma

  Compared with

  Placebo or lower doses/other combinations in included trials

  Main outcome

  Efficacy and safety for skin lightening and melasma

  Sample

  Number of included studies not clearly stated; includes 5 RCTs on oral glutathione

  Authors' conclusion

  Topical and oral glutathione give moderately efficacious but unsustainable skin lightening. IV glutathione is contraindicated due to lack of efficacy and side effects. It may work more as an antioxidant in melasma.

  Limitations

  Risk of bias was low in about half the studies and high in the rest.

  DOI 10.1111/ijd.17535PubMed 39444151
• ~ Mixed meta-analysisExp Ther Med · 2021

  Potential use of glutathione as a treatment for Parkinson's disease.

  Humans450 people7 RCTs pooled

  Systematic review and meta-analysis of randomized controlled trials

  Meta-analysis of 7 RCTs (450 Parkinson's patients): glutathione mildly improved motor scores (UPDRS III) but not daily-living or mental scores, with no increase in side effects.

  Key resultUPDRS III improved with glutathione (SMD -0.48; 95% CI -0.88 to -0.08; P=0.02); UPDRS I and II and side effects did not differ significantly.

  Study details

  Studied

  Patients with Parkinson's disease

  Compared with

  Control groups

  Main outcome

  UPDRS scores, glutathione peroxidase, side effects

  Sample

  7 RCTs, 450 participants

  Authors' conclusion

  Glutathione may mildly improve motor scores in Parkinson's disease without an increase in adverse events. Dosage (300 vs 600 mg) influenced UPDRS III.

  DOI 10.3892/etm.2020.9557PubMed 33376507Free full text
• ✗ Negative human RCTJ Parkinsons Dis · 2017

  Phase IIb Study of Intranasal Glutathione in Parkinson's Disease.

  Humans45 peopleRandomizedPlacebo-controlledDouble-blind3 months plus 1-month washout

  Double-blind, placebo-controlled phase IIb randomized trial (placebo, 100 mg or 200 mg intranasal GSH thrice daily)

  Phase IIb trial of intranasal glutathione in 45 people with Parkinson's disease: symptoms improved from baseline in all groups, but neither dose beat placebo over 3 months; one high-dose participant developed cardiomyopathy.

  Key resultHigh-dose group improved total UPDRS by -4.6 (4.7), P = 0.0025, but neither treatment group was superior to placebo.

  Study details

  Studied

  People with Parkinson's disease, Hoehn & Yahr stage 1-3

  Compared with

  Intranasal saline placebo

  Main outcome

  Total UPDRS and motor subscore

  Sample

  45 individuals with Hoehn & Yahr Stage 1-3 PD

  Authors' conclusion

  Intranasal GSH was not shown to be superior to placebo at three months; placebo improvement was unusually robust. Symptomatic effects warrant delayed-start or washout designs and larger, longer trials.

  Limitations

  Small phase IIb trial; one high-dose participant developed cardiomyopathy.

  DOI 10.3233/JPD-161040PubMed 28436395Free full text
• ✓ Positive human RCTJ Clin Oncol · 1995

  Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial.

  HumansFifty patients with advanced gastric cancerRandomizedPlacebo-controlledDouble-blind15 weeks of treatment assessed

  Randomized, double-blind, placebo-controlled trial

  Double-blind trial in 50 gastric cancer patients on cisplatin: IV/IM glutathione markedly reduced chemotherapy-induced nerve damage vs placebo without lowering tumor response.

  Key resultAfter the 15th week, 4 of 24 assessable patients in the GSH arm had neurotoxicity vs 16 of 18 in the placebo arm (P = .0001).

  Study details

  Studied

  Patients with advanced gastric cancer on weekly cisplatin-based chemotherapy

  Compared with

  Normal saline placebo

  Main outcome

  Cisplatin-induced neurotoxicity

  Authors' conclusion

  GSH appears a promising and effective drug to prevent cisplatin-induced neuropathy and did not reduce the activity of the chemotherapy.

  Limitations

  Small trial; only 24 and 18 patients assessable at week 15.

  DOI 10.1200/JCO.1995.13.1.26PubMed 7799029
• ✓ Positive human RCTEur J Nutr · 2015

  Randomized controlled trial of oral glutathione supplementation on body stores of glutathione.

  Humans54 peopleRandomizedPlacebo-controlledDouble-blind6 months

  Randomized, double-blinded, placebo-controlled trial of oral GSH 250 or 1,000 mg/day

  Six-month trial in 54 healthy adults: oral glutathione (250 or 1,000 mg/day) raised blood and cell glutathione stores by up to 30-35% (260% in cheek cells) vs placebo; levels returned to baseline a month after stopping.

  Key resultAt 6 months, high-dose GSH raised levels 30-35% in erythrocytes, plasma and lymphocytes and 260% in buccal cells (P < 0.05).

  Study details

  Studied

  Healthy non-smoking adults

  Compared with

  Placebo

  Main outcome

  GSH levels in blood, erythrocytes, plasma, lymphocytes and buccal cells

  Sample

  54 non-smoking adults

  Authors' conclusion

  Daily oral GSH supplementation effectively increased body compartment stores of GSH.

  Limitations

  Immune markers measured only in a subset of subjects.

  DOI 10.1007/s00394-014-0706-zPubMed 24791752
• ~ Mixed human RCTJ Dermatolog Treat · 2012

  Glutathione as an oral whitening agent: a randomized, double-blind, placebo-controlled study.

  HumansSixty healthy medical studentsRandomizedPlacebo-controlledDouble-blind4 weeks

  Randomized, double-blind, two-arm, placebo-controlled study (oral glutathione 500 mg/day)

  Four-week trial in 60 medical students: oral glutathione 500 mg/day lowered skin melanin more than placebo at only 2 of 6 sites (face and sun-exposed forearm); well tolerated.

  Key resultMelanin index fell more than with placebo at two of six sites: right face (p = 0.021) and sun-exposed left forearm (p = 0.036).

  Study details

  Studied

  Healthy medical students in Bangkok, Thailand

  Compared with

  Placebo

  Main outcome

  Mean reduction of melanin indices at six sites

  Authors' conclusion

  Oral glutathione lightened skin in a small number of subjects; long-term safety is not established and warrants more extensive trials.

  Limitations

  4-week study; significant at only two of six sites.

  DOI 10.3109/09546631003801619PubMed 20524875
• ~ Mixed human RCTJ Cosmet Dermatol · 2022

  The effects of the oral supplementation of L-Cystine associated with reduced L-Glutathione-GSH on human skin pigmentation: a randomized, double-blinded, benchmark- and placebo-controlled clinical trial.

  Humans124 peopleRandomizedPlacebo-controlledDouble-blind12 weeks

  Randomized, double-blind, parallel-group, benchmark- and placebo-controlled trial

  Twelve-week trial in 124 Asian women: an oral L-cystine plus glutathione combination lightened skin and shrank dark spots more than placebo and more than glutathione alone.

  Key resultL-Cystine plus L-Glutathione gave significant skin lightening at 12 weeks and smaller dark spots at 6 and 12 weeks, better than placebo, cystine alone or glutathione alone (no numbers in abstract).

  Study details

  Studied

  Asian women

  Compared with

  Placebo, L-Cystine alone, reduced L-Glutathione alone

  Main outcome

  Skin color and facial dark spot size

  Sample

  124 Asian female subjects in 4 equal groups

  Authors' conclusion

  Daily 500 mg L-Cystine plus 250 mg L-Glutathione for 12 weeks was a safe, effective way to lighten skin and reduce dark spots in Asian women.

  Limitations

  Tested as a cystine plus glutathione combination.

  DOI 10.1111/jocd.14137PubMed 33834608
• ? Inconclusive human RCTActa Dermatovenerol Alp Pannonica Adriat · 2025

  Effectiveness of oral glutathione in reducing nitric oxide and IL-1α concentrations for clinical improvement in mild to moderate acne vulgaris: a randomized controlled trial.

  Humans40 peopleRandomizedPlacebo-controlled4 weeks

  Randomized controlled trial of oral glutathione 500 mg daily

  Four-week trial in 40 people with mild-to-moderate acne: oral glutathione produced non-significant reductions in inflammatory markers; no adverse reactions reported.

  Key resultReductions in serum NO and IL-1α in the glutathione group did not reach significance (p > 0.05); clinical improvement in 7 subjects (31.8%).

  Study details

  Studied

  Patients with mild to moderate acne vulgaris

  Compared with

  Placebo

  Main outcome

  Serum nitric oxide and IL-1α; clinical severity (Lehmann criteria)

  Sample

  40 subjects (22 glutathione, 18 placebo)

  Authors' conclusion

  Oral glutathione showed a non-significant trend toward reducing oxidative and nitrosative stress markers and improving acne; further studies are recommended.

  Limitations

  Small, short trial; results not statistically significant.

  PubMed 41014073

Reported side effects

• reportedCardiomyopathy (single case, high-dose intranasal) [ref]
• reportedAdverse effects with IV use for skin lightening (type not specified in abstract) [ref]

Oral and topical glutathione were well tolerated in short trials; long-term safety, especially of IV use, has not been established.

57 registered human trials (11 active)

✓ positive · ✗ negative · ~ mixed · ? inconclusive, judged on each paper's own main outcome. Grades: A strong human evidence → D little or none. Papers and verdicts are drawn from PubMed, Europe PMC and Russian journals (CyberLeninka); not medical advice.