International Journal of Research in Dermatology

Mohan S et al. Int J Res Dermatol. 2020 Mar;6(2):284-287

http://www.ijord.com

DOI: http://dx.doi.org/10.18203/issn.2455-4529.IntJResDermatol20200615
Review Article

Glutathione for skin lightening for dermatologists and cosmetologists

Shobhit Mohan1, Lalit Mohan2*, Renu Sangal3, Neelu Singh4

1
Department of Dermatology, 1,3Medical College, Basti, Uttar Pradesh, India
2
Department of Dermatology, 2Medical College, Gorakhpur, Uttar Pradesh, India
4
Cosmetologists, Medical College Campus, Gorakhpur, UP, India

Received: 02 December 2019

Accepted: 13 February 2020

*Correspondence:
Dr. Lalit Mohan,
E-mail: [email protected]

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Glutathione is a potential antioxidant and its reduced form (GSH) has a good skin-whitening effect in humans through
its tyrosinase inhibitory activity. Many physicians consider it as a Wonder drug for skin lightening and treatment of
hyperpigmentation, especially with darker skin tones. Glutathione is available in topical, oral and injectable
formulations. Topical and oral forms are considered to be safe. Intravenous form did not prove its safety and efficacy
to till date. In this article, we shall review and discuss the current status of glutathione as a skin lightening agent and
address the miscellaneous unanswered queries regarding the dosage, duration of use and longevity of accrued effects
based on clinical evidence and recent insights into its antimelanogenic mechanism.

Keywords: Glutathione, Skin lightening, Dermatologists

INTRODUCTION these, glutathione has become a popular skin lightening

agent because of its faster action and popularity.2,3
Desire to attain skin tone lighter or fairer complexion in
adults is increasing day by day. This craze exploiting the Glutathione peptide is an antioxidant and is a
implications of topical skin lightening agents and combination of three amino acids glutamate, cystine, and
therapies containing hydroquinone, alpha and beta glycine which detoxifies xenobiotics.4 As a skin
hydroxy acids, tretinoin, arbutin, vitamin C serum, soy lightening agent, glutathione inhibits tyrosinase enzyme
extract. These agents are used generally as skin lighteners which helps in synthesis of melanin. It also modifies the
on face, neck and other exposed parts of the body. Hence production of eumelanin (produce dark brown colour to
their effect is limited to the application site without any pheomelanin (produce yellow-red colour), leads to
systemic skin lightening effect.1 lightening of skin.5

Many products are available as the over-the-counter like Glutathione is available naturally in fresh leafy
vitamin E, Hydroquinone, vitamin C serum, niacinamide vegetables, walnuts, oranges, whey protein, tomatoes and
(nicotinamide), arbutin, glycolic acid, kojic acid and a fresh fruits.6,7 Glutathione is available in different
few new products like marine algae extracts, soy, formulations like topical, oral and injectables.7 Topical
pycnogenol, Boswellia, etc. All the products are applied formulations show significant improvement in skin
locally and their effect varies from person to person. complexion on continuous use for certain period of time.
Systemic products are also available like l-cysteine Oral preparations are available in the form of tablets and
peptide, tranexamic acid, different plant extracts. Of all solution forms. Sublingual route availability is better and
requires lower doses and is considered to be safe by

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FDA.8 The required dose is 20-40 mg/kg (i.e. 1 g to 2 g in glutathione compared to placebo, with no adverse drug
two divided doses) and significant effects are seen within effects.4
3 months. Intravenous doses (600-1200 mg once/twice in
a week) known to show more adverse effects due to the The major limitation of these studies included were small
chances of overdose toxicities or may be due to the sample size consisting of healthy volunteers, extremely
additives present in glutathione injection. The common short study period with an even shorter follow-up, and
adverse effects related to intravenous preparations are lack of measurement of blood levels of glutathione.4,12,13
potentially fatal Stevens-Johnson syndrome and toxic
epidermal necrolysis, kidney dysfunction, liver Evidences favoring the use of intravenous glutathione
dysfunction, thyroid dysfunction, severe abdominal pain remain elusive. For years, manufacturers, distributors,
and lethal complications such as air embolism or skin clinics and med spas have been recommending
potentially fatal sepsis due to incorrect sterile method of arbitrary dosage schedules, despite complete lack of
IV administration.7,9 evidence.14,15 A placebo-controlled trial done by Zubair et
al, studied the efficacy and safety of IV GSH for skin
Glutathione is a ‘magical skin whitening’ molecule in tone lightening in 25 patients (1,200 mg given IV twice a
countries like the republic of Philippines. Glutathione has week for 6 weeks in the treatment group versus normal
seen a rapid spread in its popularity across the globe in saline in control group). The findings of this study did not
short duration of time. Many manufactures and media favor IV glutathione as an effective or lasting treatment
campaigns supported its outcome effects in treating the for skin tone lightening. The major adverse effect
disorders of hyperpigmentation such as melasma, but also reported in the IV GSH treated group was liver
as general skin whitening agent.10 dysfunction, which was neither qualified nor quantified.
The investigators also did not estimate baseline or post-
It is necessary to look into the literature on glutathione treatment renal or thyroid function of the subjects, both of
for detailed background, information regarding the basic which were reported to be adversely affected by IV
and applied physiology of glutathione. Glutathione exists glutathione.16
in a reduced form (GSH) and an oxidized form (GSSG).
The reduced form, GSH, seems to be instrumental in the SAFETY STATUS OF GLUTATHIONE
depigmenting properties of this unique molecule.11
As per Generally Recognized as Safe (GRAS)” consistent
UPDATE ON GLUTATHIONE AS A SKIN- with Section 201(s) of the Federal Food, Drug, and
LIGHTENING AGENT Cosmetic Act of the United States Food and Drug
Administration (US-FDA), glutathione-based oral dietary
There were only few published studies that evaluated the supplements are safe.17 No restrictions are employed on
efficacy of oral, topical and parenteral glutathione as a its oral forms in the US, Philippines and Japan. Oral
skin whitening agent. Two trails were conducted on oral forms are available as the over-the-counter drugs in India
GSH conducted in Thai population by Arjinpathana and and in other Asian countries. The major drawback of oral
in Filipino women by Handog et al, involved GSH dosage form is its low bioavailability in humans.
administering 500 g/day of GSH in two divided doses to This made manufacturers of IV injections of GSH to
the study population, the difference being the use of recommend this route of administration to achieve
buccal lozenges instead of oral capsules in latter study to anticipated therapeutic levels in the blood and skin
enhance systemic absorption of glutathione.11,12 The rapidly to yield instant skin whitening results. The
primary efficacy outcome in both the trails was to recommended dose of 600-1200 mg, to be injected
evaluate the pre- and post-treatment melanin indices. The weekly or twice a week, with no specified net duration of
study done by Arjinpathana et al, group showed a the therapy. But, the literature evaluating the efficacy of
consistent reduction in the melanin indices at all six IV GSH is still lacking.5
sites evaluated in the GSH group subjects, with a
statistically significant reduction over placebo at two LIMITATIONS OF IV GSH
sites.12
Extreme high cost of injection vials is on of the
Study conducted by Handog et al in 30 healthy Filipino compelling deterrent to its use. Other limitations include
women using buccal lozenges instead of capsules of GSH are lack of published source supporting its efficacy as a
reported significant reduction in melanin index at both skin lightening agent, undefined dose and duration of IV
sun exposed and sun-protection sites in all the subjects injections, lack of approval from US FDA and warning
and moderate skin lightening observed by 90% of the against the use of intravenous glutathione by the FDA of
subjects on global evaluation.13 Philippines, and its reported adverse effects.8

Another study by Watanabe et al, provided good RECENT INSIGHTS FROM RESEARCH
evidence favoring efficacy of topical GSSG 2% lotion
applied twice daily for 10 weeks in producing temporary A reasonable intracellular concentration of GSH and its
skin whitening and also the study revealed statistically transportation into the melanosomes are essential for
significant reduction of skin melanin index with GSH to inhibit tyrosinase and change melanogenesis

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 Mohan S et al. Int J Res Dermatol. 2020 Mar;6(2):284-287

from eumelanin to pheomelanin. Earlier reports revealed 5. Villarama CD, Maibach HI. Glutathione as a
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recently evaluated in vitro antimelanogenic effects and Lands LC. Improved glutathione status in young
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DEE), and GSH monoisopropyl ester (GSH-MIPE)).20 7. Sidharth Sonthalia1, Deepashree Daulatabad2,
The results of their research confirmed significant Rashmi Sarkar. Glutathione as a skin whitening
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Funding: No funding sources agent in Filipino women. Int J Dermatol.
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http://www.oskinmedspa.com/portfolio/iv-
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