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Glutathione for skin lightning: an update
The obsession of people with skin of color to attain a
lighter skin tone or fairer complexion has resulted in
development of various topical and oral agents with
depigmenting properties. Preparations containing
chemicals, such as hydroquinone, tretinoin, mequinol,
glycolic acid, kojic acid, arbutin, ascorbic acid, soy
extracts, and newer cosmeceuticals, have been in vogue
as popular depigmenting agents, single-agents as well as
combination topicals.
However, apart from the local
adverse effects of many of these agents, an important
limitation is the localization of their effect to the
application site alone. The quest for a systemic skin
whitening logically ensued. Oral antioxidants such as
vitamin C, vitamin E, tranexamic acid, l-cysteine
peptide, and various botanical extracts have been tried
but none is proven to provide an overall skin lightning
The latest addition to this therapeutic armamentarium
is that of glutathione (GSH) and its derivatives. GSH, a
low-molecular-weight thiol-tripeptide is primal to the
maintenance of intracellular redox balance. In addition to
it being one of the richest antioxidants, it is being promoted
as a skin lightening agent, following the discovery of its
antimelanogenic properties. It inhibits tyrosinase,
scavenges free radicals, and skews melanogenesis from
the darker eumelanin to the lighter phaeomelanin.
The mechanisms postulated to be responsible for the
skin lightning effect of GSH have been summarized in
Table 1. Unfortunately, there is a clear contradiction
between the extant evidence supporting its efficacy and
safety, and the hype around its depigmentary properties,
with pharmacosmoceuticals inundating dermatology
therapeutics with GSH tablets, capsules, topical
preparations, and parenteral preparations.
Hailed for generations as a magicalskin whitening
molecule in countries like the Republic of Phillipines,
GSH has seen a rapid spurt in its popularity across the
globe in a short duration of time. This has been the outcome
of ardent manufacturer-supported media campaign about
the almost preposterous effects of this molecule as a
wonder drug for not only disorders of hyperpigmentation
such as melasma, but also for general skin whitening.
This editorial is meant to update healthcare professionals
about the current status of efficacy, safety, and evidence
of different formulations of GSH in skin tone lightning.
For more detailed background information regarding
the basic and applied physiology of GSH, readers may
refer to a previously published exhaustive article on this
As of now, there are only two published studies that
evaluated the efficacy and safety of oral, and one each
on the efficacy and safety of topical and intravenous
(IV) GSH as a skin whitening agent. In a 4-week
randomized, double-blind, two-arm, placebo-controlled
study conducted in Thai population, Arjinpathana and
Asawanonda, assessed the effect of orally administered
GSH, 500 mg/day (in two divided doses) over the skin
melanin index (at six different sites) of 60 otherwise
healthy medical students. The results showed consistent
reduction in the melanin indices at all six sites in GSH
group subjects, with statistically significant reduction
over placebo at just two sites.
The tolerance to GSH
was excellent. To enhance the systemic absorption
of GSH, in a recent open label study involving 30
healthy Filipino women (aged 2242 years) with
Fitzpatrick skin types IV or V, Handog et al. administered
buccal lozenges of GSH (500 mg/day in two divided
doses) for 4 weeks and reported significant reduction in
melanin index at both sun-exposed and sun-protected sites
in all the subjects and moderate skin lightening in 90% of
the subjects on global evaluation.
The singular
randomized, double-blind, placebo-controlled clinical
trial by Watanabe et al., conducted in 30 healthy Filipino
women aged 30 to 50 years, has provided some
evidence favoring efficacy of topical glutathione disulfide
(oxidized form of GSH) 2% lotion, applied twice daily for 10
weeks in temporary skin whitening. The results of the split-
face protocol-based study revealed statistically significant
reduction of skin melanin index with GSH compared to
placebo, with no adverse drug effects.
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All three studies suffered from glaring limitations, especially
short study duration and follow-up period, small sample
size, choice of cohort being young and apparently healthy
subjects, and lack of measurement of blood levels of GSH.
Further, there is no Indian data till date, regarding the use of
GSH for skin lightening or treatment of hyperpigmentation.
For GSH to exert antimelanogenic effect via tyrosinase
inhibition and switching of melanogenesis from
eumelanin to pheomelanin, the intracellular
concentrations of GSH is crucial and transportation of
GSH into melanosomes becomes essential. Although
cysteine, the precursor of GSH, is known to be
transported across melanosomes through a carrier-
mediated lysosomal membrane transport system, previous
research has established lack of any significant trans-
melanosomal transportation of GSH through a membrane
channel or diffusion.
A recent research by Chung et al. has
revealed interesting facts. They evaluated the
antimelanogenic effects and cytotoxicity of GSH and its
three esterified derivatives GSH monoethyl ester (GSH-
MEE), GSH diethyl ester (GSH-DEE), and GSH monoisopropyl
ester (GSH-MIPE) in vitro in three cell culture lines.
Interestingly, GSH did not display a significant inhibitory
effect on intracellular tyrosinase activity or melanin
production, whereas GSH-MEE and GSH-MIPE did.
DEE and GSH-MIPE additionally demonstrated cytotoxic
activity. The authors concluded that the lipophilicity of
the esterified derivatives of GSH enhance their
intracellular and intramelanosomal delivery with
subsequent tyronisa inhibition and reduction of melanin
In view of in vitro efficacy and lack of
cytotoxicity of GSH-MEE, the researchers suggested the
development of GSH-MEE instead of GSH as an
efficacious and safe molecule for the treatment of
GSH-based oral dietary supplements have been accorded
the status of Generally Recognized as Safe (GRAS)
consistent with Section 201(s) of the Federal Food, Drug,
and Cosmetic Act of the United States Food and Drug
Administration (US-FDA).
There is no restriction on its
availability in this form in the United States, Philippines, and
Japan. Oral GSH has also become available over-the-counter
(OTC) in India.
Since oral GSH has a low bioavailability, manufacturers of IV
injections of GSH recommendthis route of administration
to achieve desired therapeutic levels in the blood and skin
rapidly and produce instantskin whitening results.
Despite IV GSH having been used for years in the past
(and still being practiced by many), there has been no
clinical trial for a long time evaluating its efficacy. Despite
the lack of any evidence, manufacturers of IV GSH have been
recommendinga dose of 6001200 mg, to be injected
weekly or twice a week, with no specified net duration of
the therapy.
It is only recently, that Zubair et al. published
the first placebo-controlled study of IV GSH (1200 mg given
IV twice-a-week for 6 weeks in the treatment group versus
normal saline in control group) for skin tone lightning in 25
Although the results from this singular trial did
not favor IV GSH as an effective or lasting treatment for skin
tone lightening, the sample size, study design, and high
drop-out rate from the treatment group (9 out of 25) of this
trial exhort a cautious reading and interpretation of the
The two major issues with the methodology of
this study include the use of visual Taylor scale for pre- and
post-treatment evaluation of change in skin hue and tone,
and lack of mention of statistical tests applied. The Taylor
scale is a very subjective and unreliable tool for observing
subtle changes in skin pigmentation with a very high
interinvestigator variability in its interpretation.
Results based on Taylor scale, rather than a reliable
objective parameter like the melanin index using a
mexameter can at best be speculative.
Safety of IV GSH, extrapolated from studies evaluating its
use for male infertility and liver disorders, seems to be
However, sundry adverse effects of IV GSH
have been documented from Philippines, resulting in the
release of a position paper by the Food and Drug
Administration, Department of Health, Republic of the
Philippines with a warning for the public on the subject
of the safety of the off-label use of GSH solution for
injection. The adverse effects mentioned include Adverse
cutaneous eruptions, including potentially fatal
StevensJohnson syndrome and toxic epidermal
necrolysis, thyroid dysfunction, renal dysfunction, severe
abdominal pain and lethal complications such as air
embolism, or potentially fatal sepsis due to incorrect/
unsterile method of IV administration of GSH.
effects to IV GSH were reported in all patients in the
treatment group in the trial by Zubair et al., with 32%
patients having sustained deranged liver function.
Proponents of IV GSH contest that these adverse effects
are attributable to other additives present in the GSH
injection vials and the risk is dependent on the purity of
GSH; however, this claim needs validation.
Sonthalia and Sarkar: Glutathione for skin lightning
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Apart from lack of any evidence of IV GSH for skin
lightening, the extremely high cost of injection vials
constitute another compelling deterrent to its use.
Although, relatively cheaper versions are available, they
run the risk of being counterfeit, with risk of life-
threatening events.
There is lack of clarity regarding the apparent differential
safetyof IV GSH, when administered for a medically
approved reason versus administration for skin lightning.
In contrast to the relative lack of safety of IV GSH (as per the
PhilippinesFDA, and the trial by Zubair et al.), the analysis of
two systematic reviews of IV GSH for preventing chemo-
induced toxicity and one review of its use as for Parkinsons
disease (overall 10 trials included) reported minimal-to nil-
adverse effects, and no long-term complications.
However, the number of treatments given and total
treatment duration were different in these studies
compared to the popular (but not validated) protocol of
using IV GSH for skin lightning. Thus, this conundrum needs
further exploration.
Akin to the labeling of oral GSH as GRAS by the US-FDA,
in India, oral GSH and its combinations with ingredients
like alpha-lipoic acid, ascorbic acid, and others have been
covered under the Prevention of Food Adulteration
Act as food supplement,and apparently excluded
from the purview of the Drugs and Cosmetic Acts
1940, regulated by Drug Controller General of India
Thus, these supplements can be obtained
OTC by consumers.
Lyka Labs, one of the major manufacturers of parenteral
GSH, received permission from DCGI according to their
letter dated September 14, 2011 to manufacture GSH
for injection for the following indications: (1) alcoholic
fatty liver, (2) alcoholic liver fibrosis, (3) alcoholic
liver cirrhosis, and (4) alcoholic hepatitis.
currently, the DCGI-approved indications for IV GSH are
limited to the above four hepatic disorders only.
At present, there is no DCGI-approved indication
for the use of IV GSH for any skin condition,
hyperpigmentation or general skin lightening.
At present, there is clear lack of convincing evidence
in favor of GSH as a therapy for hyperpigmentation.
The trials available till date that evaluated the role of
oral topical and parenteral GSH (oral and topical) as
a skin lightening agent suffered from many limitations.
Safety of topical and oral GSH seems to be good.
Currently, IV GSH has minimal and poor quality
evidence to support or discourage its use for
pigmentation. Adverse effect profile of IV GSH is
another serious concern. Generation of more evidence
in the form of randomized, double-blind, placebo-
controlled trials with larger sample size, long-term
follow-up, and well defined primary and secondary
outcomes, targeted to evaluate the efficacy and safety
of skin whitening effects of topical, oral as well as
parenteral GSH is warranted.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
SKINNOCENCE: The Skin Clinic & Research Centre, Sushant Lok-1,
Gurgaon-122009, Haryana,
Department of Dermatology & STD,
MAMC-LN Hospital, New Delhi, India
Address for correspondence: Dr Sidharth Sonthalia,
SKINNOCENCE: The Skin Clinic & Research Centre, C-2246 (Ground
Floor), Suhridaya, Sushant Lok-1, Block-C, Gurgaon-122009,
Haryana, India.
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3. Sonthalia S, Daulatabad D, Sarkar R. Glutathione as a skin whitening
agent: facts, myths, evidence and controversies. Indian J Dermatol
Venereol Leprol 2016;82:262-72.
Table 1: Mechanisms postulated to be responsible for the skin lightning effect of glutathione
Inhibition of Tyrosinase (the key enzyme of melanogenesis):
Direct inhibition: Thiol group binding with the copper-containing active site of the enzyme
Indirect inactivation: Exerted via the antioxidant effect of glutathione that leads to quenching of free radicals and peroxides
Switching production of eumelanin to phaeomelaninModulation of the depigmenting abilities of other melanocytotoxic agents
Sonthalia and Sarkar: Glutathione for skin lightning
Pigment International | Volume 4 | Issue 1 | January-June 2017 5
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4. Arjinpathana N, Asawanonda P. Glutathione as an oral whitening
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trial of the safety and efficacy of a novel preparation of glutathione
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whitening and skin-condition-improving effects of topical
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10. GRAS notice for Glutathione; 2009. URL
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vs. placebo for skin tone lightening. J Pak Ass Dermatol
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assessment tool for the evaluation of skin color and pigmentation.
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13. Lenzi A, Lombardo F, Gandini L, Culasso F, Dondero F. Glutathione
therapy for male infertility. Arch Androl 1992;29:65-8.
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glutathione in cases of hepatic cirrhosis. Gut 1965;6:472-6.
15. Lazo SH. Safety on the off-label use of glutathione solution for
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... Intravenous doses (600-1200 mg once/twice a week) are known to cause additional side effects due to the risk of overdosing toxicities or the presence of additives in glutathione injection, Potentially fatal Stevens-Johnson syndrome and toxic epidermal necrolysis, kidney dysfunction, liver dysfunction, thyroid dysfunction, severe abdominal pain, and lethal complications such as air embolism or potentially fatal sepsis due to improper sterile IV administration are all common side effects of intravenous preparations. [44]. ...
Full-text available
Abstract Glutathione is a thiol-tripeptide with a low molecular weight that is important for maintaining intracellular redox balance. Its antimelanogenic qualities have led to its promotion as a skin-lightening agent, in addition to its exceptional antioxidant properties. In some ethnic groups, it is commonly utilized for this purpose. There is, however, a discrepancy between the evidence supporting its efficacy and safety. The marketing gimmick surrounding its depigmenting properties could be a pharma�cosmeceutical company's marketing ploy. This article examines the different characteristics of glutathione, including its metabolism, mechanism of action, and scientific evidence to assess its usefulness as a systemic skin-lightening agent. Glutathione, in its reduced form, is found within cells and plays a crucial part in a variety of physiological functions. The direct and indirect suppression of the tyrosinase enzyme, as well as the switch from eumelanin to phaeomelanin production, are responsible for its skin-lightening effects. It can be taken orally, parent rally, or topically. Although intravenous glutathione injections are widely used, there is little proof that they are effective. Indeed, the Philippines' Food and Drug Administration has issued a public warning denouncing intravenous glutathione's usage for off-label applications such as skin whitening due to its negative consequences. There are now three randomized controlled trials that support topical and oral glutathione's skin�lightening impact and good safety profile. However, important questions such as treatment duration, skin-lightening impact lifetime, and maintenance regimens remain unsolved. To establish the importance of this chemical in hyperpigmentation and skin lightening diseases, more randomized, double-blind, placebo-controlled trials with bigger sample sizes, long-term follow-up, and well-defined efficacy outcomes are needed.
... GSH is found in large concentrations of 5 mM intracellularly. 13,14 The most important functions of glutathione known to date are i) detoxification of xenobiotics, ii) catalysis of exchange reactions, iii) scavenging of free radicals and reactive oxygen species (ROS), iv) transport of amino acids across cell 2 membranes, v) acting as a coenzyme in some processes of cellular metabolism and vi) maintenance of thiol groups of proteins and other molecules. 15,17 Glutathione's popularity in skin lightening treatments comes as a result of its antimelanogenic properties when it works as a tyrosinase inhibitor during melanogenesis (see Figure 2). ...
The skin bleaching industry is a global business with a vast array of anti-melanogenic choices including glutathione. Glutathione is synthesized in vivo but has been used as a bodily supplement by medical personnel to aid in preventative medicine. Known for its antioxidant properties, glutathione has been used for its anti-melanogenic effects. Intravenous glutathione requires more investigation to determine its safety for usage. It continues to be distributed to the cosmetic industry despite antagonism from the Philippine FDA. This study will research the potential effects of intravenous glutathione on women and it will propose the biochemical mechanisms of glutathione in induced disease states in women. The aim is to educate people about safer methods for skin lightening. Keywords: skin lightening, intravenous glutathione, pheomelanin, Fitzpatrick skin types, Stevens-Johnson syndrome.
... Many manufactures and media campaigns supported its outcome effects in treating the disorders of hyperpigmentation such as melasma, but also as general skin whitening agent. 10 It is necessary to look into the literature on glutathione for detailed background, information regarding the basic and applied physiology of glutathione. Glutathione exists in a reduced form (GSH) and an oxidized form (GSSG). ...
Full-text available
p class="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.</p
... This article is meant to update healthcare professionals about the current status of efficacy, safety, and evidence of different formulations of glutathione for skin tone lightening. For more detailed background information regarding the basic and applied physiology of glutathione, readers may refer to a previously published exhaustive article on this aspect [6]. It is important to know that glutathione exists in a reduced form (GSH) and an oxidized form (GSSG). ...
Full-text available
The recent hype surrounding the antimelanogenic properties of glutathione has resulted in physicians frequently administering it as a “wonder” drug for skin lightening and treatment of hyperpigmentation, especially in ethnic populations with darker skin tones. This phenomenon has seen a recent surge owing to aggressive marketing and capitalization of pharma-cosmeceutical companies. However, the unbridled and prodigal use of it, especially as a parenteral formulation, seems unjustified, given the lacunae in our knowledge about its antimelanogenic potential, limited clinical evidence favoring its role in skin lightening, and the statutory ban/advisory issued by certain federal agencies. Even though parenteral glutathione is approved only for severe liver disorders and for prevention of chemotherapy associated neurotoxicity, the lack of statutory laws governing the use of systemic glutathione in most countries has contributed to its unchecked use for skin lightening. The current clinical evidence of intravenous glutathione for skin lightening is limited to a single study with a dubious study design and apparently flawed analysis of results, casting doubt on the drug’s efficacy and reported adverse effects. Two studies evaluating oral/sublingual administration and one trial involving the use of topical glutathione reported good safety profile and appreciable but reversible results on skin tone. In this article, we shall review and discuss the current status of glutathione as a skin lightening agent and address the sundry unanswered queries regarding the dosage, duration of use and longevity of accrued effects based on clinical evidence and recent insights into its antimelanogenic mechanism.
Full-text available
Background: Glutathione (GSH) is the most abundant naturally occurring non-protein thiol that protects mammalian cells from oxidative stress. Intravenous (IV) GSH for skin lightening is advertised by clinics in South Africa and internationally online, yet to date no published review on the subject exists. Methods. We conducted a MEDLINE search (to 30 September 2015) of GSH use for skin lightening and of all indications in medicine, to evaluate its safety. Results. Two controlled clinical trials (GSH capsules: 60 patients; 2% glutathione disulphide lotion: 30 patients) and a case series (GSH lozenges: 30 patients) reported a significantly decreased melanin index. A case series (GSH soap: 15 patients) reported skin lightening based on photography. Two systematic reviews of IV GSH for preventing chemo-induced toxicity and a third review of adjuvant therapy for Parkinson's disease altogether included 10 trials. Most trials reported either no or minimal GSH adverse effects, but all had treatment durations of a few doses (IV) or 4 -12 weeks. No study reported long-term IV GSH use. Conclusion. In spite of widespread reported use, there are no studies of IV GSH use for skin lightening or of its safety for chronic use (for any indication). The switch from brown to red melanin production may increase the risk of sun-induced skin cancers in previously protected individuals. Regulatory assessment of systemic GSH administration for cosmetic use by the Medicines Control Council seems urgently warranted to protect consumers from potential side-effects and from complications of IV infusions. This is especially concerning because of reports of GSH bought online. Effective topical GSH may be useful for hyperpigmented skin disorders, but this requires scientific scrutiny. The debate on the merits of cosmetic skin lightening is best handled by multidisciplinary teams.
Full-text available
Glutathione in its reduced form (GSH) is an antioxidant and also is involved in pheomelanin formation. Thus, it has been long believed that GSH has a skin whitening effect. However, its actual or direct effect is unproven. We evaluated the anti-melanogenic effects of GSH and its derivatives in vitro. We examined change of melanogenesis and its related proteins by GSH itself and its derivatives, including GSH monoethyl ester (GSH-MEE), GSH diethyl ester (GSH-DEE) and GSH monoisopropyl ester (GSH-MIPE) in Melan-A cells, Mel-Ab cells, and B16F10 cells. GSH and GSH-MEE did not display cytotoxic activity, but GSH-MIPE and GSH-DEE did. Intriguingly, GSH itself had no inhibitory effect on melanin production or intracellular tyrosinase activity. Rather, it was GSH-MEE and GSH-MIPE that profoundly reduced the amount of melanin and intracellular tyrosinase activity. Thus, GSH-MEE was selected as a suitable candidate skin-whitening agent and it did not alter melanogenesis-associated proteins such as microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2, but it did increase the amount of suggested pheomelanin and suggested pheomelanin/eumelanin ratio. GSH-MEE was effective for anti-melanogenesis, whereas GSH itself was not. GSH-MEE could be developed as a safe and efficient agent for the treatment of hyperpigmentation skin disorders.
Full-text available
Glutathione is a low molecular weight thiol-tripeptide that plays a prominent role in maintaining intracellular redox balance. In addition to its remarkable antioxidant properties, the discovery of its antimelanogenic properties has led to its promotion as a skin-lightening agent. It is widely used for this indication in some ethnic populations. However, there is a dichotomy between evidence to support its efficacy and safety. The hype around its depigmentary properties may be a marketing gimmick of pharma-cosmeceutical companies. This review focuses on the various aspects of glutathione: its metabolism, mechanism of action and the scientific evidence to evaluate its efficacy as a systemic skin-lightening agent. Glutathione is present intracellularly in its reduced form and plays an important role in various physiological functions. Its skin-lightening effects result from direct as well as indirect inhibition of the tyrosinase enzyme and switching from eumelanin to phaeomelanin production. It is available in oral, parenteral and topical forms. Although the use of intravenous glutathione injections is popular, there is no evidence to prove its efficacy. In fact, the adverse effects caused by intravenous glutathione have led the Food and Drug Administration of Philippines to issue a public warning condemning its use for off-label indications such as skin lightening. Currently, there are three randomized controlled trials that support the skin-lightening effect and good safety profile of topical and oral glutathione. However, key questions such as the duration of treatment, longevity of skin-lightening effect and maintenance protocols remain unanswered. More randomized, double-blind, placebo-controlled trials with larger sample size, long-term follow-up and well-defined efficacy outcomes are warranted to establish the relevance of this molecule in disorders of hyperpigmentation and skin lightening.
Full-text available
Purpose Glutathione is a tripeptide consisting of cysteine, glycine, and glutamate and functions as a major antioxidant. It is synthesized endogenously in humans. Glutathione protects thiol protein groups from oxidation and is involved in cellular detoxification for maintenance of the cell environment. Reduced glutathione (GSH) has a skin-whitening effect in humans through its tyrosinase inhibitory activity, but in the case of oxidized glutathione (GSSG) this effect is unclear. We examined the skin-whitening and skin-condition effects of topical GSSG in healthy women. Subjects and methods The subjects were 30 healthy adult women aged 30 to 50 years. The study design was a randomized, double-blind, matched-pair, placebo-controlled clinical trial. Subjects applied GSSG 2% (weight/weight [w/w]) lotion to one side of the face and a placebo lotion to the other side twice daily for 10 weeks. We objectively measured changes in melanin index values, moisture content of the stratum corneum, smoothness, wrinkle formation, and elasticity of the skin. The principal investigator and each subject also used subjective scores to investigate skin whitening, wrinkle reduction, and smoothness. Analysis of variance was used to evaluate differences between groups. Results The skin melanin index was significantly lower with GSSG treatment than with placebo from the early weeks after the start of the trial through to the end of the study period (at 10 weeks, P<0.001). In addition, in the latter half of the study period GSSG-treated sites had significant increases in moisture content of the stratum corneum, suppression of wrinkle formation, and improvement in skin smoothness. There were no marked adverse effects from GSSG application. Conclusion Topical GSSG is safe and effectively whitens the skin and improves skin condition in healthy women.
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Melasma is one of the most common and distressing pigmentary disorders presenting to dermatology clinics. The precise cause of melasma remains unknown; however, there are many possible contributing factors. It is notably difficult to treat and has a tendency to relapse. The existing and most tried topical therapy is hydroquinone and the triple combination with tretinoin and corticosteroids, which is considered the gold standard for melasma. Besides that, azelaic acid, kojic acid, arbutin, ascorbic acid, glycolic acid and salicylic peels have also been tried with limited success. However, multiple novel topical agents are being investigated for their potential as hypopigmenting agents with unique mode of action. But, further trials are required to study their efficacy and safety before they can be further recommended. The article highlights these newer formulations and also briefly mentions about the newer chemical peels and the much hyped lasers in treating this difficult and frustrating condition.
Glutathione (GSH) is a naturally occurring thiol that has been reported to cause skin lightening in a manner for which several mechanisms have been proposed. Highest plasma concentrations are achieved with IV administration but are accompanied by greater levels of risk. Oral administration has been less successful in elevating plasma GSH levels. The use of a lozenge containing GSH was investigated in order to evaluate the buccal mucosa as a route for GSH administration. Substances that are absorbed through the buccal route go directly into the systemic circulation, effectively bypassing the gastrointestinal tract. Thirty Filipino females with Fitzpatrick skin types IV or V received a glutathione-containing lozenge daily for eight weeks. Findings showed a significant decrease in melanin indices from baseline to endpoint that became evident in as little as two weeks. There were no serious adverse events, and laboratory examination findings remained normal. The authors conclude that the lozenge containing glutathione was safe and effective in lightening the skin of Filipino women. © 2015 The International Society of Dermatology.
To determine whether orally administered glutathione, 500 mg per day for 4 weeks, affects the skin melanin index, when compared with placebo. This randomized, double-blind, two-arm, placebo-controlled study was set in the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, a teaching hospital affiliated with a medical school. Sixty otherwise healthy medical students were randomized to receive either glutathione capsules, 500 mg/day in two divided doses, or placebo for 4 weeks. The main outcome was mean reduction of melanin indices measured at six different sites. Several secondary outcomes, including UV spots, were recorded by VISIA™. Efficacies of glutathione and placebo were compared by ANCOVA with baseline values as co-variates. Sixty participants enrolled and completed the study. At 4 weeks, the melanin indices decreased consistently at all six sites in subjects who received glutathione. The reductions were statistically significantly greater than those receiving placebo at two sites, namely the right side of the face and the sun-exposed left forearm (p-values = 0.021 and 0.036, respectively). This was similarly reflected in the changes in the number of UV spots, as measured by VISIA. Both glutathione and placebo were very well tolerated. Oral glutathione administration results in a lightening of skin color in a small number of subjects. However, long-term safety has not been established and warrants more extensive clinical trials.
Eleven infertile men were treated with glutathione (600 mg/day IM) for 2 months. The patients were suffering from dyspermia associated with various andrological pathologies. Standard semen and computer analyses of sperm motility were carried out before treatment and after 30 and 60 days of therapy. Glutathione exerted significant effect on sperm motility patterns. Glutathione appears to have a therapeutic effect on some andrological pathologies causing male infertility. © 1992 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
Glutathione is not effectively transported into human lymphoid cells, normal human skin fibroblasts, and fibroblasts from patients with genetic deficiencies of gamma-glutamylcysteine synthetase or glutathione synthetase. On the other hand, the monoethyl ester of glutathione, in which the carboxyl group of the glycine residue is esterified, is readily transported into these cells and is hydrolyzed intracellularly. This leads to greatly increased cellular levels of glutathione, which often exceed those found normally. Glutathione ester was found to protect human lymphoid cells of the CEM line against the lethal effects of irradiation. Under the conditions employed, complete protection was found when the ester was added prior to irradiation. Addition of the ester after irradiation was partially effective, suggesting that GSH may also function in repair processes.