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Intravenous glutathione for skin lightening: Inadequate safety data



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.
782 August 2016, Vol. 106, No. 8
Dermatologists use depigmenting creams with various active ingre-
dients in the treatment of melasma and post-inflammatory hyper-
pigmentation.[1] Skin lightening or bleaching refers to the cosmetic
practice of applying depigmenting agents not as treatment for
hyperpigmentation but with the deliberate aim of achieving a lighter
skin colour. It is a practice that is common in many places (e.g. India,
Africa and America) with pigmented populations and a history of
improved social status with lighter complexion. Adverse effects are
associated with active ingredients (mercury, hydroquinone and potent
steroids) in depigmenting creams and are illegal in cosmetics in many
countries. Further illegal ingredients in Africa have been shown to be
imported from Europe (in spite of a European Union ban).[2]
Glutathione (GSH) was first discovered by Hopkins[3[ in 1921 in
yeasts, and subsequently in other tissues.[4] It is a tripeptide com-
posed of L-cysteine, glycine and glutamate that is synthesised
intra cellularly.[5,6] It is considered the main redox buffer in human
cells owing to its large amount of reducing equivalents,[7] and is an
impor tant enzyme cofactor that serves as a neuromodulator in the
central nervous system. The tripeptide exists intracellularly either in
an oxidised glutathione disulphide (GSSG) or reduced state (GSH),
and maintaining an optimal GSH:GSSG ratio in the cell is critical
for prevention of oxidative damage and for cell survival (Fig. 1).[8]
An imbalance in GSH and its use as a marker of oxidative stress
is reported in many diseases including cancer, neurodegenerative
disorders, cystic fibrosis, HIV,[9] diabetes mellitus,[10] anorexia
nervosa[11] and autism[12,13] and in low-birth-weight neonates.[14]
Reports of systemic skin lightening with GSH have appeared with
increasing frequency on social media, and clinics advertise it online
in many countries (Africa, the USA, Canada, Mexico, etc.). Our
objective was to conduct a literature search to identify all academic
reports of GSH use for skin lightening and all clinical trials of GSH
use for all indications in medicine.
Two MEDLINE searches for studies published up to September 2015
were conducted. The search terms for the first were ‘glutathione AND
skin lightening’, and for the second ‘glutathione AND randomised
controlled trial’. Inclusion criteria were any treatment report of
GSH for skin lightening (or hyperpigmentation) and GSH for any
randomised control trial (RCT) for the first and second searches,
respectively. Abstracts were read independently by two authors to
identify relevant articles.
Nine articles were identified from the first MEDLINE search. Six
publications mentioned GSH as part of reviews related to melanin
(kojic acid in rats,[15] piceatannol inhibition of mushroom tyrosin-
ase,[16] oral zinc sulphate murine hair hypopigmentation,[17] hydro-
quin one occupational exposure[18] (and toxicity for skin lightening)
and natural ingredient-containing treatments for hyperpigmen-
tation.[20] A seventh article was an extensive review of biochemical
mechanisms of how GSH causes depigmentation in cell cultures and
laboratory animals.[21] Five clinical reports (4 published since 2012)
of the use of GSH for skin lightening were identified (2 from the
MEDLINE search and 3 from references). The first, a pharmacokinetic
study of GSH in seven participants, did not measure skin lightening
Intravenous glutathione for skin lightening:
Inadequate safety data
L M Davids, 1 PhD; J C van Wyk, 2 PhD; N P Khumalo,2 MB ChB, FCDerm, PhD
1 Department of Human Biology, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa
2 Division of Dermatology, Faculty of Health Sciences, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa
Corresponding author: N P Khumalo (n.khumalo@
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.
S Afr Med J 2016;106(8):782-786. DOI:10.7196/SAMJ.2016.v106i8.10878
783 August 2016, Vol. 106, No. 8
or report side-effects.[22] A case series of
15 patients from India treated with a GSH-
containing soap for melanosis of the face
reported lightening (in 11/15 after 3 months)
based on clinical photographs. However, no
mention was made of how the conditions for
photography were standardised or of follow-
up on stopping treatment.[23] A controlled
trial from Thailand tested 250 mg GSH
capsules twice daily in two groups each of 30
medical students over 4 weeks. They repor-
ted a decreased melanin index measured at
six body sites (but statistically significant
only at two sites, namely the right side of
the face (p=0.021) and the sun-exposed left
forearm (p=0.036)).[24] Wata na be et al.[25]
from Japan reported a significant reduction
in the melanin index (mean (standard
deviation), week0: 272.77 (26.17); week 10:
243.47 (26.31)) in subjects treated with a
GSSG-containing lotion measured with a
Mexameter MX18 (Courage + Khazaka Elec-
tronic GmbH, Germany). Investigators and
participants also subjectively scored GSSG-
treated skin as lighter. The most recent
study is an uncontrolled trial of 30Filipino
women. The authors reported a significant
reduc tion in melanin index (measured with
a portable mexameter) (p<0.0001) after
500 mg GSH lozenges were administered
daily for 8 weeks.
[26] None of the studies
repor ted significant adverse effects or follow-
up beyond the study period (Table 1).
Of the plethora of articles retrieved from
the second MEDLINE search, we identi-
fied 28 systematic reviews of animal stud-
ies,[39-41] GSH-related genetic polymorphisms
linked to various cancers (colo rectal can-
cer,[42] leukaemia,[43,44] lung cancer,[45,46] blad-
der can cer,[47] gastric cancer,[48,49] prostate
cancer,[50-53] adult brain tumours,[54] basal cell
carcinoma[55]) and linked to other disorders
(autism,[12,13] hyper tension,[56,57] respiratory
diseases,[58,59] cataract,[60] myelo dysplastic
syndrome,[61,62] glioma[63] and male idio-
pathic infertility.
[64]) There were 9 RCTs
identified from two systematic reviews of
the use of GSH to reduce chemotherapy-
induced toxicity (6 cisplatin, 2 axaliplatin,
1platinum); most suggested less toxicity in
GSH groups. A systematic review of GSH as
an adjuvant therapy in Parkinsons disease
identified one controlled trial[65] showing
doubtful benefit. It was noteworthy that
most studies did not report adverse events of
GSH, and any reported were mild (Table 1).
The idea of GSH-induced hypopigmenta-
tion may stem from early studies linking
sulfhydral-containing compounds to the
inhi bition of melanogenesis or from early
anecdotal observations in Parkin son’s dis-
ease. Proposed mechanisms of its action
include inactivation of the melano genic
enzyme, tyrosinase, influen cing the switch
from eumelanin to phaeo melanin.
During melano genesis, tyrosinase is res-
ponsible for the con version of L-tyro sine
to L-DOPA and subse quently to dopa-
quinone, then the path way bifurcates to
produce eumela nin or phaeomelanin. At
a critical point in the melanogenic path-
way (asterisk, Fig. 1), thiols (cysteine and
GSH) can react with L-dopaquinone to
produce gluta thionyldopa, or act as a reser-
voir of L-cysteine by conjugating with L-dopa-
quinone to produce cysteinyl dopa.These two
thioldopa substrates serve as a precursor to
enhance the switch from eumelano genesis to
phaeomelano genesis, resulting in lighter skin
pigmentation.[68,69] This effect of GSH on skin
pigmentation was reported half a century ago,
with black human skin shown to exhibit lower
levels of GSH than white skin.[70] In addition,
GSH can act to lighten the skin directly
through the quenching of free radicals and
peroxides that have been shown to induce
tyrosinase activity.[71] However, more evi-
dence is needed to prove this unequivocally.
GSH therefore has the potential to light-
en human skin. However, the only relia ble
safety data on GSH are of sporadic use dur-
ing chemo therapy cycles, for a few weeks at
most. There are no data on adverse effects
of chronic high-dose GSH as used for skin
All chemotoxicity studies used injectable
GSH. Reactive oxygen species are easily
de com posed in aqueous solution; this may
explain the novelty of drug delivery as
lozenges, which may be more stable
(although two participants complained about
the taste). The oral route reduces potential
adverse events associated with intravenous
(IV) administration but is associated with
low bioavailability. Effective topical GSH[25]
may be useful for dermatologists treating
hyperpigmentation, but it is worth noting
that GSH as a thiol interacts with metalloid
complexes that render it ineffective. Patients
should be advised to avoid using GSH with
over-the-counter skin lightening creams that
may contain mercury.[1]
All identified published trials report mild
or no side-effects of GSH use. However,
study duration was a maximum of 12weeks.
We identified one case series that reported
intolerable adverse effects leading to discon-
tinuation of 5 mg oral GSH daily as adjuvant
treatment for hepatocellular carcinoma
(HCC). Seven of 8 patients died within
Tyrosinase ROS
GSH or cysteine
carboxylic acid
DHI melanins
DHICA oxidase
Benzodiazepine metabolites
Fig. 1. GSH and its eect on skin lightening. Reactive oxygen species (ROS) have a direct activation eect
on tyrosinase. Reduced GSH neutralises ROS formation and thus indirectly inhibits tyrosinase. At the
dopachrome step* of the melanogenic pathway, interaction of thiols such as reduced GSH and cysteine
bind with dopaquinone to produce thioldopas and favour phaeomelanogenesis. GST catalyses binding
of GSH and dopaquinone. (DOPA = dihydroxyphenylalanine; DHI = dihydroxyindole; DHICA=
dihydroxyindole carboxylic acid.)
784 August 2016, Vol. 106, No. 8
1year. However, the very severe prognosis associated with HCC was
a likely confounder.
[72] The effect of long-term administration of high
doses of GSH on cells or organ systems remains unclear. Further-
more, since GSH causes a switch from eumelanin to phaeomelanin,
it may increase UV photosensitivity, DNA damage and skin cancers
in previously protected populations.[73] Of major concern are
Table 1. Current list of human clinical trials associated with GSH
Country of origin
Study type
Subjects, n (sex), age
GSH dose and duration
Study duration Outcomes Adverse events
Skin whitening
Hong et al.,[22]
Cases (uncontrolled)
Pharmacokinetic study
7 (male), 22 - 23 yr
65.5 (SD 4.5) kg, 50 mg
GSH/kg body weight IV
over 10 min, 10 d
IV GSH oxidised to GSSG (half-life =
10 min)
Loading dose = 1.69 g/kg
Maintenance dose = 5.70 g/h/kg to
reach extracellular concentration
required to suppress intracellular ROS
None reported
Arjinpathana and
Asawonda,[24] 2012
Bangkok, Thailand
RCT (double-blind,
Skin whitening
60 (18 male, 42 female),
19 - 22 yr
250 mg capsules GSH twice
daily, 4 wk
Significant reduction in melanin indices
(UV spots) as measured by VISIA
(Canfield Scientific Inc., USA) at all six sites
in subjects who received GSH v. controls
Sriharsha et al.,[23]
Pilot study
GSH soap: melanosis of
the face
15, 15 - 70 yr
3 mo
Decreased hyperpigmentation in 11/15
patients after 3 mo
None reported
Wat an ab e et al.,[25]
Ibaraki, Japan
RCT (double-blind, placebo)
Skin whitening
30 (female), 30 - 50 yr
2% GSSG lotion twice daily,
10 wk
Weeks 6 and 10:
Melanin index sign lower GSSG v. placebo
Keratin index sign lower GSSG v. placebo
Mild erythema of
the face (n=1)
Handog et al.,[26]
Manilla, Phillipines
Single-arm trial (not
GSH-containing lozenges
Skin whitening
30 (female), 22 - 42 yr
500 mg daily, 8 wk
Decreased melanin index after 2 wk
All subjects showed a significant
decrease in melanin index from baseline
Sore gums (n=1)
flavour/texture of
lozenge (n=1)
Chemotherapy drugs neuroprotection
Cascinu et al.,[27]
RCT (double-blind, placebo)
Prevent cisplatin toxicity
in gastric cancer
GSH 1.5 g/m2 in 100 mL
saline IV over 15 min
600 mg GSH IM, days 2 - 5
15 wk
Week 9: 0 GSH v. 16 placebo
Week 15: 4/24 GSH v. 16/18 placebo
None reported
Colombo et al.,[28]
Random, phase II
Prevent cisplatin toxicity
in relapsed ovarian cancer
50 mg/m2 weekly ± 2.5 g/m2
GSH, 9 wk
Higher (100% dose) cisplatin intensity
was received by 56% GSH v. 27%
None reported
Parnis et al.,[29]
RCT (double-blind,
Prevent cisplatin toxicity
in ovarian cancer
GSH 1.5 g/m2 over 15 min
CDDP 40 mg/m2 over 2 h for
2, 3 or 4 consecutive days
No significant protection None reported
Bogliun et al.,[30]
Placebo controlled
Prevent cisplatin toxicity
in ovarian cancer
CDDP total dose 500 - 675
mg/m2 ± GSH 2.5 g/m2 IV
over 15 min, 1 wk
Less severe neurotoxicity after
co-treatment with all methods
Similar in both
groups except
oliguria greater in
placebo group
Smyth et al.,[31]
United Kingdom
RCT (double-blind,
Prevent cisplatin toxicity
in ovarian cancer
151 (female), 21 - 76 yr
6 cycles of 100 mg/m2 ± 3 g/
m2 + GSH IV over 15 min,
3 wk
6 courses of cisplatin, 58% GSH v. 39%
Improved creatinine, GSH 74% v. 62%
GSH improved depression, emesis,
neurotoxicity, hair loss, shortness of breath
None reported
Continued ...
785 August 2016, Vol. 106, No. 8
potentially severe complications (septicaemia, infective endocarditis
and transmission of blood-borne infections) of IV administration of
GSH by people with no health qualifications. Recent Food and Drug
Administration warnings also point to a need for increased public
awareness of potential harm.[74]
This brief review evaluates recent clinical studies on the use of GSH.
Despite widespread use of IV GSH, no clinical report was identified.
Large RCTs of long-enough duration and follow-up are warranted
for the safe treatment of pigmentary disorders. The psychosocial
impact of systemic skin lightening is a Pandora’s box best addressed
by multidisciplinary teams including social scientists, psychologists
and psychiatrists.
Source of funding. Funded by the South African Medical Research
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2. Maneli MH, Wiesner L, Tinguely C, et al. Combinations of potent topical steroids, mercury and
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Table 1. (continued) Current list of human clinical trials associated with GSH
Country of origin
Study type
Subjects, n (sex), age
GSH dose and duration
Study duration Outcomes Adverse events
Schmidinger et
al.,[32] 2000
RCT (blinding, pilot)
GSH v. intensive
hydration in cisplatin
chemo regimen for solid
80 mg/m2, 4 wk
GSH 5 gIV + 2 000 mL
saline control + 4 000 mL
saline + forced diuresis
Haemoglobin: GSH 10.7 mg v. placebo
9.5 mg (p=0.039)
White cells: GSH 3.3 × 103/mL v.
placebo 2.2 × 103/mL (p=0.004)
Platelets: GSH 167 × 103/mL v. placebo
95 × 103/mL (p=0.02)
None reported
Cascinu et al.,[33]
RCT (double-blind,
Prevent oxaliplatin
toxicity in advanced
colorectal cancer
GSH 1 500 mg/m2 IV over
15 min prior to oxaliplatin
12 treatment cycles
Cycle 4: 7 GSH v. 11 placebo
Cycle 8: 9/21 GSH v. 15/19 placebo
Cycle 12: 3 GSH arm v. 8 placebo
None reported
Milla et al.,[34]
Oxaliplatin neurotoxicity
in colorectal cancer
treated with FOLFOX4
adjuvant regimen
GSH 1 500 mg/m2 IV or
saline solution before
oxaliplatin infusion
12 treatment cycles
Reduced neurotoxicity GSH v. placebo
None reported
Leal et al.,[35] 2014 USA
RCT (double-blind, placebo)
Prevent platinum
peripheral neuropathy
1.5 g/m2 GSH IV or placebo
over 15 min
18 wk
No statistically significant differences
in peripheral neurotoxicity, degree of
paclitaxel acute pain syndrome, time to
disease progression or apparent toxicities
None reported
Neurodegenerative disorders
Sechi et al.,[36]
Cases (uncontrolled)
Parkinson’s disease
600 mg GSH IV twice daily,
30 d, 4 mo
42% decline in disability, therapeutic
effect lasted 2 - 4 mo
None reported
Hauser et al.,[37]
RCT, pilot trial (placebo)
Safety and preliminary
efficacy in Parkinson’s
1 400 mg GSH IV or
placebo 3 times a wk, 4 wk
3 mo
Unified Parkinson’s Disease Rating Scale
(UPDRS) motor scores higher in GSH
group v. placebo
No adverse events
due to GSH
Mischley et al.,[38]
Safety and tolerability
of intranasal GSH in
Parkinson’s disease
600 mg/d of intranasal
GSH v. placebo (saline) in
3divided daily doses
3 mo
All groups met tolerability criteria No adverse events
due to GSH
NR = not reported; IM = intramuscular.
786 August 2016, Vol. 106, No. 8
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subjects. J Korean Med Sci 2005;20(5):721-726. DOI:10.3346/jkms.2005.20.5.721
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33. Cascinu S, Catalano V, Cordella L, et al. Neuroprotective eect of reduced glutathione on oxaliplatin-
based chemotherapy in advanced colorectal cancer: A randomized, double-blind, placebo-controlled
trial. J Clin Oncol 2002;20(16):3478-3483. DOI:10.1200/JCO.2002.07.061
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Accepted 11 April 2016.
... The production of the brown pigment eumelanin is halted, resulting in the switch to production of pheomelanin, which is a red/orange pigment. 20 This is one of three postulated mechanisms of action for GSH. 15,20 Depleted levels of GSH in cells have been found in Parkinson's disease, cadmium exposure, HIV/AIDS, macular degeneration, and other neurodegenerative disorders. ...
... 20 This is one of three postulated mechanisms of action for GSH. 15,20 Depleted levels of GSH in cells have been found in Parkinson's disease, cadmium exposure, HIV/AIDS, macular degeneration, and other neurodegenerative disorders. 13 Supplemental dietary GSH has been tested as a treatment for liver abnormalities, deficient immunity, pre-term infant autism, chronic otitis media, Parkinson's disease and other disorders. ...
... The skin lightening effect of these compounds was discovered during their use in a study for Parkinson's disease treatments. 20 Compounds that act as scavengers for ROS, such as GSH, can slow down the effects of melanogenesis. Furthermore, if the compound has redox properties like glutathione, it can decrease melanin production by interacting with o-quinones or the thiol group at the active site of the enzyme tyrosinase. ...
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.
... Although intravenous glutathione is popular, there is no evidence of its efficacy and insufficient data on its safety, dosage, and duration of use. Additional randomized, double-blind, placebo-controlled trials with larger sample sizes, long-term follow-up, and definitive efficacy results are needed to determine the relevance of this molecule in pigmentation and skin-lightening disorders [107,108]. ...
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The global cosmetics market reached US$500 billion in 2017 and is expected to exceed US$800 billion by 2023, at around a 7% annual growth rate. The cosmetics industry is emerging as one of the fastest-growing industries of the past decade. Data shows that the Chinese cosmetics market was US$60 billion in 2021. It is expected to be the world's number one consumer cosmetics market by 2050, with a size of approximately US$450 billion. The influence of social media and the internet has raised awareness of the risks associated with the usage of many chemicals in cosmetics and the health benefits of natural products derived from plants and other natural resources. As a result, the cosmetic industry is now paying more attention to natural products. The present review focus on the possible applications of natural products from various biological sources in skin care cosmetics, including topical care products, fragrances, moisturizers, UV protective, and anti-wrinkle products. In addition, the mechanisms of targets for evaluation of active ingredients in cosmetics and the possible benefits of these bioactive compounds in rejuvenation and health, and their potential role in cosmetics are also discussed.
... There is also concern regarding the risk of transmission of blood borne infections when IV glutathione is administered by untrained professionals. 29 ...
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The quest to be fair is not a concept of the new world. For centuries untold, having a lighter skin tone has been considered as a trait of beauty and supremacy. Society implicates fairness as a factor for getting a prospective life partner. Media portrays fair skin tone as a predecessor for success. These subtle influences affect young minds and drive them towards wanting fair skin. Physicians observe that it is one of the most common forms of body dysmorphic disorder. This article aims to highlight the psychosocial factors that mold this mentality and the possible ill effects it can have on a person, both psychologically as well as physically. This article is protected by copyright. All rights reserved.
... Costs depend on the route and dose, with the PatientsLikeMe cohort reporting a range of less than $25 to more than $200 monthly (23). Most forms of glutathione have been well tolerated; less than 10% of participants with a wide range of conditions experienced side effects in short duration trials (28,(32)(33)(34)(35)(36). In the ALS trial, only 2 out of 32 PALS experienced glutathione side effects (nausea) felt to be related to treatment (28). ...
... Lastly, it switches skin pigmentation pathway from eumelanin (darker pigment) to phaeomelanin (lighter pigment). 6,8,9 There are various glutathione products for skin whitening including topical, oral, and parenteral preparation. 5 Oral glutathione is the most common product in markets as a dietary supplement. ...
Background Glutathione is one of agents which is commonly used to lighten skin color in Asia as a dietary supplement. Previous studies suggest its potential effect of glutathione on skin color. However, the clinical efficacy of glutathione in oral form is still questionable due to its limited absorption and bioavailability. Aim To determine the clinical effects of glutathione on skin color and related skin conditions. Patients/Methods A systematic review was conducted using PubMed, CINAHL, Scopus, EMBASE and Cochrane library were searched from inceptions to October 2017. All clinical studies evaluating the effect of glutathione on any skin effects in healthy volunteer were included. Results A total of four studies were included. Three studies were RCTs with placebo control, while one was a single‐arm trial. One study used topical form, while others used oral form of glutathione with 250 to 500 mg/day. We found that both oral glutathione with the dosage of 500 mg/day and topical 2.0% oxidized glutathione could brighten skin color in sun‐exposed area measured by skin melanin index. No significant differences in the reduction in skin melanin index were observed in sun‐protected area for any products. In addition, glutathione also has a trend to improve skin wrinkle, skin elasticity, and UV spots. Some adverse events but nonserious were reported. Conclusions Current evidence of the skin whitening effect of glutathione is still inconclusive due to the quality of included studies and inconsistent findings. However, there is a trend that glutathione might brighten skin color at skin‐exposed area.
... Fraksi antosianin dari ubi ungu yang mengandung senyawa aktif peonidin diketahui dapat menginduksi enzim glutation peroksidase (GPX) yang berperan dalam pemecahan ROS (Reactive Oxygen Species) secara in silico (Laksmiani et al., 2016). ROS inilah yang diketahui mampu menginduksi aktivitas tirosinase sehingga terjadi peningkatan proses melanogenesis (Davids et al., 2016). Oleh karena itu, senyawa antosianin (sianidin dan peonidin) yang terdapat pada ubi ungu berpotensi untuk dikembangkan sebagai agen depigmentasi. ...
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Hyperpigmentation is caused by enhancement of melanin production that causes skin darkening. Purple sweet potato is one of the plants that is potentially developed as skin depigmentation agent because it contains anthocyanin. The most common types of anthocyanins in purple sweet potato are cyanidin and peonidin which are in vitro proven to be used as skin lightening. The objective of this study is to determine the potential of cyanidin and peonidin as skin depigmentation agent against target protein D-Dopachrome taumerase through in silico molecular docking method. The research steps include the preparation of target protein using Chimera 1.10.1 program, optimization of cyanidine and peonidin 3D structures using Hyperchem 8 program, validation of molecular docking method, and docking of cyanidine and peonidine on target protein using Autodock 4.2 program. The bond energy between cyanidin and peonidin with the target protein D-Dopachrome taumerase are -7.75 kcal / mol and -8.38 kcal / mol. The cyanidin and peonidin bond values ??are smaller than the native ligand, suggesting that the bond between the test compound (cyanidin and peonidin) with the target protein are stronger and more stable than the native ligand, so that the affinity of the test compound was greater than the native ligand. This suggests that the cyanidin and peonidin compounds in purple sweet potato have potential as a depigmentation agent by inhibiting D-Dopachrome taumerase protein.
... Thiol also scavenges NO via S-nitrosation [8]. Because of these effects, thiol-containing compounds are often used in treating chloasma [7,9]. However, the skin whitening effect of thiols is very weak, a demand for more effective ROS and NO scavenging agents exists. ...
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Products of ultraviolet (UV) irradiation such as reactive oxygen species (ROS) and nitric oxide (NO) stimulate melanin synthesis. Reactive sulfur species (RSS) have been shown to have strong ROS and NO scavenging effects. However, the instability and low retention of RSS limit their use as inhibitors of melanin synthesis. The free thiol at Cys34 on human serum albumin (HSA) is highly stable, has a long retention and possess a high reactivity for RSS. We report herein on the development of an HSA based RSS delivery system. Sulfane sulfur derivatives released from sodium polysulfides (Na2Sn) react readily with HSA. An assay for estimating the elimination of sulfide from polysulfide showed that almost all of the sulfur released from Na2Sn bound to HSA. The Na2Sn-treated HSA was found to efficiently scavenge ROS and NO produced from chemical reagents. The Na2Sn-treated HSA was also found to inhibit melanin synthesis in B16 melanoma cells and this inhibition was independent of the number of added sulfur atoms. In B16 melanoma cells, the Na2Sn-treated HSA also inhibited the levels of ROS and NO induced by UV radiation. Finally, the Na2Sn-treated HSA inhibited melanin synthesis from L-DOPA and mushroom tyrosinase and suppressed the extent of aggregation of melanin pigments. These data suggest that Na2Sn-treated HSA inhibits tyrosinase activity for melanin synthesis via two pathways; by directly inhibiting ROS signaling and by scavenging NO. These findings indicate that Na2Sn-treated HSA has potential to be an attractive and effective candidate for use as a skin whitening agent.
... In contrast to the relative lack of safety of IV GSH (as per the Philippines' FDA, and the trial by Zubair et al.), the analysis of two systematic reviews of IV GSH for preventing chemoinduced toxicity and one review of its use as for Parkinson's disease (overall 10 trials included) reported minimal-to niladverse effects, and no long-term complications. [16] 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. ...
Background Pigmentation of the skin occurs as a result of increased melanin production or deposition due to various reasons including age, hormonal imbalances, endocrine disease, inflammation, and/or exposure to damaging radiation, resulting in dermatologic conditions such as lentigines, melasma, or postinflammatory hyperpigmentation. Although numerous topical therapies exist for skin lightening, they are limited by efficacy and pigmentation recurrence after treatment cessation. New research into systemic therapies for hyperpigmentation has been promising. Objective To summarize the current literature for systemic skin lightening therapies. Methods A review of the literature surrounding systemic skin lightening therapies was completed using PubMed (US National Library of Medicine). Results Multiple systemic therapies for skin lightening exist including oral carotenoids, glutathione, melatonin, Polypodium leucotomos hydrophilic extract, procyanidin, and tranexamic acid. Preliminary data for the treatment of hyperpigmentation are promising, and currently, these oral treatments appear safe. It is not suggested to use intravenous glutathione for skin lightening due to the increased risk of adverse events. Conclusion With the patient population seeking effective systemic treatments for skin pigmentation, it is important for dermatologists to understand the properties, the efficacy, and the adverse events profile of each compound, thus ensuring proper use by patients, and that patients are appropriately counseled regarding treatment expectation and safety.
Several depigmenting agents are now available both for topical and systemic use with varying degrees of evidence on their efficacy and safety. These agents act by inhibiting melanogenesis, interrupting melanosome transfer, accelerating epidermal desquamation with melanin turnover, antioxidant effects and by other methods. The topical agents that act mainly by inhibiting melanogenesis through tyrosinase inhibition include hydroquinone and derivatives, arbutin, kojic acid, azelaic acid, methimazole, gentisic acid, flavonoids (aloesin, licorice) and antioxidants (ascorbic acid, alpha tocopherols and grapeseed extracts). Examples of agents that interrupt melanosome transfer are niacinamide, soybeans and lectins. Topical agents that accelerate epidermal desquamation and melanin turnover include retinoids, hydroxy acids, salicylic acids and linoleic acids. Other agents that act by varying mechanisms are tranexamic acid, steroids and other active ingredients found in various plant extracts. Topical therapies in combination are found to be more effective as add-on agents to optimise the effects of the other agents and mitigate the side effects of primary agents. They are often used as first-line therapy. The systemic agents used include tranexamic acid, glutathione, oral vitamin C and vitamin E. Some systemic agents such as glutathione are often misused without adequate evidence of its efficacy and long-term safety.
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Previous studies have reported the association of glutathione S-transferase M1 (GSTM1) deletion polymorphism with genetic susceptibility of lung cancer in Chinese population. However, the results remained controversial. The aim of this study was to clarify the association of GSTM1 deletion polymorphism with lung cancer risk in Chinese population. Systematic searches were performed through the search engines of Medline/Pubmed, Web of Science, EMBASE, CNKI and Wanfang Medical Online. The pooled effects were calculated by STATA 10.0 software package and Review Manager 5.0.24. Overall, we observed an association of GSTM1 deletion polymorphism with increased lung cancer risk in Chinese population (odds ratio (OR) = 1.46, 95% confidence interval (95%CI): 1.32-1.66 for null genotype vs. present genotype) based on 53 studies including 7,833 cases and 10,353 controls. We also observed an increased risk of GSTM1 null genotype for lung cancer in stratified analyses by source of control, smoking status and histological type. The findings suggest that GSTM1 deletion polymorphism may contribute to lung cancer risk in Chinese population. Further, well-designed studies with larger sample sizes are required to verify the results.
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Because the function and mechanisms of sleep are partially clear, here we applied a meta-analysis to address the issue whether sleep function includes antioxidative properties in mice and rats. Given the expansion of the knowledge in the sleep field, it is indeed ambitious to describe all mammals, or other animals, in which sleep shows an antioxidant function. However, in this article we reviewed the current understanding from basic studies in two species to drive the hypothesis that sleep is a dynamic-resting state with antioxidative properties. We performed a systematic review of articles cited in Medline, Scopus and Web of Science until March 2015 using the following search terms: Sleep or sleep deprivation and oxidative stress, lipid peroxidation, glutathione, nitric oxide, catalase or superoxide dismutase. We found a total of 266 studies. After inclusion and exclusion criteria, 44 articles were included, which are presented and discussed in this study. The complex relationship between sleep duration and oxidative stress is discussed. Further studies should consider molecular and genetic approaches to determine whether disrupted sleep promotes oxidative stress.
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Some studies have recently focused on the association between glutathione S-transferase M1 (GSTM1) and glutathione S-transferase T1 (GSTT1) null polymorphisms and hypertension; however, results have been inconsistent. In order to drive a more precise estimation, the present systematic review and meta-analysis is performed to investigate the relationship between the GSTM1 and GSTT1 null polymorphisms and hypertension. Eligible articles were identified by a search of several bibliographic databases for the period up to August 17, 2013. Odds ratios were pooled using either fixed-effects or random-effects models. Regarding the GSTM1 null/present genotype, 14 case-control studies were eligible (2773 hypertension cases and 3189 controls). The meta-analysis revealed that it might present a small increased risk for hypertension, although the effect was not statistically significant (odd ratio (OR) = 1.16, 95% confidence interval (CI): 0.96, 1.40; P = 0.002, I2 = 59.8%). Further subgroup analysis by ethnicity and control source suggested that the association was still not significant. Thirteen case-control studies were eligible for GSTT1 (2497 hypertension cases and 3078 controls). No statistically significant association was observed between the GSTT1 null genotype and hypertension risk (OR = 1.14, 95% CI: 0.85, 1.53; P = 0.000, I2 = 80.3%). Furthermore, stratification by ethnicity and control source indicated no association between the GSTT1 null genotype and hypertension risk. We further confirmed the association by sensitivity analysis. No publication bias was detected. This meta-analysis suggests that the GSTM1 and GSTT1 null polymorphisms are not associated with the risk of hypertension. Future large well-designed epidemiological studies with individual information, lifestyle factors, and environmental factors are warranted to validate the present findings.
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Purpose. To study the effects of glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) polymorphisms on age-related cataract (ARC). Methods. After a systematic literature search, all relevant studies evaluating the association between GSTs polymorphisms and ARC were included. Results. Fifteen studies on GSTM1 and nine studies on GSTT1 were included in this meta-analysis. In the pooled analysis, a significant association between null genotype of GSTT1 and ARC was found (OR = 1.229, 95% CI = 1.057-1.429, and P = 0.007). In subgroup analysis, the association between cortical cataract (CC) and GSTM1 null genotype was statistically significant (OR = 0.713, 95% CI = 0.598-0.850, and P < 0.001). In addition, GSTM1 null genotype was significantly associated with ARC causing risk to individuals working indoors and not individuals working outdoors. The association between GSTT1 null genotype and risk of ARC was statistically significant in Asians (OR = 1.442, 95% CI = 1.137-1.830, and P = 0.003) but not in Caucasians. Conclusions. GSTM1 positive genotype is associated with increased risk of CC and loses the protective role in persons who work outdoors. Considering the ethnic variation, GSTT1 null genotype is found to be associated with increased risk of ARC in Asians but not in Caucasians.
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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.
To systematically review and meta-analyze oxidative stress and antioxidant markers in anorexia nervosa (AN). Electronic PubMed search from database inception until 12/31/2013. Out of 1062 hits, 29 studies comparing oxidative stress/antioxidant markers between patients with AN and healthy controls (HCs) with a total of 1,729 participants (AN = 895, HCs = 834) were eligible. Data about oxidative stress and antioxidant markers, independent of their source, were extracted. We calculated random effects standardized mean differences (SMDs) as effect size measures for outcomes reported in ≥5 studies; others were summarized descriptively. Compared to HCs, AN patients showed significantly higher apolipoprotein B (ApoB) levels (studies = 7; n = 551; SMD = 0.75; p = .0003, I(2) = 74%), with higher age being associated with higher ApoB (Coefficient: 0.61 ± 0.15, p < .0001), whereas BMI (p = .15) and measurement method (p = .70) did not moderate the results. Serum albumin levels were similar between AN and HCs (studies = 13; n = 509; SMD =-0.19; 95%CI: -0.62 to 0.24; p = .38; I(2) = 81%), with neither age (p = .84) nor BMI (p = .52) being significant moderators. Lower superoxide dismutase levels were reported in 2 studies, while findings for vitamin A and its metabolites were inconclusive. In single studies, patients with AN had significantly higher catalase and nitric oxide (NO) parameter levels (platelet NO, exhaled NO and nitrites), such as lower glutathione and free cysteine levels, compared to HCs. AN appears to be associated with some markers of increased oxidative stress. Additional research is needed to discern whether oxidative stress is a potential cause or effect of AN, and whether treatments improving oxidative stress could be useful in AN. © 2015 Wiley Periodicals, Inc. (Int J Eat Disord 2015). © 2015 Wiley Periodicals, Inc.
Depletion of reduced glutathione is associated with PD and glutathione augmentation has been proposed as a disease-modifying strategy. The aim of this study was to determine the safety and tolerability of intranasal reduced glutathione in individuals with PD. Thirty individuals with PD were randomized to either placebo (saline), 300 mg/day, or 600 mg/day of intranasal glutathione in three divided daily doses. Follow-up visits included side effect screening of PD symptoms and cognition, blood chemistry, sinus irritation, and hyposmia. Tolerability was measured by frequency and severity of reported adverse events, compliance, and withdrawals from the study. After 3 months, there were no substantial differences between groups in the number of adverse events reported or observed among all safety measures assessed. All groups met tolerability criteria. These data support the safety and tolerability of intranasal glutathione in this population. Pharmacokinetic and dose-finding studies are warranted. © 2015 International Parkinson and Movement Disorder Society. © 2015 International Parkinson and Movement Disorder Society.
The topical steroids betamethasone (BM) and clobetasol propionate (CP) are illegal in cosmetics. Hydroquinone (HQ) and mercury (Hg) are either illegal or allowed only in limited concentrations (2% and 1 ppm, respectively). To investigate active ingredients and countries of origin of popular skin-lightening products available in Cape Town, South Africa. In total, 29 products were examined; of these, 22 products were purchased from informal vendors, and 2 products (out of a total of 29) were purchased over the counter. HQ, Hg(2+) and steroids were quantified by high-performance liquid chromatography-ultraviolet spectrophotometry, inductively coupled plasma-mass spectrometry and liquid chromatography-mass spectrometry, respectively. Of the 29 products, 22 (75.9%), all imported and bought from informal vendors, contained illegal or banned ingredients: 13 (44.8%) contained steroids (9 CP, 4 BM), 12 (41.4%) contained Hg (30-2300 ppm), and 11 (37.9%) contained HQ. Sequentially, the products originated from Italy (27.3%, n = 6), India (22.7%, n = 5), the Democratic Republic of Congo (DRC) (22.7%, n = 5), Cote d'Ivoire (9.1%, n = 2), USA (9.1%, n = 2), UK (4.5%, n = 1) and France (4.5%, n = 1). Two products, one from India and one from the DRC, contained all four ingredients (HQ, Hg, BM, CP). Of the 12 products containing Hg, 10 also contained HQ and/or a steroid, yet none listed Hg as an ingredient. A significant proportion of the steroid-containing products (76.9%) also contained at least one other skin-lightening agent. Not all internationally available products were tested, which is a limitation of the study. In spite of a European Union ban on skin lighteners, a third of the products tested were from Europe. Combinations of Hg and ultrapotent steroids were prominent. International law enforcement and random testing is needed to encourage industry compliance and help protect consumers. © 2015 British Association of Dermatologists.
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.
OBJECTIVES: Withania somnifera has been in use for several thousand years in Ayurveda to treat various neurological disorders. There is, however, not much scientific data on its protective role in neuronal pathology specifically against brain oxidative stress. Hence, an attempt is made in this work for systematic review and meta-analysis of W. somnifera on neurobehavioural disorders induced by brain oxidative stress in rodents. METHODS: A systematic search of the effect of W. somnifera on brain oxidative stress-induced neuronal pathology was performed using electronic databases. The systematic review was performed on neurobehavioural parameters, whereas meta-analysis of W. somnifera effect was done on oxidative stress markers (superoxide dismutase, catalase, glutathione peroxidase, glutathione and lipid peroxidation), nitrite, protein carbonyl, AchE, ChAT and Ach of rodent brain. Data were analysed using Review Manager Software. KEY FINDINGS: Twenty-eight studies were selected based upon the inclusion and exclusion criteria. W. somnifera appreciably inhibited the neurological abnormalities due to oxidative stress in rodent brain produced by different physical and chemical stimuli. W. somnifera also significantly restored the altered oxidative and other stress markers in different parts of rodent brain. SUMMARY: The systematic review provides scientific evidence for the traditional claim of W. somnifera use in different neurological aliments. However, future clinical trials are mandated to establish the therapeutic efficacy and safety in human beings. KEYWORDS: Indian ginseng; antioxidant; meta-analysis; neuropathology; oxidative stress