4/23/2018 Skin Hydrating and Whitening effects of Vitamin C and Glutathione in Asian skin types | PRIME Journal

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Skin Hydrating and Whitening effects of

Vitamin C and Glutathione in Asian skin
types
BY KEITH ONG / POSTED IN ANTI-AGEING, DERMATOLOGY ON OCTOBER 14, 2015

Keith Ong describes the results from his study on the effects of multiple intravenous
injections of vitamin C and glutathione…

Keith Ong describes the results from his study on the effects of multiple intravenous injections of vitamin C and
glutathione on the skin of 283 patients.

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4/23/2018
As a person ages, hormonal Skin Hydrating
changes and Whitening
cause intrinsiceffects
aging,of Vitamin
while Cthe
andexternal
Glutathione in Asian skin types
environment, | PRIME ultraviolet
primarily Journal (UV)
radiation, accounts for much of the extrinsic aging1,2. Intrinsic aging of the skin results in the thinning of the epidermis, a
reduction in the connective tissue matrix, and a reduction in sebaceous glands. Therefore, even without UV radiation
exposure, as a person ages, their skin will look thinner, paler, more wrinkled, and drier. Genetically, men have a thicker
epidermis, connective tissue matrix, and higher sebaceous gland density, therefore the signs of intrinsic aging tend to be
less pronounced compared to a woman of the same age.

UV irradiation leads to extrinsic skin aging by inducing the production of reactive oxygen species (ROS) in the skin3. In
time the ROS generate a cascade of molecular reactions that result in mutation and destruction of collagen, elastin,
proteoglycans, and other dermal cellular structures4. Macroscopically, this ROS-induced damage will make an
individual’s skin look dry, wrinkled, dull, sallow, and unevenly pigmented5. UV irradiation also triggers melanogenesis,
hence resulting in skin darkening and pigment formation. Vitamin C (Vit C) and glutathione (GSH) are strong
antioxidants. Their strong antioxidant property helps to protect the skin against UV radiation induced photoaging4–7 by
eradicating the ROS, hence halting the destructive cascade of activities. Vit C and GSH also help to whiten the skin by
inhibiting melanogenesis, triggered by UV irradiation9–12. Vitiman C also triggers a strong reparative effect in the skin by
inducing a quantitative increase and qualitative improvement of collagen molecules thereby reversing the UV induced
skin damage4.

In summary, UV irradiation produces ROS and triggers melanogenesis, which causes the skin to become dry, dull, and
unevenly pigmented. Vitamin C and glutathione remove the ROS, repair the skin connective tissue, and inhibit skin
darkening, thereby making the skin more hydrated, fairer, and more radiant4–7, 9–12.

Vitamin C and glutathione

For these reasons, Vit C and GSH are commonly found in topical cosmetic creams for skin repair and whitening3,8. Farris
published a review article3, which stated that a significant level of scientific research supports the use of topical vitamin C
for collagen synthesis, photoprotection from ultraviolet A and B, skin lightening, and improvement of a variety of
inflammatory dermatoses3. In a double blind and placebo controlled clinical trial involving 30 adult Japanese women over
a period of 10 weeks conducted by Fumiko et al8, the subjects applied glutathione 2% lotion to one side of the face and a
placebo lotion to the other side twice daily for 10 weeks. Fumiko et al reported significant skin melanin index reduction,
significant increase in moisture content of the stratum corneum, a suppression of wrinkle formation, and improvement in
skin smoothness.

Besides using topical cream, intravenous injection containing Vit C and GSH has also been used for skin hydration and
whitening in many parts of Asia, particularly in the Philippines, Taiwan, China, and Malaysia. This was the first reported
study to evaluate the skin hydrating and whitening effects of Vit C and GSH given in the form of intravenous injections.

Aim of study
The aim of the study was to evaluate the skin hydrating and whitening effects of Vit C and GSH by reporting patients’
assessment and overall satisfaction after a course of six Vit C and GSH injections. For this study, skin hydration referred
to making skin less dry and more moist. Skin whitening referred to making skin either fairer or more radiant or both.

Material and method

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Study
4/23/2018
participants Skin Hydrating and Whitening effects of Vitamin C and Glutathione in Asian skin types | PRIME Journal

The medical records of consecutive patients newly enrolled between 1 st January to 31 st December 2014 were selected
for this study. Inclusion criteria were:

First visit for Vit C and GSH injection fell between 1 st January 2014 to 31 st December 2014
Completed six Vit C and GSH injections
Of the six Vit C and GSH injections, the interval between each injection must be equal or less than 10 days.

Material used
The vitamin C solution used for injection was under the brand
Laroscorbine® 1 g/5 ml (Bayer Sante Familiale, larosrcobine,
Gaillard, France). The glutathione powder used for injection was
under the brand Tationil® 600 mg/4 ml, (Teoforma , Tationil,
Salimbene, Italy).

Method of injection

One vial of glutathione powder (600 mg) was mixed with 10 ml

of vitamin C solution (2 g) in a 10 ml syringe. The constituted
glutathione/vitamin C solution was injected intravenously into
the patient via a Surflo® winged infusion set 23G x 3/4” (Terumo Corporation, Surflo®, Tokyo, Japan). The constituted
solution was injected slowly over 5 minutes.

Injections sites were either right cubital fossa, left cubital fossa,
dorsum of right hand or dorsum of left hand. The same doctor
constituted the solution and administered the injection to the
patient.

Treatment protocol
Patients were given an injection once every 7–10 days, a total of
six times. The first injection was given during the first visit and
assessment.

Method of assessment
Skin assessment of the face and all limbs at first visit was noted
clinically by visual assessment and the patient’s main complaints
were recorded. For the purpose of the study, the skin parameters were divided into:

Normal hydration or dry

Fair or tan
Radiant or dull.

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4/23/2018
The Skin Hydrating
first Vit C and GSH injection was givenand Whitening
during theeffects
firstof visit.
VitaminDuring
C and Glutathione
the second in Asian skin types
to sixth visit,| PRIME Journal reported on
the patients
how they felt about their skin condition over the period of time from the last injection up to the current visit to the clinic.
Patients reported whether their skin conditions were worse than before, less dry, fairer, more radiant, or no change (Table
1). One month after the sixth visit, a research assistant contacted the patients over the phone to get their feedback on
the entire treatment. Patients were asked to score their satisfaction level on their skin improvement based on a score of 1
to 7, 1 being the least satisfied and 7 being the most satisfied.

Subjective definition of skin parameters as understood by patients

Patients commonly perceived dry skin as having fine creases/wrinkles on the skin, feeling dry, feeling itchiness easily,
mild peeling, scattered erythematous patches or having scratch marks appear on the limbs easily.

They commonly complained of darker tanned skin, in relation to their previous lighter skin tone.

Patients commonly described dull skin as sallow and yellowish in tone. They wanted a more radiant skin tone, which they
describe as whitish-pink, baby-like skin.

Results
A total of 313 patients were enrolled in the study. However, 30 patients were excluded because the interval between
injections was more than 10 days. Thus, the total number of patients included in the present study was 283. The median
age of the 283 patients was 33 years old and 269 were female (Table 2). The majority of the patients were Chinese
(n=228, 80.6%), while 30 (10.6%) were Malay, 10 (3.5%) were Indian, and 15 (5.3%) were of other ethnicities.

During the first visit, most patients (n=115) complained of dry and dull skin, followed by 58 patients complaining of dry,
dull, and tanned skin (Table 3).

During the second visit, patients were asked to feedback on how they felt about their skin over the period of time from
after the first injection up to the second visit at the clinic. A total of 206 (72.8%) patients reported noticeable
improvement, their skin was less dry, more radiant, fairer or combinations. Of the 206 patients, most (n=168) reported

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 4/23/2018
that Skin
their skin was less dry, 60 Hydrating more
reported and Whitening
radianteffects
skin,ofand
Vitamin
38Creported
and Glutathione
fairerinskin.
Asian In
skintotal,
types 77
| PRIME Journal
(27.2%) patients claim
no noticeable improvement (Table 4).

From the second to sixth visit, the number of patients that reported noticeable skin improvement increased from 206
(72.8%) to 270 (95.4%). At the sixth visit, the most common skin improvement was skin being less dry, followed by more
radiant and fairer. At the sixth visit, only 13 (4.6%) patients did not notice any improvement.

One month after the sixth injection, the feedback score obtained from the patients showed a median score of 4.99 and
most patients (n=90, 31.8%) reported 5 on the scale of 1 to 7 (Table 5).

Of the 283 patients, only three complained of mild gastritis,

two complained of chills, and two complained of headache.
There was no severe complication noted in this study.

In 7 years of administering Vit C and GSH injections, the

author realised that after each treatment protocol patients
returned either monthly for maintenance injections or some
patients returned for further injections after they came back
from hot sunny overseas trips where their skin became tanned
and dried.

The author concluded from practical experience that the

duration of treatment results depends on three important
factors:

Environmental UV light exposure (for example, an outdoor job

vs indoor job)
Amount of protection against UV light (patients were advised
to carry an umbrella when walking under the sun)
Genetic conditions (patients with eczema tend to visit the clinic
monthly for maintenance).

Discussion
Most patients (n=270, 95.4%) perceived a certain degree of skin hydration and whitening after six Vit C and GSH
intravenous injections and most patients (mean score 4.99 out of 7) were satisfied with the results. This supported the
popular claim in Asia that Vit C and GSH injections had strong skin hydrating and whitening effects.

This study showed that the skin enhancement and whitening effects of Vit C and GSH injection were dose and time
dependent. Most patients experienced improved skin hydration first, followed by increased radiance and fairness. The
number of patients experiencing skin being less dry, more radiant and fairer also increased steadily from the second visit
to the sixth visit (Table 4). This demonstrated that the efficacy of the Vit C and GSH was dependent on the number of
injections received and some patients might require more than six injections to reach optimal skin enhancement whereby
they felt that their skin was hydrated, fair, and radiant. This might also infer that improved skin hydration was the first step
for skin repair and after adequate hydration, the skin will further improve to look more radiant and fairer (whitening effect).

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A4/23/2018 Skin Hydrating
person’s skin hydration, radiance, andand Whitening
tone varieseffects
dailyofand
Vitamin
evenC and Glutathione
within the dayin Asian skin
itself. types
This | PRIME Journal
variation is due to multiple
factors such as the level of stress, amount of sleep, amount of sun exposure, working environment, hormonal cycle, and
diet. Therefore, in this study, the author reported how the patients felt about their skin conditions over the period of time
between the injections, rather than just reporting on their skin conditions during the time of visit.

To date, from the manufacturer’s published literature and a search on the Internet, the author found no contraindication
for intravenous GSH injection. No side-effect has been reported from intermittent dose, short-term GSH supplementation.

The contraindications for intravenous Vit C

supplementation is glucose-6-phosphate
dehydrogenase (G6PD) deficiency13 and
chronic renal failure14. The author would
also like to highlight that in 2000, the
recommended dietary allowance (RDA) set
the tolerable upper limit (UL) of Vit C at
2000 mg daily, referencing its laxative effect
as the reason for establishing the UL15. In
this paper, the patients were given 2000 mg
of intravenous Vit C, once a week. The
author would like to emphasize that there
was no issue of Vit C overdose in the
context of this study.

Some patients had raised the concern regarding the formation of kidney stones due to a high dose of vitamin C
supplementation. Their concerns can be traced back to a Swedish study by Thomas LD et al16, involving 23,355
Swedish men taking oral vitamin C supplements with a follow-up of more than 10 years. The results indicated that high-
dose ascorbic acid are associated with a dose-dependent two-fold increased risk of kidney stone formation among men.
Thomas LD et al also mentioned in the study that their result cannot be extrapolated to women, because men intrinsically
have a higher chance of experiencing kidney stones.

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4/23/2018 Skin Hydrating and Whitening effects of Vitamin C and Glutathione in Asian skin types | PRIME Journal

To address the
patients’ concern,
the author
highlighted that the
Thomas LD et al
study is based on
oral Vit C
supplementation
(1000 mg per tab)
taken consistently,
over a long period of time (>10 years) and the study cannot be extrapolated to women. In this article, the whitening
injection treatment protocol involves intravenous Vit C (2000 mg) and GSH (600 mg) injection given only once a week,
over a period of 6 weeks. The absolute amount of vitamin C taken and the duration of the whitening injection treatment
protocol totally differs from the Thomas et al study cohort.

Conclusion
Most patients (n=270, 95.4%) perceived a certain degree of skin hydration and whitening after six Vit C and GSH
intravenous injections and most patients (mean score 4.99 out of 7) were satisfied with the results, without experiencing
any serious adverse event.

More studies could be conducted to evaluate the efficacy of intravenous Vit C and GSH injections, especially on the
areas of skin whitening, post-operation wound healing, repair of second and third degree burns, and repair of photo-aged
skin.

Acknowledgements
Declaration of interest No funding obtained from any source . The patients recruited into the study are self paying patients. The author does
not have exclusive rights to administer Vit C and GSH injections

Figures 1-2 © Keith Ong

References

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4/23/2018 SkinS,
1. El-Domyati M, Attia Hydrating
Saleh and
F etWhitening effectsaging
al. Intrinsic of Vitamin
vs Cphotoaging:
and Glutathione
a in Asian skin types
comparative | PRIME Journal
histopathological,
immunohistochemical, and ultrastructural study of skin. Exp Dermatol 2002; 11(5): 398–405
2. Gilchrest BA. A review of skin ageing and its medical therapy. Br J Dermatol 1996; 135(6): 867–875
3. Farris PK. Cosmetical Vitamins: Vitamin C. In: Draelos ZD, Dover JS, Alam M, editors Cosmeceuticals.
Procedures in Cosmetic Dermatology. 2nd ed. New York: Saunders Elsevier; 2009 pp 51–6
4. Traikovich SS. Use of Topical Ascorbic acid and its effects on Photo damaged skin topography. Arch Otorhinol
Head Neck Surg 1999; 125: 1091–8
5. Masaki H. Role of antioxidants in the skin: anti-aging effects. J Dermatol Sci 2010; 58(2): 85–90
6. Meister A. Glutathione-ascorbic acid antioxidant system in animals. J Biol Chem 1994; 269(13): 9397–9400
7. Matsuda S, Shibayama H, Hisama M, Ohtsuki M, Iwaki M. Inhibitory effects of novel ascorbic derivative VCP-
IS-2Na on melanogenesis. Chem Pharm Bull 2008; 56: 292–7
8. Fumiko Watanabe Erika Hashizume, Gertrude P Chan and Ayako Kamimur Skin-whitening and skin-
condition-improving effects of topical oxidized glutathione: a double-blind and placebo-controlled clinical trial
in healthy women Clin Cosmet Investig Dermatol 2014; 7: 267–274
9. Arjinpathana N, Asawanonda P. Glutathione as an oral whitening agent: a randomized, double-blind, placebo-
controlled study. J Dermatolog Treat 2012; 23(2): 97–102
10. Jara JR, Aroca P, Solano F, Martinez JH, Lozano JA. The role of sulfhydryl compounds in mammalian
melanogenesis: the effect of cysteine and glutathione upon tyrosinase and the intermediates of the pathway.
Biochim Biophys Acta 1988; 967(2): 296–303
11. Villarama CD, Maibach HI. Glutathione as a depigmenting agent: an overview. Int J Cosmet Sci 2005; 27(3):
147–153
12. Matsuda S, Shibayama H, Hisama M, Ohtsuki M, Iwaki M. Inhibitory effects of novel ascorbic derivative VCP-
IS-2Na on melanogenesis. Chem Pharm Bull 2008; 56: 292–7
13. Rees DC, Kelsey H, Richards JD. Acute haemolysis induced by high dose ascorbic acid in glucose-6-
phosphate dehydrogenase deficiency. British Medical Journal 1993; 306 (6881): 841–2
14. Nankivell BJ, Murali KM. Renal failure from vitamin C after transplantation NEJM 2008; 358 (4): e4
15. Institute of Medicine. Dietary reference intakes for vitamin C, vitamin E, selenium, and carotenoids.
Washington, DC: The National Academies Press, 2000
16. Thomas LD, Elinder CG, Tiselius HG, Wolk A, Akesson A. Ascorbic acid supplements and kidney stone
incidence among men: a prospective study. JAMA Intern Med 2013; 13 (173): 386–388

Keith Ong MBBS

Medical Director, Family Physician, Parsons Medical Clinic, Pacific
Healthcare Holdings, Singapore
MORE ARTICLES BY KEITH ONG

A N A LY S I S

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Clinical trial
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