Received: 23 August 2022 | Revised: 1 March 2023 | Accepted: 11 March 2023

DOI: 10.1111/jocd.15748

REVIEW ARTICLE

Efficacy of topical vitamin C in melasma and photoaging: A

systematic review

Gabriela Correia MD1 | Sofia Magina MD, PhD1,2

1
Unit of Pharmacology & Therapeutics,
Department of Biomedicine, Faculty of Abstract
Medicine, University of Porto, Porto,
Background: Vitamin C is a micronutrient present in high concentrations in normal skin
Portugal
2
Dermatology and Venereology
and a highly prescribed cosmeceutical, well known for protecting against ultraviolet-­
Department, University Hospital Center induced pigmentation and regulating collagen production. However, there is a lack of
of São João, Porto, Portugal
studies evaluating the efficacy of topical vitamin C in photoaging and melasma, with
Correspondence this systematic review being the first to assess the existing evidence.
Gabriela Correia, Unit of Pharmacology &
Therapeutics, Department of Biomedicine,
Aim: This systematic review aims to assess whether topical vitamin C could be effec-
Faculty of Medicine, University of Porto, tive in reversing photoaging signs and treating melasma.
Porto, Portugal.
Email: [email protected]
Methods: Prospective, randomized controlled trials assessing protocols with topi-
cally applied vitamin C in patients with melasma or photodamage were searched in
Medline, CENTRAL, and Scopus databases until the 12th of May 2022. Risk of bias
was conducted in accordance with Cochrane Collaboration's tool for assessing the
risk of bias in randomized trials, using RevMan 5.0.
Results: Seven publications were included, with 139 volunteers in total. Studies that
evaluated the topography of skin indicated that the treated skin appeared smoother
and less wrinkled, which was supported by biopsies data. On objective assessments
of pigmentation, there was a significant lightening of the skin treated. Hydration im-
proved equally in the vitamin C and placebo-­treated sites.
Conclusions: This study revealed that vitamin C is effective in treating uneven, wrin-
kled skin and has depigmenting properties, but long-­term use may be needed to
achieve noticeable changes. Q-­switched Nd:YAG laser-­associated protocols appear
beneficial in enhancing vitamin C effects. Topical vitamin C may be a suitable alter-
native for melasma and photoaging, but more studies are needed to confirm these
results and assess the ideal vitamin C concentration.

KEYWORDS
melasma, photoaging, photodamage, solar lentigines, vitamin C

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium,
provided the original work is properly cited.
© 2023 The Authors. Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.

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CORREIA and MAGINA 1939

1 | I NTRO D U C TI O N Nonetheless, the need to demonstrate the efficacy of ascor-

bic acid in treating melasma and photoaging is increasing as it has
Nowadays, vitamin C is one of the most prescribed cosmeceuticals quickly become part of numerous cosmetic preparations, becoming
in the world, being highly recommended by dermatologists. Its pop- an essential component in the daily skincare routine of the ordinary
ularity has exponentially grown during the past 5 years and in 2020 person.
it was the most searched cosmetic ingredient on the internet, with Thus, this systematic review wants to address this issue and
over a million searches, corresponding to a growth of 204% in a year. synthesize the current evidence on vitamin C efficacy in treating
This reaffirms the established place vitamin C occupies in the aver- melasma and photoaging and understand what preparations and
age person's skincare routine.1 concentrations may be more beneficial.
Ascorbic acid, commonly known as vitamin C, presents in high
concentrations in normal skin. Its main roles include stimulating
collagen biosynthesis, protecting against ultraviolet (UV)-­induced 2 | M ATE R I A L S A N D M E TH O DS
damage due to its antioxidant properties, stimulating the phagocytic
function of leukocytes, and proline hydroxylation. 2 Prospective, randomized controlled trials (RCT) assessing patients
Studies have shown that vitamin C levels were lower in photo- of any age or gender with melasma or photodamage were included.
aged and naturally aged skin3 and that it could also inhibit melanin Eligible interventions included the topical use of vitamin C
synthesis, through downregulating monophenolase activity of ty- whether alone or in formulations that are known to further stabilize/
rosinase enzyme. Moreover, its antioxidant effect prevents the pro- promote absorption of this molecule or its combination with ionto-
duction of free radicals that trigger melanogenesis. 2 These findings phoresis or laser.
made it look promising for pigmentary disorders such as melasma or The desired outcomes included the Melasma Area and Severity
solar lentigos. Associated with its role in regulating collagen produc- Index, the Melasma Severity Score, Pigmentation Scores using colo-
tion, stimulating type I procollagen synthesis in skin fibroblasts, and rimetric equipment, objective wrinkling evaluations, dermatologists'
promoting the stability of collagen molecules,4 vitamin C was imme- clinical evaluation, and participants' self-­assessment of change in
diately defended as the perfect molecule for prevention or reversal their own skin's appearance.
of skin aging and, more specifically, photoaging. Studies that included patients simultaneously using other bio-
Photoaging is the term used to describe the alterations in struc- active skin compounds with a possible brightening effect or using
ture, function, and appearance of skin due to prolonged or repeated vitamin C through transdermal injections or micro-­needling were
exposure to UV radiation. The main signs of photoaging include excluded. Ex vivo and in vitro studies were also excluded.
wrinkles, elastosis, dryness, laxity, rough-­textured appearance, tel- The Medline, CENTRAL (Cochrane Central Register of Controlled
5
angiectasis, and irregular pigmentation. Trials), and Scopus databases were searched until the 12th May
UV radiation contributes to dermal structure deterioration by 2022.
creating reactive oxygen species which promote collagen fragmen- The terms searched to target the intervention were vitamin C,
tation, decreased collagen biosynthesis, and therefore the observ- ascorbate, OR ascorbic acid AND to target the conditions in study
able features that characterize photodamage.6 the terms used were melasma, lentigo, hyperpigmentation, OR pho-
Melasma is an acquired hypermelanosis that is characterized by todamage. The results were filtered to only present RCTs.
light to dark-­brown symmetric macules with irregular borders that References of articles of interest were also checked for any RCTs
occurs mainly on the face and while it is known to affect darker skin that could eventually not be indexed in the searched databases.
complexions more commonly, it can occur in all skin types. The exact Attempts were also made to try to obtain unpublished RCTs from
pathogenesis of melasma is unknown, but sun exposure seems to be the cosmeceutical industry.
the most important predisposing factor, the reason why it has been Two reviewers evaluated initially both the titles and the abstracts
described as a photoaging disorder.7 of potentially relevant studies independently. The full paper was ob-
This is a highly prevalent chronic disease and a leading cause tained if it was considered that the article could meet the inclusion
of consultations that have been associated with a considerable de- criteria. Afterwards, the full text was screened to confirm that it met
crease in the patient's quality of life.8 With an unpredictable course the inclusion criteria and to assess its quality. Any disagreements
and frequent relapses, it presents a therapeutical challenge, so alter- were resolved by discussion. The authors were not blinded to the
natives must be looked onto. identity of the papers.
A meta-­analysis with over 700 volunteers, assessing vitamin C The same reviewers independently extracted, if present: the title
on healthy skin under a UV daylight-­simulated pigmentation pro- of publication, year of publication, first author, study design, charac-
vided clear evidence that ascorbic acid is effective in protecting from teristics of the participants of the trials (number of randomized sub-
9
stress-­induced pigmentation. jects, number of the ones who completed the study, demographic
However, the evidence toward its depigmenting qualities is still and baseline characteristics such as age, sex, and skin phototype),
very fragile, with most studies being in vitro and trials having a small treatment regimen (concentration received, frequency of interven-
number of participants. tion, and study duration) as well as the reported outcomes.
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1940 CORREIA and MAGINA

The assessment of the risk of bias was conducted for each study The main characteristics of the included studies are described in
following the COCHRANE Risk of Bias 2.0 tool (RoB 2.0), using Table 1 and their outcomes are explained in Table 2.
RevMan 5.0. The assessment of the risk of bias was conducted in accordance
with the Cochrane Collaboration's tool for assessing the risk of bias
in randomized trials,11 using RevMan 5.0.
3 | R E S U LT S Six specific domains (namely random sequence generation, al-
location concealment, blinding, incomplete outcome data, selective
The initial search retrieved 192 articles from the MEDLINE, CENTRAL, reporting, and other bias) were evaluated.
and EMBASE databases and 29 from the cosmeceutical industry. In Although all the studies were randomized, the method of ran-
all, 27 duplicates were excluded as well as 182 studies whose title and domization was not described in most trials. Most studies were
abstract did not meet the pre-­established criteria. In all, 12 articles double-­blinded, apart from one which was single-­blinded. Reporting
were considered relevant for a full-­text review. Of these, one article of outcomes was mainly carried out only in those who completed the
was excluded for not measuring any of the outcomes of interest, three trial, and no details were available of the outcomes of participants
were excluded for not randomizing the intervention, and another one who did not complete it, which in two studies with a more significant
was excluded for not individualizing the effect of vitamin C. dropout may lead to a higher risk of attrition bias.
Figure 1 shows the study selection flowchart, divided into the The risk of bias in the included studies is presented in a risk of
steps of identification, selection, eligibility, and inclusion, according bias graph, Figure 2, and a risk of bias summary, Figure 3.
to the PRISMA (Preferred Reporting Items for Systematic Reviews
and Meta-­analyses) recommendations for writing systematic
reviews.10 4 | DISCUSSION
A total of 139 volunteers with Fitzpatrick skin types I–­V were
included in the studies, aged from 23 to 72 years. Four of the seven There are limited clinical trials assessing the value of ascorbic acid to
studies recruited only female volunteers. The duration of the stud- improve the appearance of photoaged skin and it is being prescribed
ies ranged from 2 weeks up to 6 months with different formulations based on clinical experience, in vitro evidence of its antioxidative
and vitamin C concentrations (from 3.75% to 20%). Six of the seven properties, and its protecting effect on UV-­induced pigmentation.
studies included a placebo/control group while the one that did not, As far as we know, this is the first systematic review of RCTs assess-
had a comparison group with hydroquinone.7 ing the efficacy of topical vitamin C in melasma and photoaging and

F I G U R E 1 PRISMA flow diagram of

included studies.
 TA B L E 1 Description of the included studies.
CORREIA and MAGINA

Author (year) Participants Intervention Placebo Outcome assessment

Melasma or solar lentigines

Huh et al. (2002)12 29 female patients aged 24–­49 with Vitamin C solution (3.75% MAP) applied Yes L value of melasma measured by colorimetry; 5-­graded self-­assessment of
melasma to one side with iontophoresis for the effects of treatment
8 min, 2×/a week for 12 weeks
Ishikawa et al. 27 female patients with solar lentigos Topical application of lotion with 6% Yes Pigmentation levels measured by a color difference meter; melanin index
(2019)24 L-­ascorbate-­2-­phosphate trisodium measured by Mexameter MX18; pigmentation levels evaluated by a
salt to one-­half of the face twice a dermatologist using a photo-­scale ranging from 1 to 5.
day for 24 weeks.
Perez et al. (2004)7 16 female patients aged 23–­43 years old Topical application of lotion with 5% L-­ No Evaluation of indirect pigmentary changes using a narrow-­band
with melasma bilaterally ascorbic acid on one side of the face colorimetric equipment; patient self-­assessment.
and a 4% hydroquinone water–­oil
emulsion on the other for 16 weeks.
Kim et al. (2020)14 18 patients aged 26–­53, skin types II–­IV, Topical application of a 20% ascorbic Yes Digital photography and spectrometry were used to assess the melanin
with facial lentigines and melasma acid, vitamin E and ferulic acid serum and erythema index; MSS; Scoring of the global improvement of skin
on a side of the face after treatment texture and brightness by a dermatologist.
with a 1064 nm QSNY laser and 2×/
day for 2 weeks.
Photodamage
Traikovich (1999)19 19 patients aged 36–­72, with skin Topical daily application of a high-­ Yes Optical profilometry analysis was performed on skin surface replicas to
types I–­III, with mild to moderate potency serum (concentration not measure the degree of surface irregularities; scoring by investigator
photodamage disclosed) containing ascorbic acid of severity of wrinkling, tactile roughness, coarse rhytids, skin laxity,
on a side of the face for 3 months. dryness, and sallowness; self-­assessment questionnaires to rate the
degree of improvement
Humbert et al. 20 female patients aged 51–­59 with signs Daily topical application of a cream Yes Investigator assessment (parameters: hydration, roughness, laxity,
(2003)13 of photoaging containing 5% vitamin C for wrinkles, brown spots, glare); 10-­graded volunteer self-­assessment;
6 months skin-­relief measurements; skin biopsies.
Fitzpatrick et al. 10 patients having photodamage Daily topical application of a vitamin Yes Assessment by a physician of the hydration, wrinkling and pigmentation;
(2002)25 C complex (10% ascorbic acid and subjective self-­assessment; Grenz zone collagen and epidermal
7% tetrahexyldecyl ascorbate) for thickness measurements and type I collagen assessment through skin
12 weeks. biopsies.

Abbreviation: MSS, Melasma Severity Score.

| 1941

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1942 CORREIA and MAGINA

our results have validated its usefulness in treating photodamaged we currently have for highly prescribed high-­concentration formu-
skin and melasma. las. In vitro studies have also shown that the maximal concentration
Despite that, several questions remain unanswered. While it is for optimal percutaneous absorption was 20%,15 not supporting the
frequent to see lotions or serums with concentrations of up to 30% routine use of products over such concentration.
on the market, most studies use concentrations under 10%.7,12,13 Yokota et al.16 reported no dose–­response effect among a 1%,
Only one of the included RCTs assessed the effect of vitamin C in 2%, or 3% tetra-­isopalmitoyl vitamin C on periorbital wrinkles, with
a concentration of 20%14 which also shows the scarcity of evidence improving effects even at a low concentration of 1% VC-­IP, which

TA B L E 2 Results of individual studies.

Author (year) Self and clinical assessment results Objective assessment

Melasma or lentigines
Huh et al. (2002)12 61.5% of volunteers graded both the vitamin and placebo side Gradual reduction of ΔL values in the treated
with a score of 4/5 or 5/5. site (p = 0.002) with significant difference
to the placebo-­treated site (p = 0.03); ΔL
before treatment was on average 4/60; after
12 weeks ΔL = 2.78.
Ishikawa et al. (2019)24 No significant differences between vitamin C and placebo on Vitamin C treated SLs had a significantly higher
photo-­scale evaluation, although there was a slight decrease ΔL value vs. placebo (p < 0.001). 7/27 had
on both on solar lentigos (SL) and non-­lesional surrounding a visibly recognizable level (ΔL >2). The
skin (NLS). ΔM (melanin index) significantly decreased
for the SL (MI from 212.50 ± 33.83 to
188.65 ± 33.16) and NLS in the treated sites.
Perez et al. (2004)7 Vitamin C was considered excellent in 2/16, good in 8/16, ΔM (melanin index difference) on the patients
moderate in 4/16, and mild in 2/16. Hydroquinone was using vitamin C showed improvement of
considered excellent in 8/16, good in 7/16, moderate in hyperpigmentation in 14/16 patients and
1/16, and mild in none. Data showed statistical significance worsening in 2/16. A lightening effect was
for the hydroquinone side. noted in the third month of use. All patients
on the hydroquinone had a colorimetric
improvement with results noted in the first
month.
Kim et al. (2020)14 Moderate improvement in melasma on the treated side and Significant reduction (p < 0.05) in the MI
minimal to moderate on the non-­treated side (p < 0.05) on (182.2 ± 32.97 to 160.56 ± 29.18) and the
investigator assessment. MSS score (2.22 ± 0.56 to 1.94 ± 0.64) on the
treated side vs. placebo.
Photodamage
Traikovich (1999)19 84.2% of the volunteers preferred the results of the treatment Analysis of the skin surface impressions showed
over placebo (p = 0.002). Significantly more improvement significantly more improvement with active
with vitamin C for fine wrinkling (p = 0.002), tactile treatment in the north–­south axis in 14/19
roughness (p = 0.04), coarse rhytids (p = 0.01), skin laxity patients (p = 0.03). No significant differences
(p = 0.03), sallowness (p = 0.03), and overall assessment were seen in the east–­west orientation for
(p = 0.02). No significant differences in visual dryness, any of the parameters.
telangiectasias, mottled pigmentation, or keratoses. On
photographic assessment, the active side was preferred vs.
placebo in 11 (57.9%) subjects (p = 0.01)
Humbert et al. (2003)13 Global score (physician + volunteer assessment) was 6.7 ± 1.6 Skin relief measurements: increase in density
at baseline, 5.0 ± 1.0 at 3 M and 4.4 ± 0.7 at 6 M (p < 0.05). of skin microrelief vs. placebo (p > 0.01) and
Hydration, wrinkles, glare, and brown spots improved in a decrease in deep furrows (p < 0.01). On
both groups and roughness, suppleness and small wrinkle biopsy: re-­appearance of composite elastic
scores improved significantly only in the vitamin C group. fibers in the upper dermis and more evenly
distributed type I collagen. No changes in
fibrocytes or dermal collagen.
Fitzpatrick et al. (2002)25 4/10 patients reported greater improvement of the wrinkles Four patients had an increase in the average
and 3/10 a greater improvement in hydration. No epidermal thickness and Grenz zone collagen
differential improvement in pigment was reported. on the treated side. 3/4 patients revealed a
Excluding the forehead area, average improvement of more intense staining for type I collagen on
wrinkling scores was 25% vs. 7.67% placebo (p = 0.08). the vitamin C side.
All patients with dry skin improved to normal hydration
bilaterally. 3/5 patients with depigmentation, improved both
on the treatment and placebo-­sides.
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CORREIA and MAGINA 1943

F I G U R E 2 Risk of bias graph: review

authors' judgments about each risk of bias
item presented as percentages across all
included studies.

attractive.13 However, vitamin C is a water-­soluble and charged

molecule that is repelled by the epidermal cells. 2 To overcome this
challenge, it is necessary that the pH level is below 4 and that the
molecule is stable enough not to oxidate.17 To overcome this chal-
lenge, several derivatives, lipid-­soluble analogues, conjugates, and
protocols have been created to assist the transport into the epider-
mis. There is currently a huge variety of protocols, combining vita-
min C with procedures such as iontophoresis, ultrasound, laser, or
micro-­needling. However, these studies remain small, and there are
no comparative studies to determine the optimal delivery method.
All of the three RCTs included in this systematic review that
evaluated the topography of skin treated with topical ascorbic acid
indicated that the skin treated appeared smoother and less wrinkled
compared with placebo/control. Humbert et al.'s13 study corrobo-
rates in vitro studies that showed topical ascorbic acid may promote
the activation of a dermal synthesis of elastic fibers.18 In this study,
there were no changes in dermal collagen, but Traikovich et al.19
revealed an increase in collagen in the dermal–­epidermal junction.
Hence, these studies support what was primarily found in cultures of
fibroblasts derived from normal human skin18 and provide evidence
that topical vitamin C helps restore the elasticity of photodamaged
skin and reduce wrinkling.
Hydration improved both in the vitamin C and placebo areas
in the three studies where this was an assessed parameter, which
suggests that enhanced hydration is not an effect of vitamin C but
instead a result of more regular skincare.
On objective assessments of pigmentation, both in patients with
melasma and with solar lentigines, there was a significant lightening
of the skin treated with ascorbic acid. Nonetheless, clinical and self-­
assessment results did not corroborate this, as vitamin C was only
preferred to placebo concerning hyperpigmentation reversal in one
of the five studies that included this outcome. Besides that, although
these studies were mainly double-­blinded, it is worth mentioning that
because it is common for patients to feel a small stinging in the area
F I G U R E 3 Risk of bias summary: review authors' judgments
where vitamin C is applied, there may be some distortion in patient ap-
about each risk of bias item for each included studies.
praisal scores, leading them to overestimate the treated-­site changes.
This discrepancy between pigmentation levels and clinical or
reiterates the need to design comparative studies to find the ideal self-­assessments might have occurred because, within the time-
concentration. frame of the studies, the decrease was not distinct in visible skin
Since the levels of vitamin C available in the skin after oral inges- pigmentation and longer studies are needed to determine how long
tion are limited by regulatory mechanisms, topical delivery became the protocols must be to result in a visible change.
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1944 CORREIA and MAGINA

In Kim et al.'s study,14 the only RCT demonstrating a visible DATA AVA I L A B I L I T Y S TAT E M E N T
lightening of facial lentigines and melasma assessed by two blinded Data sharing not applicable to this article as no datasets were gener-
dermatologists after the 2-­week protocol was also the only one ated or analysed during the current study.
that included a Q-­switched 1064-­nm Nd:YAG laser pre-­treatment.
Studies have demonstrated that laser pretreatment could increase E T H I C S S TAT E M E N T
the permeability and depth of penetration of topically applied mole- The authors confirm that the ethical policies of the journal, as noted
cules so the better absorption of vitamin C and the melanin granule on the journal's author guidelines page, have been adhered to. No
dispersion caused by the selective photothermolysis could explain ethical approval was required as this is a review article with no re-
the improved results.14,20 However, a study comparing this protocol search data.
without the laser pre-­treatment is necessary to understand its role
in these results and do a risk–­benefit analysis that considers the hy- REFERENCES

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