Role of Antioxidants in Melasma: A Systematic Review

Abstract

Melasma is a common skin disorder characterized by facial hyperpigmentation, often aggravated by sun exposure. Antioxidants are being studied as a treatment option for their potential to reduce oxidative stress and improve skin pigmentation. A comprehensive literature search was conducted in PubMed for articles published over the past decade, up to January 31, 2024, on the use of antioxidants in melasma treatment. The systematic review, conducted by two independent investigators, included 30 studies on antioxidants in melasma, covering vitamin C, cysteamine, silymarin, PLE, tomato extract/lycopene, zinc sulfate, melatonin, and other antioxidants. Findings indicated that combining vitamin C with physical therapies, such as peels and lasers, yielded better results. Cysteamine, a naturally occurring aminothiol, showed efficacy comparable to hydroquinone with fewer side effects. Silymarin was effective in reducing melasma severity with minimal adverse effects. PLE showed mixed results but potential as an effective antioxidant when combined with other treatments. Lycopene from tomato extract demonstrated significant improvements in melasma when used as an adjuvant therapy. Zinc sulfate showed some effectiveness but was less potent than hydroquinone. Melatonin had antioxidant capabilities but showed no statistically significant improvement. Glutathione is emerging as a new antioxidant therapy showing efficacy in melasma in combination with other topicals and microneedling. Other antioxidants, including combinations of vitamins C, E, and ferulic acid, showed potential as adjuncts in melasma treatment. These findings highlight the diverse efficacy of antioxidants in managing melasma, suggesting their potential as safe and effective treatments.

Introduction

Melasma, a common dermatological disorder characterized by hyperpigmentation of the facial skin, particularly in sun-exposed areas, presents significant challenges in clinical practice and profoundly affects patient well-being. Predominantly affecting women, with a higher prevalence in individuals with Fitzpatrick skin types III to VI. The etiology is multifactorial, involving complex interactions between genetic, hormonal, and environmental factors.[1]

While the precise pathogenesis of melasma remains incompletely understood, recent research has increasingly focused on the role of oxidative stress in the development and progression of this condition. Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body’s antioxidant defense mechanisms. ROS, such as superoxide radicals, hydrogen peroxide, and hydroxyl radicals, cause cellular damage and promote inflammation.[1] Antioxidants defend against oxidative stress by neutralizing ROS and reducing their harmful effects. Antioxidants may be endogenous, such as enzymatic antioxidants like superoxide dismutase and catalase, or exogenous, including dietary antioxidants such as vitamins C and E.[2]

Increased levels of oxidative stress markers such as lipid peroxidation and proinflammatory cytokines have been detected in melasma-affected skin giving rise to a growing interest in exploring the potential link between oxidative stress and the pathogenesis of melasma, and investigating the potential therapeutic benefits of antioxidants in its management.[3] This systematic review aims to provide a comprehensive assessment of the existing literature regarding the antioxidants in melasma. By critically evaluating the evidence, we seek to elucidate the potential implications for melasma management, contributing to the growing body of knowledge in dermatology.

Methods

A comprehensive literature search was conducted in the PubMed electronic database covering articles published in the past 10 years up to January 31, 2024, using a combination of MeSH terms including “melasma OR chloasma, AND antioxidants”, “melasma AND vitamin C”, “melasma AND cysteamine”, “melasma AND silymarin”, “melasma AND polypodium leucotomos extract (PLE)”, “melasma AND tomato extract/lycopene”, “melasma AND zinc sulfate” “melasma AND melatonin”, “melasma AND glutathione”. Inclusion criteria comprised studies investigating the effects of antioxidants on melasma, encompassing primary research articles such as randomized control trials, clinical trials, cohort studies, case-control studies, observational studies and published in peer-reviewed journals. Exclusion criteria involved review articles and studies not published in the English language or not addressing the relationship between antioxidants and melasma, conference abstracts, and animal studies. A systematic search was undertaken by two independent investigators, RS and AS. Data extraction included study design, patient size, and efficacy parameters. The PRISMA flow chart depicting the study selection process is provided in Figure 1.

Figure 1.

The PRISMA flow chart depicting the study selection process

Results

Thirty articles were found on antioxidants in melasma, including seven on vitamin C, seven on cysteamine, three on silymarin, two on polypodium leucotomos extract (PLE), two on tomato extract/lycopene, one on zinc sulfate, one on melatonin, three on glutathione and four on other antioxidants. Table 1 demonstrates the included studies and their level of evidence.

Table 1.

Studies over antioxidants in melasma and their level of evidence

Author	Type of Study	Study Population	Objective	Result	Level of evidence
Vitamin C
Murtaza F et al.[5]	Randomized Controlled Trial	148 patients with Fitzpatrick skin type III-V	Compare the efficacy of trichloro-acetic acid peel alone versus combined topical magnesium ascorbyl phosphate for epidermal melasma.	Combination therapy led to a statistically significant reduction in MASI score of 81.1% compared to 66.2% in the peel-only group.	2
Balevi A et al.[6]	Randomized Controlled Trial	Fifty female patients	Assess the efficacy of combining salicylic acid peel with vitamin C mesotherapy in treating mixed-type melasma	No statistically significant difference between the two groups, but MASI scores were higher in Group B (hydroquinone-only) at the end.	2
Ustuner P et al.[7]	Randomized Controlled Trial	Sixteen patients with dermal- or mixed-type melasma	Compare Q-switched Nd: YAG laser plus microneedling with vitamin C vs. Q-switched Nd: YAG laser alone for melasma treatment	Group with vitamin C had significantly lower mean MASI scores and better treatment responses compared to only laser treatment.	2
Lee MC et al.[8]	Split-face Clinical Trial	Eight patients with long-term melasma	Evaluate the efficacy of a combination treatment using 1,064-nm Q-switched Nd: YAG laser with ultrasonic application of topical vitamin C.	Combination treatment, particularly with ultrasonic application of vitamin C, led to significant improvement in visual analog scores when compared to laser monotherapy.	3
Raza MH et al.[9]	Split-face Clinical Trial	30 participants	Compare the effects of micro-needling with tranexamic acid on one side and vitamin C on the other side of the face in patients with melasma by split-face clinical trial.	Both tranexamic acid and vitamin C led to significant and comparable improvements in modified MASI, Physician Global Assessment, and Patient Global Assessment.	3
El Attar Y et al.[10]	Split-face Rndomised Controlled Trial	20 participants	Evaluation of efficacy and Safety of tranexamic acid versus vitamin C after microneedling in treatment of melasma by Hemi-MASI and dermoscopy.	Reduction in Hemi-MASI scores and improvement in pigmented lesions by dermoscopy was seen on both sides but reduction in vascular component was significant on the tranexamic acid side only.	2
Zhao H et al.[11]	Split-face Randomised Controlled Trial	Seventeen patients	Comparing the efficacy of myjet-assisted transdermal injections of tranexamic acid vs. vitamin C	Both side showed reductions in MASI scores, without statistically significant difference between the two groups.	2
Cysteamine
P M et al.[13]	Randomized, Double-Blind Placebo-Controlled Trial	Fifty participants	Evaluate the efficacy of cysteamine 5% cream in treating epidermal melasma.	Significant reductions in pigmented skin and MASI scores in the cysteamine group compared to placebo.	2
Farshi S et al.[14]	Randomized Double-Blind Placebo-Controlled Study	Forty participants	Efficacy of cysteamine cream in treating epidermal melasma.	Significant reductions in MASI scores in the cysteamine group compared to placebo.	2
Lima PB et al.[15]	Quasi-Randomized Evaluator-Blinded Clinical Trial	Forty women with facial melasma	Compare 5% cysteamine vs. 4% hydroquinone over 120 days	Hydroquinone shows superior efficacy in decreasing mMASI and MELASQoL scores in comparision to cysteamine.	2
Nguyen J et al.[16]	Single-Center, Randomized, Double-Blinded Trial	Twenty participants	Compare cysteamine cream vs. hydroquinone cream efficacy over 16 weeks in melasma.	Comparable efficacy between cysteamine and hydroquinone, with hydroquinone being better tolerated.	2
Sepaskhah M et al.[17]	Single-Blind, Randomized Controlled Trial	Sixty-five patients	Compare cysteamine 5% cream vs. hydroquinone 4% and ascorbic acid 3% combination cream in treating melasma	Both treatments show an improvement in mMASI scores and quality of life index without significant differences between the two. Hydroquinone and ascorbic acid group showed a more pronounced decrease in melanin index.	2
Karrabi M et al.[18]	Double-Blind, Randomized Clinical Trial	Fifty participants	Compare cysteamine 5% cream vs. Modified Kligman’s Formula (MKF) in melasma.	Cysteamine cream demonstrates a more substantial reduction in mMASI scores compared to MKF.	2
Karrabi M et al.[19]	Randomized Clinical Trial	Sixty participants	Evaluate the efficacy of cysteamine 5% cream vs. tranexamic acid mesotherapy in melasma treatment.	Both treatments showed significant improvement in mMASI and Dermacatch without any statistically significant difference between two.	2
Silymarin
Nofal A et al.[20]	Comparative Study	30 patients with melasma	Efficacy of silymarin 0.7% cream, silymarin 1.4% cream, and hydroquinone 4% cream in melasma.	Comparable efficacy in reducing MASI score in all three groups, with lower side effects in silymarin groups.	4
Wattanakrai P et al.[21]	Randomized, Double-Blind, Split-Face Study	30 patients with melasma	Compare the efficacy of topical silymarin vs. 2% hydroquinone cream using colorimeter, modified MASI score, and patient self-assessment	Both treatments significantly improved calorimetric scores and patient satisfaction scores, with no significant difference between the two sides. Modified MASI scores were significantly reduced in the hydroquinone side. Side effects were more in the hydroquinone side.	2
Ibrahim SMA et al.[22]	Randomized Control Trial	50 female patients with melasma	Topical silymarin (0.05%) vs. low fluence 1064-nm Q-switched Nd: Yag laser for melasma treatment.	Both treatments significantly reduced modified MASI and dermoscopy, with no significant difference between the two groups.	2
Polypodium Leucotomos
Goh CL et al.[23]	Double-blind placebo-randomized Controlled Trial	Forty Asian melasma patients	Evaluate the effectiveness of Polypodium Leucotomos (PLE) extract vs. placebo in melasma patients receiving hydroquinone therapy.	Oral PLE supplementation enhances and expedites the improvement in modified MASI scores in patients receiving hydroquinone.	2
Ahmed AM et al.[24]	Double-Blinded, Placebo- Randomised Controlled Trial	Forty subjects with melasma	Assess the effectiveness of oral Polypodium leucotomos extract (PLE) vs. placebo in melasma.	Both PLE and placebo groups showed significant improvement in melanin index and MASI scores without any statistically significant difference between the two. MelasQOL score shows no improvement in either group.	2
Avianggi HD et al.[25]	Randomised Clinical Trial	62 patients with melasma	Evaluate the effectiveness of tomato extract supplements in melasma treatment	Tomato extract supplementation group exhibited statistically significant, higher serum SOD levels and decrease in MASI scores then placebo.	2
Bavarsad N et al.[26]	Double-blind, Placebo-Controlled Randomized Trial	Twenty-two patients with melasma	Assess the efficacy of a cream containing 0.05% tomato lycopene and 3.45% wheat bran extract in melasma	The formulation showed a significant reduction in MASI score and skin discoloration rate compared to placebo.	2
Zinc sulfate
Yousefi A et al.[27]	Double-Blind Randomized Comparative Study	93 women with melasma	Compare topical zinc sulfate 10% vs. hydroquinone 4% in melasma	Both groups showed a significant reduction in MASI score, but hydroquinone was statistically more effective.	2
Melatonin
Cassiano D et al.[28]	Double-Blind, Randomized, Placebo-Controlled Clinical Trial.	50 adult women with moderate to severe melasma (mMASI>5)	Evaluation of efficacy of oral 5 mg melatonin vs. placebo in the treatment of facial melasma in women	Group on melatonin showed a greater reduction in modified MASI score compared to the placebo group but without any statistically significant difference. Melasma quality of life index and colorimetry assessment showed no difference between the two groups.	2
Glutathione
Iraji F et al.[30]	A split-face randomized clinical trial	30 patients	Efficacy of mesotherapy with tranexamic acid and ascorbic acid with and without glutathione in the treatment of melasma.	Glutathione-containing cocktail A showed significantly more reduction of mMASI score results compared with a cocktail of tranexamic and vitamin C.	2
Feng C et al.[31]	Randomized control trial	180 patients diagnosed with chloasma	Evaluate the efficacy of intradermal tranexamic acid with reduced glutathione vs. hydroquinone in chloasma treatment	The group treated with tranexamic acid and glutathione had a significantly better decrease area and severity of chloasma in comparison to the hydroquinone group.	2
Mohamed M et al.[32]	Split-face comparative study	29 adult females with the epidermal type of melasma	Evaluate the effectiveness of microneedling with glutathione vs. microneedling alone in the treatment of melasma.	Hemi modified MASI score showed statistically significant reduction on both sides of the face but the side with microneedling and glutathione showed more reduction and earlier response to therapy than the side with microneedling alone.	3
Others
Kim J et al.[33]	Single-Blinded Prospective Randomized Split-Face Trial	18 individuals with lentigines and melasma	Evaluate the efficacy of topical application of combination formulation of vitamin C, vitamin E, and ferulic acid as an adjuvant to Q-switched Nd: YAG (QSNY) lasers treatment	The combination treatment side of the face exhibited a significantly greater reduction in the melanin index compared to the laser monotherapy side.	2
Kelm RC et al.[34]	Prospective, Open-Label, Evaluator-Blinded Control Trial	Ten female subjects	Assess the efficacy of 30% tetrahexyldecyl ascorbate serum with SPF 45 sunscreen in melasma	100% of patients had improvement in hyperpigmentation with an average improvement of 33.7% by Griffiths’ 10-point scale and global aesthetic improvement scale.	3
Crocco EI et al.[35]	Prospective Single-Arm Open-Label Clinical Trial	35 participants	Evaluate efficacy of cream formulation with nicotinamide, arbutin, bisabolol, and retinaldehyde	Statistically significant reduction in MASI scores, total melasma surface area, and improvement in patient satisfaction was observed.	3
Piyavatin P et al.[36]	Prospective, Double-Blind, Randomized Controlled Trial	57 Thai facial melasma patients	Assess the effects of oral synbiotics vs. placebo in melasma	Synbiotics group showed a significant reduction in modified MASI score compared to the placebo group.	2

*Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence is followed here

Vitamin C

Vitamin C, or ascorbic acid, is an essential antioxidant found in nature.[4] Various studies illustrating the role of this antioxidant agent in the treatment of melasma:

In a randomized controlled trial in 148 patients with epidermal melasma, combination therapy of 20% trichloro-acetic acid peel and 5% topical magnesium ascorbyl phosphate cream demonstrated a significant reduction in the melasma area and severity index (MASI) score compared to receiving only the peel.[5] A similar study compared the efficacy of combining salicylic acid peel with vitamin C mesotherapy in 50 patients with mixed melasma. While both groups received salicylic acid peels, group A additionally received intradermal vitamin C. Although there was no statistically significant difference, MASI scores were lower in a group with the combined approach at the end of the six-month follow-up.[6] Another randomised investigator blinded trial compared the efficacy and safety of Q-switched Nd: YAG laser plus microneedling with vitamin C to Q-switched Nd: YAG laser alone for treating recalcitrant melasma. The combined approach demonstrated significantly lower mean MASI scores and better treatment responses, suggesting its superiority over laser monotherapy.[7] Similarly, a split-face study, evaluated the efficacy of a combination treatment using the 1,064 nm Q-switched Nd: YAG laser with ultrasonic application of topical vitamin C. Post laser one side received ultrasonic application of vitamin C and the other side was covered with a moisturizing lotion. Objective evaluation using visual analog scores revealed that the combination treatment with ultrasonic application of vitamin C, led to significant improvement compared to laser monotherapy.[8] Similarly, 3 split-face studies involving micro-needling with tranexamic acid on one side and vitamin C on the other in patients with melasma revealed significant improvements in MASI scores without any significant difference between the two.[9,10,11] These observations suggest combining vitamin C with other physical therapies gives better results.

Cysteamine

Cysteamine, an aminothiol found naturally in the body, serves as an antioxidant derived from coenzyme A degradation. Traditionally, its strong odor and rapid oxidation hindered topical application until recent stabilization advancements. Since 2015, stabilized cysteamine has exhibited efficacy, safety, and tolerability in various clinical studies and case reports. Notably, it has shown significant effectiveness in treating disorders of hyperpigmentation, comparable to established depigmenting therapies like triple combination cream or tranexamic acid mesotherapy, with improved tolerability.[12]

2 studies compared its efficacy against placebo showed significant results. In a randomized, double-blind placebo-controlled trial with 50 epidermal melasma participants, cysteamine cream demonstrated significant reductions in pigmented skin, as measured by mexameter readings, compared to the placebo at 2 and 4 months.[13] Another study involving 40 participants corroborated these findings, showing significant reductions in pigmented skin score in the cysteamine-treated groups based on Dermacatch® and Mexameter® readings.[14]

When compared with conventional hydroquinone treatment it was found to be as effective or slightly less effective but safe and well-tolerated. In another quasi-randomized clinical trial comparing cysteamine and 4% hydroquinone in 40 women with facial melasma, both treatments led to reductions in melasma severity, with hydroquinone showing superior efficacy in decreasing MASI scores.[15] Another single-centre trial compared cysteamine cream with hydroquinone cream in 20 participants. Cysteamine showed comparable efficacy to hydroquinone and the study suggests that cysteamine might serve as an alternative to hydroquinone for patients seeking options to avoid or rotate off hydroquinone.[16] A recent study compared cysteamine 5% cream, with hydroquinone 4% and ascorbic acid 3% combination cream, showing both treatments effectively reduced MASI scores and improved the quality of life.[17]

Further, in a double-blind, randomized clinical trial with 50 participants, cysteamine 5% cream exhibited higher efficacy than Modified kligman’s formula (MKF) in treating epidermal melasma, with a statistically significant reduction in the MASI score.[18] And in a single-blind clinical trial compared cysteamine 5% cream with Tranexamic Acid (TA) mesotherapy in treating melasma. Both treatments showed substantial improvements in MASI scores and Dermacatch® values, with no significant differences between cysteamine and TA. However, cysteamine exhibited fewer complications, suggesting comparable efficacy and safety to TA mesotherapy.[19]

Silymarin

Silymarin is recognized for its ability to counteract the harmful effects of ultraviolet radiation, such as inflammation, immune responses, DNA damage, and excessive pigmentation.

In a three-month study involving 42 female melasma patients, silymarin creams of different concentrations (0.7% and 1.4%) were compared with hydroquinone 4%. All groups showed a significant reduction in the MASI score, with no significant differences among them. Importantly, silymarin demonstrated no adverse effects, while hydroquinone was associated with significant side effects, suggesting that silymarin cream could be an effective and safe alternative to hydroquinone for melasma treatment.[20] In another, split-face study with 25 Asian patients, 1.4% silymarin cream was compared with 2% hydroquinone for three months. Both treatments led to statistically significant improvements in both groups. While hydroquinone demonstrated a slightly better response in improving melasma, silymarin proved effective with fewer side effects, emphasizing its potential as a treatment for both epidermal and mixed-type melasma.[21] Another study compared silymarin cream (1.4%) with low fluence 1064-nm Q-switched Nd: Yag laser in 50 female melasma patients. Both treatments significantly reduced melasma severity without reported side effects, and there was no statistically significant difference between the groups in terms of improvement.[22]

These findings suggest that topical silymarin provides results equivalent to conventional depigmenting agents and physical therapies like laser therapy, with fewer side effects.

Polypodium leucotomos extract

PLE demonstrated its potential as an effective antioxidant in various studies. Two double-blind, placebo-controlled trials evaluated the effectiveness of PLE extract in melasma patients with mixed results. In the first study, Asian melasma patients receiving topical 4% hydroquinone cream and sunscreen were randomized to receive either oral PLE supplementation or a placebo for 12 weeks. The trial demonstrated a significant mMASI score reduction compared to the placebo.[23] In another older study involving forty subjects with melasma, participants received either 240 mg doses of oral PLE or a placebo three times daily for 12 weeks, along with standard topical sunscreen. Both PLE and placebo groups showed significant improvement in the change in melanin index, with no statistically significant intergroup difference.[24] The above studies suggest the potential of PLE as an effective antioxidant significantly enhancing the improvement in melasma severity when combined with other modalities of treatment.

Tomato lycopene extract

Lycopene is known for its antioxidative properties. In two double-blinded randomized control trials, the efficacy of tomato extract containing lycopene in treating melasma was explored. In the first trial, patients with melasma received oral tomato extract supplements containing lycopene (30 mg) as an adjuvant therapy alongside topical sunscreen and 4% hydroquinone cream for 12 weeks. The group receiving tomato extract supplementation exhibited significantly higher serum superoxide dismutase (SOD) levels compared to the placebo group. Additionally, the treatment group showed a significant decrease in MASI scores after therapy compared to the control group.[25] In the second study, a cream formulation containing 0.05% tomato lycopene and 3.45% wheat bran extract was applied twice daily for three months to patients diagnosed with melasma, in combination with SPF 30 sunscreen. The formulation demonstrated suitable physicochemical characteristics, and the intervention group exhibited a significant decrease in MASI scores from the sixth week until the end of the treatment compared to the placebo group. The results highlight the promising role of lycopene and wheat bran extract in cosmetic formulations as a safe and effective treatment for melasma.[26]

These findings implicate lycopene extract also has an adjuvant role in the treatment of melasma.

Zinc sulphate

As a physical blocker, zinc can provide broader protection against the sun and thus combat oxidative stress caused by it. In a double-blind randomized comparative study, the efficacy of topical zinc sulfate 10% was assessed in comparison to hydroquinone 4% as the standard treatment for melasma in 93 women. Over two months, both groups demonstrated a significant reduction in MASI score, with a greater decrease observed in the hydroquinone group compared to the zinc group (43.5 ± 15.5% vs. 18.6 ± 20.8%, P < 0.001). The study concluded that while topical zinc therapy showed some effectiveness in reducing melasma severity, it was not as potent as hydroquinone.[27]

Melatonin

Melatonin is known to have antioxidant capabilities, including scavenging free radicals and activating antioxidant enzymes. It also inhibits tyrosinase and iNOS production, affecting melanogenesis directly.[28]

A prospective, randomized, double-blind, placebo-controlled multicentre clinical trial in fifty adult women with moderate to severe melasma (mMASI>5), who had not received specific treatment for at least 45 days were included. On 8 weeks follow-up, the group receiving melatonin showed a greater reduction in modified MASI score compared to the placebo group but without any statistically significant difference. Further melasma quality of life index and colorimetry assessment showed no difference among the two groups. Thus, even though slight improvement in the modified MASI score compared to placebo was noted but was not relevant due to a lack of statistical significance and no impact on the quality of life of patients.[29]

Glutathione

Glutathione is a known antioxidant, and various studies have explored the efficacy of antioxidants in melasma treatment. A split-face randomized clinical trial with 30 patients found that a mesotherapy cocktail containing tranexamic acid, ascorbic acid, and glutathione led to a greater reduction in mMASI scores compared to a cocktail without glutathione.[30] A randomized control trial with 180 patients with chloasma showed that treatment with tranexamic acid and glutathione resulted in significantly better outcomes than hydroquinone.[31] A split-face study on 29 females with epidermal melasma demonstrated that microneedling combined with glutathione achieved a more significant and faster reduction in hemi-mMASI scores compared to microneedling alone. These findings suggest that adding glutathione to treatment regimens can enhance the efficacy of melasma therapies.[32]

Other antioxidants

In this single-blinded, prospective, randomized split-face trial, 18 individuals with lentigines and melasma, aged between 26 and 53 years, received Q-switched Nd: YAG laser treatment. Following the laser treatment, a combination antioxidant serum containing vitamins C, E, and ferulic acid was applied on one side of their face, twice daily for two weeks. Evaluation through digital photography and spectrometry showed a notable reduction in the melanin index on the treated side compared to the untreated side. However, there was no significant difference in post-treatment erythema. Clinically, greater improvement was observed on the side treated with the antioxidant serum. The study concluded that the topical application of this antioxidant combination might serve as an effective adjunct to laser treatment for individuals with lentigines and melasma, highlighting its potential as an adjuvant option in such therapies.[33]

In another prospective, open-label, evaluator-blinded study, ten female subjects between 18 and 60 years old underwent a 12-week treatment during summer using a 30% tetrahexyldecyl ascorbate serum combined with a mineral-based SPF 45 sunscreen moisturizer. The aim was to evaluate the efficacy of this regimen in treating melasma. Results showed an average improvement of 33.7% in hyperpigmentation and 70% of subjects demonstrated improved skin tone evenness, averaging at 33.3%. Blinded evaluators noted a median global aesthetic improvement score of 2.0, signifying significant improvement. The study highlighted the effectiveness and safety of the ascorbate serum along with a purely mineral-based sunscreen in addressing both pigmentary and vascular aspects of melasma during the summer months.[34]

Another prospective single-arm open-label study, aimed to assess the efficacy of a novel cream formulation comprising nicotinamide 4% (essentially acts as an antioxidant, with most of its effects exerted through adenosine diphosphate–ribose polymerase inhibition), arbutin 3%, bisabolol 1%, and retinaldehyde 0.05%. The evaluation included reductions in both MASI scores and the total melasma surface area, as determined through medical imaging software. The outcomes demonstrated positive results, indicating that this cosmetic compound holds promise in the treatment of epidermal melasma.[35]

In a prospective, double-blind, randomized controlled trial involving 57 Thai facial melasma patients, the study aimed to assess the effects of oral synbiotics (anti-inflammatory, anti-oxidant, ultraviolet protective, and tyrosinase inhibitory agent) supplementation on melasma improvement, evaluated through the mMASI score. Participants received either synbiotics or a placebo for 12 weeks. The synbiotics group demonstrated a significant reduction in the mMASI score, compared to the placebo group at week 12 (P = 0.008).[36]

Conclusion

Overall, the evidence suggests a significant role for antioxidants in melasma treatment, with compounds like vitamin C, cysteamine, silymarin, glutathione, and polypodium leucotomos extract showing promising results. While some antioxidants may offer comparable efficacy to conventional therapies like hydroquinone, others demonstrate synergistic effects when combined with existing treatments or physical therapies like laser. The role of melatonin in melasma management needs further exploration. Further research exploring the mechanisms of action and long-term efficacy of antioxidants in melasma management is warranted to optimize treatment strategies and improve patient outcomes.

Key messages

(Provide appropriate messages of about 35-50 words to be printed in the centre box): A systematic review of antioxidants in melasma treatment revealed significant benefits from various antioxidants, including vitamin C, cysteamine, silymarin, and lycopene, particularly when combined with other therapies, highlighting their potential to enhance treatment efficacy and provide safer alternatives to traditional depigmenting agents like hydroquinone.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.