Alpha-Arbutin and Kojic Acid Cream: Potential Treatment for Melasma

Image Credit: © joey333 - stock.adobe.com

Alpha-arbutin 5% and kojic acid 2% cream (AAK) can be just as effective as triple combination cream (TCC) for the treatment of melasma, with a lower recurrent rate and fewer adverse events, according to a new study.¹ This may be suitable in sensitive skin patients with melasma or when used as maintenance treatment.

TCC containing hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01% is the current gold standard of melasma treatment. However, persistent use may increase the risk of skin atrophy and hypopigmentation.

The split-faced, randomized study was done in Thailand from May to December 2022 for 12 weeks, plus a 4-week follow-up period. The trial included 27 adults between the ages of 25 and 60 with mild to moderate bilateral and symmetrical facial melasma. Most were female (85.2%) with an average age of 46 years.

AAK was applied on one side of the face twice a day while TCC was applied on the other side once before bedtime. Participants were told to avoid sun exposure from 9 a.m. until 5 p.m. and use broad-spectrum sunscreen SPF 50.

Clinical evaluation was performed, and photographs were taken at weeks 4, 8, 12, and 16. Melanin index (MI), modified Melasma Area Severity Index (mMASI), and physician global assessment (PGA) scores were used to measure the severity and improvement of pigmentation. Patient satisfaction was also considered, and adverse events were assessed by dermatologists on a 4-point scale.

The mean of MI and mMASI scores were not significantly different between groups (mMASI [p = 0.344] and MI [p = 0.268]). The MI scores at baseline were 286.89 ± 70.83 for the AAK groups and 283.36 ± 73.97 for the TCC group. At week 12, scores were 266.77 ± 67.75, and 241.68 ± 73.26, for the TCC and AAK, respectively. Likewise, there was a nonsignificant difference during the follow-up period (p = 0.069).

Similar results were demonstrated in the mMASI scores. The mean mMASI scores at Week 12 were 2.19 ± 1.64 in the AAK group and 1.87 ± 1.48 in the TCC group. At week 16, scores were 2.48 ± 1.54 in the AAK group and 2.78 ± 1.67 in the TCC group.

The PGA scores only showed improvement on the TCC-treated side, especially at week 12 (p = 0.032). At week 12 in the AAK group, 14.8% of the patients had no improvement, 51.9% had slightly improved, 18.5% had fair improvement, and 11.1% had good improvement. Conversely, in the TCC group, 3.7% of the participants had no improvement, 33.3% had slight improvement, 37% had fair improvement, 18.5% had good improvement, and 3.7% had excellent improvement results.

Compared to the AKK group, the patients using TCC showed higher severity of recurrence at week 16 (MI [p = 0.004] and mMASI [p = 0.045]). Despite this, there was no significant difference in patient satisfaction scores between the two groups.

In terms of adverse events, erythema, dryness, stinging, and itching occurred in both groups as early as week 4. Erythema was higher in the TCC group, which was present in 40.7% at week 12. By week 12, erythema was no longer detected in the AAK group but was still observed in the TCC group (11.1%). Patients in the TCC cohort had mild to moderate stinging, most prevalent at week 4 with 25.9%. These adverse effects were temporary and did not lead to the discontinuation of treatment. Neither group experienced telangiectasia, atrophy, or hypopigmentation.

The investigators noted limitations including the small sample size and short follow-up period. An extended study duration with a larger included population could provide more accurate findings and allow researchers to observe long-term complications. Although clinical evidence is still limited, these results are consistent with what was found in a previous study comparing AAK to hydroquinone 4%.²

“It is noteworthy that arbutin could be another fascinating substitute in melasma treatment as it is less toxic than hydroquinone,” the authors wrote. “We believed that adding the AAK to the standard therapy may lead to synergistic effects, then promoting treatment outcomes. Besides, the AAK can also be initiated as a maintenance treatment, after termination of the TCC, due to its satisfactory safety profile.”

References

1. Tantanasrigul P, Sripha A, Chongmelaxme B. The Efficacy of Topical Cosmetic Containing Alpha-Arbutin 5% and Kojic Acid 2% Compared With Triple Combination Cream for the Treatment of Melasma: A Split-Face, Evaluator-Blinded Randomized Pilot Study. J Cosmet Dermatol. Published online November 18, 2024. doi:10.1111/jocd.16562

2. A. Costa, L. H. de Arruda, E. S. Pereira, et al. “Evaluation of the Whitening Properties of Combined Kojic Acid, Arbutin, Sepiwhite® and Achromaxyl® Vs. 2% and 4% Hydro-Quinone in the Treatment of Melasma,” Surgical and Cosmetic Dermatology 4, no. 1 (2012): 22–30.