Which active ingredients should be combined with arbutin?

Glycolic acid is an alpha-hydroxy acid (AHA) derived from sugarcane, known for its low molecular weight and therefore excellent skin penetration. It primarily acts by breaking the bonds between corneocytes, thereby promoting the removal of stratum corneum cells and accelerating epidermal renewal. In melasma, this keratolytic action of glycolic acid helps to gradually diminish the intensity of hyperpigmented spots by accelerating the removal of melanin already present in the epidermis.

In order to target the various mechanisms involved in hyperpigmentation, some individuals consider combining arbutin with glycolic acid in their treatment regimen.

These two active ingredients indeed act via complementary mechanisms: glycolic acid primarily works at the surface, whereas arbutin functions further upstream by modulating the melanogenesis. However, to date, no clinical study has evaluated the efficacy or tolerability of their combination, which does not allow a conclusion regarding a potential synergistic effect. Moreover, the glycolic acid can prove irritating, particularly on sensitive or reactive skin, and its combination with other active ingredients should be approached with caution when they are not already formulated together.

The combination of arbutin acid and glycolic acid may be of theoretical interest, but it has not been investigated in practice.

Lactic acid is an alpha-hydroxy acid (AHA) naturally present in the skin, forming part of the natural moisturising factor (NMF). It exerts a more gradual exfoliating action than glycolic acid, weakening the bonds between corneocytes while helping to maintain skin hydration. This dual gentle keratolytic and humectant action makes it a particularly interesting active ingredient for sensitive skin.

In the context of a multifactorial approach to managing hyperpigmentation, some publications mention the formulation of emulsions combining lactic acid and arbutin for a lightening purpose. These studies show that the resulting emulsified systems are physico-chemically stable and could allow the use of lower concentrations of each active ingredient, suggesting a potential synergistic effect. However, these investigations are limited to formulation and stability considerations, without any clinical evaluation on volunteers.

In the absence of data in vivo, it therefore remains difficult to draw definitive conclusions regarding the actual efficacy and benefits of combining alpha-arbutin with lactic acid.

The azelaic acid is an acid of particular interest in dermatology, combining anti-inflammatory, antibacterial and exfoliating properties. Furthermore, it inhibits tyrosinase activity, thereby targeting hyperpigmentation. In this context, the combination of azelaic acid with arbutin appears relevant to address pigmentation issues.

A clinical study evaluated the efficacy and tolerability of a moisturiser containing 3% azelaic acid and 2% alpha-arbutin in subjects with oily, dull skin prone to blemishes. Conducted over 12 weeks with 64 volunteers of phototypes I to VI, it demonstrated a significant improvement in radiance and skin texture, a reduction in redness in lighter phototypes and a decrease in post-inflammatory hyperpigmentation in darker phototypes. A second phase of the study, supported by confocal microscopy, also showed reduced follicular keratinisation and decreased pore size. However, although the researchers indicate that the results were statistically significant, the study does not provide numerical data, which limits interpretation regarding this combination.

In practice, the arbutin–azelaic acid combination is supported by encouraging clinical data, but further targeted studies with quantified outcomes are still required.

The salicylic acid belongs to the family of beta-hydroxy acids (BHA) and is recognised for its keratolytic, comedolytic and anti-inflammatory properties. Lipophilic, it can penetrate the pores to dissolve excess sebum and promote the removal of dead skin cells. It is therefore highly prized for caring for blemish-prone skin.

One can assume that the combination of salicylic acid with arbutin exerts both preventive and corrective effects on post-inflammatory hyperpigmentation, limiting the appearance of blemishes likely to leave brown spots and acting directly on existing marks.

Nevertheless, the interactions between arbutin and salicylic acid have predominantly been described in the field of plant biology rather than in dermatology. Several studies indicate that salicylic acid functions as an elicitor in certain plants, enhancing the expression of genes involved in arbutin biosynthesis—particularly in pear trees—while arbutin in turn can modulate salicylic acid signalling pathways, as observed in cucumber. These findings suggest the presence of a biochemical regulatory loop between the two compounds within plant metabolism. However, to date there are no clinical studies demonstrating a synergistic effect of their combination when applied topically.

Their combination in cosmetics therefore relies more on the complementarity of their actions than on any demonstrated synergy, emphasising the need for further clinical research.

The kojic acid is an extensively studied active ingredient for its effect on hyperpigmentation. Derived from fungal sources, it acts by chelating copper ions essential to tyrosinase function, which allows to limit melanin production. However, its use in cosmetics is subject to controversy. Kojic acid is indeed suspected of being an endocrine disruptor, a potential allergen and a skin irritant. Concerns regarding its carcinogenicity and mutagenicity have also been raised in certain experimental models, leading to strict concentration limits and tight regulation of its use.

Despite these reservations, kojic acid is regularly combined with arbutin to enhance its depigmenting action.

A clinical study involving 30 participants with melasma compared the efficacy of a cream combining 5% alpha-arbutin and 2% kojic acid with another formulation based on the Kligman trio—a benchmark for hyperpigmentation treatment (hydroquinone, hydrocortisone and retinoic acid). Both creams were applied to each half of the face over a 12-week period. Efficacy was assessed using the MASI score. The results demonstrated comparable improvement between the two groups, with no statistically significant difference. However, the cream containing alpha-arbutin and kojic acid exhibited better tolerability, with fewer instances of redness and stinging sensations.

The combination of arbutin and kojic acid is promising for targeting hyperpigmentation; however, due to the controversies surrounding kojic acid, we recommend exercising caution.

Initially known for its medical use, tranexamic acid is now also used in cosmetics, particularly to address hyperpigmentation. It acts at various levels of melanogenesis and helps to even out the complexion. Multiple scientific studies suggest potential benefits of combining tranexamic acid with other depigmenting agents, such as arbutin, to act in a complementary manner on the various pathways involved in hyperpigmentation.

A study conducted in Indonesia involving 66 female patients with melasma evaluated the efficacy of a formulation combining 3% tranexamic acid, 2% arbutin, 4% of niacinamide, and 2% ferment of Galactomyces, known for its soothing effects. Patients applied a serum followed by a cream containing these actives for four weeks. Melasma severity was assessed using a clinical severity score (MSS) as well as an imaging analysis system to quantify dermal and epidermal pigmentation. A global improvement in hyperpigmentation was observed as early as two weeks.

However, even though this study indicates potential interest in the combination of tranexamic acid and arbutin, it is important to bear in mind that the observed efficacy is based on a multi-active formulation, in which other ingredients also contribute to the effects on complexion uniformity and luminosity.

The mandelic acid is an alpha-hydroxy acid (AHA) that has a progressive exfoliating action and is generally well tolerated due to its relatively large molecular structure (152.14 g/mol), which limits its penetration into the skin. In addition to enhancing skin radiance and caring for blemish-prone skin, the keratolytic properties of mandelic acid facilitate the removal of pigmented cells, thereby reducing hyperpigmentation.

While arbutin and mandelic acids could theoretically act in a complementary manner on brown spots, no study has yet evaluated the efficacy of this combination, warranting a cautious approach.

The ferulic acid is a potent antioxidant naturally found in certain plants and cereals, known for its ability to neutralise free radicals and protect the skin from oxidative stress and UV-induced damage. It is often used in association with vitamin C and vitamin E to strengthen their efficacy and improve complexion radiance while limiting the photoageing.

Although the combination of ferulic acid and arbutin has not yet been studied in clinical trials, these two actives appear to be compatible without any known contraindications, with ferulic acid providing complementary antioxidant support to the depigmenting properties of arbutin.

The retinoids, derivatives of vitamin A, are among the most popular active ingredients in dermatology and cosmetics. Although they are chiefly known for their ability to slow down skin ageing and diminish wrinkles, the retinoids also have depigmenting effects. More precisely regarding their mechanisms of action, this family of actives stimulates cellular renewal and supports collagen production.

At present, no clinical study has evaluated the combination of retinoids with arbutin acid. It is therefore difficult to confirm a genuine synergistic effect. Furthermore, depending on the type of retinoid used, some can be irritating, especially on sensitive skin, and caution is advised when they are combined with other potent actives.

In the absence of robust clinical evidence and given the potential irritant effects of retinoids, we recommend exercising caution if you wish to combine them with arbutin acid.

Ascorbic acid, better known as vitamin C, is a potent antioxidant widely used in cosmetics for its brightening and protective effects. It neutralises free radicals, participates in collagen synthesis and helps to reduce uneven skin tone as well as signs of photoageing. Its ability to stabilise certain actives, such as arbutin, enhances its appeal in formulations aimed at evening out and brightening the skin.

The combination of arbutin acid and vitamin C appears promising due to their complementary mechanisms. Arbutin acid inhibits tyrosinase activity and limits melanin production, while vitamin C regenerates oxidised arbutin and enhances its stability, also reinforcing the overall brightening and antioxidant effect. These results demonstrate that it is possible to use these two actives together: they are compatible and their association appears relevant in view of the scientific literature. However, the study that tested this combination did not proceed to clinical trials, making it difficult to determine its concrete effects on the skin. Further studies are therefore required to confirm their synergistic potential.

Remark : It is important to note that pure vitamin C can sometimes be irritating, and it is generally inadvisable to combine it with other active ingredients (except in formulations where it is already combined). However, this precaution does not concern vitamin C derivatives, which are better tolerated.

Hyaluronic acid is a polysaccharide naturally present in the skin, renowned for its ability to retain water and maintain cutaneous hydration. By holding moisture within the epidermis, it helps to plump the skin and smooth out dehydration lines. Thanks to its high tolerability, hyaluronic acid can be easily incorporated into any skincare regimen, regardless of skin type, including sensitive or reactive skin, and can be used daily without risk of irritation.

Hyaluronic acid can readily be combined with arbutin to complete a skincare routine targeting both hydration and the management of hyperpigmentation.

Although no specific synergy between these two active ingredients has been demonstrated in the scientific literature, their combination remains both relevant and complementary : hyaluronic acid ensures optimal skin hydration, while arbutin acts on pigmentation spots and evens out the complexion.

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