Which active ingredients should be combined with arbutin acid?

The glycolic acid is an alpha-hydroxy acid (AHA) derived from sugarcane, known for its low molecular weight, which gives it excellent skin penetration ability. It acts primarily by breaking the bonds between corneocytes, thereby promoting the removal of cells from the stratum corneum and epidermal renewal. In cases of melasma, this keratolytic action of glycolic acid gradually reduces the intensity of dark spots by accelerating the clearance of melanin already present in the epidermis.

To target different mechanisms involved in hyperpigmentation, some individuals consider combining arbutin with glycolic acid in their skincare routine.

These two active ingredients indeed work by complementary mechanisms of action: glycolic acid mainly acts at the surface while arbutin works upstream by modulating melanogenesis. However, to date, no clinical trial has evaluated the efficacy or tolerability of their combination, which prevents any conclusion regarding a possible synergistic effect. Moreover, glycolic acid can be irritating, particularly on sensitive or reactive skin, and combining it with other actives should be approached with caution unless they are already formulated together.

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

Lactic acid is a naturally occurring alpha-hydroxy acid (AHA) in the skin that is part of the natural moisturizing factor (NMF). It delivers a more gradual exfoliating action than glycolic acid, weakening the bonds between corneocytes while supporting skin hydration. This dual mild keratolytic and humectant action makes it particularly suitable for sensitive skin.

In a multifactorial approach to managing hyperpigmentation, some publications mention the formulation of emulsions combining lactic acid and arbutin acid for a brightening effect. These studies demonstrate that the resulting emulsion systems are physicochemically stable and could allow the use of lower concentrations of each active ingredient, suggesting a potential synergistic effect. However, these studies 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 about the actual efficacy and benefits of the association between alpha-arbutin and lactic acid.

The azelaic acid is a particularly interesting acid 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 for addressing pigmentary concerns.

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

In practice, the arbutin–azelaic acid combination is supported by encouraging clinical data, but more targeted studies with quantified results are still needed.

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

It can be assumed that the combination of salicylic acid and arbutin exerts both preventive and corrective effects on post-inflammatory hyperpigmentation by limiting the development of blemishes that may leave brown spots and by acting directly on existing marks.

Nevertheless, the interactions between arbutin and salicylic acid have primarily been described in the field of plant biology rather than in dermatology. Several studies show that salicylic acid acts as an elicitor in certain plants, stimulating the expression of genes involved in arbutin biosynthesis—particularly in pear trees—while arbutin can in turn modulate salicylic acid signaling pathways, as observed in cucumber. These findings suggest the existence of a biochemical regulatory loop between these two compounds in plant metabolism. However, to date, no clinical studies have demonstrated a synergistic effect from their combined topical application.

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

The kojic acid is a widely studied active ingredient for its effect on hyperpigmentation. Of fungal origin, it works by chelating the copper ions essential for tyrosinase activity, thereby limiting melanin production. However, its use in cosmetics is controversial. Kojic acid is suspected of being an endocrine disruptor, a potential allergen, and a skin irritant. Concerns about carcinogenicity and mutagenicity have also been raised in certain experimental models, leading to concentration limits and strict regulation of its use.

Despite these concerns, kojic acid is regularly combined with arbutin to intensify its depigmenting action.

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

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

Originally identified for its medical use, the tranexamic acid is now also used in cosmetics, particularly for managing hyperpigmentation. It acts at multiple levels of melanogenesis and helps to even out skin tone. Several scientific studies suggest a benefit to combining tranexamic acid with other depigmenting agents, such as arbutin, to work synergistically on the various pathways involved in hyperpigmentation.

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

However, even though this study indicates a potential benefit of the combination of tranexamic acid and arbutin, it should be kept in mind that the observed efficacy is based on a multi‐active formulation, in which other ingredients also contribute to effects on skin tone uniformity and brightness.

The mandelic acid is an alpha-hydroxy acid (AHA) that has a gradual 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, mandelic acid’s keratolytic properties help remove pigmented cells, thereby reducing hyperpigmentation.

While arbutin acid and mandelic acid could theoretically act in a complementary manner on brown spots, no study has yet evaluated the efficacy of this combination, which suggests caution.

The ferulic acid is a powerful antioxidant naturally found in certain plants and cereals, known for its ability to neutralize free radicals and protect the skin from oxidative stress and UV-induced damage. It is often used alongside vitamin C and vitamin E to boost their effectiveness and improve skin radiance while limiting photoaging.

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

The retinoids, vitamin A derivatives, are among the most popular actives in dermatology and cosmetics. While they are best known for their ability to slow skin aging and reduce wrinkles, the retinoids also have depigmenting effects. More specifically regarding their mechanisms of action, this class of actives stimulates cell turnover and promotes collagen production.

To date, no clinical study has evaluated the combination of retinoids with arbutin. Therefore, it is difficult to confirm a true synergistic effect. Moreover, depending on the type of retinoid used, some may be irritating, especially for sensitive skin, and caution is advised when they are combined with other potent actives.

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

Ascorbic acid, better known as vitamin C, is a powerful antioxidant widely used in cosmetics for its brightening and protective effects. It neutralizes free radicals, participates in collagen synthesis and contributes to reducing skin tone irregularities as well as signs of photoaging. Its ability to stabilize certain actives, such as arbutin, further enhances its appeal in formulations aimed at evening 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 oxidized arbutin and enhances its stability, all while boosting the overall brightening and antioxidant effects. These results show that it is possible to use both actives together: they are compatible and their combination appears relevant in light of the scientific literature. However, the study testing this combination did not proceed to clinical trials, making it difficult to know what concrete effects it would have on the skin. Further studies are therefore needed to confirm their synergistic potential.

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

The hyaluronic acid is a polysaccharide naturally found in the skin, known for its ability to retain water and maintain skin hydration. By holding moisture in the epidermis, it helps to plump the skin and smooth the dehydration lines. Thanks to its good tolerability, the hyaluronic acid can be easily integrated into any skincare routine, regardless of skin type, including sensitive or reactive skin, and can be used daily without risk of irritation.

Hyaluronic acid can easily be combined with arbutin to supplement a skincare routine aimed at both hydration and addressing hyperpigmentation.

Although no specific synergy between these two active ingredients has been demonstrated in the scientific literature, their combination remains relevant and complementary : hyaluronic acid provides optimal hydration to the skin, while arbutin targets dark spots and evens out skin tone.

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