Which active ingredients should azelaic acid be paired with?

The vitamin C, or ascorbic acid, is widely recognized for its antioxidant properties, its role in collagen synthesis, and its complexion-unifying effect. It acts by neutralizing free radicals induced by UV rays or pollution and by inhibiting tyrosinase, an enzyme required for melanin synthesis. The vitamin C is therefore the active ingredient of choice for those aiming to even out their complexion. It could be useful to pair it with azelaic acid for the skin prone to hyperpigmented spots and residual redness following inflammation.

A study conducted with 20 volunteers evaluated the effect of a protocol consisting of eight weekly sessions that combined the application of a 20% azelaic acid and 30% phytic acid treatment to the entire face, with an additional 40% L-ascorbic acid applied only to the left side. After two months, the results showed a significant improvement in erythema and hyperpigmentation, especially pronounced when all three active agents were combined. A notable increase in skin hydration was also observed, and all participants expressed satisfaction, reporting better firmness, elasticity, skin tone uniformity, and a reduction in redness and wrinkles. The combination of azelaic acid and vitamin C thus appears effective for enhancing overall skin appearance.

The glycolic acid, an alpha-hydroxy acid (AHA), is an active ingredient known for its keratolytic properties. Thanks to its small molecular size, it easily penetrates the stratum corneum and promotes the elimination of dead cells, thus improving skin texture and pigment irregularities. Combining glycolic acid with azelaic acid could improve the management of skin prone to blemishes or brown spots.

A 24-week study was conducted on 60 patients with melasma. Volunteers were randomly assigned to two groups: the first received a 30% glycolic acid peel every three weeks combined with a twice-daily application of 20% azelaic acid cream, while the second used only the cream. Efficacy was assessed using the MASI score. Although the MASI score decreased significantly in both groups, the reduction was more pronounced in the group receiving glycolic acid peels alongside azelaic acid cream.

For sensitive skin, it is recommended not to apply a glycolic acid–containing treatment and an azelaic acid product simultaneously, as this may lead to irritation.

The salicylic acid is a beta-hydroxy acid (BHA) with a strong affinity for lipid-rich environments. It is therefore capable of penetrating deeply into sebum-clogged pores to unclog them. Moreover, salicylic acid exhibits mild antimicrobial and anti-inflammatory properties that may complement those of azelaic acid to target imperfections.

A trial involving 34 patients with mild to moderate acne evaluated the effect of four peeling sessions performed at two-week intervals. A combined solution of 20% salicylic acid (SA) and 20% azelaic acid (AA) was applied to one half of the face, while the other half was treated with a 25% trichloroacetic acid (TCA) peel. Clinical assessments showed a faster improvement in inflammatory lesions on the side treated with SA/AA, and in non-inflammatory lesions on the TCA-treated side. After four sessions, both treatments provided significant improvement, with no marked difference between them, although participants expressed a preference for the SA/AA side, which was considered more comfortable.

The gluconolactone is a polyhydroxy acid (PHA) that stands out from other exfoliants due to its high skin tolerability. Thanks to its larger molecular structure, it penetrates the skin slowly, which significantly limits the risks of irritation. Gluconolactone is thus an exfoliant of choice for sensitive skin. Its combination with azelaic acid may suit weakened skin with imperfections, vascular sensitivity, or rosacea flare-ups.

No clinical study has yet validated this combination. Nevertheless, their complementary mechanisms of action suggest that combining azelaic acid with gluconolactone could be beneficial for sensitive, combination skin prone to acne or redness.

Well known to acne-prone skin, benzoyl peroxide exhibits keratolytic and antibacterial properties that help prevent skin pore obstruction by the accumulation of dead cells and eliminate Cutibacterium acnes, the bacterium involved in the inflammation of acne lesions. The idea of combining benzoyl peroxide with azelaic acid is based on the complementarity of their antibacterial and anti-inflammatory actions. While benzoyl peroxide rapidly targets bacterial proliferation, azelaic acid works more gently by limiting inflammation and reducing the redness associated with breakouts.

It would be worthwhile for clinical studies to investigate this combination in order to evaluate its efficacy and tolerability.

The retinoids represent a benchmark class of active ingredients in dermatology for managing acne and skin aging. Their mechanism of action relies on regulating cell turnover, boosting collagen synthesis, reducing inflammation, and, for oral retinoids, decreasing sebaceous gland activity. Combining retinoids with azelaic acid could help optimize the management of acne-prone, inflamed skin.

However, this combination is not without risk for sensitive skin. Indeed, retinoids—particularly retinol and tretinoin—can cause irritation, dryness, and flaking. Layering them with azelaic acid, known for its mattifying properties, could further weaken the skin barrier. We therefore recommend introducing these two active ingredients progressively into your routine. Furthermore, when undergoing oral isotretinoin therapy, adding topical azelaic acid is generally discouraged, as the skin is already highly sensitized by the systemic treatment.

The arbutin acid is a derivative of hydroquinone naturally found in certain plants such as bearberry. In cosmetics, it is recognized for its depigmenting action, mainly via the inhibition of tyrosinase. Arbutin acid is particularly indicated to reduce pigmented spots and is well tolerated by most skin types. Combining azelaic acid with arbutin acid could enhance its depigmenting effects. However, this remains a hypothesis since, to date, no study has examined the potential synergy between these actives.

For the same reasons, some people have raised concerns about the combination of azelaic acid and hydroquinone. As a reminder, hydroquinone is a very effective depigmenting agent but controversial because it is suspected of being carcinogenic, allergenic, and reprotoxic. In Europe, only professional use is authorized. At Typology, we advise against using hydroquinone, alone or in combination with azelaic acid, as a precaution. If you suffer from hyperpigmentation, we recommend instead turning to arbutin, a derivative with a better safety profile.

It is also possible to combine azelaic acid with tranexamic acid, another agent known for its depigmenting properties. A study investigated this combination by enrolling 33 women with moderate to severe hyperpigmentation. For six weeks, participants applied a cream containing azelaic acid and tranexamic acid daily (concentrations not specified). Skin pigmentation was monitored throughout the study using photographs and dermatologist assessments. At the end of the study, a improvement in skin pigmentation of the patients was observed by computer software.

Some individuals also question the relevance of combining azelaic acid with kojic acid to lighten their brown spots. However, if the kojic acid is approved for cosmetic use, it is suspected of penetrating the skin barrier and being carcinogenic, mutagenic, and an endocrine disruptor. That is why we recommend against using kojic acid, whether alone or in combination with azelaic acid. If you have hyperpigmentation, there are other active ingredients whose safety profile is better documented.

The mandelic acid is a fruit acid in the AHA family, derived from bitter almonds. Its unique characteristic is its larger molecular size compared to other AHAs, such as glycolic acid, which leads to slower skin penetration and a lower risk of irritation. This makes it a well-tolerated exfoliant, even for sensitive skin or skin prone to post-inflammatory hyperpigmentation. Combining it with azelaic acid could be an interesting strategy to simultaneously address uneven skin texture, imperfections, and residual pigmentation spots.

In the absence of scientific research on this subject, the potential synergy between azelaic acid and mandelic acid remains hypothetical.

Urea is an interesting cosmetic active ingredient, both hydrating and exfoliating. At low concentrations (about 2 to 10%), it acts as a humectant, drawing water into the superficial layers of the epidermis and strengthening the skin’s barrier function. At higher concentrations (above 10%), it exhibits keratolytic activity and helps remove dead cells from the skin’s surface while softening it. It may be beneficial to combine urea with azelaic acid to amplify its exfoliating properties while benefiting from azelaic acid’s anti-inflammatory virtues. This combination could be particularly beneficial for individuals prone to psoriasis, an inflammatory skin disorder characterized by skin thickening.

Again, no study to date has investigated the combination of azelaic acid and urea, which calls for caution.

The bakuchiol is a plant-derived compound extracted from the seeds of Psoralea corylifolia, often touted as a gentle alternative to retinol. It is recognized for its antioxidant and anti-inflammatory properties and its ability to reduce brown spots and signs of aging, without causing skin sensitization. Bakuchiol and azelaic acid may offer a synergistic approach to simultaneously target imperfections, excess sebum, redness, and photoaging.

Azelaic acid and bakuchiol could be an intriguing option for individuals seeking an active yet gentle skincare regimen, particularly in cases of mild rosacea or frequent blemishes. Future research into this potential synergy would be valuable.

Tea tree essential oil is well known for its antibacterial, antifungal, and anti-inflammatory properties. When diluted in a carrier oil, it is frequently applied topically to reduce blemishes. It is possible that combining it with azelaic acid could enhance its antibacterial and soothing effects and help prevent acne breakouts. However, we recommend proceeding with caution before mixing azelaic acid with tea tree essential oil, as this combination can be irritating for sensitive skin or at high concentrations.

Furthermore, to date, no clinical trial has validated the efficacy and tolerability of the combination of azelaic acid and tea tree essential oil.

The vitamin E, or tocopherol, is a lipid-soluble antioxidant naturally found in human sebum. It plays a central role in stabilizing cell membranes under oxidative stress by neutralizing free radicals generated by UV radiation, pollution, or certain inflammatory processes. This protective action is particularly important since the oxidation of sebum lipids, such as squalene, can contribute to skin issues like acne. In cosmetic formulations, vitamin E is used not only for its biological properties but also for its ability to limit oxidation of formulations, thereby extending their efficacy and tolerability. Although azelaic acid itself is not particularly prone to oxidation, it is frequently combined with other compounds that are. In this context, adding vitamin E can be beneficial.

The hyaluronic acid is a glycosaminoglycan naturally present in the skin’s extracellular matrix, known for its water-retention capacity. Depending on its molecular weight, it can hydrate the superficial layers of the epidermis or penetrate more deeply to support cellular cohesion and the skin’s barrier function. It is therefore widely used to rehydrate the skin and improve its elasticity. It may be advisable to combine azelaic acid with hyaluronic acid. This helps reduce imperfections and redness while preventing skin weakening and dehydration. Indeed, although azelaic acid is recognized for its anti-inflammatory and antibacterial effectiveness, it can sometimes slightly dry out the skin, especially at higher concentrations (15 to 20%). Hyaluronic acid, by providing immediate hydration, counteracts this drying effect and improves long-term tolerance.

Note : Despite some common misconceptions, hyaluronic acid alone is not enough to provide lasting hydration to the skin. Without the addition of fatty substances, such as creams or balms, the water it attracts can evaporate from the skin.

Rosehip oil is a plant-derived oil rich in polyunsaturated fatty acids, particularly linoleic acid and alpha-linolenic acid. It is reputed to promote skin regeneration, diminish the appearance of scars, pigmented spots, and fine lines, while improving skin elasticity. Therefore, one can hypothesize that using azelaic acid and rosehip oil concomitantly could be a strategic approach to target both blemishes, redness, and the post-inflammatory marks.

Nevertheless, some qualifications are in order, as rosehip oil is known to be mildly comedogenic. Its undiluted application is therefore not recommended for oily or acne-prone skin. This does not mean, however, that it is unsuitable for all skin types: normal to dry skin generally tolerates it very well. Moreover, its behavior can vary depending on the formulation. When incorporated into a skincare product, its comedogenic potential depends on its concentration and the overall composition of the ingredients. In any event, to date, no study has demonstrated any specific benefit from combining rosehip oil with azelaic acid.

The sulfur is a longstanding active ingredient still used in cosmetics, primarily for its mattifying, anti-inflammatory, keratolytic, and antimicrobial properties, similar to those of azelaic acid. Its main drawback is its odor, which can deter some individuals. The combination of azelaic acid and sulfur presents an interesting rationale. Since both exert largely identical effects, their combination could target multiple factors in the development of blemishes, such as excess sebum, hyperkeratinization, bacterial proliferation, and inflammation.

The synergy between azelaic acid and sulfur remains hypothetical today due to a lack of clinical studies. Moreover, the sulfur, much like azelaic acid, can have a slightly drying effect on the skin. Their combination, although potentially complementary, could therefore prove too irritating.