Which active ingredients should be combined with azelaic acid?

The niacinamide is a particularly well-documented active ingredient for its anti-inflammatory, soothing and reparative effects. It helps reinforce the skin barrier by stimulating ceramide synthesis and limiting transepidermal water loss. The niacinamide is also capable of reducing redness, attenuating post-inflammatory hyperpigmentation and may modulate sebum production. Well tolerated, it is often included in products formulated for sensitive skin or skin prone to chronic inflammation.

The combination of niacinamide with azelaic acid thus appears particularly relevant for reactive skin or those suffering from couperosis. While the azelaic acid inhibits neutrophil metabolic function, affecting the release of pro-inflammatory reactive oxygen species, niacinamide enhances skin tolerance and soothes the skin. This combination may also improve the evenness of skin tone by targeting both post-inflammatory hyperpigmentation and diffuse redness, an effect that would be worthwhile to confirm in clinical studies.

The zinc, often found as zinc gluconate, zinc PCA or zinc oxide, is an active ingredient recognised for its sebum-regulating, antibacterial and anti-inflammatory properties. It is therefore frequently used to formulate products for oily or acne-prone skin. Depending on its form, zinc may also support the healing process. Pairing it with the azelaic acid, which has mattifying and anti-inflammatory effects, could therefore be relevant for reducing hyperseborrhoea and minimising shine. However, this combination has not yet been tested in clinical studies for this purpose.

On the other hand, work carried out by SLUZEVICH and his team focussed on its effects on the melasma. The researchers evaluated the efficacy and tolerability of a treatment combining 0.075% tazarotene, a retinoid, 20% azelaic acid, 0.1% tacrolimus, an immunosuppressant, and 10% zinc oxide. Sixteen patients presenting with hyperpigmentation applied this formulation daily for 20 weeks. The results demonstrated a significant improvement in MASI score (Melasma Area and Severity Index), from an average of 18.9 to 13.3. A quarter of participants achieved a MASI score below 8 by the end of the study. Reported adverse effects were mostly mild and transient. However, it is difficult to determine the specific role of the azelaic acid and zinc oxide combination, since they were administered alongside other active agents.

The vitamin C, or ascorbic acid, is widely recognised for its antioxidant properties, its role in collagen synthesis and its complexion-unifying effect. It acts both by neutralising free radicals induced by UV or pollution and by inhibiting the activity of tyrosinase, an enzyme required to synthesise melanin. The vitamin C is therefore a highly valued active ingredient for those seeking to even out their skin tone. It may be beneficial to combine it with azelaic acid for skin prone to pigmentation spots and residual redness following inflammation.

A study conducted with 20 volunteers evaluated the effect of a protocol of eight weekly sessions combining the application of a treatment containing 20% azelaic acid and 30% phytic acid across 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, particularly marked when all three active ingredients were combined. A notable increase in skin hydration was also observed and all participants expressed their satisfaction, reporting improved firmness, elasticity, even skin tone, and a reduction in redness and wrinkles. The combination of azelaic acid and vitamin C thus appears effective in improving the overall appearance of the skin.

The glycolic acid, an alpha-hydroxy acid (AHA), is an active ingredient known for its keratolytic properties. Owing to its low molecular weight, it readily penetrates the stratum corneum and promotes the removal of dead cells, thereby improving skin texture and addressing pigmentary irregularities. Combining glycolic acid with azelaic acid could enhance the management of skin prone to blemishes or brown spots.

A 24-week study was conducted in 60 patients with melasma. The volunteers were divided into two groups: the first received a 30% glycolic acid peel every three weeks combined with a twice-daily application of 20% azelaic acid cream, whereas the second group used the cream alone. Efficacy was assessed using the Melasma Area and Severity Index (MASI). Although MASI scores decreased significantly in both groups, the reduction was more pronounced in the group receiving glycolic acid peel sessions plus the azelaic acid cream.

For sensitive skin, it is preferable not to apply a treatment containing glycolic acid and a product containing azelaic acid simultaneously, at the risk of causing irritation.

The salicylic acid is a beta-hydroxy acid (BHA) with a strong affinity for lipid environments. It can thus penetrate deeply into sebum-clogged pores and help dislodge them. Furthermore, salicylic acid possesses mild antimicrobial and anti-inflammatory properties that may complement those of azelaic acid to target blemishes.

A study of 34 patients with mild to moderate acne evaluated the effect of four chemical peel sessions conducted 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 underwent a 25% trichloroacetic acid (TCA) peel. Clinical evaluations demonstrated a more rapid improvement in inflammatory lesions on the SA/AA-treated side, and of non-inflammatory lesions on the TCA-treated side. After the four sessions, both treatments achieved significant improvements, with no marked difference between them, although participants expressed a preference for the SA/AA-treated side, which was deemed more comfortable.

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

No clinical study has yet validated this combination. Nevertheless, their complementary mechanisms of action suggest that the combination of azelaic acid and gluconolactone may benefit sensitive or combination skin prone to acne or redness.

Well-known to acne-prone skin, benzoyl peroxide possesses keratolytic and antibacterial properties that help prevent the clogging of skin pores by accumulated dead cells and eliminate Cutibacterium acnes, the bacterium involved in the inflammation of acne lesions. The rationale for combining benzoyl peroxide with azelaic acid is based on the complementarity of their antibacterial and anti-inflammatory actions. Whilst benzoyl peroxide swiftly targets bacterial proliferation, azelaic acid works more gently, curbing inflammation and soothing the redness associated with spots.

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

The retinoids are a benchmark class of active ingredients in dermatology for the management of acne and skin ageing. Their mechanism of action relies on regulating cell turnover, increasing collagen synthesis, reducing inflammation and, for oral retinoids, decreasing sebaceous gland activity. Combining retinoids with azelaic acid could help optimise the management of acne-prone and inflammatory skin.

However, this combination is not without risk for sensitive skin. Indeed, retinoids, notably retinol and tretinoin, can cause irritation, dryness and peeling. Layering them with azelaic acid, which has mattifying properties, could further weaken the skin barrier. We therefore recommend introducing these two actives gradually into your routine. Furthermore, in the case of oral isotretinoin treatment, the addition of topical azelaic acid is generally discouraged, as the skin is already highly sensitised systemically.

The arbutin acid is a derivative of hydroquinone naturally found in certain plants such as bearberry. In cosmetics, it is recognised for its depigmenting action, primarily via inhibition of tyrosinase. Arbutin acid is particularly indicated for attenuating pigment spots and is well tolerated by most skin types. Combining azelaic acid with arbutin acid could enhance its depigmenting effects. This remains a hypothesis, however, since to date no study has investigated any potential synergy between these actives.

For these same reasons, some individuals question the combination of azelaic acid with hydroquinone. As a reminder, hydroquinone is a highly effective depigmenting agent but remains controversial as it is suspected of being carcinogenic, allergenic and reprotoxic. In Europe, only professional use is authorised. At Typology, we advise against using hydroquinone, either on its own or in conjunction with azelaic acid, as a precaution. If you suffer from hyperpigmentation, we instead recommend turning to arbutin, a derivative with a better safety profile.

It is also possible to combine azelaic acid with tranexamic acid, another active ingredient renowned for its depigmenting properties. A study investigated this combination by enrolling 33 women with moderate to severe hyperpigmentation. Over six weeks, participants applied a cream containing azelaic acid and tranexamic acid daily (concentrations unspecified). Their skin pigmentation was monitored throughout the study using photographic documentation and dermatological assessment. At the end of the study, a improvement in skin pigmentation in the patients was observed using computer software.

Some individuals also question the relevance of combining azelaic acid with kojic acid to reduce brown spots. However, while kojic acid is authorised in cosmetics, it is suspected of penetrating the skin barrier and being carcinogenic, mutagenic and an endocrine disruptor. Consequently, we advise against using kojic acid, whether alone or in combination with azelaic acid. If you are experiencing hyperpigmentation, there are other active ingredients whose safety profile is more comprehensively documented.

Mandelic acid is a fruit acid in the AHA family, derived from bitter almonds. Its notable characteristic is its larger molecular size compared with other AHAs, such as glycolic acid, which slows its cutaneous penetration and reduces the 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 address simultaneously the skin texture irregularities, blemishes 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. Indeed, at low concentrations (around 2–10%), it acts as a humectant, drawing water into the superficial layers of the epidermis and reinforcing the skin’s barrier function. At higher concentrations (above 10%), it exhibits keratolytic activity and facilitates the removal of dead cells from the skin’s surface, while softening it. It may be beneficial to combine urea with azelaic acid in order to amplify its exfoliating properties, while taking advantage of azelaic acid’s anti-inflammatory virtues. This combination could be particularly beneficial for people prone to psoriasis, an inflammatory dermatosis characterised by a thickening of the skin.

Once again, no study to date has investigated the combination of azelaic acid and urea, which warrants caution.

The bakuchiol is a plant-derived compound extracted from the seeds of Psoralea corylifolia, often promoted as a gentle alternative to retinol. It is renowned for its antioxidant and anti-inflammatory properties and its ability to reduce brown spots and signs of ageing without causing skin sensitisation. Bakuchiol and azelaic acid may offer a synergistic approach to target both blemishes, excess sebum, redness and photoageing.

Azelaic acid and bakuchiol could offer an interesting option for those seeking an active yet gentle routine, especially in cases of mild rosacea or frequent imperfections. It would be worthwhile for further research to be conducted on this potential synergy in the future.

Tea tree essential oil is well recognised for its antibacterial, antifungal and anti-inflammatory properties. When diluted in a carrier oil, it is frequently used as a topical treatment to diminish skin blemishes. Pairing it with azelaic acid may enhance its antibacterial and soothing actions and contribute to preventing acne flare-ups. However, we recommend exercising caution before combining azelaic acid with tea tree essential oil, as this combination can be irritating for sensitive skin or at high concentrations.

Moreover, 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 naturally occurring liposoluble antioxidant present in human sebum. It plays a central role in stabilising cell membranes under oxidative stress by neutralising free radicals generated notably by UV radiation, pollution or certain inflammatory processes. This protective action is all the more significant given that the oxidation of sebum lipids, such as squalene, can contribute to skin issues such as acne. In cosmetic formulations, Vitamin E is used not only for its biological properties, but also for its capacity to limit the oxidation of formulations, thereby extending their efficacy and tolerance. Although azelaic acid is not particularly prone to oxidation, it is frequently combined with other compounds that are. In this context, the addition of Vitamin E may be beneficial.

The hyaluronic acid is a glycosaminoglycan naturally present in the extracellular matrix of the skin, recognised for its capacity to retain water. 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 relevant to combine azelaic acid with the hyaluronic acid. This helps reduce imperfections and redness while avoiding weakening and dehydrating the skin. Indeed, although azelaic acid is recognised for its anti-inflammatory and antibacterial efficacy, it can sometimes slightly dry out the skin, especially when used at high concentrations (15 to 20%). Hyaluronic acid, by providing immediate hydration, counteracts this drying effect and improves long-term tolerability.

Note : Despite some common misconceptions, hyaluronic acid alone is not sufficient to provide lasting hydration to the skin. Without the addition of lipid-based ingredients, such as a cream or balm, the water it attracts is likely to evaporate from the skin.

Rosehip seed oil is a plant-derived oil rich in polyunsaturated fatty acids, particularly linoleic acid and alpha-linolenic acid. It is renowned for promoting skin regeneration, diminishing the appearance of scars, pigmented spots and fine lines, while improving skin elasticity. It can therefore be assumed that the simultaneous use of azelaic acid and rosehip oil could be judicious for targeting blemishes, redness and the post-inflammatory marks.

However, some qualifications are necessary, 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, however, mean that it is unsuitable for all skin types: normal to dry skin generally tolerates it very well. Furthermore, its behaviour can vary according to the formulation. When incorporated into a skincare product, its comedogenic potential depends on its concentration and the complete set of ingredients present. In any case, to date, no study has demonstrated any particular benefit from combining rosehip oil with azelaic acid.

The sulphur is an age-old active ingredient still used in cosmetics, primarily for its mattifying, anti-inflammatory, keratolytic and antimicrobial properties akin to those of azelaic acid. Its main drawback is its odour, which can deter some people. The combination of azelaic acid and sulphur thus offers an interesting rationale. Both exert broadly identical effects, and their combination could target multiple factors in the development of blemishes, such as excess sebum, hyperkeratinisation, bacterial proliferation and inflammation.

The synergy between azelaic acid and sulphur is still hypothetical today, owing to a lack of clinical studies. Moreover, the sulphur, like azelaic acid, can exert a mildly drying effect on the skin. Their combined use, though potentially complementary, could therefore prove excessively irritating.

• DUA R. & al. Combination of glycolic acid peel and topical 20% azelaic acid cream in melasma patients: Efficacy and improvement in quality of life. Journal of Cosmetic Dermatology (2016).

• SLUZEVICH J. & al. Evaluating the efficacy, safety, and tolerability of the combination of tazarotene, azelaic acid, tacrolimus, and zinc oxide for the treatment of melasma: A pilot study. The Journal of Clinical and Aesthetic Dermatology (2019).

• HAY R. A. & al. Clinical and dermoscopic evaluation of combined (salicylic acid 20% and azelaic acid 20%) versus trichloroacetic acid 25% chemical peel in acne: An RCT. Journal of Dermatological Treatment (2019).

• PEINEMANN F. & al. Topical azelaic acid, salicylic acid, nicotinamide, sulphur, zinc and fruit acid (alpha‐hydroxy acid) for acne. Cochrane Database of Systematic reviews (2020)

• ERKIERT-POLGUJ A. & al. Clinical evaluation of anti-aging effects of combined therapy—Azelaic acid, phytic acid, and vitamin C applied layer by layer in females with Fitzpatrick skin types II and III. Journal of Cosmetic Dermatology (2022).

• MAYBURY C. & al. A systematic review to evaluate the efficacy of azelaic acid in the management of acne, rosacea, melasma and skin aging. Journal of Cosmetic Dermatology (2023).

• CHABERT L. & al. In vitro and in vivo assessment of an innovative peeling system with azelaic and tranexamic acids for targeted hyperpigmentation reduction. Dermatology and Therapy (2025).