Azelaic acid: which other active ingredients should it be combined with?

The niacinamide is known to strengthen the skin barrier by stimulating ceramide synthesis, thereby reducing water loss. It also diminishes redness, alleviates post-inflammatory hyperpigmentation, and may help regulate sebum production. Well tolerated, it is particularly suitable for sensitive skin or skin prone to chronic inflammation. Combining niacinamide with azelaic acid therefore appears relevant for reactive skin or skin affected by couperose.

While theazelaic acid inhibits neutrophil metabolic function, thereby limiting the release of pro-inflammatory reactive oxygen species, niacinamide enhances skin tolerance and soothes the skin. This combination may also improve skin tone uniformity by targeting both post-inflammatory hyperpigmentation and diffuse redness, effects that would be interesting to confirm through clinical studies.

The vitamin C is recognized for its antioxidant properties, its role in collagen synthesis, and its complexion-unifying effect. It neutralizes free radicals generated by UV exposure or pollution and inhibits the activity of tyrosinase, an enzyme involved in melanin synthesis. Its combination with azelaic acid could be particularly beneficial for skin prone to hyperpigmentation and residual post-inflammatory redness.

A study conducted on 20 volunteers evaluated the effect of eight weekly sessions combining a 20% azelaic acid and 30% phytic acid treatment applied to the entire face, with an additional 40% L-ascorbic acid applied only to the left side. After two months, results demonstrated a significant improvement in erythema and hyperpigmentation, particularly pronounced with the combination of all three active ingredients.

An increase in skin hydration was also observed, and participants reported improvements in firmness, elasticity, and evenness of complexion, as well as a reduction in redness and wrinkles. This combination thus appears effective in improving the skin’s overall appearance.

The retinoids are a gold-standard class of active ingredients in dermatology for the management of acne and skin aging. Their mechanism of action is based on regulating cellular renewal, increasing collagen synthesis, reducing inflammation, and, in oral formulations, decreasing sebaceous gland activity. Their combination with azelaic acid may optimize the management of acne-prone, inflamed skin.

This combination, however, requires precautions for sensitive skin. The retinoids, particularly retinol and tretinoin, can cause irritation, dryness, and peeling. Layering them with azelaic acid, known for its mattifying properties, could further weaken the skin barrier. It is therefore recommended to introduce these two active ingredients gradually into one's skincare routine.

In the case of oral isotretinoin treatment, adding topical azelaic acid is generally not recommended, as the skin is already highly sensitized by systemic therapy.

Thesalicylic acid is a lipid-soluble beta-hydroxy acid (BHA) capable of deeply penetrating pores clogged with sebum and dead cells to unclog them. Its antimicrobial and anti-inflammatory properties may complement those ofazelaic acid to target imperfections.

A trial involving 34 patients with mild to moderate acne assessed the effect of four peeling sessions administered 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 received a 25% trichloroacetic acid (TCA) peel.

The results showed a faster improvement of inflammatory lesions with the AS/AA combination, and of non-inflammatory lesions with TCA. After four sessions, both treatments resulted in comparable, significant improvements, although participants expressed a preference for the side treated with AS/AA, which they considered more comfortable.

Well known for acne-prone skin, benzoyl peroxide has keratolytic and antibacterial properties that prevent pore blockage from dead cell buildup and eliminate Cutibacterium acnes, the bacterium involved in the inflammation of acne lesions. Its combination with azelaic acid relies on their complementary actions: while the benzoyl peroxide rapidly targets bacterial proliferation, azelaic acid works more gently by reducing inflammation and alleviating associated redness.

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

Thehyaluronic acid is a glycosaminoglycan naturally present in the skin’s extracellular matrix, known for its ability to retain water. Depending on its molecular weight, it hydrates the superficial layers of the epidermis or penetrates more deeply to support cell cohesion and skin barrier function.

Its combination with azelaic acid is relevant for reducing blemishes and redness while preserving skin hydration. Indeed,azelaic acid can sometimes slightly dry the skin, particularly at high concentrations (15–20%). Hyaluronic acid, by providing immediate hydration, counteracts this effect and improves long-term tolerability.

Despite certain misconceptions, hyaluronic acid alone isn’t enough to provide lasting hydration for the skin. Without the addition of lipid-based ingredients, such as those found in a cream or balm, the water it attracts is likely to evaporate from the skin.

Thearbutin acid is a derivative of hydroquinone naturally found in certain plants, such as bearberry. In cosmetics, it is recognized for its depigmenting action, primarily via inhibition of tyrosinase. Alpha-arbutin is particularly indicated for reducing brown spots and is well tolerated by most skin types. Combining azelaic acid with arbutin acid may enhance its depigmenting effects. However, this remains a hypothesis, as to date no study has investigated any potential synergy between these active ingredients.

Some individuals also wonder about the relevance of combining azelaic acid with kojic acid to reduce their brown spots. However, ifkojic acid is permitted in cosmetics, it is suspected of penetrating the skin barrier and being carcinogenic, mutagenic, and endocrine-disrupting. That is why we recommend against using kojic acid, with or without azelaic acid. If you experiencehyperpigmentation, there are other active ingredients whose safety is better documented.

For the same reasons, some people are questioning the combination of azelaic acid and hydroquinone. As a reminder, thehydroquinone is a highly effective yet controversial depigmenting agent: it is suspected of being carcinogenic, allergenic, and reprotoxic. In Europe, its use is limited to professional settings. At Typology, we advise against using hydroquinone—whether alone or in conjunction with azelaic acid—as a precautionary measure.

Azelaic acid can also be combined withtranexamic acid, an active ingredient recognized for its depigmenting properties. A study conducted in 33 women with moderate to severe hyperpigmentation assessed the daily application of a cream combining these two active ingredients (concentrations not specified) over six weeks. Analysis by photography, dermatological evaluation, and computer software revealed a improvement in skin pigmentation at the end of the study.

Alpha-hydroxy acids (AHAs), such as glycolic acid and mandelic acid, exert a keratolytic action that promotes cell renewal and improves skin texture and evens out skin tone. The combination of azelaic acid with these fruit acids can reinforce the management of skin prone to imperfections and pigmented spots.

A 24-week study involving 60 patients with melasma showed that a 30% peel ofglycolic acid combined with a 20% azelaic acid cream produced a more significant reduction in the MASI score than treatment with azelaic acid alone. However, for sensitive skin, simultaneous application should be avoided to limit the risk of irritation.

Regarding themandelic acid, which is milder and better tolerated than glycolic acid, no study has yet confirmed the benefit of its combination with azelaic acid, although the combination could theoretically offer an interesting synergy.

The sulfur is a long-established 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 may deter some individuals. The combination of azelaic acid and sulfur presents an interesting rationale. Since both exert essentially the same actions, their combination could target multiple factors involved in the development of imperfections, 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 trials. Furthermore, the sulfur, like azelaic acid, can have a mildly drying effect on the skin. Their combination, although potentially complementary, could therefore prove too irritating.

The bakuchiol is a plant-derived compound extracted from the seeds of Psoralea corylifolia, often described as a gentle alternative to retinol. It is valued for its antioxidant and anti-inflammatory properties, as well as its ability to diminish brown spots and signs of aging without causing skin sensitization. Bakuchiol and azelaic acid may offer a synergistic approach to simultaneously target blemishes, 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. It would be beneficial for future research to explore this potential synergy.

The zinc, often found as zinc gluconate, zinc PCA, or zinc oxide, is recognized for its sebum-regulating, photoprotective, antibacterial, and anti-inflammatory properties. When combined with azelaic acid, it may be relevant for reducing excessive sebum production and diminishing shine in oily or acne-prone skin, although this synergy has not yet been clinically tested in this context.

In contrast, studies have evaluated the efficacy of a treatment combining 0.075% tazarotene, 20% azelaic acid, 0.1% tacrolimus, and 10% ofzinc oxide for melasma. Sixteen patients with hyperpigmentation applied this formulation daily for 20 weeks. The results demonstrated a significant improvement in MASI score (Melasma Area and Severity Index), which decreased on average from 18.9 to 13.3, with one-quarter of participants achieving a score below 8. Reported adverse effects were mostly mild and transient.

However, it remains difficult to isolate the specific role of the azelaic acid–zinc oxide association, as the active ingredients are combined with other components.

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

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

The vitamin E (tocopherol) is a fat-soluble antioxidant naturally present in sebum, where it protects cell membranes from oxidative stress by neutralizing free radicals generated by UV exposure, pollution, or inflammation. By limiting the oxidation of skin lipids such as squalene, it helps prevent certain issues, including acne. In formulations, it also protects oxidation-sensitive actives. Thus, although azelaic acid is stable, combining it with vitamin E can be beneficial in formulas containing other oxidizable compounds.

Thetea tree essential oil is well-known for its antibacterial, antifungal, and anti-inflammatory properties. When diluted in a carrier oil, it is commonly used as a topical treatment to reduce blemishes. Combining it with azelaic acid may enhance its antibacterial and soothing effects and help prevent acne flare-ups. However, we recommend proceeding with caution before combining azelaic acid with tea tree essential oil, as this combination can be irritating to 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.

Urea is an active ingredient that both hydrates and exfoliates. At low concentrations (2–10%), it acts as a humectant by reinforcing the skin barrier function, while at higher concentrations (>10%), it exerts a keratolytic action that softens and smooths the skin. Its combination with azelaic acid can amplify exfoliation while benefiting from the latter’s anti-inflammatory properties, a particularly interesting approach for skin prone to psoriasis, an inflammatory dermatosis characterized by skin thickening.

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

Rich in essential fatty acids (linoleic acid and alpha-linolenic acid), therosehip oil promotes skin regeneration, reduces scars, pigmentation spots, and fine lines, while improving skin elasticity. Its combination with azelaic acid could therefore simultaneously target imperfections, redness, and post-inflammatory marks.

However, this oil is known to be mildly comedogenic, and its undiluted application is discouraged for oily or acne-prone skin, although it is generally well tolerated by normal to dry skin. Nevertheless, its comedogenic potential depends on its formulation and concentration. To date, no studies have demonstrated a specific benefit to combining it with azelaic acid.

• DUA R. et al. Combination of Glycolic Acid Peel and 20% Topical Azelaic Acid Cream in Melasma Patients: Efficacy and Quality-of-Life Improvement. Journal of Cosmetic Dermatology (2016).

• SLUZEVICH J. et al. Assessment of the efficacy, safety, and tolerability of a 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. et al. Clinical and dermoscopic evaluation of combined 20% salicylic acid and 20% azelaic acid versus 25% trichloroacetic acid chemical peels in acne: a randomized controlled trial. Journal of Dermatological Treatment (2019).

• PEINEMANN F. et al. Topical azelaic acid, salicylic acid, niacinamide, sulfur, zinc, and fruit acid (alpha‐hydroxy acid) for acne. Cochrane Database of Systematic Reviews (2020)

• ERKIERT-POLGUJ A. et al. Clinical evaluation of anti-aging effects of a combined therapy—layered application of azelaic acid, phytic acid, and vitamin C—in women with Fitzpatrick skin types II and III. Journal of Cosmetic Dermatology (2022).

• MAYBURY C. et al. A systematic review evaluating the efficacy of azelaic acid in treating acne, rosacea, melasma, and skin aging. Journal of Cosmetic Dermatology (2023).

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