Azelaic Acid

A natural compound found in whole grains, azelaic acid is a good alternative to hydroquinone as a skin lightener due to its efficacy and safety. It is also effective in treating melasma, rosacea and acne.


Grade Level of Evidence
A Multiple double-blind, controlled clinical trials.
B 1 double-blind, controlled clinical trial.
C At least 1 controlled or comparative clinical trial.
D Uncontrolled, observational, animal or in-vitro studies only.
Grade Effect Size of Effect Comments


Acne treatment


Reduces acne lesions, papules and pustules through a variety of mechanisms. Also effective in treating postinflammatory hyperpigmentation, a common sequelum of acne.


Rosacea treatment


15% azelaic acid gel is a standard therapy for subtype 1 rosacea, and it is often combined with an oral antibiotic to treat subtype 2 rosacea.


Skin lightening


Depigments the skin by killing abnormal melanocytes and inhibiting tyrosinase. Not effective against age spots, however.


Melasma treatment


20% azelaic acid cream lightens melasma as effectively as 4% hydroquinone.


Psoriasis treatment


Improves scaling and hyperkeratosis but not the itching of psoriatic plaques.

Looking to buy skin care products containing Azelaic Acid?

Buy from

Scientific Research

Caution: Please read's medical disclaimer.

Table of contents

1. Sources

Azelaic acid is a dicarboxylic acid that exists naturally in many whole grains, namely wheat, rye, barley, oat seeds and sorghum.[1] It is also produced by Malassezia furfur (also known as Pityrosporum ovale), a yeast that lives on normal human skin as part of the commensal flora.[2]

2. Bioavailability

Azelaic acid is most commonly formulated as a 20% cream or as a 15% gel. Percutaneous absorption of azelaic acid into human skin from the 20% cream formulation is 3.6% of the dermally applied dose.[3] The 15% gel formulation probably delivers higher amounts of azelaic acid to the skin, as studies on mice showed an 8-fold higher delivery (25.3% versus 3.4%) into viable skin for the gel than the cream, despite the better percutaneous absorption (16.3% versus 5.8%) of the cream.[4] However, with both formulations the majority of the applied azelaic acid dose remains on the skin surface.[5]

pH also affects the penetration and absorption of azelaic acid; a higher concentration was retained in the skin for a formulation with a pH of 4.9, compared to that with a pH of 3.9. Moreover, the flux of the ionized species of azelaic acid was 5-fold greater with the pH 4.9 formulation, suggesting that ionized azelaic acid penetrates through the skin.[6]

The use of a co-drug of azelaic acid and hydroquinone can also improve the dermal delivery of both parent drugs, enhancing the uptake of azelaic acid by 1.4-fold and that of hydroquinone by 8.1-fold.[7]

The addition of 1,4-cyclohexanediol, meanwhile, has been demonstrated to retard the penetration of azelaic acid without decreasing its retention in the skin, indicating that it may be useful in topical formulations to reduce potential systemic side effects.[8]

The small proportion of azelaic acid that is systematically absorbed is mainly eliminated unchanged in the urine, though some will undergo mitochondrial β-oxidation to acetyl-CoA and malonyl-CoA.[5]

3. Effects on the skin

3.1 Lightening effect

Azelaic acid has been evaluated as a treatment option for hyperpigmentation in skin of colour.

Azelaic acid 20% cream significantly and objectively decreased pigmentation intensity following 24 weeks of treatment in a double-blind, vehicle-controlled trial of darker-skinned patients.[9] Azelaic acid 20% cream + glycolic acid 15% or 20% lotion has also been demonstrated to be as effective as hydroquinone 4% cream in treating hyperpigmentation in darker-skinned patients,[10] indicating that this combination may be a viable alternative to hydroquinone, which safety has come under scrutiny.

However, 20% azelaic acid was not effective in improving solar lentigines (age spots) in Southeast Asian women after 2-3 months of twice daily applications.[11]

Azelaic acid has several mechanisms of depigmenting the skin, including tyrosinase inhibition.[12] Its selective action is also believed to be due to its specific cytotoxic and antiproliferative effects towards abnormal melanocytes, via inhibiting DNA synthesis and mitochondrial enzymes.[13][14]

3.2 Melasma treatment

Azelaic acid has been compared to hydroquinone as a treatment for melasma, a common skin disorder that manifests as dark skin discoloration of the sun-exposed areas of the face and neck.[15] 20% azelaic acid is superior to 2% hydroquinone[15] and is at least as effective as 4% hydroquinone[16][17] in lightening melasma, yielding good or excellent results in 65% of cases in a study on 329 women.[18]

Tretinoin appears to enhance the efficacy of azelaic acid in treating melasma, leading to a higher proportion of excellent responders following treatment.[19] Sequential therapy using 0.05% clobetasol propionate cream + 20% azelaic acid cream also improved melasma in 30 Indian patients more markedly than 20% azelaic acid cream alone, though at the end of 24 weeks, the vast majority of patients in both groups (96.7% for sequential therapy and 90% for azelaic acid monotherapy) had achieved good to excellent responses to treatment.[20]

Another alternative treatment for melasma is the combination of 20% azelaic acid cream with low-fluence Q-switched Nd: YAG laser (QSNYL), which is more efficacious than low-fluence QSNYL and azelaic acid alone.[21]

3.3 Acne vulgaris treatment

Azelaic acid targets several key pathophysiological features of acne.[22] It is an anti-keratinizing agent that exerts cytostatic effects on keratinocytes and modulates epidermal differentiation, enabling it to inhibit comedones which result from the blockade of pores by keratin and oil.[23] It also accumulates in follicles after a single topical application to concentrations high enough to inhibit the growth of Propionibacterium acnes and Staphylococcus epidermidis,[24] bacteria often found in acne lesions,[25] possibly by disrupting the transmembrane pH gradient.[26]

These explain the observed clinical efficacy of azelaic acid in clearing acne in numerous clinical trials. Preliminary studies as early as the 1980s demonstrated that 20% azelaic acid cream was an effective therapy for papulopustular and comedonal acne.[27][28][29] 20% azelaic acid cream also compares well with 0.05% tretinoin, 5% benzoyl peroxide, 2% topical erythromycin and oral tetracycline, being of similar efficacy[29][30][31][32][33] but lacking the systemic side effects of oral antibiotics and causing less irritation than benzoyl peroxide and tretinoin.[34]

Later studies on 15% azelaic acid gel have also confirmed its effectiveness, reducing lesion count by 60.6% in one study[35] and facial papules and pustules by 70-71% in another.[36] It is also effective in treating postinflammatory hyperpigmentation, a common sequelum of acne, due to its anti-tyrosinase activity,[37] as well as adult-onset acne.[38]

Combining azelaic acid with other topical or oral anti-acne agents also seems to be beneficial; when combined with 4% benzoyl peroxide gel, 1% clindamycin gel, 0.025% tretinoin cream or 3% erythromycin/5% benzoyl peroxide gel, the efficacy of azelaic acid cream is enhanced.[39] Other studies have also shown that 20% azelaic acid cream + a glycolic acid lotion was as effective and better-tolerated than 0.025% tretinoin therapy,[40] and that 20% azelaic acid cream + oral minocycline is highly effective in treating severe forms of acne, making it a suitable alternative to oral isotretinoin, especially in female acne patients of child bearing potential.[41]

In addition, the combination of 5% azelaic acid and 2% erythromycin or clindamycin is also more effective than 2% erythromycin alone or 20% azelaic acid cream alone, as well as individual treatment with 5% azelaic acid or 2% clindamycin, respectively.[42][43]

3.4 Rosacea treatment

Rosacea is a chronic inflammatory disease of the skin that commonly presents as facial redness, papules, pustules or telangiectasias.[44] Azelaic acid is approved by the US FDA as an intervention for rosacea and has been shown to maintain control over rosacea over 6 months,[45] significantly decreasing mean inflammatory lesion count and erythema severity compared to vehicle in a review of randomized controlled trials.[46]

As a single treatment, once-daily dosing with 15% azelaic acid gel is safe, effective and economical.[47] It is more effective than 0.75% metronidazole gel,[48] probably more effective than 5% permethrin cream,[49] and as effective as once-daily 1% metronidazole gel when used on a twice daily basis.[50] In 2013, a new foam formulation of 15% azelaic acid was also established to be efficacious and well-tolerated.[51]

While topical azelaic acid is one of the standard therapies for erythematotelangiectatic rosacea (subtype 1), it is usually combined with an oral antibiotic for managing papulopustular rosacea (subtype 2).[52][53] Oral doxycycline + azelaic acid 15% gel in particular has been shown to be appropriate for initial therapy of mild to severe papulopustular rosacea,[54][55] with subantimicrobial dosing helping to avoid the risk of antibiotic resistance.[56]

Azelaic acid's mechanism of action in rosacea has not been clarified, but has been linked to its antimicrobial, anti-inflammatory and antioxidant effects.[57] It inhibits protein synthesis by Staphylococcus epidermidis and Propionibacterium acnes and decreases the free fatty acid content of skin surface lipids, making the skin environment less hospitable to microbes.[30][58] It also reduces the generation and action of reactive oxygen species in vitro,[59] including those produced by neutrophils.[60] Additionally, azelaic acid seems to modulate the inflammatory response in human keratinocytes through the activation of PPAR-γ[61] and directly inhibiting the expression of kallikrein 5,[62] a serine protease that is thought to initiate the heightened inflammatory response in rosacea.[63]

Apart from topical medication, skin moisturization is important as well since epidermal barrier dysfunction and transepidermal water loss play a pathophysiologic role in rosacea.[64] Hence, the use of a mild cleanser and moisturizer before the application of azelaic acid can help relieve symptoms and maintain the integrity of the skin barrier.[65]

3.5 Psoriasis treatment

Psoriasis is a chronic inflammatory skin disorder characterized by the occurrence of red and silver scaly plaques.[66] A single-blind, controlled clinical trial of 31 patients suffering from psoriasis found that 15% azelaic acid applied twice daily for 1 month effectively reduced the scaling and hyperkeratosis, but not pruritus (itching) of psoriatic plaques. More and longer studies are needed to confirm the efficacy however.[67]

4. Side Effects

Azelaic acid is not toxic, teratogenic, associated with systemic adverse events or photodynamic reactions.[31] [68] The most frequent adverse events that occur during administration of topical azelaic acid are stinging/burning and pruritus (itching) sensations that are mostly transient and of mild to moderate intensity.[5]

Also, the gel formulation has a lower lipid concentration than the cream formulation and hence requires less emulsifiers. Because emulsifiers tend to function as surfactants or detergents that can irritate the skin, the result is that the gel formulation causes less skin irritation.[4][58] Azelaic acid entrapped in nanovesicles are also suitable for topical use, as it did not cause toxicity to normal cell lines or allergies on rabbit skin in a safety assessment.[69]

Despite the adverse skin reactions, topical azelaic acid does not actually disrupt or damage the skin barrier, as evidenced by tests on transepidermal water loss and corneometry.[70] It does not enhance the erythema and therefore increased sunburn risk induced by UVB exposure, either.[71]

Scientific References

  1. Muthulakshmi S, Saravanan R. Efficacy of azelaic acid on hepatic key enzymes of carbohydrate metabolism in high fat diet induced type 2 diabetic mice. Biochimie. (2013)
  2. Ashbee HR, Evans EG. Immunology of diseases associated with Malassezia species. Clin Microbiol Rev. (2002)
  3. Täuber U, Weiss C, Matthes H. Percutaneous absorption of azelaic acid in humans. Exp Dermatol. (1992)
  4. Draelos ZD. The rationale for advancing the formulation of azelaic acid vehicles. Cutis. (2006)
  5. Frampton JE, Wagstaff AJ. Azelaic acid 15% gel: in the treatment of papulopustular rosacea. Am J Clin Dermatol. (2004)
  6. Li N, et. al. Effect of ionization and vehicle on skin absorption and penetration of azelaic acid. Drug Dev Ind Pharm. (2012)
  7. Hsieh PW, et. al. The co-drug of conjugated hydroquinone and azelaic acid to enhance topical skin targeting and decrease penetration through the skin. Eur J Pharm Biopharm. (2012)
  8. Li N, et. al. Effect of 1,4-cyclohexanediol on percutaneous absorption and penetration of azelaic acid. Int J Pharm. (2010)
  9. Lowe NJ, et. al. Azelaic acid 20% cream in the treatment of facial hyperpigmentation in darker-skinned patients. Clin Ther. (1998)
  10. Kakita LS, Lowe NJ. Azelaic acid and glycolic acid combination therapy for facial hyperpigmentation in darker-skinned patients: a clinical comparison with hydroquinone. Clin Ther. (1998)
  11. Hermanns JF, et. al. Assessment of topical hypopigmenting agents on solar lentigines of Asian women. Dermatology. (2002)
  12. Schallreuter KU, Wood JW. A possible mechanism of action for azelaic acid in the human epidermis. Arch Dermatol Res. (1990)
  13. Halder RM, Richards GM. Topical agents used in the management of hyperpigmentation. Skin Therapy Lett. (2004)
  14. Nguyen QH, Bui TP. Azelaic acid: pharmacokinetic and pharmacodynamic properties and its therapeutic role in hyperpigmentary disorders and acne. Int J Dermatol. (1995)
  15. Verallo-Rowell VM, et. al. Double-blind comparison of azelaic acid and hydroquinone in the treatment of melasma. Acta Derm Venereol Suppl (Stockh). (1989)
  16. Piquero Martín J, Rothe de Arocha J, Beniamini Loker D. Double-blind clinical study of the treatment of melasma with azelaic acid versus hydroquinone. Med Cutan Ibero Lat Am. (1988)
  17. Farshi S. Comparative study of therapeutic effects of 20% azelaic acid and hydroquinone 4% cream in the treatment of melasma. J Cosmet Dermatol. (2011)
  18. Baliña LM, Graupe K. The treatment of melasma. 20% azelaic acid versus 4% hydroquinone cream. Int J Dermatol. (1991)
  19. Breathnach AS. Melanin hyperpigmentation of skin: melasma, topical treatment with azelaic acid, and other therapies. Cutis. (1996)
  20. Sarkar R, Bhalla M, Kanwar AJ. A comparative study of 20% azelaic acid cream monotherapy versus a sequential therapy in the treatment of melasma in dark-skinned patients. Dermatology. (2002)
  21. Bansal C, et. al. A Comparison of Low-Fluence 1064-nm Q-Switched Nd: YAG Laser with Topical 20% Azelaic Acid Cream and their Combination in Melasma in Indian Patients. J Cutan Aesthet Surg. (2012)
  22. Sieber MA, Hegel JK. Azelaic acid: Properties and mode of action. Skin Pharmacol Physiol. (2014)
  23. Mayer-da-Silva A, et. al. Effects of azelaic acid on sebaceous gland, sebum excretion rate and keratinization pattern in human skin. An in vivo and in vitro study. Acta Derm Venereol Suppl (Stockh). (1989)
  24. Bojar RA, et. al. Follicular concentrations of azelaic acid after a single topical application. Br J Dermatol. (1993)
  25. Nishijima S, et. al. The bacteriology of acne vulgaris and antimicrobial susceptibility of Propionibacterium acnes and Staphylococcus epidermidis isolated from acne lesions. J Dermatol. (2000)
  26. Bojar RA, Cunliffe WJ, Holland KT. Disruption of the transmembrane pH gradient--a possible mechanism for the antibacterial action of azelaic acid in Propionibacterium acnes and Staphylococcus epidermidis. J Antimicrob Chemother. (1994)
  27. Cavicchini S, Caputo R. Long-term treatment of acne with 20% azelaic acid cream. Acta Derm Venereol Suppl (Stockh). (1989)
  28. Cunliffe WJ, Holland KT. Clinical and laboratory studies on treatment with 20% azelaic acid cream for acne. Acta Derm Venereol Suppl (Stockh). (1989)
  29. Katsambas A, Graupe K, Stratigos J. Clinical studies of 20% azelaic acid cream in the treatment of acne vulgaris. Comparison with vehicle and topical tretinoin. Acta Derm Venereol Suppl (Stockh). (1989)
  30. Fitton A, Goa KL. Azelaic acid. A review of its pharmacological properties and therapeutic efficacy in acne and hyperpigmentary skin disorders. Drugs. (1991)
  31. Graupe K, et. al. Efficacy and safety of topical azelaic acid (20 percent cream): an overview of results from European clinical trials and experimental reports. Cutis. (1996)
  32. Gibson JR. Azelaic acid 20% cream (AZELEX) and the medical management of acne vulgaris. Dermatol Nurs. (1997)
  33. Bladon PT, et. al. Topical azelaic acid and the treatment of acne: a clinical and laboratory comparison with oral tetracycline. Br J Dermatol. (1986)
  34. Mackrides PS, Shaughnessy AF. Azelaic acid therapy for acne. Am Fam Physician. (1996)
  35. Iraji F, et. al. Efficacy of topical azelaic acid gel in the treatment of mild-moderate acne vulgaris. Indian J Dermatol Venereol Leprol. (2007)
  36. Thiboutot D. Versatility of azelaic acid 15% gel in treatment of inflammatory acne vulgaris. J Drugs Dermatol. (2008)
  37. Kircik LH. Efficacy and safety of azelaic acid (AzA) gel 15% in the treatment of post-inflammatory hyperpigmentation and acne: a 16-week, baseline-controlled study. J Drugs Dermatol. (2011)
  38. Vargas-Diez E, et. al. Azelaic acid in the treatment of acne in adult females: case reports. Skin Pharmacol Physiol. (2014)
  39. Webster G. Combination azelaic acid therapy for acne vulgaris. J Am Acad Dermatol. (2000)
  40. Spellman MC, Pincus SH. Efficacy and safety of azelaic acid and glycolic acid combination therapy compared with tretinoin therapy for acne. Clin Ther. (1998)
  41. Gollnick HP, Graupe K, Zaumseil RP. Comparison of combined azelaic acid cream plus oral minocycline with oral isotretinoin in severe acne. Eur J Dermatol. (2001)
  42. Pazoki-Toroudi H, et. al. Combination of azelaic acid 5% and erythromycin 2% in the treatment of acne vulgaris. J Dermatolog Treat. (2010)
  43. Pazoki-Toroudi H, et. al. Combination of azelaic acid 5% and clindamycin 2% for the treatment of acne vulgaris. Cutan Ocul Toxicol. (2011)
  44. Scheinfeld N, Berk T. A review of the diagnosis and treatment of rosacea. Postgrad Med. (2010)
  45. Del Rosso JQ, Bhatia N. Azelaic acid gel 15% in the management of papulopustular rosacea: a status report on available efficacy data and clinical application. Cutis. (2011)
  46. Liu RH, et. al. Azelaic acid in the treatment of papulopustular rosacea: a systematic review of randomized controlled trials. Arch Dermatol. (2006)
  47. Thiboutot DM, et. al. Azelaic acid 15% gel once daily versus twice daily in papulopustular rosacea. J Drugs Dermatol. (2008)
  48. Elewski BE, Fleischer AB Jr, Pariser DM. A comparison of 15% azelaic acid gel and 0.75% metronidazole gel in the topical treatment of papulopustular rosacea: results of a randomized trial. Arch Dermatol. (2003)
  49. Mostafa FF, et. al. Comparative study of some treatment modalities of rosacea. J Eur Acad Dermatol Venereol. (2009)
  50. Wolf JE Jr, Kerrouche N, Arsonnaud S. Efficacy and safety of once-daily metronidazole 1% gel compared with twice-daily azelaic acid 15% gel in the treatment of rosacea. Cutis. (2006)
  51. Draelos ZD, et. al. Azelaic acid foam 15% in the treatment of papulopustular rosacea: a randomized, double-blind, vehicle-controlled study. Cutis. (2013)
  52. Odom RB. The subtypes of rosacea: implications for treatment. Cutis. (2004)
  53. Dahl MV. Rosacea subtypes: a treatment algorithm. Cutis. (2004)
  54. Thiboutot DM, et. al. A multicenter study of topical azelaic acid 15% gel in combination with oral doxycycline as initial therapy and azelaic acid 15% gel as maintenance monotherapy. J Drugs Dermatol. (2009)
  55. Del Rosso JQ, et. al. Efficacy of topical azelaic acid (AzA) gel 15% plus oral doxycycline 40 mg versus metronidazole gel 1% plus oral doxycycline 40 mg in mild-to-moderate papulopustular rosacea. J Drugs Dermatol. (2010)
  56. Bhatia ND, Del Rosso JQ. Optimal management of papulopustular rosacea: rationale for combination therapy. J Drugs Dermatol. (2012)
  57. Del Rosso JQ, et. al. Azelaic acid gel 15%: clinical versatility in the treatment of rosacea. Cutis. (2006)
  58. Downie J. Azelaic Acid 15% Gel: The Versatile Foundation of Combination Therapy in Mild to Moderate Rosacea in Various Patient Types. Cosmet Dermatol. (2008)
  59. Jones DA. Rosacea, reactive oxygen species, and azelaic Acid. J Clin Aesthet Dermatol. (2009)
  60. Akamatsu H, et. al. Inhibitory effect of azelaic acid on neutrophil functions: a possible cause for its efficacy in treating pathogenetically unrelated diseases. Arch Dermatol Res. (1991)
  61. Mastrofrancesco A, et. al. Azelaic acid modulates the inflammatory response in normal human keratinocytes through PPARgamma activation. Exp Dermatol. (2010)
  62. Coda AB, et. al. Cathelicidin, kallikrein 5, and serine protease activity is inhibited during treatment of rosacea with azelaic acid 15% gel. J Am Acad Dermatol. (2013)
  63. Two AM, Del Rosso JQ. Kallikrein 5-Mediated Inflammation in Rosacea: Clinically Relevant Correlations with Acute and Chronic Manifestations in Rosacea and How Individual Treatments May Provide Therapeutic Benefit. J Clin Aesthet Dermatol. (2014)
  64. Del Rosso JQ, Lehman PA, Raney SG. Impact of order of application of moisturizers on percutaneous absorption kinetics: evaluation of sequential application of moisturizer lotions and azelaic acid gel 15% using a human skin model. Cutis. (2009)
  65. Del Rosso JQ. The use of moisturizers as an integral component of topical therapy for rosacea: clinical results based on the Assessment of Skin Characteristics Study. Cutis. (2009)
  66. Palfreeman AC, McNamee KE, McCann FE. New developments in the management of psoriasis and psoriatic arthritis: a focus on apremilast. Drug Des Devel Ther. (2013)
  67. Iraji F, et. al. Efficacy of 15% azelaic acid in psoriasis vulgaris: a randomized, controlled clinical trial. J Drugs Dermatol. (2010)
  68. Töpert M, Rach P, Siegmund F. Pharmacology and toxicology of azelaic acid. Acta Derm Venereol Suppl (Stockh). (1989)
  69. Panyosak A, et. al. Safety assessment of azelaic acid and its derivatives entrapped in nanovesicles. Hum Exp Toxicol. (2009)
  70. Draelos ZD. Noxious sensory perceptions in patients with mild to moderate rosacea treated with azelaic acid 15% gel. Cutis. (2004)
  71. Cetiner S, Ilknur T, Ozkan S. Phototoxic effects of topical azelaic acid, benzoyl peroxide and adapalene were not detected when applied immediately before UVB to normal skin. Eur J Dermatol. (2004)