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  • Writer's pictureSolomon Matzner

Azelaic Acid for the Treatment of Acne

Azelaic acid is highly effective for the treatment of acne due to its multifaceted mechanisms of action that address the primary pathological factors of acne: hyperkeratinization, microbial colonization, and inflammation.



Here's a detailed scientific breakdown of how azelaic acid works against acne:


1. Antimicrobial Action

Azelaic acid possesses a strong antimicrobial effect, particularly against Cutibacterium acnes (formerly Propionibacterium acnes), the bacterium largely responsible for acne development. It does so by:

  • Inhibiting Bacterial Protein Synthesis: Azelaic acid interferes with the synthesis of microbial cellular proteins, impairing bacterial growth and survival. This effect helps reduce the bacterial population on the skin, decreasing the likelihood of acne flare-ups.

  • Reducing Fatty Acids: It also reduces the concentration of free fatty acids in the sebum, which diminishes the pro-inflammatory properties of the skin surface lipids, creating a less favorable environment for bacteria.


Key Mechanism: Azelaic acid has bacteriostatic and bactericidal properties against Cutibacterium acnes.

  • Scientific Evidence: A study published by Fitton and Goa (1991) in "Drugs" reviews the pharmacological profile of azelaic acid, highlighting its significant antimicrobial activity against several bacteria, including C. acnes, the bacteria predominantly responsible for acne. This is primarily through the inhibition of microbial cellular protein synthesis, which impairs bacterial replication and survival.

  • Reference: Fitton, A., & Goa, K. L. (1991). Azelaic Acid. Drugs, 41(5), 780-798.

2. Anti-inflammatory Properties

Inflammation is a key aspect of both non-inflammatory (comedones) and inflammatory (pustules, papules) acne lesions. Azelaic acid addresses this through:

  • Inhibiting Neutrophil Activity: It reduces the production and release of reactive oxygen species (ROS) by neutrophils, which are part of the body’s immune response to bacterial infection. By controlling these inflammatory mediators, azelaic acid reduces inflammation and prevents damage to sebaceous follicles.

  • Modulation of Inflammatory Cytokines: Azelaic acid can modulate the skin's inflammatory response by affecting the cytokine network, potentially reducing the levels of pro-inflammatory cytokines involved in acne pathology.


Key Mechanism: Reduction of neutrophil-generated reactive oxygen species and modulation of inflammatory cytokines.

  • Scientific Evidence: According to a study by Akamatsu et al. (1991), azelaic acid inhibits the generation of reactive oxygen species (ROS) by neutrophils. The reduction of ROS is crucial as these molecules contribute to the inflammatory cascade typical in acne.

  • Reference: Akamatsu, H., Komura, J., Asada, Y., Miyachi, Y., & Niwa, Y. (1991). Mechanism of anti-inflammatory action of azelaic acid. Journal of International Medical Research, 19(6), 451-457.



3. Keratolytic and Comedolytic Effects

Azelaic acid helps to normalize the disordered growth of the skin cells lining the follicles (hyperkeratinization), which is one of the initial steps in acne formation:

  • Normalization of Keratinization: It decreases the thickness of the stratum corneum (outermost layer of the skin) by influencing the process of keratinocyte differentiation. This action helps to prevent the blockage of pores.

  • Prevention of Comedones: By ensuring a more regular shedding of skin cells and preventing the buildup of dead skin cells, azelaic acid helps to keep the follicles open and free from blockages, thereby reducing the formation of comedones (both blackheads and whiteheads).


Key Mechanism: Normalization of the disordered growth of skin cells lining the follicles and promotion of skin cell turnover.

  • Scientific Evidence: A publication by Graupe et al. (1996) demonstrates how azelaic acid influences keratinocyte differentiation, promoting the normalization of hyperkeratinization. This effect is crucial for preventing the formation of comedones, as it keeps pores clear of excess keratin and dead skin cells.

  • Reference: Graupe, K., Cunliffe, W. J., Gollnick, H. P., & Zaumseil, R. P. (1996). Efficacy and safety of topical azelaic acid (20 percent cream): an overview of results from European clinical trials and experimental reports. Cutis, 57(1 Suppl), 20-35.


4. Sebum Reduction

While not primarily known for reducing sebum production, the overall effects of azelaic acid lead to an environment that mitigates the conditions under which sebum exacerbates acne.

  • Molecular Level Interaction: On a molecular level, azelaic acid has been found to interfere with the cellular pathways that lead to acne. For example, it may inhibit the enzyme 5α-reductase, which is involved in the metabolism of hormones that can increase sebum production. By modulating this enzyme's activity, azelaic acid indirectly helps control one of the factors that can lead to acne.


Key Mechanism: Indirect modulation of sebum production possibly through inhibition of 5α-reductase.

  • Scientific Evidence: Although azelaic acid is not primarily known for affecting sebum production, studies suggest it may inhibit 5α-reductase. This enzyme is crucial in the conversion of testosterone to dihydrotestosterone (DHT), a hormone that increases sebum production. By modulating this enzyme, azelaic acid can help manage sebum-related exacerbation of acne.

  • Reference: Zouboulis, C. C. (2009). Azelaic acid: pharmacological and toxicological properties. Giornale italiano di dermatologia e venereologia: organo ufficiale, Società italiana di dermatologia e sifilografia, 144(3), 21-29.



Conclusion

The mechanisms through which azelaic acid acts against acne are well-supported by empirical evidence demonstrating its effectiveness at various stages of acne pathogenesis, including microbial growth inhibition, inflammatory response modulation, keratinization normalization, and possibly sebum regulation. This scientific validation underpins azelaic acid's use as a versatile and effective acne treatment, capable of addressing both the symptoms and the underlying causes of the condition. This multi-targeted approach makes it uniquely effective as a treatment, capable of addressing various forms of acne, from mild and moderate to inflammatory types.


Usage and Concentrations

Azelaic acid is available in various formulations, including creams, gels, and foams. The typical concentrations are:

  • Over-the-Counter Products: These generally contain azelaic acid at concentrations up to 10%, suitable for mild acne treatment and general skincare.

  • Prescription Formulations: More potent formulations contain 15% to 20% azelaic acid, indicated for more severe cases of acne and other skin conditions like rosacea.


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