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Azelaic acid

1.0 Last Updated August 30, 2021

Ingredient Profile

Common Name: Azelaic Acid
INCI: Azelaic Acid
Source: Malassezia furfur (a.k.a. Pityrosporum ovale), wheat, rye, and barley
Azelaic Acid Molecule

kligman ingredient evaluation

Penetration: Low Penetration
Biochemical Mechanism: antimicrobial activity, normalization of keratinization, reduction in the amount of filaggrin, reduction in the thickness of the stratum corneum, and antioxidant activity.
Level of Evidence: Level A; Good Quality

Regimen's Take

Azelaic acid is a promising skincare ingredient with several studies demonstrating its efficacy against a variety of skin conditions. For many years, AzA has been included as an active ingredient in over the counter and prescription products. Known for its antimicrobial properties and ability to regulate/control skin cell turnover, azelaic acid has been widely used for the treatment of acne and hyperpigmentation. Extensive clinical studies have also demonstrated its ability to act on other skin conditions such as rosacea and melasma. A unique advantage of AzA is its relative safety, being a naturally occurring molecule present on human skin, and small side effect profile. The main disadvantage of Azelaic acid is its solubility. Since it required higher amounts of active ingredient to deliver effective amounts to the skin, transient irritation is often seen.

TLDR

  • helps fight acne through antimicrobial action
  • improves barrier through its anti-inflammatory action
  • helps prevent dead skin cell build-up that may cause pimples

What is it?

Azelaic acid is a naturally occurring dicarboxylic acid (a chemical compound that possesses two carboxylic acid functional groups). In nature, it is produced by Malassezia furfur (a.k.a. Pityrosporum ovale) – a type of yeast found on normal human skin and other animals. You can also find azelaic acid in wheat, rye, barley, and animal products (NCI Thesaurus, n.d.)

Does it penetrate?

AzA products can be found in a cream or gel-based formulation. Gel-based formulations tend to be more effective at skin permeation compared to cream. When tested on mice, it was determined that 25.3% of a 15% AzA gel formula penetrated the skin, compared to only 3.4% penetration in a 20% AzA cream formula (Draelos, 2006). Another study found that 8% of a gel formulation penetrates the skin compared to 3% penetration of a cream, which amounts to a 2.5-fold increase in penetration (Maru et al., 1982). Additionally, moisturizing agents can be applied before or after AzA gel products without significantly impacting its penetration (Del Rosso et al., 2009).

How does it work?

Anti-inflammatory function

Azelaic acid has been well-documented to help reduce the amount of acne lesions in patients with acne. Several mechanisms have been studied that demonstrate the anti-inflammatory activity of AzA. One such mechanism is its ability to inhibit the synthesis of UVB-induced IL-6, IL-1β, and TNFα, all of which are proinflammatory cytokines, which are molecules that produce inflammatory responses in the skin and body (Mastrofrancesco et al., 2010). Another mechanism involves the scavenging of reactive oxygen species (ROS) by reducing the release of superoxide and ·OH from neutrophils (Akamatsu et al., 1991; Passi, Picardo, De Luca, et al., 1991; Passi, Picardo, Zompetta, et al., 1991).

Antibacterial effects on the skin

Different bacterial species amount to a significant cause of acne. The use of antibiotics for the treatment of acne can exacerbate the issue by allowing antibiotic-resistant bacteria to grow and flourish on the skin. Since AzA is not an antibiotic, it works on all bacteria including antibiotic-resistant strains (Ozkan et al., 2000). Some evidence suggests that AzA executes its antimicrobial activity by entering bacterial cells and reduces their intracellular pH. The drastic reduction in pH inhibits the bacteria’s ability to produce energy and survive (Bojar et al., 1994; Holland & Bojar, 1993).
Overall, AzA helps combat acne through a variety of mechanisms including:
  • Inhibiting the production of proinflammatory cytokines
  • Acting as an antioxidant by scavenging radical oxygen species
  • Attacking bacterial cells on the skin

Normalization of keratinization

Another element that contributes to acne is a process known as hyperkeratinisation. Keratinocytes are cells that compose 90% of the epidermis (the outermost layers of the skin) and they are constantly sloughed off by new keratinocytes that originated from the deeper layers of the skin. However, hyperkeratinisation is when these cells do not shed normally and clog the pores, contributing to increased sebum production, bacterial growth, and inflammation (Iraji et al., 2007). Application of 20% AzA was shown to significantly reduce the thickness of the stratum corneum (the outermost layer of the epidermis) and reduces the size and number of keratohyalin granules - a key component of keratinization (Iraji et al., 2007). AzA also has antiproliferative effects on keratinocytes, meaning that it reduces the process of cell division among keratinocytes (Detmar et al., 1989).

Anti-hyperpigmentation

Melanin is a group of molecules present in the skin (as well as hair and eyes) that is responsible for pigmentation. Melanogenesis is the technical word for “melanin production” which occurs in cells known as melanocytes found in the basal layer of the epidermis. This process involves the conversion of tyrosine (an amino acid) into melanin through a variety of biochemical reactions. One of the key players in these reactions is tyrosinase – an enzyme that helps mediate and allow the reactions to take place (Schlessinger et al., 2021). AzA has been shown to help with hyperpigmentation (i.e. the accumulation of melanin) by inhibiting the activity of tyrosinase and other important enzymes (Briganti et al., 2003). It may also have inhibitive functions on overactive or abnormal melanocytes, thereby preventing hyperpigmentation from occurring (Nazzaro-Porro, 1987).

Some studies have shown promising results of AzA for the treatment of melasma – a condition characterised by patches of darkened skin and often associated with pregnancy, UV exposure, and skin sensitivity (Rajaratnam et al., 2010). One study also demonstrated that 20% AzA was more effective at lightening melasma compared to 2% hydroquinone (a potent skin-whitening ingredient) when applied twice daily for 24 weeks along with a broad spectrum sunscreen (Verallo-Rowell et al., 1989).

Helps with rosacea

Some of the strongest evidence supporting the use of AzA is for a common skin condition known as rosacea. Rosacea is characterised by redness, dilated blood vessels beneath the skin (i.e. erythema), pimples, flushing, and pustules mainly on the nose, cheeks, chin and forehead. AzA has been shown, with high quality evidence, to help control the symptoms of rosacea (van Zuuren et al., 2015) due to its anti-inflammatory, antioxidant and antimicrobial functions.

More specifically, rosacea has been associated with the excessive production of kallikrein-5 (KLK5) and cathelicidin (CAMP). KLK5 is an enzyme that has several biological functions. However, for those with rosacea, the increased levels of KLK5 is thought to be involved in the cleavage and activation of CAMP. The cleavage and activation of CAMP results with undesirable outcomes such as leukocyte chemotaxis (i.e. the accumulation of immunological cells, contributing to inflammation) and angiogenesis (i.e. the formation of new blood vessels, contributing to redness) (Two & Del Rosso, 2014). The negative impact of KLK5 and CAMP was confirmed when researchers injected these compounds into mouse skin and observed an inflammatory reaction that was representative of rosacea (Yamasaki et al., 2007).

When mice receive a daily application of 15% AzA, researchers saw a decline in KLK5 and CAMP levels in the skin. Similar results were observed when AzA was applied to cultured human keratinocytes which helps demonstrate the efficacy of AzA in the treatment of rosacea (Gallo & Yamasaki, 2010).

Conclusion

Azelaic acid is one of the multifunctional active in dermatology. Recently, it garnered more attention as it not only targets acne but is also being studied as a rosacea treatment. Other modified derivatives have been developed to improve its solubility and penetration. All in all, it is a very promising active in spite of its side effects. 

To be continued 

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The Skincare Encyclopedia aims to improve public understanding of the biology and chemistry of skincare. The Encyclopedia is rooted in core scientific principles and extensive research, in many cases in collaboration with the authors of the original studies referenced. This is a project of Regimen Lab, maintained by a group of multidisciplinary scientists, MDs, and researchers.