Azelaic Acid Benefits You Need to Know

Article Contents

• Azelaic Acid Benefits for Skin 

• What does Azelaic Acid Do? 

• Synergistic Active Ingredients to Pair with Azelaic Acid 

• Timeline of Azelaic Acid's Adoption into Cosmetics

Azelaic acid is a widely recognized ingredient in skincare, celebrated for its ability to address various skin concerns. Known for its antibacterial, anti-inflammatory, and skin-brightening properties, it has become a staple in many effective skincare routines.

Azelaic Acid Benefits for Skin 

Azelaic acid is a naturally occurring dicarboxylic acid with a nine-carbon chain, widely recognized for its diverse applications in dermatology. Its therapeutic effects are driven by several key biochemical mechanisms:

• Antibacterial Activity: Azelaic acid inhibits the growth of both aerobic and anaerobic bacteria, reducing the inflammatory response associated with acne lesions.

• Anti-Inflammatory Effects: It modulates inflammatory pathways by decreasing the production of reactive oxygen species (ROS), making it especially beneficial for conditions like rosacea, where inflammation plays a central role.

• Antioxidant Effects: Azelaic acid protects skin cells from oxidative damage with its antioxidant properties, supporting overall skin health.

• Keratolytic Effects: By gently promoting the shedding of dead skin cells and regulating keratinocyte (cells that form the bulk of the upper skin layers) activity, azelaic acid helps smooth rough or uneven skin textures.

• Regulation of Melanin: It effectively reduces hyperpigmentation by altering the activity of melanocytes (melanin producing cells), making it useful for treating melasma, post-inflammatory hyperpigmentation (PIH), and sunspots.

• 5α-Reductase Inhibition: By inhibiting this key enzyme, azelaic acid reduces dihydrotestosterone (DHT) production, potentially addressing abnormal skin turnover. however,  this mechanism is less emphasized in clinical dermatology

What does Azelaic Acid Do? 

Azelaic acid interacts with key skin cells, such as keratinocytes, and melanocytes, to provide its benefits. These interactions are essential for maintaining healthy, glowing skin. 

Efficient Cell Turnover – and Improved Skin texture (Keratinocytes) 

Keratinocytes are cells that make up the majority of the upper layers of the skin and play a vital role in protecting the skin from external damage. During the normal process of skin turnover, keratinocytes migrate from the deeper layers of the skin to the surface. Upon reaching the surface, they undergo cornification—a maturation process in which they lose their nucleus and transform into flattened, hardened cells filled with keratin, called corneocytes. These cells form the stratum corneum, the outermost layer of the skin. 

In some cases, keratinocytes can become hyperactive and enter an abnormal state called hyperkeratosis. In this state, they produce excessive amounts of keratin and fail to properly mature into corneocytes. As a result, the cells remain in a less exfoliative form, making it harder for them to be naturally sloughed off during normal skin turnover. This disruption can lead to rough skin texture and clogged pores, exacerbating conditions such as acne.

Azelaic acid influences keratinocyte growth by disrupting critical processes involved in DNA replication, cell division, and metabolism. Hyperactive keratinocytes, which divide rapidly and exhibit higher metabolic activity than normal keratinocytes, are particularly susceptible to azelaic acid's inhibitory effects.

Hyperactive keratinocytes have an increased metabolic demand, requiring more energy and resources to sustain their accelerated growth. Mitochondria, the organelles responsible for cellular energy production, are more active in these cells. Azelaic acid has been shown to influence mitochondrial function in hyperactive keratinocytes, with some studies suggesting it can disrupt processes such as energy production. Given the heightened metabolic load of hyperactive keratinocytes, this disruption significantly impairs their growth and division.

Azelaic acid also targets the rough endoplasmic reticulum (RER), a critical protein-processing center in keratinocytes, causing it to swell and disrupting its functionality. The RER is essential for synthesizing keratin and structural proteins like filaggrin. Filaggrin aggregates keratin filaments into a dense network, supporting the formation of corneocytes. Azelaic acid’s inhibitory effects are more pronounced in hyperactive keratinocytes, as their accelerated protein synthesis cannot be sustained, ultimately preventing the formation of an excessively cornified cell layer.

Azelaic acid inhibits 5α-reductase, the enzyme responsible for converting testosterone into its more potent form, dihydrotestosterone (DHT). Elevated levels of DHT are linked to increased keratinocyte hyperactivity, particularly in conditions like acne. By reducing DHT levels, azelaic acid indirectly diminishes a key stimulus for abnormal keratinocyte growth, promoting normal cell maturation and turnover.

Azelaic Acid for Hyperpigmentation and Skin Brightening (Melanocytes)  

Melanocytes are the cells responsible for producing melanin, the pigment that determines skin color. Azelaic acid influences melanocytes in several distinct ways:

Azelaic acid inhibits melanin synthesis by modulating gene expression. Specifically, it suppresses the Microphthalmia-associated transcription factor (MITF), a key regulator of genes involved in melanin production, including those coding for the enzymes tyrosinase (TYR) and tyrosinase-related protein 1 (TRP-1). Tyrosinase and its related proteins are crucial in the melanin synthesis pathway. Beyond downregulating the genes responsible for its production, azelaic acid also binds directly to tyrosinase, impairing its enzymatic activity and further inhibiting melanin production.

Overactive melanocytes are a common cause of pigmentation issues, often entering a state of metabolic stress due to various triggers, including:

• UV exposure: Excessive sunlight stimulates melanocyte activity, leading to increased melanin production.

• Inflammation or skin injury: Conditions such as acne or cuts can trigger post-inflammatory hyperpigmentation (PIH).

• Hormonal changes: Fluctuations, such as those occurring during pregnancy or with certain medications, can stimulate melanin overproduction, contributing to conditions like melasma.

• Oxidative stress: An imbalance of free radicals can exacerbate melanocyte activity, further disrupting pigmentation balance.

Inflammation plays a significant role in triggering melanocyte hyperactivity, particularly in conditions like acne, eczema, and rosacea. Post-inflammatory hyperpigmentation (PIH) arises when inflammation stimulates melanocytes to overproduce melanin, resulting in dark spots after the skin heals. Azelaic acid’s anti-inflammatory properties help reduce the release of pro-inflammatory mediators, such as interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-α). By mitigating inflammation, azelaic acid indirectly prevents the overactivation of melanocytes, thereby reducing the risk of PIH.

Azelaic acid disrupts mitochondrial function in hyperactive melanocytes by inhibiting enzymes involved in cellular respiration. This interference reduces energy availability in melanocytes with abnormally high activity levels, leading to decreased ATP production and energy depletion. As a result, melanin production is normalized.

Azelaic Acid for Acne and Rosacea 

Azelaic acid is a highly regarded treatment for acne and rosacea, thanks to its unique combination of anti-inflammatory, antioxidant, and antibacterial properties. Each of these attributes plays a vital role in addressing the root causes of these skin conditions, leading to significant symptom improvement and enhanced skin health. Below is a detailed exploration of how these properties contribute to its effectiveness.

Acne is a multifactorial condition driven by four primary factors:

• Hyperkeratinization: Excessive keratinocyte activity leads to clogged pores, which can progress into inflammatory acne lesions.

  
  

• Overproduction of sebum: Sebaceous glands produce excessive amounts of sebum, often due to hormonal changes during puberty or imbalances, which play a critical role in acne lesion formation.

  
  

• Overgrowth of Cutibacterium acnes: This bacterium, previously known as Propionibacterium acnes, thrives in the anaerobic environment of clogged pores, contributing to acne development.

  
  

• Inflammation: The metabolic byproducts of C. acnes trigger an immune response, exacerbating inflammation and causing redness, swelling, and pain.

Rosacea is a chronic inflammatory condition that primarily affects the central areas of the face, including the cheeks, nose, chin, and forehead. It is characterized by symptoms such as flushing, persistent redness, and acne-like lesions. While the exact cause of rosacea remains unclear, several contributing factors have been identified:

• Dysregulated innate immune responses: Chronic inflammation in rosacea is linked to overactivity of the innate immune system, resulting in the persistent redness and inflammatory lesions characteristic of the condition.

  
  

• Increased vascular reactivity: Heightened sensitivity of blood vessels is a well-established feature of rosacea, leading to redness and visible blood vessels (telangiectasia).

  
  

• Overgrowth of Demodex folliculorum mites: The proliferation of these mites, along with the bacteria they harbor, has been implicated in rosacea development. These factors may trigger inflammation and exacerbate rosacea symptoms.

Anti-Inflammatory Properties of Azelaic Acid 

Both acne and rosacea are driven by inflammation, characterized by elevated levels of cytokines (immune signals), immune cell activation, and other inflammatory markers. Azelaic acid’s well-documented ability to modulate inflammation makes it an effective treatment for both conditions.

• Azelaic acid inhibits pro-inflammatory mediators by downregulating the expression of key immune signals, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), in keratinocytes and fibroblasts (collagen building cells). These immune signals are elevated in both acne and rosacea, where they contribute to persistent inflammation and skin damage.

• Azelaic acid suppresses neutrophil (a type of white blood cell) activity, a critical factor in amplifying inflammation in rosacea. It reduces neutrophil infiltration and inhibits the release of reactive oxygen species (ROS) and proteolytic enzymes, both of which exacerbate inflammation and contribute to tissue damage.

• Azelaic acid modulates the expression of Toll-like receptor 2 (TLR2), which is upregulated in both rosacea and acne. TLR2 enhances the immune response to microbial fragments, contributing to inflammation and heightened skin sensitivity. By downregulating TLR2 expression, azelaic acid helps reduce inflammation and sensitivity in these conditions.

Antioxidant Properties of Azelaic Acid 

Oxidative stress plays a significant role in both acne and rosacea, with excess free radicals contributing to inflammation, tissue damage, and the persistence of lesions. Azelaic acid has several antioxidant benefits: 

• Azelaic acid acts as a free radical scavenger, neutralizing reactive oxygen species (ROS) and reducing oxidative damage to keratinocytes and fibroblasts. By protecting these cells, azelaic acid helps maintain the integrity of the skin barrier and prevents the continuation of inflammatory cascades.

  
  

• In acne, sebum-rich environments are highly susceptible to lipid oxidation, which triggers inflammation and contributes to lesion formation. Azelaic acid prevents lipid oxidation in sebum glands, reducing this inflammatory stimulus and helping to control acne development.

Synergistic Active Ingredients to Pair with Azelaic Acid 

Azelaic acid is a multifaceted skincare ingredient with anti-inflammatory, antioxidant, antibacterial, and melanin-inhibiting properties. Its versatility lies in its ability to address acne, rosacea, and pigmentation issues. Pairing azelaic acid with complementary active ingredients can enhance its efficacy and improve treatment outcomes. Below is a comprehensive list of active ingredients that can be combined with azelaic acid.

1. Niacinamide (Vitamin B3) 

Azelaic acid and niacinamide both possess anti-inflammatory properties, making them effective in calming irritated skin conditions like acne and rosacea.

Additionally, niacinamide reduces transepidermal water loss (TEWL), reinforcing the skin barrier, while azelaic acid protects the skin by reducing oxidative damage to keratinocytes and fibroblasts.

Together, they have a synergistic effect on melanin regulation. Azelaic acid inhibits tyrosinase through direct binding at its active site and by suppressing its gene expression, while niacinamide prevents melanin transfer from melanocytes to keratinocytes. This three-pronged approach makes the combination particularly effective for addressing pigmentation concerns and promoting skin brightening.

2. Salicylic Acid 

Salicylic acid, being lipid-soluble, penetrates deeply into the pores, dissolving excess sebum and dead skin cells. This action complements azelaic acid’s effects on keratinocytes by further promoting the shedding of abnormal keratinocytes in clogged pores.

While salicylic acid reduces the pore-clogging component of acne, azelaic acid addresses inflammation and bacterial overgrowth. Together, they work synergistically by targeting multiple pathways, with azelaic acid also enhancing the removal of dead skin cells, providing a comprehensive anti-acne strategy.

3. Retinoids (Retinol, Retinaldehyde, Tretinoin, Adapalene) 

Retinoids accelerate epidermal cell turnover, complementing azelaic acid’s desquamatory (skin-shedding) and anti-inflammatory actions. Although retinoids can initially cause skin irritation, azelaic acid’s anti-inflammatory properties help mitigate the redness and discomfort often associated with their use. Together, they enhance the fading of post-inflammatory hyperpigmentation by promoting the replacement of pigment-laden cells while normalizing melanin synthesis.

4. Vitamin C (Ascorbic Acid, Sodium Ascorbyl Phosphate) 

Azelaic acid and vitamin C both inhibit tyrosinase, a key enzyme involved in melanin synthesis. Their shared antioxidant properties enhance this effect by scavenging free radicals that trigger melanogenesis. Together, they provide a synergistic approach to targeting pigmentation issues, such as melasma and post-inflammatory hyperpigmentation..

5. Tranexamic Acid 

Azelaic acid and tranexamic acid both address pigmentation issues by interfering with inflammatory pathways that stimulate melanin overproduction. This combination targets pigmentation through multiple mechanisms: azelaic acid reduces melanocyte hyperactivity, while tranexamic acid inhibits vascular and inflammatory triggers that exacerbate melasma by blocking the enzyme plasmin. Together, they form a highly effective pair for managing stubborn pigmentation concerns.

6. Zinc PCA 

Zinc PCA helps control excess sebum, a key factor in acne development. While azelaic acid targets bacterial overgrowth and inflammation, zinc PCA reduces the oily environment that promotes bacterial multiplication. This dual-action approach is particularly beneficial for individuals with oily, acne-prone skin.

7. Green Tea Extract (EGCG) 

Green tea extract contains epigallocatechin gallate (EGCG), a powerful polyphenol known for its anti-inflammatory and antioxidant properties. Both green tea extract and azelaic acid strengthen the skin’s defense against reactive oxygen species (ROS). Additionally, EGCG supports sebum regulation, making this combination particularly beneficial for managing acne and oxidative stress.

Timeline of Azelaic Acid's Adoption into Cosmetics 

1. 1970s: Initial dermatological studies on azelaic acid focus on its use for fungal infections and acne treatment. During this period, its potential to regulate keratinization and pigmentation is also observed.

   
   

2. 1980s: Azelaic acid creams and gels (15%–20%) become available as prescription medications in Europe and North America for acne and rosacea.

   
   

3. 1990s: Clinical trials confirm the efficacy of azelaic acid in treating hyperpigmentation disorders such as melasma. Dermatologists increasingly prescribe it for post-inflammatory hyperpigmentation (PIH).

   
   

4. 2000s: Lower-concentration azelaic acid products become more widely available, primarily through niche and specialty skincare lines. The cosmetic industry shows growing interest in azelaic acid as a multifunctional ingredient.

   
   

5. 2010s: Azelaic acid gains popularity in luxury and high-performance skincare products, celebrated for its versatility and suitability for sensitive skin.

   
   

Conclusion 

Azelaic acid is a versatile and highly effective skincare ingredient that offers multiple benefits. It treats acne and rosacea, fades hyperpigmentation, and promotes an even skin tone, providing a comprehensive approach to skin health. Its gentle yet potent nature makes it suitable for all skin types, including sensitive skin. Incorporating azelaic acid into your routine can help you achieve healthier, clearer, and more radiant skin.