Azelaic AcidvsMandelic Acid

Azelaic acid exhibits multi-modal activity: (1) Tyrosinase inhibition—competitively inhibits tyrosinase selectively in hyperactive melanocytes (melasma, PIH) while sparing normal ones; may involve mitochondrial enzyme interference in dysregulated melanocytes. (2) Antimicrobial—bacteriostatic against Cutibacterium acnes by inhibiting bacterial protein synthesis. (3) Comedolytic—normalizes follicular keratinization, reducing hyperkeratinization and corneocyte cohesion; may modulate keratinocyte differentiation. (4) Anti-inflammatory—scavenges ROS, inhibits neutrophil free radicals, reduces pro-inflammatory cytokines. Inhibits 5-alpha-reductase in sebocytes, potentially reducing sebum. Multi-pathway activity explains efficacy in acne, rosacea, and hyperpigmentation. Safe during pregnancy.

Mandelic acid (152 Da, the largest common AHA) exfoliates through calcium chelation and corneodesmosome disruption like other AHAs, but its large molecular size results in slower, more even epidermal penetration with reduced risk of hot-spot irritation and stratum corneum over-exfoliation. Its phenyl ring confers partial lipophilicity, enabling penetration into the pilosebaceous unit and follicular infundibulum—unlike purely hydrophilic glycolic and lactic acids. Within pores, mandelic acid exerts mild comedolytic effects by disrupting keratinocyte cohesion in the follicular epithelium, similar to salicylic acid. It demonstrates antibacterial activity against Cutibacterium acnes (Propionibacterium acnes) through membrane disruption. Mandelic acid also inhibits tyrosinase and reduces melanosome transfer to keratinocytes, providing brightening benefits. This profile makes it particularly suitable for acne-prone skin, hyperpigmentation, and darker skin tones (Fitzpatrick IV–VI) where gentler exfoliation minimizes post-inflammatory hyperpigmentation risk.