Quick Comparison

Azelaic AcidRetinaldehyde
Typical ConcentrationOTC: 10% (The Ordinary). Prescription: 15% gel (Finacea for rosacea), 20% cream (Azelex for acne). Apply twice daily. Well-tolerated but may sting/itch initially. Full effects at 8-12 weeks.Concentrations: 0.025-0.1%. Start at 0.025% every other night. More effective than retinol at equivalent concentrations but less irritating than tretinoin. Products are less common and more expensive than retinol.
ApplicationTopical (gel, cream, serum). Slightly gritty texture in some formulations. Apply to clean skin.Topical (serum, cream). Apply at night. Less stable than retinol — requires careful formulation.
Research Papers9 papers10 papers
Categories

Mechanism of Action

Azelaic 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.

Retinaldehyde

Retinaldehyde is converted to retinoic acid by retinaldehyde dehydrogenase (RALDH) in a single enzymatic step within keratinocytes and fibroblasts. This makes it more potent than retinol (which requires alcohol dehydrogenase then RALDH) but less irritating than tretinoin (the active form). The single-step conversion produces a more controlled retinoic acid flux, reducing RAR-mediated irritation while still activating collagen synthesis, normalizing keratinocyte differentiation, and inhibiting matrix metalloproteinases. It uniquely has direct antimicrobial activity against Cutibacterium acnes through disruption of bacterial membrane integrity and interference with bacterial fatty acid metabolism — no other retinoid has this property. Clinically, this dual mechanism addresses both acne pathogenesis and photoaging.

Risks & Safety

Azelaic Acid

Common

Stinging, burning, itching on initial application (usually subsides within 2 weeks). Mild dryness.

Serious

None. Safe during pregnancy and breastfeeding.

Rare

Allergic contact dermatitis, hypopigmentation (rare at cosmetic concentrations).

Retinaldehyde

Common

Dryness, peeling, mild redness — less than tretinoin but more than retinol.

Serious

Avoid in pregnancy (retinoid class).

Rare

Contact dermatitis.

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