Quick Comparison
| Azelaic Acid | Tretinoin | |
|---|---|---|
| Typical Concentration | OTC: 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%, 0.05%, 0.1%. Start with 0.025% every other night for 4-6 weeks, then increase frequency. Apply pea-sized amount to dry face 20 minutes after cleansing. Always use with SPF 30+ during the day. Retinization period: 4-12 weeks of initial irritation. |
| Application | Topical (gel, cream, serum). Slightly gritty texture in some formulations. Apply to clean skin. | Topical (cream, gel, microsphere). Apply to clean, dry skin at night. Microsphere formulations (Retin-A Micro) release tretinoin slowly, reducing irritation. |
| Research Papers | 9 papers | 10 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.
Tretinoin
Tretinoin binds nuclear retinoic acid receptors (RAR-alpha, beta, gamma), forming RAR/RXR heterodimers that bind retinoic acid response elements and activate gene transcription. This accelerates keratinocyte proliferation, reducing stratum corneum transit from ~28 to ~14 days. In the dermis, tretinoin stimulates fibroblasts and upregulates collagen I and III via TGF-beta while downregulating MMP-1, MMP-3, and MMP-9 that degrade the extracellular matrix. It normalizes melanocyte distribution and melanosome transfer. In acne, it prevents microcomedo formation by normalizing follicular keratinocyte differentiation and reducing corneocyte cohesion. RAR activation also modulates genes for epidermal growth factors and differentiation markers.
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).
Tretinoin
Common
Dryness, peeling, redness, increased sun sensitivity (mandatory SPF). Initial purging (breakouts) for 4-8 weeks.
Serious
Teratogenic — absolutely contraindicated in pregnancy and breastfeeding.
Rare
Severe irritant contact dermatitis, eczema flare-ups.
Full Profiles
Azelaic Acid →
A dicarboxylic acid naturally produced by yeast on the skin. Azelaic acid is a true multi-tasker that treats acne, rosacea, and hyperpigmentation simultaneously. It is one of the few active ingredients considered safe during pregnancy, and it uniquely targets only abnormal melanocytes — meaning it brightens dark spots without lightening normal skin. Effective for both inflammatory acne and post-inflammatory hyperpigmentation (PIH).
Tretinoin →
The gold standard anti-aging ingredient with the most clinical evidence of any topical. Tretinoin (all-trans retinoic acid) is the active form of vitamin A that directly binds to retinoic acid receptors in skin cells. It accelerates cell turnover, stimulates collagen synthesis, reduces fine lines and wrinkles, fades hyperpigmentation, and improves skin texture. Prescription-only in most countries.