Quick Comparison

AdapaleneMandelic Acid
Typical ConcentrationOTC: 0.1% gel, apply pea-sized amount once nightly to clean, dry skin. Prescription: 0.3% gel for more resistant acne. Can be applied to slightly damp skin with less irritation than tretinoin. Results visible at 8-12 weeks.Concentrations: 5-10% for daily use. 25-40% for professional peels. Can be used daily with minimal irritation for most skin types. Particularly effective for skin of color (Fitzpatrick IV-VI) due to lower risk of post-inflammatory hyperpigmentation.
ApplicationTopical (gel, cream, lotion). More stable than tretinoin — can tolerate some benzoyl peroxide layering (Epiduo combines both).Topical (serum, peel, toner). Safe for daily use. Apply at night.
Research Papers8 papers10 papers
Categories

Mechanism of Action

Adapalene

Adapalene selectively binds RAR-beta and RAR-gamma (minimal RAR-alpha affinity), reducing inflammatory signaling compared to pan-RAR agonists. It normalizes follicular epithelial differentiation and reduces corneocyte cohesion in the pilosebaceous unit, preventing microcomedo formation. Adapalene inhibits AP-1 transcription factor (c-Fos/c-Jun dimerization), suppressing IL-6, TNF-alpha, and neutrophil chemotaxis. It promotes comedolysis by accelerating desquamation of existing comedones. For anti-aging, it stimulates fibroblast collagen I and III via RAR-beta/gamma, with comparable efficacy to tretinoin. Its lipophilic naphthoic acid structure confers superior follicular penetration and light stability.

Mandelic Acid

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.

Risks & Safety

Adapalene

Common

Dryness, peeling, redness — generally less than tretinoin. Initial purging for 4-6 weeks.

Serious

Avoid in pregnancy (retinoid class).

Rare

Allergic contact dermatitis, severe peeling.

Mandelic Acid

Common

Very mild — less irritating than any other AHA. Slight tingling.

Serious

None.

Rare

Contact dermatitis. Cross-reactivity in people with almond allergies is theoretically possible but unconfirmed.

Full Profiles