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Head-to-head evidence comparison — which supplement is right for you?
Tretinoin (Retin-A) wins 2 of 3 categories. Both are solid choices — the best pick depends on your specific goals.
Verdict
Mostly mechanism / observational
Top outcomes
Verdict
Mostly mechanism / observational
Top outcomes
Shared outcomes (1)
Outcomes where both Matrixyl and Tretinoin (Retin-A) have evidence — compare verdict strength side-by-side.
Topical cosmetic only. Matrixyl (palmitoyl pentapeptide-4 / pal-KTTKS, or the Matrixyl 3000 blend of palmitoyl tripeptide-1 + palmitoyl tetrapeptide-7) is used at very low concentrations in leave-on serums and creams — clinical benefit was shown at as little as 3 ppm pal-KTTKS, and consumer products commonly list 3-10% of the branded blend. Applied to the target area once or twice daily. There is no oral, injectable, or systemic dose — it is not ingested.
any
Leave-on topical cosmetic (serum or cream) containing palmitoyl pentapeptide-4 or the Matrixyl 3000 blend
Prescription topical: a pea-sized amount of 0.025%-0.1% cream or gel applied to clean, dry skin once nightly. Start low-strength and every-other-night to build tolerance. A prescription drug used under clinician direction — not a supplement regimen.
before-bed
Topical cream or gel, 0.025%-0.1% (prescription)
Throughout
8-12 weeks
Cell studies
Throughout
12-24 weeks
12-24 weeks
Months
8-12 weeks
Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin.
Int J Cosmet Sci (2005) · Rct
The strongest human evidence: a 12-week, double-blind, placebo-controlled, split-face, left-right randomized trial in 93 women aged 35-55 (Procter & Gamble)
Double-blind, Randomized Trial on the Effectiveness of Acetylhexapeptide-3 Cream and Palmitoyl Pentapeptide-4 Cream for Crow's Feet.
J Clin Aesthet Dermatol (2023) · Rct
Double-blind randomized trial in 21 Indonesian women applying palmitoyl pentapeptide-4 (PPP-4) cream, acetyl hexapeptide-3 cream, or placebo twice daily for 8 weeks
Dermal Stability and In Vitro Skin Permeation of Collagen Pentapeptides (KTTKS and palmitoyl-KTTKS).
Biomol Ther (Seoul) (2014) · In vitro
In-vitro stability and permeation study in hairless-mouse skin comparing KTTKS with its palmitoylated derivative pal-KTTKS (Matrixyl)
Topical tretinoin improves photoaged skin. A double-blind vehicle-controlled study.
JAMA (1988) · Rct
Randomized, double-blind, vehicle-controlled trial of topical tretinoin for photoaged forearm and facial skin
Tretinoin emollient cream: a new therapy for photodamaged skin.
J Am Acad Dermatol (1992) · Rct
Multicenter double-blind vehicle-controlled trial of tretinoin emollient cream for photodamaged skin
Long-term treatment of photoaged human skin with topical retinoic acid improves epidermal cell atypia and thickens the collagen band in papillary dermis.
J Am Acad Dermatol (2005) · Open label
Long-term topical retinoic acid on photoaged human skin assessed histologically
Tretinoin (Retin-A) has a higher evidence score (8/10 vs 3/10) and wins in 2 of 3 categories.
For reduce wrinkles & fine lines, Tretinoin (Retin-A) has a higher relevance score (80 vs 60).
No known interactions between Matrixyl and Tretinoin (Retin-A) have been documented in our database. However, always consult a healthcare provider before combining supplements.