The receipts.

The reason Bright Side exists. This exact trio is one of the best-documented topical antioxidant systems in dermatology, and ferulic acid is what keeps the vitamin C from giving up in the bottle.

Adding ferulic acid to 15% vitamin C and 1% vitamin E stabilized the solution and doubled its antioxidant protection of skin in the study, from roughly 4-fold to 8-fold. Pig skin in vivo; the same formula was then shown to protect human skin (Murray 2008).

Study

Lin FH, et al. Ferulic acid stabilizes a solution of vitamins C and E and doubles its photoprotection of skin. 2005.

Journal

Journal of Investigative Dermatology 125:826-832

Design

Controlled in vivo study, solar-simulated UV irradiation

Subjects

Pig skin in vivo. The same 15% C, 1% E, 0.5% ferulic formula was then tested on human skin: Murray JC, et al. JAAD 2008;59:418-425, PMID 18603326

Concentration

15% L-ascorbic acid, 1% alpha-tocopherol, 0.5% ferulic acid

Duration

4 days of application before irradiation

Outcome

Erythema and sunburn cell formation, both roughly halved vs C+E alone

The most dependable supporting actor in skincare. It does several unexciting things, tone, texture, barrier function, with the kind of human data most trendy actives can only dream about.

In a 12 week split-face trial, 5% niacinamide significantly improved fine lines, hyperpigmented spots, red blotchiness, and sallowness compared to the same base without it.

Study

Bissett DL, Oblong JE, Berge CA. Niacinamide: a B vitamin that improves aging facial skin appearance. 2005.

Journal

Dermatologic Surgery 31:860-866

Design

Double-blind, randomized, split-face, vehicle-controlled

Subjects

50 women with signs of photoaging

Concentration

5% niacinamide

Duration

12 weeks, twice daily

Outcome

Significant improvement in fine lines, spots, blotchiness, and sallowness

One conversion step away from retinoic acid, which is why it acts faster than retinol. The rare active where the interesting version and the evidenced version are the same molecule.

Over 44 weeks, 0.05% retinaldehyde reduced wrinkles and roughness comparably to prescription 0.05% retinoic acid, with meaningfully better tolerability.

Study

Creidi P, et al. Profilometric evaluation of photodamage after topical retinaldehyde and retinoic acid treatment. 1998.

Journal

Journal of the American Academy of Dermatology 39:960-965

Design

Randomized, vehicle-controlled, comparative

Subjects

125 patients with photodamaged facial skin

Concentration

0.05% retinaldehyde vs 0.05% retinoic acid vs vehicle

Duration

44 weeks

Outcome

Wrinkle and roughness reduction by optical profilometry, comparable between actives

The barrier's own vocabulary, restocked. The stratum corneum is built from three lipid families, and putting only one or two of them back turns out to be worse than none. The ratio is the point.

Only mixtures of all three lipids allowed normal barrier repair after damage. Raising the ratio of any one of them up to threefold accelerated repair further, first in mouse skin and then confirmed in damaged human skin.

Study

Man MQ, Feingold KR, Thornfeldt CR, Elias PM. Optimization of physiological lipid mixtures for barrier repair. 1996.

Journal

Journal of Investigative Dermatology 106:1096-1101

Design

Controlled barrier-recovery experiments, transepidermal water loss as the readout

Subjects

Murine skin, with preliminary validation in damaged human skin

Concentration

Ceramides, cholesterol and free fatty acids in equimolar to 3:1:1 ratios

Duration

Recovery tracked after acute barrier disruption

Outcome

Equimolar mixtures restore normal repair; skewed ratios up to threefold accelerate it

Keeps stronger actives from feeling like a dare. Squalene is the main lipid your own skin surface makes; squalane is its stable, saturated cousin, so it sits on skin like something skin already recognizes.

A review of the in vitro and in vivo literature finds squalene and squalane act as emollients and antioxidants that support hydration, and are well established as vehicles in topical lipid emulsions. Good comfort evidence, no anti-aging promise attached.

Study

Huang ZR, Lin YK, Fang JY. Biological and pharmacological activities of squalene and related compounds: potential uses in cosmetic dermatology. 2009.

Journal

Molecules 14:540-554

Design

Narrative review of in vitro and in vivo studies

Subjects

Human and animal skin models across the reviewed studies

Concentration

Varies by study

Duration

Varies by study

Outcome

Emollient, antioxidant and hydration effects; established topical vehicle

Ancient. Unglamorous. Still undefeated. Your skin makes and moves its own glycerol through aquaporin channels, which is why a cleanser that leaves some behind feels less like a punishment.

The review concludes that topical glycerol improves stratum corneum hydration, barrier function and skin mechanical properties, protects against irritants, and helps in dry-skin conditions such as winter xerosis and atopic dermatitis.

Study

Fluhr JW, Darlenski R, Surber C. Glycerol and the skin: holistic approach to its origin and functions. 2008.

Journal

British Journal of Dermatology 159:23-34

Design

Review of mechanistic and clinical literature

Subjects

Human skin across the reviewed studies

Concentration

Varies by study

Duration

Varies by study

Outcome

Improved hydration, barrier function and mechanical properties; protection against irritants

Newborn skin arrives wrapped in the most overdesigned moisturizer in biology. Our lab rebuilt its lipid logic as one patent-pending complex, and Baby's Bottom is built on it. The published anchor is a human study of a vernix-based formulation on disrupted skin.

In healthy volunteers, a ceramide-containing formulation modeled on vernix caseosa accelerated barrier recovery over 16 days after tape-stripping, and the ceramide profile of treated skin stayed closer to normal than at untreated sites.

Study

Boiten WA, Berkers T, Absalah S, et al. Applying a vernix caseosa based formulation accelerates skin barrier repair by modulating lipid biosynthesis. 2018.

Journal

Journal of Lipid Research 59:250-260

Design

Controlled in vivo study, barrier disruption by tape-stripping, four skin sites per subject

Subjects

Healthy volunteers

Concentration

A ceramide-containing vernix caseosa based formulation

Duration

16 days of recovery, TEWL monitored, lipid analysis at day 16

Outcome

Faster barrier recovery by TEWL; the ceramide shifts seen in untreated recovering skin were diminished by treatment

Hyaluronic acid is only as useful as its size. Our lab ferments it into a spectrum, so about a third is small enough to get past the surface. The published anchor is a human trial that tested five sizes head to head.

In 76 women aged 30 to 60, 0.1% hyaluronic acid creams at 50, 130, 300, 800 and 2000 kDa all significantly improved skin hydration and elasticity against a vehicle over 60 days, and only the 50 and 130 kDa sizes significantly reduced wrinkle depth, which the authors attribute to better penetration of the smaller molecule.

Study

Pavicic T, Gauglitz GG, Lersch P, et al. Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment. 2011.

Journal

Journal of Drugs in Dermatology 10:990-1000

Design

Randomized, vehicle-controlled, periocular, one formulation per eye

Subjects

76 women aged 30 to 60 with periocular wrinkles

Concentration

0.1% hyaluronic acid at 50, 130, 300, 800 or 2000 kDa

Duration

60 days, twice daily

Outcome

Hydration and elasticity improved at all sizes; wrinkle depth reduced at 50 and 130 kDa

A naturally occurring copper complex that declines with age and resets a startling number of genes toward a regenerative state in laboratory models. The blue in the bottle. The reason the serum is named what it is.

GHK-Cu shifts expression of a large fraction of the human genome toward a repair-associated pattern in gene profiling studies, and stimulates collagen synthesis in skin models. Preclinical, deep, and decades in the making: the interesting tier, worn on purpose.

Study

Pickart L, Margolina A. Regenerative and protective actions of the GHK-Cu peptide in the light of the new gene data. 2018.

Journal

International Journal of Molecular Sciences 19:1987

Design

Peer-reviewed review of gene expression and preclinical studies

Subjects

Human cell and tissue models, small clinical studies

Concentration

Varies by study

Duration

Varies by study

Outcome

Broad regenerative gene expression signature; collagen stimulation in models

A memo to skin, and skin reads it. In the best-known split-face trial, 93 women used 3 ppm of the peptide on one side of the face for 12 weeks and had fewer wrinkles and fine lines on that side, by instrument and by expert eye. One trial puts it in the interesting tier; the result puts it in the bottle.

In a 12-week, double-blind, placebo-controlled split-face study in 93 women aged 35 to 55, a moisturizer with 3 ppm palmitoyl pentapeptide significantly reduced wrinkles and fine lines versus the same moisturizer without it, by instrument and expert grading.

Study

Robinson LR, Fitzgerald NC, Doughty DG, et al. Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin. 2005.

Journal

International Journal of Cosmetic Science 27:155-160

Design

Double-blind, placebo-controlled, split-face, left-right randomised

Subjects

93 women aged 35 to 55 with photoaged skin

Concentration

3 ppm palmitoyl pentapeptide (pal-KTTKS) in a moisturizer

Duration

12 weeks

Outcome

Significant reduction in wrinkles and fine lines versus placebo

They are there because they look good. That is allowed. Jojoba wax does have a literature of its own, as an emollient with anti-inflammatory activity, but be clear: the receipt is for the wax, not for the beads.

A review of the dermatology literature reports anti-inflammatory activity for jojoba and roles in wound healing, skin aging and moisturizers. In Clean Slate the beads are suspended for pleasure, and they melt on contact rather than scrub.

Study

Pazyar N, Yaghoobi R, Ghassemi MR, et al. Jojoba in dermatology: a succinct review. 2013.

Journal

Giornale Italiano di Dermatologia e Venereologia 148:687-691

Design

Narrative review

Subjects

Human and experimental studies across the reviewed literature

Concentration

Varies by study

Duration

Varies by study

Outcome

Anti-inflammatory activity; roles in moisturizers, wound healing and skin aging

A beta-glucan from the split-gill mushroom, in the retinal serum to keep redness down. Our lab's own test on people is the reason it is here; the published work is laboratory, which is why it sits in the interesting tier.

Schizophyllan produced by fermenting Schizophyllum commune showed antioxidant, anti-photoaging and melanin-inhibiting activity in laboratory assays, and in a porcine skin explant model exposed to cigarette smoke it was among the polysaccharides that significantly prevented oxidative stress and inflammatory gene expression.

Study

Gou Z, Peng Z, Wang S, et al. Efficient production and skincare activity evaluation of schizophyllan, a beta-glucan derived from Schizophyllum commune NTU-1. 2023.

Journal

International Journal of Biological Macromolecules 241:124504

Design

Fermentation optimization and in vitro bioactivity assays

Subjects

Laboratory assays, no human subjects. Skin explant data: Hergesell K, et al. Skin Pharmacol Physiol 2022;35:156-165, PMID 35100602

Concentration

Not stated for the bioactivity assays

Duration

Not applicable

Outcome

Antioxidant, anti-photoaging and melanin-inhibition activity in vitro

The other half of the copper complex our lab makes for Mixed Signals: a six-amino-acid peptide originally isolated from yeast. One good paper on what it does inside skin cells, with a human elasticity measurement in the same paper. Interesting tier, with a named mechanism, which is more than most peptides on a label can say.

In normal human skin and lung fibroblasts, Hexapeptide-11 activated proteasome, autophagy, chaperone and antioxidant response genes, increased nuclear Nrf2, and protected cells against oxidative-stress-induced premature senescence; in skin deformation assays in human subjects it improved skin elasticity.

Study

Sklirou AD, Ralli M, Dominguez M, et al. Hexapeptide-11 is a novel modulator of the proteostasis network in human diploid fibroblasts. 2015.

Journal

Redox Biology 5:205-215

Design

In vitro cell studies plus in vivo skin deformation assays

Subjects

Human diploid skin and lung fibroblasts; human subjects for the elasticity assay

Concentration

Dose- and time-dependent series in culture

Duration

Varies by assay

Outcome

Nrf2 activation, proteasome and autophagy gene induction, protection from premature senescence; improved skin elasticity in subjects

In cultured human hair follicles, caffeine did something almost rude: it counteracted testosterone-driven growth suppression and stimulated growth on its own. Human follicles, from real scalps, in a lab that could measure it.

Caffeine at 0.001% and 0.005% counteracted testosterone-induced suppression of hair follicle growth in vitro, and caffeine alone significantly stimulated follicle growth. Lab evidence on human follicles, which is why it is in the conditioner and on the label.

Study

Fischer TW, Hipler UC, Elsner P. Effect of caffeine and testosterone on the proliferation of human hair follicles in vitro. 2007.

Journal

International Journal of Dermatology 46:27-35

Design

Ex vivo organ culture, controlled conditions

Subjects

Hair follicles from 14 scalp biopsies, male AGA patients

Concentration

0.001% and 0.005% caffeine

Duration

120 to 192 hours in culture

Outcome

Growth suppression by testosterone counteracted; growth stimulated by caffeine alone