Serums, vitamin C to peptides.

The phase 3 trials: "AzA gel yielded statistically significantly higher reductions in mean inflammatory lesion count than vehicle: 58% versus 40%, study 1; 51% versus 39%, study 2", erythema improvement in 44% and 46% against 29% and 28%, and therapeutic success "in 61% and 62% of patients treated with AzA gel" against 40% and 48% on vehicle (Thiboutot 2003); against 0.75% metronidazole, "mean percent decrease in inflammatory lesions (−72.7% vs −55.8%)", erythema improved in 56% against 42%, and "the effectiveness of metronidazole gel on these variables seemed to plateau after week 8, whereas azelaic acid gel demonstrated progressive improvement through week 15" (Elewski 2003); the 961-participant foam trial "support[s] the therapeutic superiority of AzA foam over vehicle foam" (Solomon 2016). The systematic review of five randomised trials in 873 patients found four showing significant decreases in lesion count and erythema against vehicle and no effect on telangiectasia (Liu 2006); the Cochrane review pooled participants' assessments as a risk ratio of 1.52 for azelaic acid over placebo (van Zuuren 2011) and its 2015 update covers 106 studies and 13,631 participants (van Zuuren 2015). A niacinamide moisturiser improved barrier function and the dermatologist-rated condition of rosacea skin over four weeks (Draelos 2005).

Strong, as the facial redness guide grades it. The 10% cosmetic products have no trials of their own; the 15% gel and 20% cream are the studied strengths, and in most European countries they are dispensed on prescription. Nothing in this row treats the flushing or the visible vessels, which are the facial redness guide's laser section.

Niacinamide: the split-face trial found "reductions in fine lines and wrinkles, hyperpigmented spots, red blotchiness, and skin sallowness (yellowing)" and improved elasticity on cutometry (Bissett 2005), confirmed for "fine lines/wrinkles, hyperpigmentation spots, texture, and red blotchiness" plus sallowness in the earlier report (Bissett 2004), and a placebo-controlled split-face trial in Asian skin found reduced spot, pore, wrinkle and evenness counts with niacinamide and kinetin together (Chiu 2007). Vitamin C: "a highly significant increase in the density of skin microrelief and a decrease of the deep furrows" with "ultrastructural evidence of the elastic tissue repair" after six months of 5% cream against placebo (Humbert 2003); a half-face study with "decreased photoaging scores of the cheeks (P = 0.006) and the peri-oral area (P = 0.01)" and biopsies showing "increased Grenz zone collagen, as well as increased staining for mRNA for type I collagen" (Fitzpatrick 2002); a systematic review of seven studies finding smoother, less wrinkled skin with biopsy support and "long-term use may be needed" (Correia 2023). Acids: "76% glycolic acid, 71% lactic acid, and 40% vehicle" improved at least one photodamage grade at 22 weeks (Stiller 1996); a daily 5% glycolic cream improved texture and discolouration significantly and wrinkles as a trend (Thibault 1998).

Moderate, as the dull skin, crow's feet and collagen loss guides grade these actives; the collagen guide grades L-ascorbic acid strong as a collagen cofactor. Deep or etched lines are the retinoid's and the resurfacing guide's.

Azelaic acid: "azelaic acid cream yielded 65% good or excellent results; no significant treatment differences were observed" against 4% hydroquinone, with no sensitisation or ochronosis (Baliña 1991); "73% of the azelaic acid patients, compared with 19% of the hydroquinone patients, had good to excellent overall results" over 24 weeks (Verallo-Rowell 1989); a lower melasma score with azelaic acid at two months in an open comparison (Farshi 2011); the meta-analysis of six randomised trials and 673 patients found "a lower mean change in melasma area severity index" favouring azelaic acid by 1.23 points and no difference in adverse events (Albzea 2023); a glycolic-peel-plus-azelaic regimen matched a low-potency triple cream in Indian patients (Mahajan 2015). The newer inhibitors: thiamidol improved "79%" of subjects against hydroquinone's 61% with no worsening on the thiamidol side (Arrowitz 2019) and reduced the melasma score 43% against 33% with no significant difference in the evaluator-blinded head-to-head (Lima 2021); cysteamine 5% beat placebo (standardised mean difference −0.84) and showed "no significant difference when compared with hydroquinone 4%" across seven randomised trials (Mawu 2024). The gentler actives: niacinamide "good to excellent improvement was observed in 44% of patients, compared to 55% with HQ", side effects 18% against 29%, with less mast-cell infiltrate and solar elastosis on biopsy (Navarrete-Solís 2011), on a mechanism of blocking melanosome transfer (Hakozaki 2002); vitamin C "62.5% on the ascorbic acid side" against 93% for hydroquinone, with side effects in 6.2% against 68.7% (Espinal-Perez 2004); topical 5% tranexamic acid "neither superior nor different" from its vehicle despite lightening on both sides (Kanechorn Na Ayuthaya 2012), while the meta-analysis of 22 trials found the oral route "the most substantial decrease" followed by injections and then topical use (Calacattawi 2024); kojic acid added to a hydroquinone-glycolic gel cleared more than half the melasma in 60% against 47.5% (Lim 1999) and matched hydroquinone in a glycolic base while irritating more (Garcia 1996).

Moderate, in line with the dark spots guide, which grades hydroquinone, the triple cream and oral tranexamic acid strong and sets out the sunscreen without which every row above relapses. The review of melasma topicals sums up the shelf: triple combination and hydroquinone "the most well-studied agents", ascorbic acid, azelaic acid, glycolic acid, kojic acid and niacinamide "effective as adjuvant therapies", tranexamic acid and cysteamine "recent agents of interest" (González-Molina 2022).

The trials: "all HA-based creams utilized in this study demonstrated a significant improvement in skin hydration and overall elasticity values when compared to placebo", with wrinkle depth significantly improved in the 130 and 50 kDa groups at 60 days, "which may be due to better penetration abilities of LMW HA" (Pavicic 2011); low-molecular-weight hyaluronic acid raised capacitance to 56.37 against 52.37 for high-molecular-weight and 49.01 for vehicle after four weeks on the dry legs of the elderly, with no difference in water loss or symptom scores (Muhammad 2024); an open-label nano-hyaluronic range reported hydration up to 96% and wrinkle depth down up to 40% at eight weeks, with no control (Jegasothy 2014); a crosslinked hyaluronic serum after procedures improved topography and hydration against untreated skin in a split-face study (Sundaram 2018); the 20% glycerin cream showed "equal effects on skin dryness" to urea-saline with less smarting (Lodén 2002).

Moderate, as the dry skin guide grades the humectants, with the rule that a humectant on its own in dry air pulls water outward and needs an occlusive over it; the same guide grades the ceramide half of the barrier and the injected hyaluronic acid that a "hyaluronic serum" borrows its name from.

The acids: the vehicle-controlled trial (Stiller 1996) and the daily 5% glycolic trial with "statistically significant improvement favoring the active-cream in general skin texture and discoloration" (Thibault 1998); the polyhydroxy regimen with "only 2 statistically significant differences" from the alpha-hydroxy one — sallowness 12.4% against 17.1% and pinch recoil 10.2% against 13.5% at week 12 — and "stinging and burning were significantly worse for subjects in the AHA treatment group" (Edison 2004); an enzyme exfoliant compared with glycolic creams over twelve weeks, each improving different instrument scores (Mekas 2015); the reviews of mechanism, concentration and the open question of whether the acids increase or decrease photodamage (Tang 2018; Babilas 2012). Salicylic acid: on biopsy, "the vehicle- and salicylic-acid-treated areas had an aspect similar to untreated control sites", while beta-lipohydroxy acid and tretinoin thickened the epidermis (Piérard 1997); in acne a salicylic dermocosmetic "significantly reduces the need for BPO" and cut relapse after it (Khammari 2023); salicylic peels with a post-peel retinoid improved texture, roughness and pores (Kligman 2016). Pores: reduced pore counts with niacinamide and kinetin in the Asian split-face trial (Chiu 2007).

Moderate, as the dull skin guide grades the acids, with salicylic acid for pores at emerging there. The clinic versions — the peels in the peels guide — do in one session what a leave-on acid does in three months, at the price of a week.

The Cochrane verdict: "azelaic acid is probably less effective than benzoyl peroxide (risk ratio 0.82)" but "probably little or no difference when comparing azelaic acid to tretinoin"; salicylic acid "little or no difference" from tretinoin on low-quality evidence; nicotinamide studied against antibiotics in four trials with no difference in withdrawals or minor adverse events (Liu 2020). The niacinamide trial: "82% of the patients treated with nicotinamide gel and 68% treated with clindamycin gel were improved", lesions down 60% against 43%, "a desirable alternative" because it breeds no resistance (Shalita 1995). The vitamin C derivative: 5% sodium L-ascorbyl-2-phosphate "demonstrated statistically significant improvement when compared to vehicle in all of the parameters measured" with vehicle-like tolerability (Woolery-Lloyd 2010), and combined with 0.2% retinol reduced inflammatory lesions 63% at eight weeks (Ruamrak 2009). Salicylic acid as a benzoyl-peroxide sparer and maintenance (Khammari 2023); the dermocosmetic review notes that despite the mechanisms "there still remains a lack of rigorous controlled studies" (Araviiskaia 2016).

Moderate. The retinoids guide grades the topical retinoids strong for acne and covers the isotretinoin question; benzoyl peroxide and the prescription options are a dermatologist's, and the serums on this row are what keeps a mild case quiet between them.

The laboratory: ferulic acid added to 15% L-ascorbic acid and 1% alpha-tocopherol stabilised the solution and "doubles its photoprotection of skin", reducing sunburn cells, apoptosis and thymine-dimer formation (Lin 2005). The clinic: the solution "provided significant and meaningful photoprotection for skin by all methods of evaluation", "particularly effective for reducing thymine dimer mutations known to be associated with skin cancer", in a small number of volunteers, and "would be expected to supplement the sun protection provided by sunscreens" (Murray 2008). The procedure trial: with microneedling, the antioxidant side improved the photoaging score 23.9% against 6.8%, the melasma score 31.2% against 5.1% and elasticity 39.0% against 6.8% (Liu 2026). Vitamin C's older name in the same role: it "protects porcine skin from ultraviolet radiation-induced damage" (Darr 1992).

Moderate, as the collagen guide grades topical antioxidants and the sun damage guide the actives under sunscreen. The botanical antioxidants sold beside it are graded emerging in Part 02; the sunscreen is graded in its own guide and is the half of the morning that a serum cannot do.

The evidence: niacinamide on rosacea skin, with barrier function and hydration measured on the forearms and the face (Draelos 2005); the ectoine systematic review, in which "topical formulations containing 5.5–7.0% ectoine positively influenced skin dryness and, consequently, pruritus and dermatitis-specific scores" and reduced the need for pharmacological therapy, including in retinoid dermatitis (Kauth 2022); the polyhydroxy comparison (Edison 2004); centella's clinical trials, which are in diabetic ulcers and burns with hydrogels and microneedles rather than in serums on faces (Witkowska 2024); the snail secretion trials, in which periocular wrinkles and texture improved against placebo on the treated side while "subjects did not report a significant difference in the quality of their skin" (Fabi 2013) and a later open study found both groups improved in fine lines (Lim 2020).

Emerging for the extracts and moderate for niacinamide, in line with the facial redness guide's barrier row. The ceramides guide and dry skin guide cover the moisturiser that a sensitive face needs more than a serum.

The evidence: the dark-circle serum study reporting "an average overall reduction in under-eye hyperpigmentation of 47.94%" without a control arm (Brady 2025); the cyclised hexapeptide-9 trial in which the peptide reduced crow's-feet and forehead wrinkle counts, area and roughness more than retinol in a manufacturer-run randomised trial (Chang 2025); the periocular wrinkle improvement on the snail-secretion side at 12 weeks (Fabi 2013); the medium-length polynucleotide eye cream that outperformed 0.1% retinol on periocular wrinkles and eye-bag parameters over 28 days in a manufacturer split-face study (Ye 2026); and the vitamin C half-face trial in which "the peri-orbital area improved bilaterally, probably indicating improved hydration" (Fitzpatrick 2002).

Emerging, as the eye bags and dark circles guides grade the caffeine, peptide and brightening eye products; those guides sort the fat pad from the shadow from the pigment and grade what treats each. An "eye serum" is the face serum in a smaller, dearer bottle, and the retinoid at the outer eye is the one topical with a tier above emerging there.

Peptides: pal-KTTKS "provided significant improvement vs. placebo control for reduction in wrinkles/fine lines by both quantitative technical and expert grader image analysis" (Robinson 2005); argireline "total anti-wrinkle efficacy in the argireline group was 48.9%, compared with 0% in the placebo group" with roughness parameters decreased (Wang 2013), and with tripeptide-10 citrulline in a four-arm study of cutometer and water-loss readings (Raikou 2017); the cyclised hexapeptide-9 against retinol and vehicle (Chang 2025); a tripeptide-hexapeptide serum before facelift surgery with histological changes on the treated side (Widgerow 2025); copper tripeptide after CO2 resurfacing, where "objective evaluation found no significant improvement in wrinkles or overall skin quality" though satisfaction was higher (Miller 2006). Growth factors: the fibroblast-derived product "demonstrated significantly greater reductions in the appearance of fine lines/wrinkles, coarse line/wrinkles, and overall photodamage, compared to the placebo group" (Kadoya 2017); the EGF review found "uncontrolled or randomized trials abound, so that does not represent enough evidence" (Miller-Kobisher 2021); a 2026 pilot comparing synthetic and human-derived EGF found "global wrinkle severity ratings changed minimally in both cohorts" (Abud 2026); the review of the field puts topical growth factors at evidence levels II and III (Fabi 2014).

Emerging, as the collagen, collagen loss and crow's feet guides grade them, and limited for the "Botox in a bottle" claim in the botox guide. A peptide small enough to enter can signal a fibroblast; a growth factor is usually too large to enter intact skin (Bos 2000), which is why the products that work are paired with needling in the trials.

The collagen trial: "oral or topical collagen peptides used alone or in combination do not have benefits on forearm skin after 6 months of intervention, and therefore should not be used routinely in this population" — with dermal elasticity, thickness, echogenicity and immunohistochemistry all unchanged (Guadanhim 2023). Exosomes: "the current published research literature does not yet provide a clear consensus on long-term use for skin rejuvenation" and "there are no currently US FDA-approved exosome products" (Vyas 2023); the scoping review of 17 studies found 76% reporting improvements, "small sample sizes and short follow-up", "non-randomized, single-arm designs and potential conflicts of interest", and granulomas, necrosis and allergic reactions after injection (Wang 2026). Stem cells: "blinded investigator assessments did not detect any statistically significant differences between the two halves of the face" (Alhaddad 2019). The size rule that makes all of them implausible as topicals (Bos 2000).

Limited, as the collagen loss and biostimulator guides grade the exosome and stem-cell products, and as the aging hands guide grades the collagen creams. The collagen guide grades the oral peptides on their own trials; the topical ones have now had theirs.