A grade is not an opinion about how good an ingredient is. It states what has
been trialled, in which condition. Four cells are deliberately empty: we found
no evidence for that pairing, so it gets no grade.
Grades: A = Meta-analysis, systematic review, or randomised trial in this specific condition · B = Controlled clinical trial in this condition, or a strong trial in an adjacent one · C = Small or open-label human data, or mechanism plus supporting human evidence · D = In vitro or mechanism only.
Numbers are footnotes to the studies below. Take the grid: JSON · CSV, CC BY 4.0.
Tranexamic Acid — works at 2-5%
Topical tranexamic acid is used at 2-5% in cosmetic and clinical formulations; 3% is the most common clinical benchmark. The original mechanism study used 2-3% in guinea pig models. Expert consensus supports topical TXA at 2%, particularly with delivery-optimized systems. Oral dosing (250-500 mg/day, off-label) is a separate route used in clinical practice for refractory melasma.
A Melasma: The best-evidenced over-the-counter option for melasma. A 2024 randomised trial found 3% topical tranexamic acid comparable to 4% hydroquinone.
B Post-inflammatory hyperpigmentation: Works, though azelaic acid has the more direct trial in post-inflammatory pigment.
B Post-inflammatory erythema: The one brightening active with real evidence on the vascular component — it inhibits angiogenesis, not only melanin. If the mark is red, this is the active to reach for.
C Sun spots and age spots: Prevents UV-driven pigmentation; the evidence for clearing established sun spots is thin.
What we don't know: The landmark mechanism study (Maeda & Naganuma 1998, PMID:10093913) used a guinea pig model; the arachidonic acid/prostaglandin pathway for melanogenesis inhibition has not been replicated in a controlled human keratinocyte or in vivo human skin study at the molecular level.; No published head-to-head RCT directly compares topical tranexamic acid to L-ascorbic acid or kojic acid for melasma using standardized MASI scoring in a well-powered trial.; The skin penetration of topical tranexamic acid is limited by its hydrophilicity; most clinical trials do not report measured drug levels in skin, so effective local concentration at the keratinocyte level is inferred, not directly quantified.; Long-term (>6 months) clinical data on topical tranexamic acid for maintenance therapy of melasma are limited; recurrence rates after discontinuation are not well-characterized in the topical TXA literature.; The optimal topical concentration for cosmetic use has not been established by dose-ranging trials in humans; the 2-5% range derives from mechanism studies (guinea pig), comparative RCTs, and expert consensus rather than dedicated dose-finding studies.; Evidence for tranexamic acid in post-inflammatory hyperpigmentation, Riehl's melanosis, and rosacea is emerging but based on smaller or retrospective studies; it is not as robustly supported as its melasma evidence base.; CIR has not issued a finalized safety assessment specifically for tranexamic acid as a cosmetic ingredient; the safety profile is inferred from pharmaceutical use data (oral/IV) and cosmetic clinical trials.; The vascular/anti-angiogenic mechanism data (PMID:32308543, PMID:31074159) come from in vitro cell models; the relative contribution of anti-angiogenesis vs anti-melanogenesis to the clinical lightening effect in human melasma lesions is not quantified.
Azelaic Acid — works at 10-20%
OTC products (e.g., 10% suspension) show clinical activity; FDA-approved Rx formulations are 15% (rosacea) and 20% (acne/melasma). No head-to-head data establishes minimum effective OTC concentration.
A Melasma: 20% azelaic acid matched 4% hydroquinone in head-to-head trials. Over-the-counter products are around 10%.
A Post-inflammatory hyperpigmentation: The most directly evidenced active for acne marks — trialled in PIH itself rather than extrapolated from melasma.
B Post-inflammatory erythema: Anti-inflammatory as well as anti-pigment, which is why it is the single active that earns a place for both red and brown marks.
C Sun spots and age spots: Selective for overactive melanocytes, so it is modest on ordinary sun spots.
What we don't know: No independent peer-reviewed RCT has specifically tested a 10% OTC azelaic acid formulation (the most common consumer-market concentration) for any indication. All clinical evidence comes from 15% or 20% Rx formulations.; The selective cytotoxicity on hyperactive vs normal melanocytes (PMID:2114832) is foundational to the safety profile, but the molecular mechanism of this selectivity is not fully characterized; increased membrane permeability in abnormal melanocytes is hypothesized but not confirmed.; Most anti-inflammatory ROS data (PMID:1867478) comes from ex vivo neutrophil studies; in vivo quantification of ROS inhibition in rosacea skin after topical application has not been published.; The 2025 pregnancy retrospective (PMID:40873252) involved only 26 patients in the azelaic acid arm; a large prospective controlled trial in pregnancy is still lacking, meaning the safety classification relies on low systemic absorption and preclinical data rather than powered human trials.; Head-to-head comparison of azelaic acid 10% OTC versus prescription 15% in the same patients for PIH, acne, or rosacea has not been published in peer-reviewed literature.; Long-term data (beyond 24 weeks) on sustained azelaic acid use for melasma maintenance are limited; relapse rates after discontinuation versus hydroquinone have not been systematically compared.; Potassium azeloyl diglycinate (PAD) lacks head-to-head data against free azelaic acid; all PAD trials use multi-ingredient formulations, making it impossible to isolate PAD's contribution.
Niacinamide (Vitamin B3) — works at 2–5%
2% is sufficient for sebum regulation and barrier benefits; 4% has clinical evidence for acne; 5% is the most-studied concentration for anti-aging and brightening endpoints. Some tolerability concerns exist above 5% (see detail).
C Melasma: A useful partner active. Not a melasma treatment on its own.
B Post-inflammatory hyperpigmentation: Blocks pigment transfer rather than pigment production — a different mechanism from every tyrosinase inhibitor here, which is why it layers with all of them.
C Post-inflammatory erythema: Measurably reduces red blotchiness. Gentle and slow.
B Sun spots and age spots: Reliable, unspectacular, and tolerated by almost everyone.
What we don't know: Most melanosome-transfer inhibition data is from in vitro co-culture models (Hakozaki 2002, Greatens 2005). Randomized controlled clinical trials with blinded photography and colorimetry specifically testing niacinamide monotherapy for hyperpigmentation are fewer; existing clinical evidence is predominantly from multi-benefit photoaging studies (Bissett 2004/2005) rather than dedicated pigmentation RCTs.; The ceramide synthesis data (Tanno 2000, PMID:10971324) is from cultured human keratinocytes; the clinical topical TEWL reduction evidence (Soma 2005, PMID:15807725) was in atopic dry skin patients, not normal skin. Generalization to healthy skin barriers is reasonable but not directly demonstrated in a large controlled trial.; Sebum reduction and pore improvement evidence (Draelos 2006) was a single 4-week study (n=100); longer-term studies and independent replication are limited in peer-reviewed literature.; The claim that high-dose niacinamide (>5%) can cause irritation attributable to niacin contamination rather than niacinamide itself is mechanistically plausible and referenced in the CIR report, but no published dose-response study systematically varied niacin impurity levels against skin response in human volunteers.; Nearly all Bissett et al. clinical data originates from Procter & Gamble research (manufacturer-affiliated); independent academic replication of the 5% aging endpoint package is limited.; Optimal delivery vehicle, penetration characteristics, and bioavailability of niacinamide in different formulation types have not been systematically compared in peer-reviewed literature.; Long-term use safety above 5% in cosmetic formulations has not been studied in controlled trials; the CIR 2005 safe-as-used conclusion is based on available data at that time and has not been formally updated as of the date of this dossier.
Retinol (Vitamin A) — works at 0.1-1%
OTC retinol products typically range 0.1–1%. Clinical trial evidence for visible anti-aging effects exists from 0.3–0.4% upward; 1% produces greater retinoid effects but also greater irritation than 0.3%.
C Melasma: Can help, but irritation cuts both ways: in deeper skin tones an irritated retinoid can add post-inflammatory pigment of its own.
C Post-inflammatory hyperpigmentation: Speeds clearance of existing marks by accelerating turnover. Graded C rather than B deliberately: our corpus holds no trial of retinol in post-inflammatory pigment specifically, so this rests on mechanism and on photoaging data.
— Post-inflammatory erythema: No pigment target and a real irritation risk. Not the tool for red marks.
A Sun spots and age spots: The best-evidenced active for sun-damage pigmentation, and the only one here with decades of photoaging trials behind it.
What we don't know: The conversion efficiency of retinol to retinoic acid in human skin in vivo is not precisely quantified. Bailly et al. (1998, PMID:9517919) showed that topical retinol and retinal produce only low amounts of retinoic acid in skin (30–90 pmol) compared to direct tretinoin application (2050 pmol epidermal), but the percentage of applied retinol that converts has not been characterized across skin types, ages, or sites.; The roughly '10-fold greater potency' of retinaldehyde versus retinol is derived from a single study using retinoic acid 4-hydroxylase enzyme induction as the endpoint (Duell et al., 1997, PMID:9284094). Head-to-head clinical trials comparing retinal and retinol at matched concentrations for long-term anti-aging endpoints (wrinkles, collagen) in large samples have not been published.; Most mechanistic retinoid data — including MMP suppression, procollagen upregulation, RAR signaling — comes from studies using tretinoin (retinoic acid), not retinol. The assumption that retinol produces these effects because it converts to retinoic acid is well-supported but extrapolated; the in-skin conversion is partial and variable.; Long-term (>6 month) randomized controlled trials of OTC retinol concentrations for photoaging are limited. The Kafi et al. (2007) study (PMID:17515510) is the best-designed retinol (not tretinoin) RCT for natural aging but involved elderly subjects (mean age 87) and a non-standard frequency (3×/week); generalizability to younger photoaged populations is reasonable but not directly tested.; The safety of retinyl palmitate in SPF products under UV irradiation was the subject of an NTP photocarcinogenesis study in hairless mice (PMID:23001333) showing dose-related increases in UV-induced skin tumors with retinyl palmitate. This finding has not been replicated in human data and regulatory agencies have not concluded retinyl palmitate in sunscreen products poses a cancer risk; the issue remains unresolved and is actively debated.; The 'purging' phenomenon attributed to retinol — an initial increase in acne lesions preceding improvement — is widely stated in consumer contexts. Primary literature on the mechanism specifically for retinol (not tretinoin) in non-acne-prone skin is not well-characterized.; Encapsulated and time-release retinol formulations are widely marketed as providing superior tolerability or bioavailability compared to free retinol. Independent peer-reviewed head-to-head studies are sparse; performance comparisons rely largely on manufacturer-sponsored data.
Kojic Acid — works at 1-2%
1–2% in leave-on formulations; the EU SCCS sets a regulatory maximum of 1% in face creams and body lotions. Clinical efficacy for hyperpigmentation is demonstrated at 1% monotherapy (Deo 2013) and at 2% in combination products (Lim 1999).
B Melasma: Effective, but see the sensitisation record — this is the least well tolerated active on the list.
C Post-inflammatory hyperpigmentation: Reasonable, rarely the first choice.
— Post-inflammatory erythema: No vascular activity.
C Sun spots and age spots: Works slowly, and stability in the bottle is a genuine problem.
What we don't know: The classic mechanism paper (Cabanes et al. 1994, DOI:10.1111/j.2042-7158.1994.tb03741.x) is not indexed in PubMed/MEDLINE for this journal issue; the record was confirmed via Oxford Academic but no PMID exists.; Direct head-to-head RCTs comparing kojic acid monotherapy to hydroquinone monotherapy at matched concentrations in the same patient population are limited; most comparison data comes from combination formulations.; Kojic dipalmitate's in vivo conversion rate to free kojic acid in human skin has not been quantified in independent peer-reviewed literature; efficacy claims for KDP rely primarily on in vitro tyrosinase inhibition and formulation studies.; The SCCS/1637/21 opinion applies specifically to kojic acid (free acid); the ester derivative kojic dipalmitate has not been separately reviewed by SCCS and is not covered by the 1% concentration limit (or the affirmative safety conclusion).; Long-term (>3 month) clinical data on kojic acid monotherapy for hyperpigmentation is sparse; maintenance and recurrence rates after discontinuation are not well characterised.; The sensitisation rate of kojic acid relative to other brighteners (niacinamide, alpha-arbutin, azelaic acid) in a controlled, powered, comparative patch-test study has not been published; the 'higher sensitisation' characterisation is based on case series and the frequency of reported reactions rather than a formal comparative HRIPT.; Systemic absorption from topical 1% kojic acid in humans (which underpins the SCCS margin of safety calculation) is modelled rather than directly measured in well-designed pharmacokinetic studies.; The CIR amended safety assessment (2025, issued for public comment) reached an insufficient-data determination; the final outcome and any updated concentration guidance had not been published as of the date of this dossier.
Alpha-Arbutin — works at 1–2%
1–2% in topical leave-on formulations; the EU SCCS confirmed safety at ≤2% in face creams and ≤0.5% in body lotions. The 2% ceiling is both the studied effective concentration and the regulatory safe-use limit.
C Melasma: Gentle and safe; modest against established melasma.
C Post-inflammatory hyperpigmentation: A sensible everyday choice when tolerance matters more than speed.
— Post-inflammatory erythema: A tyrosinase inhibitor has nothing to act on in a vascular mark.
C Sun spots and age spots: Slow and steady.
What we don't know: No standalone, peer-reviewed human randomized controlled trial evaluating alpha-arbutin alone (without co-actives) as the sole intervention for hyperpigmentation with blinded colorimetric endpoints was identified. All human clinical data found involved alpha-arbutin as part of a multi-ingredient formulation.; The bacterial hydrolysis study (PMID:18789053) was conducted with beta-arbutin; the alpha form's greater enzymatic resistance is structurally and mechanistically expected, but has not been directly quantified in a controlled experiment simulating cosmetic application to colonized skin.; The combined exposure risk from alpha-arbutin used simultaneously with other hydroquinone-releasing substances (e.g., beta-arbutin, deoxyarbutin, resveratrol) has not been formally evaluated in either SCCS opinion (explicitly acknowledged as a limitation in SCCS/1552/15).; Long-term repeat-use safety data for topical alpha-arbutin beyond 90-day study windows is not available in the peer-reviewed literature reviewed here.; No published head-to-head randomized clinical trial comparing alpha-arbutin directly against 4% hydroquinone in humans using blinded objective endpoints was located; the PMID:40091954 comparison is from an in vitro keratinocyte-melanocyte co-culture model, not a clinical study.; No CIR (US Cosmetic Ingredient Review) standalone monograph for alpha-arbutin or arbutin was identified in the published International Journal of Toxicology archive. The dominant regulatory source is EU SCCS.; The CosIng reference number 56844 for alpha-arbutin could not be independently confirmed via live database retrieval during compilation of this document due to access limitations; the number is widely cited in industry contexts.
L-Ascorbic Acid (Vitamin C) — works at 8-20%
8-20% in stable formulations at pH < 3.5; tissue levels plateau at 20% with no additional skin uptake above this ceiling.
C Melasma: A supporting player in melasma rather than a lead.
C Post-inflammatory hyperpigmentation: Helps, mostly by preventing the next mark rather than clearing this one.
— Post-inflammatory erythema: No vascular evidence.
B Sun spots and age spots: Its real value against sun spots is prevention — it blunts the UV oxidative stress that produces new ones.
What we don't know: All percutaneous absorption data establishing the pH < 3.5 requirement and 20% ceiling comes from a single porcine skin model study (Pinnell et al. 2001). Human replication of the specific saturation threshold has not been independently published.; The 4-fold antioxidant protection factor (Lin et al. 2003) was measured in porcine skin, not in a randomized human clinical trial with blinded outcome assessment.; Direct human clinical evidence for L-ascorbic acid improving visible photoaging (wrinkles, firmness) from topical application is limited; most collagen synthesis data is in vitro or from dermal fibroblast cell culture.; Long-term comparative trials between L-ascorbic acid and its stable derivatives for anti-aging endpoints have not been published.; Melanin inhibition data comes largely from in vitro melanoma cell lines; controlled human trials on topical ascorbic acid for hyperpigmentation are sparse and the effect size is modest.; Stability in consumer products after opening is highly variable and poorly characterized in peer-reviewed literature; most data is from controlled laboratory conditions.; THD ascorbate conversion rate to free L-AA in human skin in vivo is not quantified in independent peer-reviewed literature; efficacy claims rely on manufacturer-sponsored or single-group studies.
Licorice Root (Glycyrrhiza Glabra) — works at varies
There's no validated 'use this %' for licorice, because the active you care about depends on the species and extract: glabridin (brightening) comes mainly from G. glabra, licochalcone A (anti-redness) from G. inflata / G. uralensis, and the glycyrrhizin-derived soothers (e.g. dipotassium glycyrrhizate) are different again. A label reading 'licorice root extract' tells you neither which marker compound is present nor how much, so potency isn't comparable between products.
C Melasma: Gentle, and what you actually get varies enormously by species and extract.
C Post-inflammatory hyperpigmentation: Mild.
C Post-inflammatory erythema: Licochalcone A has genuine anti-redness data — but that comes from a different licorice species than the brightening compound does.
D Sun spots and age spots: Mechanism only.
What we don't know: 'Licorice' is really two different stars from different species: glabridin (brightening, mainly Glycyrrhiza glabra) and licochalcone A (anti-redness, Glycyrrhiza inflata / uralensis) — a product's species and marker compound determine what it actually does.; Glabridin's brightening evidence is largely in-vitro (tyrosinase kinetics, melanoma-cell and zebrafish models, MITF pathway); controlled human facial-pigmentation trials of licorice/glabridin are limited.; The strongest human (RCT) evidence is for licochalcone A reducing redness and irritation, not for glabridin fading pigment — the soothing and brightening claims rest on different molecules and shouldn't be transferred to one another.; Glabridin and licochalcone A content varies widely by species, extract solvent and processing (heat treatment and fermentation change the activity), and labels rarely disclose it, so potency isn't comparable between products.; Brightening is gradual and supportive — best paired with niacinamide, vitamin C, tranexamic acid or alpha-arbutin — not hydroquinone-level depigmentation.; Clarification, not a flaw: the blood-pressure / glycyrrhizin concern relates to DIETARY licorice (a systemic effect), not to topical licorice cosmetics — the two are sometimes conflated and shouldn't be.
