Dark spots, honestly.

UV makes every kind of dark spot and visible light makes melasma, and ordinary sunscreens block only the first. In a double-blind randomised trial, melasma patients using a sunscreen with iron oxides (which absorb visible light) alongside hydroquinone lightened significantly more than those using a UV-only sunscreen (Castanedo-Cázares 2014); in a prospective randomised comparison, an iron-oxide sunscreen significantly reduced melasma relapses over six months against a UV-only one, and tinted cosmetics without iron oxides did nothing (Boukari 2015); a 2025 investigator-blinded trial through a summer reached the same conclusion (2025 trial). Reviews put visible-light blocking by iron-oxide tints at 80–97% (JAAD review). For sun spots and post-inflammatory marks the visible-light story matters less and the daily habit matters just as much: the Nambour trial's 24% less measured aging with daily use applies (Hughes 2013).

What to buy: SPF 50, broad-spectrum with a UVA seal, containing iron oxides (they are on the label, usually as CI 77491/77492/77499, and they give the tint), applied generously every morning and again after sweating or at midday outdoors. A hat and shade do the rest. No brightener on this page outperforms the sun it is competing with.

Retinoids speed the turnover that carries pigment out and thin the pigmented layer; in doing so they fade sun spots by about half over six months and clear post-inflammatory marks faster. The evidence is randomised and vehicle-controlled: tretinoin lightened hyperpigmented lesions of photoaging in a controlled trial in Chinese and Japanese patients (JAAD, 1994); a mequinol–tretinoin combination cleared or improved solar lentigines in two double-blind multicentre studies (two studies); and adapalene 0.1% and 0.3% gel produced "lighter" or "much lighter" lentigines in 57% and 59% of patients against 36% on vehicle over nine months (Kang 2003). For post-inflammatory marks, retinoids were the commonest intervention in a 48-study review and produced partial improvement in 85% (systematic review).

Start low and slow — irritation itself causes post-inflammatory pigment in darker skin — always with sunscreen, and not in pregnancy. Adapalene is the pregnancy-avoided but over-the-counter option in several EU countries; tretinoin is prescription. Retinoids do not remove a sun spot; a laser does. Our wrinkles guide covers the retinoid ladder.

Azelaic acid inhibits tyrosinase in overactive melanocytes and calms the inflammation that drives post-inflammatory marks, while leaving normal skin alone. Against the reference drug it holds up: in a double-blind comparison, 20% azelaic acid matched 4% hydroquinone for melasma (double-blind trial); a 2011 randomised comparison found the azelaic group's MASI scores at least as good (Farshi 2011); a meta-analysis of the randomised trials pools the comparison (meta-analysis); a 2023 systematic review covers acne, rosacea, melasma and aging (systematic review); and a randomised, placebo-controlled trial of 15% gel in 72 acne patients improved post-inflammatory marks and redness (2024 trial). It is graded moderate rather than strong because the melasma trials are small and old, not because the effect is in doubt.

Prescription 15–20% (Skinoren, Finacea) or over-the-counter 10% versions; twice daily; a sting for the first week; safe in pregnancy and breastfeeding, which makes it the pregnancy melasma treatment. Our 30s guide covers it as the pregnancy-safe pigment workhorse.

Cysteamine is a natural antioxidant that inhibits pigment synthesis and, stabilised in a cream, has the rare distinction among cosmetic brighteners of a placebo-controlled randomised trial: 50 melasma patients, 4 months, significant lightening versus placebo (Mansouri 2015, BJD). Randomised comparisons found it roughly equivalent to hydroquinone (2020 trial) and to a hydroquinone–vitamin C combination (2022 trial), a 2024 meta-analysis pools the randomised evidence (meta-analysis), and a controlled study supports it for acne marks (PIH study). It is applied for 15 minutes and washed off, it smells of sulphur, it stings at first, and it is expensive; it is also one of the few things that competes with hydroquinone without being hydroquinone.

Niacinamide blocks the transfer of pigment packets from melanocytes to skin cells rather than pigment production, which is why it is gentle and why it layers with the tyrosinase inhibitors. In a double-blind, randomised split-face trial, 27 melasma patients applied 4% niacinamide to one side and 4% hydroquinone to the other for eight weeks: colorimetry showed no difference, good-to-excellent improvement was 44% with niacinamide against 55% with hydroquinone, and side effects were 18% versus 29% (Navarrete-Solís 2011); a 2025 randomised trial of a 10% nicotinamide combination against hydroquinone reached a similar place (2025 trial). The 4–5% concentration in the trials is the useful one; it also improved fine lines and blotchiness in the wrinkle literature. Slow, safe in pregnancy, and best as the second active in a routine rather than the only one.

Thiamidol (isobutylamido thiazolyl resorcinol) was designed against the human enzyme rather than the mushroom tyrosinase most brighteners were screened on, and it inhibits it more strongly than hydroquinone, kojic acid or arbutin in the laboratory. Clinically it has a randomised, double-blind, vehicle-controlled trial for facial hyperpigmentation (2025 RCT), an evaluator-blinded randomised comparison with 4% hydroquinone in melasma in which it held its own, and a controlled study showing effective reduction of post-inflammatory marks (PIH study). Its cousin 4-n-butylresorcinol has a similar, smaller evidence base (Kolbe 2013). Every trial is by the manufacturer, which caps it at moderate. Sold as Eucerin Anti-Pigment in Europe at pharmacy prices; a reasonable first over-the-counter brightener for sun spots and mild melasma.

Tranexamic acid, applied to the skin, damps the signalling between blood vessels, keratinocytes and melanocytes that drives melasma. The trials disagree on how much gets through: a double-blind study of 5% gel in Asian patients found lightening no different from vehicle (2012 trial), while a randomised comparison of oral against topical found MASI reductions of 59% and 51% respectively with no significant difference (2025 trial), and a 2026 meta-analysis of the tranexamic literature supports both routes with the oral one ahead (meta-analysis). Formulation decides penetration. A sensible over-the-counter add-on to azelaic acid or niacinamide, and a poor stand-alone; the tablets are the version with the consistent evidence.

Ascorbic acid interrupts pigment synthesis and reduces the oxidation that darkens it, and it has one direct comparison with the reference drug: 16 women with melasma, 5% ascorbic acid on one side and 4% hydroquinone on the other for 16 weeks, with good-to-excellent results in 62.5% against 93% — and fewer side effects on the vitamin C side (Espinal-Pérez 2004). A 2023 systematic review of topical vitamin C in melasma and photoaging finds small, heterogeneous studies with consistent modest benefit (systematic review). Its best role is under sunscreen in the morning, adding UV protection and slowing the re-darkening of treated skin; as a sole treatment for a visible spot it will disappoint.

Kojic acid (from fermentation), arbutin (a plant-derived hydroquinone precursor) and licorice extract (glabridin) all inhibit tyrosinase weakly. The best kojic data are as an add-on: in a randomised, single-blind comparison, kojic acid combined with hydroquinone outperformed the other combinations (2013 trial). An arbutin 5% plus kojic 2% cosmetic was not significantly different from the triple combination cream in a small split-face pilot (2025 pilot). Arbutin can release hydroquinone in the skin, which is why the EU's scientific committee reviewed it and the Commission limited alpha-arbutin to 2% in face creams and kojic acid to 1% in 2024 (Regulation 2024/996). Licorice has open-label data and a place in gentle routines. None of the three is a first choice; all are reasonable in a serum layered under azelaic acid or a retinoid.

Alpha-hydroxy acids exfoliate the pigmented upper layers and, over months, even out mottled tone. In the reference trial, 74 women used 8% glycolic acid, 8% lactic acid or vehicle for 22 weeks: on the forearms lactic acid significantly reduced mottled hyperpigmentation and sallowness and both acids improved overall photodamage over vehicle (Stiller 1996). Two cautions: acids increase sun sensitivity, so the sunscreen row is not optional, and in darker skin an acid used too often inflames and creates the post-inflammatory marks it was bought to fade. A few nights a week, low strength, and never the same night as a retinoid. Our peel guide covers the clinic strengths.

The extract of a Central American fern is an oral antioxidant that blunts UV damage in laboratory and small human studies. For melasma it has been tested twice as an adjunct to sunscreen: in a double-blind pilot in 33 Asian women, melasma severity fell 49% on the extract against 33% on placebo over 12 weeks, though instrumental melanin measures did not differ (Goh 2018), and an earlier randomised trial found it helped as an adjunct to sunscreen (JAMA Dermatology). It is not a sunscreen substitute — the protection factor is small — and the melasma effect is modest. A reasonable summer add-on for someone whose melasma relapses despite good sunscreen, and nothing more.

Glutathione shifts pigment synthesis toward the lighter pheomelanin, and oral supplements produce small, variable and transient lightening in the few controlled trials — the effect fades within months of stopping (2025 narrative review). The intravenous version, sold as a "whitening drip", has no established superiority over the oral route and a documented list of harms: liver failure in a proportion of reported cases, allergic reactions, anaphylaxis, and a 2019 FDA warning to compounding pharmacies after endotoxin-contaminated injections hospitalised patients. It also lightens the whole body rather than a spot, which is not what someone with three sun spots wants. Nothing here for a dark spot; a real hazard in a drip.

Citrus juice is the worst thing on the internet for a dark spot: lemon and lime carry furanocoumarins that react with UVA to produce a phototoxic burn — blisters, then dark pigment that can last years, and sometimes permanent white patches (University Hospitals; case report). Undiluted vinegar is acetic acid and causes chemical burns that darken as they heal. A systematic review of natural ingredients for hyperpigmentation found small trials supporting a handful of standardised extracts — licorice, soy, niacinamide-containing botanicals — and nothing for the kitchen cupboard (JCAD review). The natural remedy that works is shade.

Hydroquinone inhibits tyrosinase and is toxic to overactive melanocytes, and it is the drug every other brightener is compared with. The Cochrane review of melasma treatments — 20 randomised trials, 2,125 participants — found it effective and found the triple combination built around it more effective still (Cochrane 2010; abridged review). In the comparisons on this page it beats vitamin C, matches azelaic acid, cysteamine and niacinamide, and outperforms most cosmetics.

Europe treats it with respect: it is prohibited in cosmetics (Annex II of the Cosmetics Regulation) and available only on prescription, usually compounded at 2–4% or in the triple cream (regulatory summary). The reason is exogenous ochronosis — a permanent blue-black darkening after long use, especially above 2% and in darker skin — which a systematic review finds rare but real (ochronosis review). Used the way dermatologists use it — 12–16 weeks, then a break on a non-hydroquinone maintenance — it is the most effective cream for melasma there is. Used from an unlabelled pot for years, it is the cause of the next problem.

Kligman's formula pairs hydroquinone with tretinoin (which speeds pigment out and improves penetration) and a mild corticosteroid (which damps the irritation and the pigment-provoking inflammation). In the Cochrane review the triple combination was 1.58 times as likely to lighten melasma as hydroquinone alone and beat every dual combination (Cochrane review); a trial in Middle Eastern skin confirms efficacy and tolerability (2019 study). Marketed as Tri-Luma in some countries and compounded in others, it is prescription-only everywhere.

The relapse problem is the honest half of the story. Among patients who cleared and moved to a twice-weekly maintenance regimen, about half stayed clear at six months and the rest needed daily therapy again (maintenance study; maintenance regimens); earlier data found half needed a second course within two months. Melasma is treated in cycles, with an iron-oxide sunscreen doing the work in between, and the steroid is the reason it cannot be used continuously.

Tranexamic acid, a clotting drug used for heavy periods, damps the plasmin signalling that links UV, blood vessels and melanocytes in melasma, and taken by mouth it reaches all of it. In the double-blind randomised trial, 250 mg twice daily for three months reduced the modified MASI by 49% against 18% on placebo, with the severe cases improving most (Del Rosario 2018); a network meta-analysis puts the optimal dose at 250 mg three times daily for 12 weeks with twice daily acceptable (network meta-analysis); a 2024 meta-analysis of the randomised trials confirms the class effect (2024 meta-analysis). It is the largest single effect on melasma outside a clinic and it works alongside the creams. Our 30s guide grades it the same way.

Safety is about clots in theory and reassuring in practice: a multicentre propensity-matched cohort found no association between melasma-dose tranexamic acid and thromboembolism (2025 cohort), and the dose is comparable to the monthly dose used for heavy periods (DermNet). It is still contraindicated with a history of clots, clotting disorders, the combined pill in higher-risk women, and severe kidney disease, and it is off-label and prescription-only for melasma. Relapse follows stopping, as with everything else in this condition; repeat courses are usual.

Because estrogen and progesterone act directly on melanocytes, removing or reducing a hormonal trigger is part of every melasma plan — in principle. In practice the evidence is observational: melasma that began with a pill often improves after switching to a progestin-only or non-hormonal method, pregnancy melasma fades in most women within a year of delivery, and hormone therapy that provoked it can sometimes be continued at a lower dose or by a transdermal route (pathogenesis review). No trial randomises women off their contraception, so this stays emerging. Heat is the other trigger worth naming: cooks, sauna habits and hot yoga relapse, and the fix is a fan, not a cream.