Research Desk · Skin whitening
Skin whitening products promise a lot. This guide keeps to what randomized trials, drug labels and regulators say about treating dark patches such as melasma, which agents were compared head to head, and what is and is not legal to buy in Canada and the United States. Every claim cites its source.
38% and 13%
Complete clearing at week 8 with the prescription triple cream, in its two label trials.9
65%
Good or excellent results with 20% azelaic acid in a 329-woman, 24-week trial.1
13th of 14
Where topical hydroquinone ranked against placebo in a 59-trial network meta-analysis.7
June 30, 2019
Date topical hydroquinone above 2% began requiring a prescription in Canada.1112
01 · What we reviewed
The trials on this page treated melasma or facial hyperpigmentation, meaning uneven dark patches on the face. We did not review evidence for lightening skin that is already evenly pigmented, and we do not make claims about it.
The AAD says sunlight, birth control pills and stress can trigger melasma, and it also lists pregnancy and certain medications as triggers.15 It may fade after a trigger ends, but it can also last for years or a lifetime.15 Results from treatment usually take 3 to 12 months.15
Trial scores use the Melasma Area and Severity Index (MASI), which one trial describes as a subjective scale.6 A lower score indicates improvement.5 Several trials below also used colour measurements.
02 · The evidence
Each row gives the trial we checked, what it found and the safety points its source reports. The right-hand column is not a ranking. These are different trials, with different patients, doses and lengths.
| Agent | Trial checked | What it found | Safety noted by the source |
|---|---|---|---|
| Triple creamHydroquinone 4%, tretinoin 0.05%, fluocinolone 0.01%. Prescription. | Two label trials, 641 subjects, 8 weeks, against its own two-ingredient components.9 | Complete clearing at week 8: 38% and 13% with the triple cream, against 15% and 4% for hydroquinone plus tretinoin. In the open-label extension only about 1 to 2% kept complete clearing.9 | For short-term use, not maintenance. Possible reversible adrenal (HPA axis) suppression and ochronosis. Tretinoin is a teratogen. Not studied in Fitzpatrick skin types V and VI.9 |
| Hydroquinone alone2% to 4% in the trials below. | Used as the comparison arm in the azelaic acid, niacinamide and tranexamic acid trials. Also pooled in a network meta-analysis of 59 trials.1237 | Ranked 13th of 14 treatments against placebo in the meta-analysis.7 A 2022 review still lists it among the most well-studied agents.8 | The FDA reports rashes, facial swelling and ochronosis, which may be permanent.10 Health Canada notes cancer in laboratory animals and possibly humans.11 |
| Azelaic acid 20% | Double-blind, 329 women, 24 weeks, against 4% hydroquinone. Both used a broad-spectrum sunscreen.1 | 65% good or excellent results with azelaic acid. No significant difference between the creams on overall rating, lesion size or pigment intensity.1 | No allergic sensitization or ochronosis observed.1 |
| Niacinamide 4% | Randomized split-face trial, 27 patients, 8 weeks, against 4% hydroquinone on the other side. Sunscreen throughout.2 | All patients improved on both sides and colour measures did not differ. Good to excellent improvement in 44% with niacinamide and 55% with hydroquinone.2 | Side effects in 18% with niacinamide against 29% with hydroquinone.2 |
| Topical tranexamic acid 5% | Randomized, single-blind, 100 patients, 12 weeks, against 3% hydroquinone cream.3 | MASI fell 27% with tranexamic acid and 26.7% with hydroquinone, not a significant difference. Patient satisfaction was higher with tranexamic acid.3 | The trial reported fewer adverse effects with tranexamic acid.3 Pooled across trials, the meta-analysis put topical tranexamic acid’s side-effect rate at 36.75%, against 18.2% for hydroquinone.7 |
| Cysteamine 5% | Double-blind, placebo-controlled, 50 patients, once daily for 4 months.4 | Final MASI 7.2 with cysteamine against 11.6 with placebo (P = 0.02). One author is affiliated with Scientis Pharma.4 | A 2022 review reports no known severe adverse effects, and says more trials are needed.8 |
| Thiamidol 0.2% | Randomized, double-blind, vehicle-controlled, 200 participants, 12 weeks.5 | mMASI fell 36.1% with thiamidol and 16.1% with vehicle. Patient global assessments and digital colour analysis showed no significant difference. One author is from Beiersdorf AG.5 | No significant adverse events in either group.5 |
| Topical vitamin C | We checked it only through the network meta-analysis, where it ranked 5th of 14 against placebo.7 | A 2022 review lists ascorbic acid as an effective adjuvant with minimal side effects.8 | Not assessed on this page. |
How to read this. A single trial that finds “no significant difference” does not prove two treatments are equal. These trials were mostly small, and they ran 8 to 24 weeks. The AAD says results usually take 3 to 12 months.15 The 2022 review says some studies had low sample sizes, and that recent larger studies with long-term follow-up are lacking.8
03 · Sun protection
In a double-blind trial, 68 patients with melasma were randomized to a sunscreen with iron oxide, which absorbs visible light, or a UV-only sunscreen, both SPF 50 or higher, for 8 weeks. Everyone also used 4% hydroquinone.6 Of the 61 who finished, the iron-oxide group improved 15% more on MASI, 28% more on colorimetry and 4% more on melanin assessment.6
The AAD recommends wide-brimmed hats, shade and broad-spectrum SPF 30 or higher sunscreen, and lists zinc oxide, titanium dioxide and iron oxide sunscreens, and tinted sunscreen, as options.15 For general sunscreen amounts and reapplication, see our sunlight and skin guide.
04 · Rules in Canada and the US
05 · Safety
Unauthorized creams.12
Health Canada says seized creams labelled with 4% hydroquinone may pose serious health risks, such as blisters, scarring, skin discolouration and possibly cancer. It advises people to stop using them and to consult a health professional.
Mercury.14
The WHO says mercury-containing skin lightening products are hazardous to health and banned in many countries, yet some are still advertised and available online.
Prescription products need a plan.911
Health Canada advises asking a pharmacist or doctor whether a hydroquinone product is right for you, using it only for the recommended time, applying sunscreen after each use, and stopping if dark spots worsen or irritation occurs. It says not to use it on children or during pregnancy or breastfeeding. The Tri-Luma label rates pregnancy risk as Category C and notes tretinoin is a teratogen.
Oral tranexamic acid is a doctor’s decision.15
The AAD says to tell your dermatologist if you have had a blood clot.
06 · What we could not confirm
Our DermaGlass® masks are hydrating skincare. They are not a lightening treatment, and this page makes no claim about them.
07 · Questions
Not above 2%. Health Canada says products containing more than 2% hydroquinone require a prescription from a health care practitioner, effective June 30, 2019. We did not find a Health Canada page that states what is allowed at or below 2% in a finished product, so ask a pharmacist. 1112
No. The FDA says there are no FDA-approved or otherwise legally marketed OTC skin lightening products. Tri-Luma is the only FDA-approved hydroquinone drug, and it is a prescription product. 10
In head-to-head trials, 20% azelaic acid, 4% niacinamide and 5% tranexamic acid each showed no significant difference from hydroquinone on the main measures. The trials were small to moderate, one was single-blind, and none settles the question alone. 123
The AAD says results usually take 3 to 12 months. Melasma may fade on its own after a trigger ends, but it can also last for years or a lifetime, and sun protection helps prevent it from returning. 15
In one randomized trial of 68 patients who all used 4% hydroquinone, a sunscreen containing iron oxide, which absorbs visible light, gave 15% greater MASI improvement at 8 weeks than a UV-only sunscreen. The AAD lists iron oxide, zinc oxide and titanium dioxide sunscreens, and tinted sunscreen, as options. 615
The AAD says oral tranexamic acid is used when other treatments fail, and to tell your dermatologist if you have had a blood clot. This is a prescription decision for a doctor, not something to buy online. 15
No. DermaGlass® is a hydrating mask for skin that looks hydrated and refreshed. We make no lightening claim for it, and nothing on this page is a claim about it.
Sources
Numbers in brackets link to these entries. Entries 1 to 8 were read as their PubMed abstracts; entries 9 to 15 were read on the page linked. The date shown is the one the source gives.
All sources across the Research Desk are collected, by page, in the master source list.
This page is general health information from the Vanu Health Research Team. It is not medical advice and does not replace a conversation with a doctor or pharmacist. Last updated October 29, 2026.