Although harmless, brown spots can be a source of discomfort and frustration for many people in pursuit of an even complexion. However, retinol presents itself as one of the effective options to diminish the appearance of these stubborn marks. Here, we explain how retinoids work against this dermatological condition.
Retinol, a molecule that combats brown spots?
Summary
Published on April 22, 2025, by Stéphanie, PhD, Doctorate in Life and Health Sciences — 12 min of reading
Themes:
What are brown spots?
Pigmentation disorders , such as post-inflammatory hyperpigmentation, actinic lentigines, or melasma, are characterised by irregular macules ranging from light brown to grey-brown, which can appear anywhere on the body but are particularly common on the face and hands. This is the result of changes in various aspects of pigmentation, including an increased production and accumulation of melanin or irregular clumping of melanin in the epidermis or dermis .
While they can persist for months or even years, the precise cause of pigment spots remains unknown. However, intense exposure to UV rays, hormones (endogenous and exogenous), inflammatory diseases (acne, contact dermatitis, psoriasis, folliculitis, impetigo, etc.), familial predisposition, photosensitising medications, and endocrine dysfunctions have been identified as pathophysiological factors that could be involved in the pathogenesis of this common skin condition.
Using retinol to lighten pigmentation spots?
Generally challenging to treat, retinoids topicals (tretinoin, adapalene, tazarotene, etc.) apparently constitute a favourable option for lightening hyperpigmented lesions, without reducing the normal colour of the skin. Indeed, there are several pieces of evidence from clinical trials in favour of the continuous use of topical retinoids either as monotherapy or in conjunction with other topical depigmenting agents (azelaic acid, hydroquinone, etc.) in the treatment of pigmentation disorders. The results of these studies have shown effectiveness on the severity of the disease, the intensity of pigmentation and the surface area of the lesions.
| References | Participants | Treatments | Results |
|---|---|---|---|
| VOORHEES J. J. & others. (1993) - | 19 patients exhibiting melasma | 0.1% retinoic acid cream applied once daily for 40 weeks | Clinical lightening of melasma observed in 68% of patients after 24 weeks of treatment |
| VOORHEES J. J. & others. (1993) - | 24 adults with dark phototypes exhibiting moderate to severe hyperpigmented lesions due to acne, shaving irritation, eczema, ingrown hairs and folliculitis | 0.1% Tretinoin cream for 40 weeks | 92% of patients showed a significantly greater lightening with tretinoin than with the control from week 4 |
| BULGER L. & al. (2000) | 800 individuals with moderate to severe photo-damaged skin | 0.1% Isotretinoin cream applied once daily for 36 weeks | Significant reduction in facial, forearm, and hand pigmentation after just 12 weeks of treatment, increasing throughout the 36-week treatment period |
| GIBSON J. R. & al. (2001) - | 349 subjects exhibiting facial photodamage | Tazarotene cream at various concentrations (0.1%, 0.05%, 0.025%, and 0.01%) for 24 weeks | Reduction in melanin content in the epidermis over the course of 24 weeks of treatment |
| GIBSON J. R. & others. (2002) - | 542 patients exhibiting photodamage to the face | Tazarotene cream at varying concentrations (0.1%, 0.05%, 0.025%, and 0.01%) applied once daily for 24 weeks, followed by a 28-week open-label extension | Clinical improvement of hyperpigmentation at week 24, continuing with the ongoing treatment |
| PARSAD D. & al. (2002) | 31 Indian female patients (with skin phototype IV) exhibiting a clinical diagnosis of epidermal type facial melasma | 0.05% Retinoic Acid (Tretinoin) Cream versus 0.1% Adapalene Gel over a 14-week period | A reduction of 37% in the area and severity of melasma was observed in the retinoic acid group, compared to a 41% reduction in the adapalene group. |
| GRIFFITHS C. E. M. & et al. (2003) | 90 Caucasian patients aged between 18 and 85 years suffering from age spots | Adapalene gel at 0.1% or 0.3% once daily for 4 weeks, followed by twice-daily applications, if tolerated, up to 9 months | Lightening of senile lentigines was observed in 57% and 59% of patients treated with 0.1% and 0.3% adapalene, respectively, compared to patients treated with the control gel after 9 months of treatment |
| CALLENDER V. & et al. (2006) | 74 patients aged over 12 years, with phototypes III to VI, suffering from post-inflammatory hyperpigmentation caused by acne | 0.1% Tazarotene cream applied once daily for 18 weeks | Significant reduction in the overall severity of hyperpigmentation, intensity and surface area of hyperpigmented lesions after 18 weeks |
| LE GALL N. & al. (2010) | 180 patients aged over 12 years with post-inflammatory hyperpigmentation | 0.1% Tazarotene cream versus 0.3% Adapalene gel once daily for a 16-week treatment period | Significantly greater reduction in hyperpigmented lesions with tazarotene cream than with adapalene gel |
| TAYLOR S. C. & et al. (2012) | 33 patients, aged over 12 years, with phototypes IV to VI suffering from post-inflammatory hyperpigmentation caused by acne | 1.2% Clindamycin Phosphate Gel + 0.025% Tretinoin once daily for 12 weeks | Improvement in the overall severity of hyperpigmentation was observed in 33% of patients between the start of the study and week 12 |
| BHATT V. & al. (2019) | 766 Hispanic subjects aged between 11 and 50 years suffering from moderate to severe acne | 0.05% Tretinoin lotion applied once daily for 12 weeks | Gradual reduction in the severity of hyperpigmentation with treatment |
| GUÉNIN E. & al. (2020) - | 41 black patients aged over 9 years suffering from moderate to severe post-inflammatory hyperpigmentation facial lesions | 0.05% Tretinoin lotion applied once daily for 12 weeks | Overall improvement in the severity of hyperpigmentation in 58.5% of subjects after 12 weeks |
| HARRIS S. & et al. (2020) | 1,614 participants suffering from moderate to severe acne | 0.045% Tazarotene lotion over a period of 12 weeks | Improvement of hyperpigmentation sequelae associated with inflammation after 12 weeks of treatment |
What are the mechanisms that underpin these effects?
To induce skin depigmentation, retinoids trigger numerous structural modifications and histological changes. The depigmenting effects of topical retinoids involve theacceleration of epidermal cell renewal, meaning that keratinocytes differentiate more rapidly from the basal layer to the horny layer, which leads to a rapid loss of melanin pigment through epidermopoiesis. However, by modifying the horny layer, retinoids also facilitate the penetration of other depigmenting agents into the epidermis, when they are used in combination to optimise the depigmenting potential.
Another theory suggests that retinoids could induce a uniform dispersion/distribution of melanin granules within the keratinocytes. It has also been demonstrated that topical retinoids directly affect melanogenesis through the inhibition of the expression of the melanin-forming enzyme tyrosinase, as well as the TRP-1 and TRP-2 proteins, thereby interrupting melanin synthesis. It has also been suggested that they could modulate the epidermal melanin content through an indirect action on the keratinocytes. However, the fundamental mechanisms underlying the lightening effect of retinoids are not fully understood.
In the skin, the various retinoids are converted into retinoic acid, which is the active form.
Hyperpigmented Marks: How to Use Retinoids?
Thus, we can anticipate improvements in hyperpigmentation. However, it is crucial to apply retinoids as prescribed to further minimise the side effects (irritation, skin dryness, exacerbation of existing brown spots, flaking, etc.), to avoid any application during pregnancy and breastfeeding, to use a sunscreen daily, to use a pH-balanced cleanser and a non-comedogenic moisturiser after the retinoids, to start the retinoid treatment as early as possible unless contraindicated or there are tolerance issues, and to apply a moisturiser before the retinoid for those with sensitive skin without affecting its percutaneous absorption.
Sources
PAWELEK J. M. & al. Retinoic acid is a potent inhibitor of inducible pigmentation in murine and hamster melanoma cell lines. Journal of Investigative Dermatology (1990).
GRIFFITHS C. E. M. & al. Cellular, immunologic and biochemical characterization of topical retinoic acid-treated human skin. Journal of Investigative Dermatology (1991).
VOORHEES J. J. & al. An in vivo experimental model for effects of topical retinoic acid in human skin. British Journal of Dermatology (1993).
VOORHEES J. J. & al. Topical tretinoin (retinoic acid) therapy for hyperpigmented lesions caused by inflammation of the skin in black patients. New England Journal of Medicine (1993).
BULGER L. & al. Isotretinoin improves the appearance of photo-damaged skin: results of a 36-week, multicenter, double- blind, placebo-controlled trial. Journal of the American Academy of Dermatology (2000).
GIBSON J. R. & al. Tazarotene cream for the treatment of facial photodamage: a multicenter, investigator- masked, randomized, vehicle-controlled, parallel comparison of 0.01%, 0.025%, 0.05%, and 0.1% tazarotene creams with 0.05% tretinoin emollient cream applied once daily for 24 weeks. Archives of Dermatology (2001).
GIBSON J. R. & al. Efficacy of 0.1% tazarotene cream for the treatment of photodamage: a 12-month multicenter, randomized trial. Archives of Dermatology (2002).
PARSAD D. & al. Adapalene in the treatment of melasma: a preliminary report. Journal of Dermatology (2002).
GRIFFITHS C. E. M. & al. Assessment of adapalene gel for the treatment of actinic keratoses and lentigines: a randomized trial. Journal of the American Academy of Dermatology (2003).
CALLENDER V. & al. Tazarotene cream for postinflammatory hyperpigmentation and acne vulgaris in darker skin: a double-blind, randomized, vehicle-controlled study. Cutis (2006).
ORTONNE J.-P. Retinoid therapy of pigmentary disorders. Dermatologic Therapy (2006).
LE GALL N. & al. Randomized comparison of the safety and efficacy of tazarotene 0.1% cream and adapalene 0.3% gel in the treatment of patients with at least moderate facial acne vulgaris. Journal of Drugs in Dermatology (2010).
TAYLOR S. C. & al. Efficacy and safety of clindamycin phosphate 1.2% and tretinoin 0.025% gel for the treatment of acne and acne-induced post-inflammatory hyperpigmentation in patients with skin of color. Journal of Clinical and Aesthetic Dermatology (2012).
BHATT V. & al. Novel tretinoin 0.05% lotion for once-daily treatment of moderate-to-severe acne vulgaris in a hispanic population. Journal of Drugs in Dermatology (2019).
GUENIN E. & al. Tolerability of tretinoin lotion 0.05% for moderate to severe acne vulgaris: a post hoc analysis in a black population. Cutis (2020).
HARRIS S. & al. Novel polymeric tazarotene 0.045% lotion for moderate-to-severe acne: Pooled phase 3 analysis by race/ethnicity. Journal of Drugs in Dermatology (2020).
