Does retinol help against pigmentation spots?

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.

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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.