Journal September 27, 2026 6 min read

Common misconceptions about hyperpigmentation

Hyperpigmentation is an umbrella term for acquired disorders in which melanin is overproduced or unevenly distributed in the skin. This page reviews what registered research studies and case reports actually measured, an

peptides-pro Editorial

What hyperpigmentation actually is

Hyperpigmentation is not a single diagnosis. It is an umbrella term covering acquired disorders in which melanin is overproduced or unevenly distributed in the skin, and the literature treats each subtype as a separate condition with its own pathogenesis. Melasma is described as an acquired hyperpigmentation disorder with a multifactorial etiology and complex pathogenesis [5]. Post-inflammatory hyperpigmentation (PIH) is described as an acquired hypermelanosis occurring after cutaneous inflammation or injury, and it is reported to affect darker-skinned individuals frequently [8]. The general process is described as involving the overproduction and uneven distribution of melanin, with treatment approaches focused mainly on melanocyte reduction and on stopping melanosome production [12].

The mechanistic work in this area centres on the tyrosinase enzyme and on MITF transcription, the two nodes most commonly named in the depigmentation literature: Curcuma xanthorriza Roxb. is described as operating by inhibiting tyrosinase and reducing MITF transcription [5], and kojic acid is reviewed as a natural hypopigmenting agent with the same general target [12].

Research Studies

Bakuchiol and post-inflammatory hyperpigmentation in a validated model

Bakuchiol is derived from plants and has inhibitory effects on melanin synthesis, which is the stated rationale for testing it in PIH [8]. A registered study aims to evaluate the efficacy of bakuchiol in treating post-inflammatory hyperpigmentation using the investigators' previously validated model, in comparison to acne-induced PIH [8]. This is a study design, not a reported result.

Curcuma xanthorriza Roxb. 10% cream and melasma

Hydroquinone is described as the first-line depigmentation agent for melasma, but its use is reported to often lead to adverse effects, which is the stated reason alternative agents are sought [5]. A registered trial evaluates a Curcuma xanthorriza Roxb. 10% cream for melasma, on the basis that the plant inhibits tyrosinase and reduces MITF transcription [5]. Melasma therapy is described as challenging because of a high recurrence rate and the common occurrence of treatment-related side effects [5].

Kojic acid, glycolic acid, lactic acid and vitamin C in a multi-agent regimen for PIH

A registered 12-week study evaluates a comprehensive skin care regimen for reduction of PIH in skin of colour patients [4]. The regimen features a pigment balancing peel combining glycolic acid, lactic acid, kojic acid, vitamin C, and emblica, supplemented with a hydrating gel, a discoloration product, a cleansing gel, and a brightening sunscreen [4]. The study is single-centre, prospective, non-blinded and non-randomised [4].

Oral glutathione in effervescent form and facial dark spots

A randomised, double-blinded, single-centre, two-arm, placebo-controlled, prospective study evaluates the clinical safety, efficacy and in-use tolerability of an effervescent glutathione product in subjects with facial hyperpigmentation and dark spots, including pimple marks, sunspots, age spots and uneven skin tone [3]. The outcome measures are clinical safety, efficacy and in-use tolerability [3].

1064-nm Q-switched fractional laser combined with oral tranexamic acid in melasma

Melasma is described as a common acquired condition of symmetric hyperpigmentation, typically occurring on the face, with higher prevalence in females and darker skin types [7]. The 1064-nm Q-switched laser is described as one of the most widely used lasers for pigmented diseases in recent years, with the wavelength effectively absorbed by pigment, leading to damage of pigment and melanocyte [7]. A registered study evaluates this laser combined with oral tranexamic acid in melasma [7].

Zinc-containing sunscreen and post-surgical scar pigmentation

A randomised split-wound study examines the influence of sun protection on the aesthetic outcome of post-surgical scars after reconstruction of Mohs micrographic surgery defects via linear repair [6]. Half of each wound receives zinc-containing sunscreen and the other half does not; at three months the scar is assessed with the patient observer scar assessment scale and with a colorimeter measuring vascularity and hyperpigmentation in the treated and untreated areas compared with surrounding skin [6].

Retinal and azelaic acid in blemish-prone skin

Blemish-prone skin is described as driven by follicular hyperkeratinization, excessive sebum production, microbial dysbiosis and inflammation, often accompanied by post-inflammatory erythema and hyperpigmentation [11]. An eight-week randomised prospective split-face, vehicle-controlled study assessed a novel anhydrous 0.1% retinal and 10% azelaic acid concentrate in this population, with retinal and azelaic acid described as established topical actives with complementary mechanisms of action [11].

Setmelanotide and MC4R agonism in monogenic obesity

Setmelanotide is a melanocortin 4 receptor (MC4R) agonist studied as a pharmacological treatment option for rare monogenic obesity conditions affecting the leptin-melanocortin signalling pathway, including proprotein convertase subtilisin/kexin type 1 (PCSK1) gene mutations [2]. In a reported case, a 40-year-old female with a heterozygous PCSK1 N221D (c.661 A>G) variant, severe early-onset treatment-resistant obesity, and previous suboptimal response to bariatric surgery and conventional obesity medications achieved a total weight loss of 11.8% with setmelanotide [2]. This is a single case report in a heterozygous PCSK1 population, not a pigmentation study.

Setmelanotide after paediatric kidney transplantation in Bardet-Biedl syndrome

Bardet-Biedl syndrome is a genetically heterogeneous ciliopathy associated with hyperphagic obesity and kidney disease, and evidence on setmelanotide after paediatric kidney transplantation is described as limited [1]. Two children with BBS were evaluated after kidney transplantation, with anthropometric, hunger, metabolic, graft-function, cyclosporine and genetic data collected [1]. Patient 1, a 17-year-old boy with a homozygous pathogenic SDCCAG8 exon deletion, improved over 12 months: weight 55.6 to 48.0 kg, BMI 26.6 to 23.0 kg/m², BMI-for-age z-score +1.60 to +0.43, maximal-hunger score 8/10 to 5/10, and HbA1c 6.5% to 5.1% [1].

Measure	Patient 1, baseline	Patient 1, 12 months
Weight	55.6 kg	48.0 kg
BMI	26.6 kg/m²	23.0 kg/m²
BMI-for-age z-score	+1.60	+0.43
Maximal-hunger score	8/10	5/10
HbA1c	6.5%	5.1%

Where the evidence is animal-only or in vitro

Several of the mechanistic claims above are not clinical findings. The tyrosinase-inhibition and MITF-transcription mechanism attributed to Curcuma xanthorriza Roxb. is the stated rationale for a registered trial rather than a reported clinical outcome [5]. The inhibitory effect of bakuchiol on melanin synthesis is likewise the stated basis for a registered study, not a reported result [8]. The review of kojic acid as a natural hypopigmenting agent covers biological activities, delivery challenges and nanotechnology-based strategies, which is a formulation and mechanism literature rather than a clinical efficacy literature [12].

If you are reading this for personal health reasons

The materials described on this page are supplied for laboratory research use only. We do not provide dosing information, treatment protocols, or medical guidance of any kind. Anyone considering a compound or procedure for their own skin or health should speak to a licensed clinician.