Journal September 26, 2026 6 min read

What does the research say about hyperpigmentation?

Hyperpigmentation is a broad term for acquired darkening of the skin. This page summarises registered clinical studies and case reports on melasma, post-inflammatory hyperpigmentation, and related pigmentary conditions,

peptides-pro Editorial

Hyperpigmentation is the acquired excess of melanin in the skin, producing dark spots or uneven tone. It is not a single disease but a clinical sign with many causes. The most studied forms are melasma, an acquired symmetric facial hyperpigmentation that occurs more often in females and darker skin types [7], and post-inflammatory hyperpigmentation (PIH), an acquired hypermelanosis that follows cutaneous inflammation or injury and frequently affects darker-skinned individuals [8]. Other presentations include facial dark spots such as pimple marks, sunspots, and age spots [3]. The condition is common: hyperpigmentation represents the most frequent complaint in dermatology clinics [12].

At the cellular level, the work centres on melanocytes and the tyrosinase enzyme, which catalyses a rate-limiting step in melanin synthesis. Agents studied for hyperpigmentation typically aim to reduce melanocyte activity or interrupt melanosome production and transfer [12].

Research Studies

Kojic acid and melanin synthesis inhibition in hyperpigmentation

Kojic acid is a natural hypopigmenting agent. A review describes hyperpigmentation as a multifaceted process involving overproduction and uneven distribution of melanin, and notes that treatment focuses mainly on melanocyte reduction and stopping melanosome production [12]. The same review discusses delivery challenges and nanotechnology-based strategies for kojic acid [12]. Kojic acid also appears as one component of a multi-agent topical regimen in a registered study of PIH in skin of colour [4].

Curcuma xanthorriza Roxb. and tyrosinase inhibition in melasma

Curcuma xanthorriza Roxb., a native plant of Indonesia, operates by inhibiting the tyrosinase enzyme and reducing MITF transcription [5]. A registered clinical study is evaluating a 10% cream of this plant for melasma [5]. The study background notes that hydroquinone is the first-line depigmentation agent for melasma but that its use often leads to adverse effects, and that alternative depigmentation agents are needed [5]. Melasma therapy remains challenging because of its high recurrence rate and the common occurrence of treatment-related side effects [5].

Bakuchiol and post-inflammatory hyperpigmentation

Bakuchiol is derived from plants and has inhibitory effects on melanin synthesis, which makes it a promising candidate for PIH management [8]. A registered study aims to evaluate the efficacy of bakuchiol in treating PIH using a previously validated model, in comparison to acne-induced PIH [8].

Retinal and azelaic acid in blemish-prone skin with post-inflammatory hyperpigmentation

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

Glycolic, lactic, kojic acid, vitamin C, and emblica in a comprehensive regimen for PIH

A single-centre, prospective, non-blinded, non-randomized 12-week clinical study is evaluating the efficacy of a comprehensive skin care regimen in the reduction of PIH in skin of colour patients [4]. The regimen features a pigment balancing peel that combines glycolic acid, lactic acid, kojic acid, vitamin C, and emblica [4]. Participants supplement the peel with an 11-week regimen that includes a hydrating B5 gel, a discoloration defence product, an LHA cleansing gel, and a brightening UV defence sunscreen [4].

Oral tranexamic acid combined with 1064-nm Q-switched fractional laser for melasma

Melasma is a common acquired condition of symmetric hyperpigmentation, typically occurring on the face, with higher prevalence in females and darker skin types [7]. Treatments include topical, oral, procedural, and combination approaches [7]. The 1064-nm Q-switched laser is one of the most widely used lasers for pigmented diseases in recent years; this wavelength is effectively absorbed by pigment, leading to damage of pigment and melanocytes [7]. A registered clinical observation study is evaluating 1064-nm Q-switched fractional laser combined with oral tranexamic acid for melasma [7].

Zinc-containing sunscreen and post-surgical scar hyperpigmentation

A randomized split-wound study is investigating the influence of sun protection on the aesthetic outcome of post-surgical scars following reconstruction of Mohs micrographic surgery defects via linear repair [6]. Half of the wound is treated with zinc-containing sunscreen and the other half is not [6]. Three months post-surgery, the scar is evaluated with the patient observer scar assessment scale (POSAS) and a colorimeter to measure vascularity and hyperpigmentation between treated and non-treated areas compared with surrounding skin [6].

Oziva Bioactive Gluta Fizzy effervescent tablets and facial hyperpigmentation

A randomized, double-blinded, single-centre, two-arm, placebo-controlled, prospective study is evaluating the clinical safety, efficacy, and in-use tolerability of Oziva Bioactive Gluta Fizzy effervescent tablets in subjects with facial hyperpigmentation and dark spots [3]. The study population includes subjects with facial dark spots such as pimple marks, sunspots, and age spots, and uneven skin tone [3].

Setmelanotide and melanocortin 4 receptor signalling in monogenic obesity

Setmelanotide is a melanocortin 4 receptor (MC4R) agonist [2]. It has been studied in people with rare monogenic obesity conditions affecting the leptin-melanocortin signalling pathway, including proprotein convertase subtilisin/kexin type 1 (PCSK1) gene mutations [2]. A case report describes a 40-year-old female with a heterozygous PCSK1 N221D (c.661 A>G) variant leading to severe early-onset treatment-resistant obesity, with previous suboptimal response to bariatric surgery and conventional obesity medications, who achieved a total weight loss of 11.8% with setmelanotide [2]. This work concerns obesity, not hyperpigmentation, and is included here only because MC4R signalling is part of the melanocortin pathway.

Setmelanotide in Bardet-Biedl syndrome after paediatric kidney transplantation

Bardet-Biedl syndrome (BBS) is a genetically heterogeneous ciliopathy associated with hyperphagic obesity and kidney disease [1]. Evidence on setmelanotide after paediatric kidney transplantation is limited [1]. A report evaluated two children with BBS treated with setmelanotide after kidney transplantation, collecting anthropometric, hunger, metabolic, graft-function, cyclosporine, and genetic data [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]. Patient 2, an 8-year-old girl, was also described [1]. As with the PCSK1 report, this work concerns obesity and not hyperpigmentation.

Comparison of selected registered studies

Study	Population	Intervention	Design
NCT07162623 [3]	Facial hyperpigmentation and dark spots	Oziva Bioactive Gluta Fizzy effervescent tablets	Randomized, double-blinded, placebo-controlled
NCT06938815 [4]	Skin of colour with PIH	Comprehensive regimen including pigment balancing peel	Single-centre, prospective, non-blinded, non-randomized, 12 weeks
NCT06153134 [5]	Melasma	Curcuma xanthorriza Roxb. 10% cream	Registered clinical study
NCT06833996 [8]	PIH	Bakuchiol	Registered clinical study
NCT05074238 [6]	Post-surgical scars after Mohs micrographic surgery	Zinc-containing sunscreen vs no sunscreen	Randomized split-wound
NCT03963466 [7]	Melasma	1064-nm Q-switched fractional laser plus oral tranexamic acid	Clinical observation

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