The science behind hyperpigmentation [02/11/25]

Skin pigmentation is a complex biological process governed by specialised cells know as melanocytes, located in the basal layer of the epidermis. These cells synthesise melanin, the pigment responsible for the skin, hair and eye colour, and distribute it the surrounding keratinocytes. Melanin serves a protective role by absorbing ultraviolet radiation whilst also neutralising reactive oxygen species such as hydrogen peroxide, together both reducing the chances of skin cancer. 

However, when this usually tightly regulated system is dysregulated, hyperpigmentation can occur, characterised with darkened patches of skin. This phenomenon can result in UV exposure, inflammation, hormonal changes, or skin injury, which all trigger melanocytes to overproduce or unevenly distribute melanin. 

The biological basis of Hyperpigmentation 

Melanogenesis (melanin synthesis) begins with the amino acid tyrosine, which is converted to the DOPA amino acid and oxidated to become dopaquinone by the enzyme tyrosinase, the step which limits the rate of the pathway. This process is modulated by signalling molecules called alpha-melanocyte-stimulating hormone (α-MSH for short) and endothelin-1, which activate the MC1R receptor on melanocytes and upregulate MITF, a transcription factor controlling melanin-related genes. 

Environmental stressors such as UV radiation increase oxidative stress, stimulating further melanogenesis through p53 activation and increased tyrosinase expression. Inflammation can also contribute by releasing cytokines and prostaglandins that enhance melanin synthesis or transfer. 

How Niacinamide (Vitamin b3) Works 

Niacinamide is one of the most used topical agents for treating hyperpigmentation. Rather than directly inhibiting the synthesis of new melanin, niacinamide works by blocking the transfer of melanosomes, the vesicles which carry the pigment, from the melanocytes to the keratinocytes. 

By interfering with the PAR-2 [protease-activated receptor-2] signalling in keratinocytes niacinamide is able to reduce the pigment disposition in the epidermis, leading to a more even skin tone over time. Additionally, it has antioxidant and anti-inflammatory properties helping reduce UV-induce oxidative stress and post-inflammatory pigmentation. 

Other popular anti-hyperpigmentation agents include retinoids which accelerate epidermal turnover, dispersing existing pigment granules, vitamin C, which acts as a reducing agent, converting oxidised dopaquinone back to DOPA and proving antioxidant protection, and azelaic acid which inhibits tyrosinase and selectively targets hyperactive melanocytes making it useful for melasma and acne-related pigmentation. 

Sources:

• Ebanks J.P., Wickett R.R., Boissy R.E. (2009). Mechanisms Regulating Skin Pigmentation: The Rise and Fall of Complexion Coloration.  

• Desai S.R., Alexis A. (2014). Post‐inflammatory Hyperpigmentation: A Review of the Epidemiology, Pathogenesis, Clinical Features, and Treatment Options. 

• Pillai S., et al. (2022). Niacinamide for the treatment of melasma: an integrative review of randomised clinical trials. RSD Journal. 

• Kwak S.W., et al. (2023). Mechanistic Insights into the Multiple Functions of Niacinamide. 

• Kim J.E., et al. (2004). The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. 

• Practical Dermatology. (2021). Niacinamide: A Multi-functional Cosmeceutical Ingredient.