What causes pigmentation?
Responsible for providing color to our skin, hair, and eyes, melanin is an essential, naturally produced pigment that our body–and most organisms— is constantly producing. Our natural skin tone is largely accredited to our genetically determined melanin production rate, which vastly varies across ethnicities. Inhabitants of regions with more intense UV radiation have evolved to develop genetic mutations that increase their melanin production and thus have darker skin tones, whereas people in lower UV regions have lighter skin tones. The process of melanin production—otherwise known as melanogenesis—entails the conversion of tyrosinase—a natural enzyme—into melanin.
(ResearchGate)
How does UV radiation influence melanin production?
As a defense mechanism against UV radiation, the skin initiates melanogenesis. Melanin then transfers to keratinocytes—the cell that produces keratin, an essential protein in the epidermis—where the melanin internally absorbs UV rays and reduces DNA damage. However, if the skin receives excessive exposure to UV radiation—without sun protection—the melanin will eventually fail to provide skin protection, leading to sun damage and, soon enough, hyperpigmentation. Although tyrosinase production is also largely influenced by genetics and exposure to UV radiation, tyrosinase and melanin production can be reduced by tyrosinase inhibitors.
What are tyrosinase inhibitors?
Whether found synthetically in ingredients like azelaic acid or naturally in ingredients like aloe vera, tyrosinase inhibitors are widely used to even out skin tone by blocking tyrosinase activity during catalytic reaction, thereby reducing melanin production and, in some cases, breaking down and degrading pre-existing melanin. Their versatility makes them a key component in the treatment of hyperpigmentation, melasma, and age spots. While different tyrosinase inhibitors function differently, they ultimately yield the same results—reduced melanin synthesis and a more even complexion. Here are some examples of tyrosinase inhibitors with varying potency.
Niacinamide: Although not technically a tyrosinase inhibitor, niacinamide Inhibits melanosome transfer—the process of turning melanin into a visible pigment. Niacinamide does not alter tyrosinase production, making it a more gentle alternative to typical tyrosinase inhibitors. It can be applied up to twice daily.
Azelaic acid: Inhibits tyrosinase and gently reduces pigmentation by targeting hyperactive melanocytes—cells that produce melanin. Azelaic acid is slightly more potent than niacinamide. It can be applied up to twice daily.
Hydroquinone: Directly inhibits tyrosinase and melanin synthesis. It can be used up to twice a day for 3-6 months as treatment for intense hyperpigmentation or melasma; to avoid irritation, it should not be used any longer, as it is highly potent.
Melanogenesis inhibitors are often confused with tyrosinase inhibitors, and although they yield similar results—reducing pigmentation—tyrosinase inhibitors are a subset of melanogenesis inhibitors, which differ in that they affect melanin synthesis as a whole rather than directly targeting tyrosinase. Alongside just targeting tyrosinase production, melanogenesis inhibitors also promote melanin degradation and target melanogenesis pathways, blocking melanin from transferring to keratinocytes.
Which inhibitor is better?
Although melanogenesis inhibitors target several steps in melanogenesis as opposed to directly targeting tyrosinase activity—as seen with tyrosinase inhibitors—that doesn’t necessarily mean that one is stronger or more effective than the other. In general, melanogenesis inhibitors are preferred for more gradual and long-term treatment for pigmentation, whereas tyrosinase inhibitors are stronger for more rapid pigmentation treatment and results. While both are effective in their own ways, combining these treatments with sun protection, exfoliants, and antioxidants ensures the best results for maintaining an even skin tone and treating hyperpigmentation.
Bibliography
Boissy, R. E. “Melanosome Transfer to and Translocation in the Keratinocyte.” Experimental Dermatology, vol. 7, no. 3, 1998, pp. 143-150. PubMed.
National Cancer Institute. “Melanocyte.” NCI Dictionary of Cancer Terms, n.d., [https://www.cancer.gov/publications/dictionaries/cancer-terms/def/melanocyte](https://www.cancer.gov/publications/dictionaries/cancer-terms/def/melanocyte#:~:text=(meh%2DLAN%2Doh%2D,contains%20the%20pigment%20called%20melanin.).
University of Rochester Medical Center. “What Is Skin Pigmentation?” Health Encyclopedia, n.d., https://www.urmc.rochester.edu/encyclopedia/content?contenttypeid=85&contentid=p01359.
Costin, G. E., and V. J. Hearing. “Human Skin Pigmentation: Melanocytes Modulate Skin Color in Response to Stress.” The FASEB Journal, vol. 21, no. 4, 2007, pp. 976-994. PMC.
Burkhart, C. G., and H. R. Burkhart. “Hydroquinone.” StatPearls, StatPearls Publishing, 2019. NCBI.
Pillaiyar, T., M. Manickam, and V. Namasivayam. “Skin Whitening Agents: Medicinal Chemistry Perspective of Tyrosinase Inhibitors.” Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 32, no. 1, 2017, pp. 403-425. PMC.
Chang, T. S. “Natural Melanogenesis Inhibitors Acting Through the Down-Regulation of Tyrosinase Activity.” International Journal of Molecular Sciences, vol. 10, no. 6, 2009, pp. 2440-2475. PMC.
Sasaki, M., K. Hasegawa, and Y. Takahashi. “Recent Advances in Skin Lightening Agents: A Comprehensive Review.” Journal of Dermatological Science, vol. 110, no. 1, 2023, pp. 12-24. PMC.