Hyperpigmentation Care

The potential targets for the depigmenting and hyperpigmentation control agents include inhibitors of melanocyte stimulation, tyrosinase enzyme inhibitors, inhibitors of melanosome transfer, and degraders of formed melanin in keratinocytes. The widely targeted approach includes the inhibition of tyrosinase, most important rate-limiting enzyme of the melanogenesis pathway (1).

Glutathione

Glutathione, a powerful antioxidant found within cells, plays a vital role in many physiological functions and now is getting recognized as a skin-lightening agent. It reduces hyperpigmentation by inhibiting the tyrosinase enzyme, blocking its activity, and interfering with melanin synthesis. It promotes phaeomelanin synthesis. Additionally, glutathione’s antioxidant properties scavenge free radicals and protect against UV-induced damage. It also offers benefits such as wrinkle reduction, improved skin brightness, and anti-aging effects (2).

N-Acetyl L-Cysteine (NAC)

Glutathione (GSH) is not easily absorbed when taken orally due to the action of an intestinal enzyme called γ-glutamyl transpeptidase (GGT). To increase GSH levels, a strategy is to use N-acetylcysteine (NAC), a precursor to cysteine. Cysteine is essential for GSH synthesis. Studies have shown that NAC is well absorbed by the intestine and supplementation with NAC effectively raises GSH levels (3, 4).

ELLAGIC ACID

Ellagic acid has both anti-fibrosis and antioxidant properties. It works by inhibiting the production of melanin, which is responsible for skin pigmentation, through its effect on an important enzyme called tyrosinase. When ellagic acid is taken orally, it has been found to have a skin-lightening effect on mild sunburn. In an animal study, ellagic acid was administered orally and showed a dose-dependent effect in reducing the number of melanocytes in the skin’s outer layer. Furthermore, when humans were given orally administered pomegranate extract rich in ellagic acid, it demonstrated a protective effect against mild sunburn caused by exposure to UV radiation (5).

VITAMIN C:

Vitamin C, a powerful antioxidant, plays a crucial role in collagen synthesis, offers photoprotection, reduces melanin production, acts as a free radical scavenger, and modulates the immune system. By interacting with copper ions at the active site of tyrosinase, vitamin C inhibits its action, resulting in reduced melanin formation. Additionally, vitamin C aids in the regeneration of glutathione, converting oxidized glutathione back into its active form (6, 7, 8).

VITAMIN B12:

People with severe hyperpigmentation in different areas of their skin often suffer from Vitamin B12 deficiency. It is hypothesized that Vitamin B12 deficiency affects melanin synthesis and transfer of melanin between melanocytes and keratinocytes, resulting in hyperpigmentation (9).

Vitamin E:

Vitamin C works synergistically with vitamin E to protect the skin from oxidative damage. It plays an important role in photoprotection & also inhibits UV-induced free radical damage to the skin. By working together, vitamins C and E provide enhanced antioxidant protection and help maintain the health and integrity of the skin (10).

Lycopene:

Lycopene, a natural antioxidant, has been extensively studied for its ability to protect against ultraviolet radiation (UVR) and effectively scavenge reactive oxygen species (ROS). It has shown promise in reducing skin redness, improving skin appearance and pigmentation, and mitigating damage and aging caused by sunlight exposure. Lycopene-rich products can serve as internal sun protection and may have the potential as a nutraceutical for sun protection (11).

References

1. Nautiyal, A., & Wairkar, S. (2021). Management of hyperpigmentation: Current treatments and emerging therapies. Pigment cell & melanoma research, 34(6), 1000-1014.
2. Sonthalia, S., Daulatabad, D., & Sarkar, R. (2016). Glutathione as a skin whitening agent: facts, myths, evidence and controversies. Indian journal of dermatology, venereology and leprology, 82(3).
3. Schmitt, B., Vicenzi, M., Garrel, C., & Denis, F. M. (2015). Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: A comparative crossover study. Redox Biology, 6, 198-205.
4. Janeczek, M., Moy, L., Riopelle, A., Vetter, O., Reserva, J., Tung, R., & Swan, J. (2019). The potential uses of N-acetylcysteine in dermatology: a review. The Journal of Clinical and Aesthetic Dermatology, 12(5), 20.
5. Kasai, K., Yoshimura, M., Koga, T., Arii, M., & Kawasaki, S. (2006). Effects of oral administration of ellagic acid-rich pomegranate extract on ultraviolet-induced pigmentation in the human skin. Journal of nutritional science and vitaminology, 52(5), 383-388.
6. Sanadi, R. M., & Deshmukh, R. S. (2020). The effect of Vitamin C on melanin pigmentation–A systematic review. Journal of Oral and Maxillofacial Pathology: JOMFP, 24(2), 374.
7. Pullar, J. M., Carr, A. C., & Vissers, M. C. (2017). The roles of vitamin C in skin health. Nutrients, 9(8), 866.
8. Sitohang, I. B. S., Anwar, A. I., Jusuf, N. K., Arimuko, A., Norawati, L., & Veronica, S. (2021). Evaluating Oral Glutathione Plus Ascorbic Acid, Alpha-lipoic Acid, and Zinc Aspartate as a Skin-lightening Agent: An Indonesian Multicenter, Randomized, Controlled Trial. The Journal of Clinical and Aesthetic Dermatology, 14(7), E53.
9. Agrawala, R. K., Sahoo, S. K., Choudhury, A. K., Mohanty, B. K., & Baliarsinha, A. K. (2013). Pigmentation in vitamin B12 deficiency masquerading Addison’s pigmentation: A rare presentation. Indian Journal of Endocrinology and Metabolism, 17(Suppl1), S254.
10. Pullar, J. M., Carr, A. C., & Vissers, M. C. (2017). The roles of vitamin C in skin health. Nutrients, 9(8), 866.
11. Zhang, X., Zhou, Q., Qi, Y., Chen, X., Deng, J., Zhang, Y., Li, R., & Fan, J. (2023). The effect of tomato and lycopene on clinical characteristics and molecular markers of UV-induced skin deterioration: A systematic review and meta-analysis of intervention trials. Critical reviews in food science and nutrition, 1–20.