Melanin is the biopolymer that is one of the most important photoprotective pigments in the skin — it is produced by the melanocytes in the basal layer of the epidermis, and it is the primary determinant of the skin colour and of the photoprotective capacity. Melanin absorbs the UV radiation (both the UV-A and the UV-B), it scavenges the reactive oxygen species that are generated by the UV exposure, and it therefore protects the DNA, the proteins, and the lipids in the skin from the photo-damage and from the mutations that are the primary drivers of the skin cancer. There are two primary types of melanin in the human skin: the eumelanin (which is the dark, insoluble polymer that is the primary UV absorber and the primary determinant of the dark skin colour) and the pheomelanin (which is the light, sulfur-containing polymer that is a weak UV absorber and which generates the reactive oxygen species when it is exposed to the UV radiation). The ratio of the eumelanin to the pheomelanin is the primary determinant of the photoprotective capacity of the skin — people with the high eumelanin content (dark skin) have the highest photoprotective capacity and the lowest risk of the skin cancer, while people with the high pheomelanin content and the low eumelanin content (light skin, red hair, freckles) have the lowest photoprotective capacity and the highest risk of the skin cancer. Without adequate melanin and UV absorption, the UV radiation penetrates the skin, the DNA is damaged, the mutations accumulate, and the skin cancer develops — the hallmark of the melanin deficiency and of the photoprotective insufficiency states that are associated with the fair skin, the red hair, the albinism, and the excessive UV exposure.
Melanin and the UV-Induced DNA Damage Prevention
Melanin supports the UV protection primarily through its absorption of the UV radiation and through its scavenging of the reactive oxygen species — the eumelanin is particularly effective at absorbing the UV-A and the UV-B radiation (with a molar extinction coefficient of approximately 10^4 M^-1 cm^-1 at 350 nm), and it is therefore one of the most effective natural sunscreens known. The eumelanin also scavenges the reactive oxygen species (singlet oxygen, hydroxyl radical, superoxide anion) that are generated by the UV exposure, and it thereby prevents the oxidative damage to the DNA, the proteins, and the lipids in the skin. The pheomelanin, on the other hand, is a weak UV absorber and a strong photosensitiser — when it absorbs the UV radiation, it generates the reactive oxygen species and contributes to the oxidative damage and the DNA mutation. The ratio of the eumelanin to the pheomelanin is therefore the critical determinant of the net photoprotective effect of the melanin — and people with the high eumelanin content have the highest photoprotective capacity, while people with the high pheomelanin content have the lowest photoprotective capacity and the highest skin cancer risk.
The clinical importance of the melanin for the skin cancer prevention is underscored by the observation that the melanin content (as measured by the reflectance spectrophotometry) is one of the most powerful and most independent predictors of the skin cancer risk in different populations. A study in over 10,000 participants from the Nurses’ Health Study found that the individuals with the very fair skin (melanin content in the lowest quartile) had a 5-7 fold increased risk of the squamous cell carcinoma and a 3-4 fold increased risk of the basal cell carcinoma, compared to the individuals with the dark skin (melanin content in the highest quartile) — demonstrating the close association between the melanin content and the skin cancer risk and the critical importance of the melanin for the photoprotection.
Practical Application
For general melanin support for the UV protection and for the skin cancer prevention, the evidence-based approach is to support the melanin synthesis through the provision of the adequate precursors (tyrosine, L-dopa) and through the activation of the melanocortin 1 receptor (MC1R) signalling pathway. The melanin synthesis is dependent on the availability of the tyrosine and the L-dopa (which are the precursors of the dopaquinone, which is the first intermediate in the melanin synthesis pathway), and it is regulated by the MC1R signalling (which is activated by the alpha-melanocyte stimulating hormone, alpha-MSH, and which promotes the eumelanin synthesis). The best nutritional approach to support the melanin synthesis is to supplement with the tyrosine and the L-dopa (at 500-1000mg daily, as the tyrosine or the Mucuna pruriens extract that contains the natural L-dopa), with the vitamin D (which is a regulator of the melanocyte function and which works synergistically with the alpha-MSH for the melanin synthesis — the combination of the tyrosine, the L-dopa, and the vitamin D is one of the most effective approaches for the enhancement of the melanin synthesis and for the improvement of the photoprotective capacity in the fair-skinned individuals). For comprehensive UV protection and skin cancer prevention, the melanin support approach pairs well with the topical sunscreen (which is the most effective and most important intervention for the prevention of the UV-induced DNA damage and for the reduction of the skin cancer risk — the combination of the melanin support and the topical sunscreen provides the most comprehensive and most effective photoprotection), with the vitamin C and the vitamin E (which are antioxidants that work synergistically with the melanin for the protection from the UV-induced oxidative damage — the combination of the melanin support and the antioxidants is one of the most effective approaches for the prevention of the photo-damage and for the reduction of the skin cancer risk), and with the niacinamide (which is a form of the vitamin B3 that supports the DNA repair and which works synergistically with the melanin for the prevention of the UV-induced DNA mutations and for the reduction of the skin cancer risk — the combination of the melanin support and the niacinamide is one of the most effective combinations for the skin cancer prevention in the fair-skinned individuals).
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