The lack of a consistent increase in pheomelanin levels in skin, measured as the oxidation product AHP, following melanotan-1 therapy is intriguing. Only two subjects demonstrated a >50% increase in pheomelanin levels. Subject No. 1 demonstrated a substantial increase in pheomelanin expression after melanotan-1 without UV exposure, and subject No. 7 experienced a significant increase only after receiving both melanotan-1 and UV-B light exposure. Thus, only one subject, No. 1, experienced a significant increase in pheomelanin levels after receiving only melanotan-1. Of interest, this subject responded similarly to UV-B light exposure with a doubling of pheomelanin, after receiving 3 MED of simulated UV-B light.

Since only individuals with Type III or IV skin were studied in the current trial, no conclusions can be extended to subjects with other skin types, and an important question is whether melanotan-1 could preferentially enhance eumelanin expression in Type I redheaded individuals with a predominance of pheomelanin expression. The recent finding of altered genes for the melanocortin-1 receptor (MC-IR) in many such redheaded or fair-skinned individuals with auburn colored hair (30) suggests that experiments to determine melanotan-1 binding and signal transduction in the epidermal melanocytes of such individuals should be performed. These studies may determine whether melanotan-1 therapy could be used therapeutically to switch melanin production from pheomelanin to eumelanin and thereby, induce a photoprotective tan. This has obvious potential as a skin cancer prevention strategy (31).

Melanotan promotes eumelanin production only.

In fact, for those of us who only produce pheomelanin, Melanotan will override this process in favor of eumelanin.