Linoleic acid in vivo showed the greatest lightening effect in UVB-induced pigmentation, without toxic effects on melanocytes (53). Several protease inhibitors caused the accumulation of an approximately 60 kDa tyrosinase doublet promoted the translation of the enzyme to melanosomes (60). The evidence suggests that tyrosinase in selectively targeted by fatty acids, which seem to act on the degradation of the enzyme during the physiologic proteasome-dependent mechanism (61). Linoleic acid accelerates the process whereas palmitic acid works in an antagonistic manner mimicking protease inhibitors (61).
In vitro experiments using cultured murine melanoma cells showed that melanin production was inhibited most effectively by alpha-linolenin acid, followed by linoleic acid and then by oleic acid. Furthermore, the turnover of the stratum corneum, which plays an important role in the removal of melanin pigment from the epidermis, was accelerated by linoleic acid and by alpha-linolenic acid (62). Topical application of linoleic acid is considered to be effective in the treatment of melasma patients (63).