Protection against ultraviolet-A and -B with systemic nicotinamide and Polypodium leucotomos extract-A narrative...

Keratinocyte cancers (KCs) are increasing in incidence, and ultraviolet radiation (UVR) remains the main environmental risk factor. While topical sunscreens are effective photoprotectants, imperfect use has led to interest in oral supplements. This narrative review summarizes wavelength-specific mechanisms of two widely studied oral agents-nicotinamide (NAM) and Polypodium leucotomos (PL), across UVB, UVA, and solar-simulated radiation (SSR), focusing on DNA damage, erythema, immunosuppression, inflammation, oxidative stress, and tumor development. A PRISMA-informed search of PubMed, Embase, and Cochrane (inception to 28 November 2025) identified 36 eligible studies (18 NAM; 18 PL), including in vitro, animal, and human models. For NAM, clinical data demonstrated reduced KC incidence in immunocompetent patients, while no consistent changes in UVR-induced cyclobutane pyrimidine dimers (CPDs) or minimal erythema dose (MED) were seen. In murine SSR models, NAM reproducibly delayed KC development, supporting effects downstream of initial DNA damage. In vitro, NAM reduced inflammation and oxidative stress and, in limited data, oxidative stress signaling following UVA. For PL, human studies more consistently reported reduced erythema and oxidative stress, whereas effects on DNA damage were heterogeneous and limited, particularly for UVA in humans. Across both agents, mechanistic and wavelength-specific evidence remains incomplete, and study heterogeneity in UVR sources and endpoints limits comparability. Future research should establish standardized methods for UVR exposure assessment and focus on outcomes that are clinically relevant, to determine if the molecular effects observed lead to in vivo photoprotection.