BACKGROUND: Ultraviolet (UV) radiation can profoundly suppress the cutaneous 
immune system, thus enhancing carcinogenesis. Agents that prevent UV-induced 
immunosuppression may thus reduce skin cancer. Nicotinamide (vitamin B3) 
prevents UV-induced immunosuppression and carcinogenesis in mice, and 
solar-simulated (ss) UV-induced immunosuppression in humans. Its effectiveness 
against different UV wavebands and mechanism of action is as yet unknown.
OBJECTIVES: To determine the effects and mechanisms of topical nicotinamide on 
UV-induced suppression of delayed type hypersensitivity (DTH) responses in 
humans.
METHODS: Healthy Mantoux-positive volunteers in four randomised, double-blinded 
studies were irradiated with solar-simulated (ss)UV (UVB + UVA) or narrowband 
UVB (300 nm) or UVA (385 nm). Topical nicotinamide (0.2% or 5%) or its vehicle 
were applied immediately after each irradiation. Mantoux testing was performed 
at irradiated sites and adjacent unirradiated control sites 48 h after the first 
irradiation and measured 72 h later. Immunosuppression was calculated as the 
difference in Mantoux-induced erythema and induration at test sites compared to 
control sites. Human keratinocyte cell cultures, with and without ssUV and 
nicotinamide, were used for quantitative real-time reverse 
transcriptase-polymerase chain reaction assessment of TP53 and enzymes that 
regulate oxidative phosphorylation.
RESULTS: Nicotinamide cooperated with ssUV to increase enzymes involved in 
cellular energy metabolism and p53, and significantly protected against 
immunosuppression caused by UVB, longwave UVA and single and repeated ssUV 
exposures.
CONCLUSIONS: Longwave UVA, which is poorly filtered by most sunscreens, was 
highly immune suppressive even at doses equivalent to 20 min of sun exposure. 
Nicotinamide, which protected against both UVB and UVA, is a promising agent for 
skin cancer prevention.