BACKGROUND: Nonmelanoma skin cancers, such as basal-cell carcinoma and 
squamous-cell carcinoma, are common cancers that are caused principally by 
ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have 
protective effects against damage caused by UV radiation and to reduce the rate 
of new premalignant actinic keratoses.
METHODS: In this phase 3, double-blind, randomized, controlled trial, we 
randomly assigned, in a 1:1 ratio, 386 participants who had had at least two 
nonmelanoma skin cancers in the previous 5 years to receive 500 mg of 
nicotinamide twice daily or placebo for 12 months. Participants were evaluated 
by dermatologists at 3-month intervals for 18 months. The primary end point was 
the number of new nonmelanoma skin cancers (i.e., basal-cell carcinomas plus 
squamous-cell carcinomas) during the 12-month intervention period. Secondary end 
points included the number of new squamous-cell carcinomas and basal-cell 
carcinomas and the number of actinic keratoses during the 12-month intervention 
period, the number of nonmelanoma skin cancers in the 6-month postintervention 
period, and the safety of nicotinamide.
RESULTS: At 12 months, the rate of new nonmelanoma skin cancers was lower by 23% 
(95% confidence interval [CI], 4 to 38) in the nicotinamide group than in the 
placebo group (P=0.02). Similar differences were found between the nicotinamide 
group and the placebo group with respect to new basal-cell carcinomas (20% [95% 
CI, -6 to 39] lower rate with nicotinamide, P=0.12) and new squamous-cell 
carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). The number of actinic 
keratoses was 11% lower in the nicotinamide group than in the placebo group at 3 
months (P=0.01), 14% lower at 6 months (P<0.001), 20% lower at 9 months 
(P<0.001), and 13% lower at 12 months (P=0.001). No noteworthy between-group 
differences were found with respect to the number or types of adverse events 
during the 12-month intervention period, and there was no evidence of benefit 
after nicotinamide was discontinued.
CONCLUSIONS: Oral nicotinamide was safe and effective in reducing the rates of 
new nonmelanoma skin cancers and actinic keratoses in high-risk patients. 
(Funded by the National Health and Medical Research Council; ONTRAC Australian 
New Zealand Clinical Trials Registry number, ACTRN12612000625875.).