Abstract
Nicotinamide has been widely promoted as a low-cost safe chemopreventive agent against non-melanoma skin cancer. A recent large retrospective study of more than 33,000 US veterans reported a 14% reduction in overall skin cancer risk and a 22% reduction in cutaneous squamous cell carcinoma with nicotinamide use, with greater benefit observed when initiated early. This critical appraisal identifies key methodological limitations of that study, including unmeasured confounders, immortal time bias, exposure misclassification, flexible analytical modelling and limited external validity. The findings are discussed in the context of two recent systematic reviews (2022 and 2023) to provide a balanced appraisal of the evidence and clarify whether nicotinamide should be recommended in routine practice. Current evidence does not yet confirm the chemopreventive efficacy of nicotinamide. Caution is warranted before its widespread clinical adoption-the jury, as it stands, is still out.