Nicotinamide (vitamin B3) prevents photocarcinogenesis in mice (Gensler et al., 1999) and photoimmunosuppression in humans (Damian, 2010). Actinic keratoses (AKs) strongly predict nonmelanoma skin cancer risk (Green and Battistutta, 1990). These phase II studies aimed to determine whether oral nicotinamide, at different doses, reduced AKs in sun-damaged individuals. Healthy, immune-competent volunteers with X4 palpable AKs (face, scalp and upper limbs) were recruited from Royal Prince Alfred Hospital Dermatology Clinics, Sydney, Australia. The study protocols(ACTRN12609000490279; ACTRN12610000689077; http://www. anzctr. org. au) adhered to Helsinki Guidelines and were approved by the Sydney South West Area Health Service and University of Sydney ethics committees. All volunteers provided written informed consent.

Participants were randomly assigned (1: 1) to take nicotinamide 500 mg (Nature’s Own, Virginia, Queensland, Australia) or matched placebo (Australian Custom Pharmaceuticals, Sydney, New South Wales, Australia) twice daily (Study 1) or once daily (Study 2) for 4 months. The treatment allocation sequence was determined by a computergenerated randomization list prepared using a permuted blocks method (block size 6) by an investigator (DLD) not involved in AK assessment. Participants underwent complete skin examination before randomization, were encouraged to use daily sunscreen, and remained blinded throughout the study. At baseline, 2 and 4 months, palpable AKs were identified visually and by touch by a blinded observer (DS),