Nicotinamide May Reduce Risk of Skin Cancer

Lee Wheless, MD, PhD, Vanderbilt University Medical Center, Nashville, Tennessee, discusses a retrospective study which found an association between nicotinamide exposure and a reduced risk of skin cancer, with the greatest risk reduction for cutaneous squamous cell carcinoma (cSCC).

Transcript:

My name is Lee Wheelis and I'm an assistant professor of dermatology and epidemiology at Vanderbilt University Medical Center and the Tennessee Valley Healthcare System, VA Medical Center.

Nicotinamide is a form of vitamin B3 that has been used for skin cancer chemoprevention since roughly 2015, when a clinical trial of about 400 patients showed that there was a 23% reduction in the number of new skin cancers. The group who did this followed up with a study in a really high-risk population of solid organ transplant recipients in 2023, and while that study had several issues, they found that there was no difference in the number of new skin cancers in patients taking nicotinamide versus not. And so, this really kind of threw some confusion into the dermatology population as to, does nicotinamide work at all? That was one of the reasons why we wanted to look at this.

In our study, Nicotinamide for Skin Cancer Chemoprevention, we included a cohort of just over 33,000 veterans, including over 12,000 who had been exposed to nicotinamide for at least 30 days, and we found that there was overall a 14% reduction in the rate of development of new skin cancers among patients exposed to nicotinamide compared to those not exposed to nicotinamide. This was found for both squamous cell and basal cell carcinomas.

When we stratified by the number of prior skin cancers however, we found that there was the greatest benefit when started after earlier numbers of skin cancers — such that when starting after the first skin cancer, there was a 54% reduction in the rate of overall skin cancer development and a 53% reduction in the rate of cutaneous squamous cell carcinoma in particular. With each subsequent skin cancer, this benefit decayed until there was really no benefit of taking nicotinamide when starting after 7 or 8 skin cancers.

We did look specifically at organ transplant recipients, and while we did not find an overall benefit among this high-risk population, we did find that solid organ transplant recipients who started nicotinamide after 1 or 2 skin cancers did have roughly a 50% decreased rate of development of new cutaneous squamous cell carcinomas. It was difficult to get good power in this group, because most of the transplant patients started after a high number of skin cancers. And so, if we were to believe the rest of the data, this is already a population that is not going to be seeing much of a benefit.

Based off our findings, you would think that the recommendation then would be to start nicotinamide on everybody after that first skin cancer, and I think it's a little premature to jump to that conclusion. From prior work that I've done with a couple collaborators, pooling 5.5 million skin cancer patients together, what we found was that only about 40% of patients are going to be developing another skin cancer within roughly 10 years after that first skin cancer. And so that means that about 60% of skin cancer patients aren't going to be seeing a reduced risk of new skin cancers after that first skin cancer. On the flip side, in that same study we saw that 3% of all skin cancer patients developed just an insanely high number of skin cancers and contributed 22% of all the skin cancers in the whole study.

And so what this means is that we have a great opportunity for personalized medicine if we can identify both the patients who are not going to be developing another skin cancer and really would not benefit from taking nicotinamide, but also identifying the patients who are going to be at very high risk of developing lots of skin cancers and would really, really benefit from taking nicotinamide. That would kind of be the goal and the next steps of our work.

Source:

Breglio KF, Knox KM, Hwang J, et al. Nicotinamide for Skin Cancer Chemoprevention. JAMA Dermatol. Published online September 17, 2025. doi: 10.1001/jamadermatol.2025.3238