Nicotinamide Cuts Skin Cancer Risk by Up to 54% in Large Veterans Study

Skin cancer is the most common malignancy in the United States, and identifying safe, affordable chemopreventive agents is a major clinical priority. Nicotinamide (vitamin B3 amide) has shown promise in smaller randomized trials, but large real-world data have been lacking. This study aimed to fill that gap using one of the largest health systems in the country.

Researchers conducted a retrospective cohort study using electronic health records from the Veterans Affairs (VA) Corporate Data Warehouse, spanning October 1999 to December 2024. A total of 33,822 patients were analyzed. Those exposed to nicotinamide 500 mg twice daily for more than 30 days (n=12,287) were propensity score matched to unexposed controls (n=21,479), balancing for age, sex, race, prior skin cancer burden, acitretin use, field therapy, chronic lymphocytic leukemia history, and solid organ transplant status. Stratified Cox proportional hazards models assessed time to next skin cancer after the index date.

The matched cohort was predominantly older White male veterans (mean age ~77 years; ~95% White; ~98% male), reflecting the VA population. Overall, nicotinamide use was associated with a statistically significant 14% reduction in skin cancer risk. Strikingly, when nicotinamide was initiated after a patient's first skin cancer diagnosis, the risk reduction reached 54%. This protective effect diminished progressively as nicotinamide was started after subsequent skin cancers, suggesting that earlier intervention yields the greatest benefit. Risk reductions were observed for both basal cell carcinoma and cSCC, with cSCC showing the largest effect size.

Among the 1,334 solid organ transplant recipients in the cohort (3.9% of matched patients), no statistically significant overall risk reduction was observed with nicotinamide. However, early initiation of nicotinamide in this subgroup was associated with reduced cSCC incidence, hinting that timing of treatment may matter even in this immunosuppressed population.

The proposed mechanism involves nicotinamide replenishing cellular NAD+ stores depleted by UV-induced DNA damage, thereby enhancing DNA repair capacity and reducing immunosuppression caused by UV radiation. The study's large scale and real-world design strengthen the external validity of prior randomized controlled trial findings. Limitations include the retrospective design, the predominantly older White male VA population limiting generalizability, potential confounding despite propensity matching, and inability to verify adherence. Nonetheless, the results provide compelling evidence that nicotinamide—an inexpensive, well-tolerated supplement—may meaningfully reduce skin cancer incidence, especially when prescribed early in a patient's skin cancer history.