Nicotinamide delivers for skin cancer prevention

Treatment with the over-the-counter vitamin B3 derivative nicotinamide can lower the risk of new skin cancers, and this risk reduction is greater for cutaneous squamous cell carcinoma (cSCC) and when treatment is initiated after the first skin cancer, according to a large retrospective study.

Compared with unexposed patients, those who took nicotinamide 500 mg twice daily for longer than 30 days had a 14-percent lower risk of developing new skin cancers (hazard ratio [HR], 0.86, 95 percent confidence interval [CI], 0.82–0.89). [JAMA Dermatol 2025;doi:10.1001/jamadermatol.2025.3238]

Looking at the risk of skin cancer types, a 22-percent reduction was observed for cSCC (HR, 0.78, 95 percent CI, 0.75–0.82) but none for basal cell carcinoma (BCC) (HR, 1.00, 95 percent CI, 0.96–1.05).

The risk reduction was greatest, at approximately 50 percent, when nicotinamide was initiated soon after the first skin cancer diagnosis (overall: HR, 0.44, 95 percent CI, 0.39–0.49; cSCC: HR, 0.47, 95 percent CI, 0.41–0.55; BCC: HR, 0.51, 95 percent CI, 0.43–0.59). This protective effect diminished when nicotinamide was initiated after each subsequent skin cancer.

In the subset of solid organ transplant recipients, the overall risk of skin cancers did not significantly differ between nicotinamide-exposed and -unexposed patients (HR, 1.02, 95 percent CI, 0.84–1.25). However, early nicotinamide use (ie, after 1 or 2 skin cancers) was associated with reduced cSCC incidence (HR, 0.47, 95 percent CI, 0.23–0.97). 

“Our results aligned with the risk estimates previously reported that showed a 30-percent to 50-percent reduction in the risk of skin cancer… Timing of treatment was a crucial variable in our study, with patients experiencing benefit only when initiated after the first few skin cancers and then a gradual attenuation of the protective effect,” the investigators said. [N Engl J Med 2015;373:1618-1626; N Engl J Med 2023;388:804-812; J Cutan Med Surg 2022;26:297-308]

“While there is some evidence suggesting that nicotinamide could potentiate cancer growth and metastasis, our data did not support this concern. Rather, our results argued that earlier initiation of chemoprevention with nicotinamide might yield better results,” they added. [Biosens Bioelectron 2023;220:114826]

For the study, the investigators used data from the Veterans Health Administration Corporate Data Warehouse. They established a propensity-score matched cohort of 12,287 patients (mean age 77.2 years, 2 percent female, 94.9 percent White) exposed to oral nicotinamide and 21,479 unexposed patients (mean age 76.9 years, 2 percent female, 95.3 percent White). Matching was performed according to the number and year of skin cancers, exposure to acitretin and field therapy, history of chronic lymphocytic leukaemia, and history of solid organ transplantation.

In the overall cohort, 1,334 patients (3.9 percent) were recipients of solid organ transplant, and roughly 84 percent had been exposed to some type of field treatment. A total of 10,994 BCC and 12,551 cSCC cases were documented after nicotinamide exposure.

Prompt vitamin B3 supplementation

The present study adds to the growing body of literature supporting early nicotinamide initiation for the secondary prevention of skin cancers, noted Dr Sara Arron from the Palo Alto Foundation Medical Group, Palo Alto, California, US, in an accompanying editorial. [JAMA Dermatol 2025;doi:10.1001/jamadermatol.2025.3237]

“The medication is widely available and has minimal adverse effects so long as patients are properly counselled to buy the amide form rather than niacin (nicotinic acid),” Arron said. However, she pointed to the lack of evidence to suggest whether vitamin supplementation is preferable to getting vitamin B3 from foods such as poultry, beef, fish, legumes, and nuts.

Arron emphasized that nicotinamide should be used as part of a “multimodal approach to skin cancer prevention” that includes sun protection, skin cancer education, and topical and photodynamic therapies. An ideal time to recommend nicotinamide is after the first skin cancer diagnosis, when patients may be most receptive to the information, she said. “Another opportunity for counselling is during skin cancer surgery or in the postoperative information packet.”