Evidence on Nicotinamide for High-Risk Non-Melanoma Skin Cancers

Nicotinamide offers various photoprotective and anti-inflammatory effects, and phase III evidence now supports its ability to reduce non-melanoma skin cancers and actinic keratoses in high-risk patients, according to a recent review article published in the journal Experimental Dermatology.

“Theoretically, nicotinamide may be able to protect against UV-induced immune suppression and possibly skin cancer development. However, the jury may still be out,” said Jerry D. Brewer, MD, MS, a professor of dermatology at the Mayo Clinic in Rochester, Minnesota, in an interview with Cancer Network.

Researchers examined the role of nicotinamide, a water-soluble vitamin B3 derivative that reduces ATP levels and inhibits glycolysis, thereby preventing an energy crisis. They found that randomized controlled clinical trials have demonstrated that nicotinamide limits transepidermal water loss and the growth of non-melanoma skin cancer in high-risk individuals.

In addition, they found that patients with normal renal function tolerate nicotinamide well with minimal, if any, side effects, even at doses of about 1 g daily. However, diarrhea was reported among patients on hemodialysis-especially those taking phosphate binders.

Patients with end-stage renal disease experienced thrombocytopenia when taking nicotinamide, and they should therefore be monitored for this event. To reverse thrombocytopenia, nicotinamide therapy should be stopped. Rarely, nicotinamide can cause hepatotoxicity at dosages higher than 3 g/d, the researchers found.

Lastly, the authors described the first phase III study demonstrating the ability of oral nicotinamide to reduce skin cancer incidence in immune-competent patients at high risk for skin cancer (at least 2 non-melanoma skin cancers in the previous 5 years). Conducted in 2015, Chen et al randomized a total of 386 adults to receive either 500 mg nicotinamide twice daily or placebo.

Chen et al found that, after 1 year, the incidence of new non-melanoma skin cancer was reduced by 23% (P = .02) in patients who received oral nicotinamide vs placebo. Nicotinamide also reduced the number of basal cell carcinomas and squamous cell carcinomas by 20% (P = .12) and 30% (P = .05), respectively.

“The future of NAM [nicotinamide] as a photoprotective agent is promising, with this paper highlighting its positive safety profile and showing evidence supporting its utility in those patients at high risk for the development of non-melanoma,” the authors concluded.

Brewer noted that the phase III trial evidence may not be as promising as it sounds. “Although a phase III trial demonstrated nicotinamide as effective in reducing skin cancer development, particularly in high risk individuals, a Bayesian analysis performed later suggested that the evidence was insufficient and the outcomes might not be reproducible,” he explained.

“Having said that, nicotinamide is relatively safe, and if there is a chance it could help, particularly in immunosuppressed patients that are burdened with high volumes of skin cancer, it might not hurt to take it until more evidence is available,” he concluded.