A comprehensive analysis of more than 33,000 US veterans has demonstrated that nicotinamide, a common vitamin B3 derivative, significantly reduces the risk of developing new skin cancers. The study, published in JAMA Dermatology, represents the largest real-world evaluation of nicotinamide's protective effects to date and could reshape skin cancer prevention strategies.
Researchers from Vanderbilt University Medical Center found that veterans prescribed nicotinamide experienced a 14% overall reduction in skin cancer risk compared to matched controls. The protective effect was dramatically enhanced when supplementation began after a first skin cancer diagnosis, yielding a 54% reduction in risk of developing subsequent cancers.
Strongest Protection Against Squamous Cell Carcinoma
The analysis revealed that nicotinamide's benefits varied by cancer type. Cutaneous squamous cell carcinoma showed the most robust response, with a 22% reduced risk among treated patients. The effect on basal cell carcinoma was weaker and statistically neutral in the overall group, though both cancer types showed some degree of protection.
"There are no guidelines for when to start treatment with nicotinamide for skin cancer prevention in the general population," said corresponding author Lee Wheless, M.D., assistant professor of Dermatology and Medicine at Vanderbilt University Medical Center. "These results would really shift our practice from starting it once patients have developed numerous skin cancers to starting it earlier."
Real-World Evidence Supports Clinical Trials
The veterans study drew on data from over 12,000 patients prescribed nicotinamide 500 mg twice daily for at least 30 days, matched against more than 21,000 unexposed controls. Researchers tracked more than 23,000 new cancers during the follow-up period, including nearly 11,000 basal cell carcinomas and 12,500 cutaneous squamous cell carcinomas.
These findings align with the groundbreaking 2015 ONTRAC phase-3 trial in Australia, which demonstrated that 500 mg of nicotinamide twice daily lowered the incidence of new non-melanoma skin cancers by about 23% over 12 months in 386 high-risk adults with prior skin cancers.
"Our results aligned with the risk estimates previously reported that showed a 30% to 50% reduction in risk of skin cancer," the researchers noted. "While these reports have been criticized for being underpowered, our study included more than 4 times the number of cases included in a recent systematic review and meta-analysis."
Timing Matters for Maximum Benefit
The study revealed that timing of nicotinamide initiation significantly impacts its effectiveness. Benefits diminished when supplementation was started after patients had already developed multiple prior cancers, suggesting that earlier intervention may be critical for optimal protection.
Among solid organ transplant recipients, who face extremely high skin cancer rates, nicotinamide did not significantly reduce overall risk. However, in those who began treatment after only one or two cancers, the incidence of cutaneous squamous cell carcinoma dropped by more than 50%.
Safety Profile Supports Widespread Use
Unlike systemic retinoids such as acitretin, which require monitoring and carry significant side effects, nicotinamide is inexpensive, well-tolerated, and available without a prescription. The supplement does not cause the flushing associated with niacin and has been explored for its ability to support DNA repair and reduce ultraviolet-induced immune suppression.
"Beyond nicotinamide, other modalities exist for skin cancer prevention, although these are often not as well tolerated," the researchers noted. "Acitretin requires laboratory monitoring and is associated with dryness, lipid elevations, and less commonly birth defects, liver failure, and pseudotumor cerebri."
Clinical Implications and Future Directions
The study's population—predominantly White, older men with an average age of 77—reflects the demographics of US veterans and may not generalize fully to broader populations. The researchers acknowledge that studies on a more diverse demographic are needed to confirm these results can be replicated more broadly.
"Nicotinamide, a simple vitamin B3 derivative, is showing real promise as a practical tool for skin cancer prevention," said Dr. Yousuf Mohammed, a Senior Research Fellow at the University of Queensland. "These findings highlight that timing matters; starting earlier may be the key to stronger protection."
The US spends more than $8 billion each year treating skin cancer, with $4.8 billion addressing non-melanoma types. The researchers emphasize that nicotinamide supplementation should not replace sun protection measures but could serve as an additional preventive strategy for high-risk patients.
As an observational study, the research cannot prove causation, though the consistency with prior randomized trials strengthens confidence in the results. The authors are planning a prospective clinical trial to confirm these findings and provide definitive evidence for clinical guidelines.
