Nicotinamide Reduces New Skin Cancer Risk in Large Veteran Study

A commonly used vitamin supplement may offer meaningful protection against skin cancer, according to the largest study to date evaluating nicotinamide, a derivative of vitamin B3, in patients.

Researchers analyzing health records of more than 33,000 US veterans with a history of skin cancer found that oral nicotinamide was associated with a significant reduction in new skin cancers, particularly when started early in the disease course. The findings, published in JAMA Dermatology, add weight to previous smaller trials and could influence future prevention strategies.

Nicotinamide, unlike niacin, does not cause flushing and has been explored for its ability to support DNA repair and reduce ultraviolet-induced immune suppression. A phase 3 trial in 2015 showed reduced skin cancer rates with nicotinamide use in patients with prior disease,² prompting many dermatologists to recommend it. Yet, questions remained about its long-term benefits and real-world impact.

Now, the real-world, retrospective study showed that nicotinamide use was linked to a 14% reduction in new skin cancers compared with matched controls.¹ The protective effect was even stronger when supplementation began after a first skin cancer diagnosis, yielding a 54% reduction in risk. However, benefits diminished when nicotinamide was initiated after multiple prior cancers.

“Our results aligned with the risk estimates previously reported that showed a 30% to 50% reduction in risk of skin cancer,” explained the researchers. “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. However, most of these studies were randomized controlled trials, whereas ours was observational.”

As an observational study, it 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.

The researchers drew on data from over 12,000 veterans in the Veterans Affairs Corporate Data Warehouse who were prescribed nicotinamide 500 mg twice daily for at least 30 days and matched them to more than 21,000 unexposed controls. Patients were balanced for various factors including prior skin cancer history, age, race, field therapy exposure, and solid organ transplant status.

The primary end point was time to next skin cancer following baseline. Researchers tracked more than 23,000 new cancers during the follow-up period, including nearly 11,000 basal cell carcinomas (BCCs) and 12,500 cutaneous squamous cell carcinomas (cSCCs).

Type-specific analyses revealed the most robust benefit of nicotinamide against squamous cell carcinoma, with a 22% reduced risk, while the effect on basal cell carcinoma was weaker and statistically neutral in the overall group.

The supplement’s favorable safety profile further supports its 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.

“Beyond nicotinamide, other modalities exist for skin cancer prevention, although these are often not as well tolerated,” described the researchers. “Acitretin requires laboratory monitoring and is associated with dryness, lipid elevations, and less commonly birth defects, liver failure, and pseudotumor cerebri. Topical field treatments, including PDT and fluorouracil can be effective additions to skin cancer prevention, but can be painful, invasive, and require downtime.”

Among solid organ transplant recipients, who face extremely high skin cancer rates, nicotinamide did not significantly reduce overall risk. But in those who began treatment after only one or two cancers, the incidence of cSCC dropped by more than 50%, suggesting earlier intervention may be critical.

Importantly, the study also showed risk reduction in patients not receiving other preventive treatments, indicating that nicotinamide may provide unique added value.

The study’s population—predominantly White, older men—reflects the demographics of U.S. veterans and may not generalize fully to broader populations. Additionally, because nicotinamide is sold over the counter, some control patients may have taken it outside VA prescriptions, potentially underestimating the true effect.

References

1. 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

2. Chen AC, Martin AJ, Choy B, et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med. 2015;373(17):1618-1626. doi:10.1056/NEJMoa1506197