In recent years, the pursuit of effective strategies to prevent skin cancer has gained significant momentum, particularly as the global incidence of this disease continues to rise. Among the various interventions investigated, nicotinamide, a derivative of vitamin B3, has emerged as a promising chemopreventive agent. Originally recommended by dermatologists in 2015 following a clinical trial with 386 participants, nicotinamide demonstrated a capacity to reduce the occurrence of new skin cancers among individuals with prior history. Despite these encouraging results, the broader validation of nicotinamide’s preventive potential in larger populations remained elusive, largely because the supplement’s over-the-counter availability leads to underreporting in medical records.
A groundbreaking study published on September 17, 2025, in JAMA Dermatology sheds new light on nicotinamide’s real-world effectiveness by leveraging the extensive Veterans Affairs Corporate Data Warehouse. This data repository contains comprehensive medical records, allowing researchers to track the usage of nicotinamide prescribed through the VA formulary and its impact on skin cancer diagnoses. By analyzing the medical histories of over 33,800 veterans, the research team sought to quantify the degree to which nicotinamide administration at a dose of 500 milligrams twice daily for more than 30 days influenced the incidence of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), the two most common forms of non-melanoma skin cancers.
The study cohort consisted of 12,287 patients who were treated with nicotinamide and 21,479 patients who were not. The comparison revealed a compelling overall 14% reduction in the risk of developing new skin cancers in those receiving nicotinamide. Significantly, the protective effect was substantially amplified among patients who initiated nicotinamide after their first skin cancer diagnosis, with risk reduction escalating to 54%. This suggests a potent role for nicotinamide in mitigating subsequent carcinogenic events if introduced early during the patient’s clinical course. The data also demonstrated that the benefit diminished when nicotinamide therapy was started following multiple skin cancer occurrences.
Delving deeper into the cellular pathology, the researchers observed that nicotinamide’s impact was particularly pronounced for squamous cell carcinoma. This subtype is known for its aggressive nature and propensity for metastasis, highlighting nicotinamide’s potential in addressing not only skin cancer prevention but potentially modifying progression risk. The biochemical basis for these effects resides in nicotinamide’s role in enhancing cellular energy metabolism, promoting DNA repair, and mitigating ultraviolet-induced immunosuppression, which collectively converge to inhibit carcinogenesis in epidermal tissues.
Despite these promising findings, clinical guidelines for nicotinamide initiation lack consensus, with recommendations varying widely. Dr. Lee Wheless, MD, PhD, assistant professor of Dermatology and Medicine at Vanderbilt University Medical Center and staff physician at the VA Tennessee Valley Healthcare System, emphasizes that the new evidence could catalyze a paradigm shift. According to Dr. Wheless, the data advocates for earlier prophylactic use of nicotinamide, potentially at the stage of the first skin cancer, rather than waiting for patients to accumulate multiple lesions. Nonetheless, there remains a critical need to refine patient selection, as nearly half of individuals with a history of skin cancer do not go on to develop multiple tumors, and thus may not derive equivalent benefit from chemoprevention.
The study also ventured into the nuanced domain of immunocompromised populations, specifically solid organ transplant recipients, who experience dramatically increased skin cancer risk attributable to lifelong immunosuppressive therapy. Among the 1,334 transplant patients assessed, nicotinamide did not yield a statistically significant reduction in overall skin cancer occurrence. However, there was an intriguing signal suggesting that early use of nicotinamide might reduce instances of cutaneous squamous cell carcinoma in this high-risk group. This finding warrants further exploration, as immunosuppression profoundly alters skin carcinogenesis pathways and may modulate the response to preventive interventions.
At the molecular level, nicotinamide serves as a precursor to nicotinamide adenine dinucleotide (NAD+), a pivotal coenzyme involved in redox reactions and crucial for energy production and cellular repair mechanisms. By replenishing NAD+ pools, nicotinamide enhances the capacity of keratinocytes to repair ultraviolet radiation-induced DNA damage, thereby preventing mutations that drive malignant transformation. Moreover, nicotinamide’s anti-inflammatory properties counteract UV-induced immunosuppression, preserving skin immune surveillance against emerging tumor cells.
The clinical implications of this research are far-reaching. If nicotinamide can indeed halve the risk of subsequent skin cancers when administered after the initial tumor, this intervention could significantly reduce the morbidity associated with repeated surgical excisions, healthcare costs, and the psychological burden borne by patients. Wider adoption of nicotinamide as a standard element of skin cancer preventive care could also fuel novel therapeutic avenues combining nutritional supplementation with established dermatological treatments.
It is important to note that the research was funded by the Department of Veterans Affairs and involved multidisciplinary collaboration among Vanderbilt University Medical Center researchers, including Katyln Knox, Rachel Weiss, Siwei Zhang, PhD, Lydia Yao, MS, Yaomin Xu, PhD, and Kyle Maas. Dr. Wheless received support from a VA grant (IK2CX002452), underscoring the institutional commitment to advancing skin cancer prevention in veteran populations.
Looking forward, unanswered questions remain regarding the optimal duration of nicotinamide therapy, potential long-term side effects, and whether specific genetic or phenotypic profiles can predict individual responsiveness. Additionally, the delivery method and dosage warrant optimization to balance efficacy and compliance. Future randomized controlled trials with broader, ethnically diverse cohorts could illuminate these facets and facilitate evidence-based clinical guidelines.
While nicotinamide’s accessibility as an over-the-counter supplement offers advantages in cost and convenience, it also poses challenges for tracking usage and outcomes outside formal healthcare systems. The innovative approach of analyzing electronic medical records, as demonstrated in the VA study, provides a powerful template for observational pharmacoepidemiology that could be extended to other nutritional and preventive interventions.
In summary, this landmark investigation illuminates nicotinamide’s significant potential to reshape skin cancer chemoprevention strategies. By facilitating early intervention, particularly after a first diagnosis, nicotinamide may alter disease trajectories, improve patient quality of life, and reduce the global burden of skin cancer. As the scientific community continues to unravel the complexities of skin carcinogenesis and host defense, nicotinamide stands out as a promising agent bridging nutritional biochemistry and clinical oncology.
Subject of Research: Skin cancer chemoprevention using nicotinamide
Article Title: Nicotinamide for Skin Cancer Chemoprevention
News Publication Date: 17-Sep-2025
Web References: JAMA Dermatology Article DOI
Image Credits: Vanderbilt University Medical Center
Keywords: Skin cancer, Nicotinamides, Chemoprevention, Basal cell carcinoma, Squamous cell carcinoma, Vitamin B3, Nicotinamide adenine dinucleotide, Dermatology, Veterans Affairs
Tags: basal cell carcinoma incidence reductionchemopreventive agents for skin cancerclinical trial results for nicotinamidedermatological research advancementsJAMA Dermatology study findingsNicotinamide skin cancer preventionover-the-counter supplements impact on healthpreventive strategies for skin cancerreal-world effectiveness of nicotinamideskin cancer incidence trendsVeterans Affairs health data analysisvitamin B3 efficacy in dermatology
