By Suherman Candra Maholtra 
A comprehensive study involving more than 33,000 patients within the Veterans Affairs (VA) health system has provided robust new evidence regarding the efficacy of nicotinamide, a form of vitamin B3, in preventing non-melanoma skin cancers. The research, led by experts from the Vanderbilt University Medical Center and the VA Tennessee Valley Healthcare System, suggests that early intervention with this widely available supplement could drastically reduce the incidence of new skin cancer diagnoses, particularly among individuals who have recently experienced their first occurrence of the disease. This finding marks a pivotal moment in dermatological preventative care, offering a potential shift in how clinicians manage patients at risk for basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (SCC).
The Evolution of Nicotinamide in Preventative Dermatology
The medical community’s interest in nicotinamide as a chemopreventive agent began to gain significant momentum nearly a decade ago. In 2015, the results of the Oral Nicotinamide to Reduce Actinic Cancer (ONTRAC) clinical trial were published in the New England Journal of Medicine. That study, which followed 386 participants, demonstrated that a 500-milligram dose of nicotinamide taken twice daily reduced the rate of new non-melanoma skin cancers by approximately 23% compared to a placebo group.
While the 2015 findings were groundbreaking, the small sample size left many questions unanswered. Specifically, clinicians remained uncertain about the long-term efficacy of the supplement across diverse populations and whether the timing of the intervention—at what stage of a patient’s skin cancer history the supplement was introduced—impacted the final outcome.
Nicotinamide, also known as niacinamide, is a water-soluble amide of nicotinic acid. Unlike niacin (vitamin B3), nicotinamide does not cause the "flushing" or redness of the skin that often leads to poor patient compliance. Biologically, it serves as a precursor to nicotinamide adenine dinucleotide (NAD+), a coenzyme essential for cellular energy production. In the context of skin health, nicotinamide is believed to enhance DNA repair following ultraviolet (UV) radiation exposure and prevent the UV-induced immunosuppression that often allows skin cancers to take hold.
Overcoming Data Challenges Through the VA Health System
One of the primary obstacles in conducting large-scale longitudinal studies on supplements like nicotinamide is that they are available over the counter (OTC). Most patients purchase these vitamins at pharmacies or grocery stores without a prescription, meaning their use is rarely captured in standard electronic health records. This "data gap" has historically prevented researchers from analyzing the real-world impact of the supplement on tens of thousands of patients.
To circumvent this issue, the research team, led by corresponding author Lee Wheless, MD, PhD, utilized the Veterans Affairs (VA) Corporate Data Warehouse. The VA health system is unique because nicotinamide is listed on its official formulary. This means that for many veterans, the supplement is prescribed by their physicians and dispensed through the VA pharmacy system, creating a verifiable paper trail of dosage, duration, and patient adherence.
The researchers reviewed the records of 33,833 veterans. This massive cohort allowed for a level of statistical power that was previously unattainable. The study focused on patients who had received a baseline treatment of 500 milligrams of nicotinamide twice daily for a period exceeding 30 days. By comparing these individuals against a control group of more than 21,000 veterans who did not take the supplement, the team was able to track the subsequent diagnoses of basal cell carcinoma and cutaneous squamous cell carcinoma over an extended period.
Detailed Findings: The Power of Early Intervention
The results of the study, published in a recent medical journal, revealed a complex but encouraging picture of skin cancer prevention. Overall, the use of nicotinamide was associated with a 14% decrease in the risk of developing any new non-melanoma skin cancer. While this figure is lower than the 23% reported in the 2015 ONTRAC trial, the sheer scale of the VA study provides a more grounded estimate of the supplement’s impact in a broad, real-world population.
The most striking discovery, however, concerned the timing of the treatment. For patients who began taking nicotinamide immediately after their very first skin cancer diagnosis, the risk of developing a subsequent skin cancer plummeted by 54%. This suggests a "golden window" for intervention where the supplement is most effective at stabilizing the skin’s cellular environment before cumulative damage leads to a cycle of recurring tumors.
Interestingly, the study found that this protective benefit began to diminish as the patient’s history of skin cancer became more extensive. For those who had already developed multiple skin cancers before starting the supplement, the degree of risk reduction was less pronounced. This suggests that while nicotinamide is a powerful tool for prevention, it may not be as effective at reversing the advanced "field cancerization" seen in patients with decades of severe sun damage and dozens of prior malignancies.
The researchers also noted that the supplement’s effect was strongest against cutaneous squamous cell carcinoma (SCC). SCC is the second most common form of skin cancer and has a higher potential for metastasis (spreading to other parts of the body) compared to basal cell carcinoma. The ability of a simple vitamin supplement to specifically target the more aggressive of the two common non-melanoma cancers has significant implications for reducing the overall morbidity associated with the disease.
The Impact on Immunocompromised Populations
A secondary focus of the study involved 1,334 patients who were immunocompromised, primarily due to solid organ transplants. Transplant recipients are at a vastly increased risk for skin cancer—sometimes up to 100 times higher than the general population—because the immunosuppressive drugs required to prevent organ rejection also inhibit the body’s ability to detect and destroy cancerous skin cells.
In this specific subgroup, the overall reduction in skin cancer risk did not reach statistical significance. This indicates that for those with severely suppressed immune systems, nicotinamide alone may not be enough to counter the aggressive development of tumors. However, the data did show a trend toward fewer cases of squamous cell carcinoma in transplant patients who began nicotinamide early in their post-transplant course. This suggests that while the supplement may not be a "silver bullet" for the immunocompromised, it could still serve as a valuable component of a multi-faceted preventative strategy.
Shifting Clinical Guidelines and Practice
The findings from Dr. Wheless and his colleagues are expected to spark a reevaluation of clinical guidelines for skin cancer prevention. Currently, there is no universal standard for when a dermatologist should recommend nicotinamide to a patient. Many clinicians wait until a patient has become a "high-frequency" producer of skin cancers—someone who returns every few months for new biopsies—before suggesting the supplement.
"These results would really shift our practice from starting it once patients have developed numerous skin cancers to starting it earlier," said Dr. Wheless. "We still need to do a better job of identifying who will actually benefit, as roughly only half of patients will develop multiple skin cancers."
The study suggests that the "wait and see" approach may be counterproductive. By the time a patient has developed five or ten skin cancers, the preventative efficacy of nicotinamide appears to wane. By moving the intervention to the point of the first diagnosis, healthcare providers may be able to prevent the progression toward chronic skin cancer development.
Broader Implications for Public Health and Economics
Beyond the clinical benefits, the widespread adoption of nicotinamide for skin cancer prevention carries significant economic implications. Non-melanoma skin cancers are the most common cancers in the United States, with millions of cases diagnosed annually. The cost of treating these cancers—involving surgical excisions, Mohs micrographic surgery, and follow-up care—amounts to billions of dollars each year for the healthcare system.
Nicotinamide is an exceptionally low-cost intervention. A monthly supply of the supplement often costs less than ten dollars. If even a fraction of the 54% risk reduction observed in the VA study can be replicated in the general population through early intervention, the potential savings in surgical costs and healthcare resources would be astronomical. Furthermore, because nicotinamide has a high safety profile with minimal side effects, it represents a low-risk, high-reward strategy for public health.
The study also highlights the importance of the VA health system as a powerhouse for medical research. By maintaining integrated, long-term data on a large and often high-risk population, the VA allows researchers to answer public health questions that private sector data, which is often fragmented and short-term, cannot address.
Future Research and Limitations
While the VA study provides the largest data set to date on nicotinamide, researchers acknowledge that further work is needed. The veteran population is predominantly male and often has higher rates of occupational sun exposure compared to the general public. Future studies will need to confirm if the 54% risk reduction for early-intervention patients holds true across more diverse demographics, including women and younger populations.
Additionally, the research team is interested in exploring the biological reasons why the supplement’s effectiveness decreases after multiple cancers have occurred. Understanding the molecular "tipping point" where nicotinamide can no longer adequately support DNA repair could lead to the development of even more potent chemopreventive agents or combination therapies.
The work of Dr. Wheless and his team at Vanderbilt and the VA was supported by a Department of Veterans Affairs grant (IK2CX002452). The collaborative effort involved experts in dermatology, medicine, and data science, including Katyln Knox, Rachel Weiss, Siwei Zhang, PhD, Lydia Yao, MS, Yaomin Xu, PhD, and Kyle Maas.
As the medical community digests these findings, the message for patients and dermatologists is clear: when it comes to skin cancer prevention with nicotinamide, earlier is likely better. For the millions of people diagnosed with their first skin cancer each year, this simple B3 vitamin may offer a powerful shield against the recurrence of the disease, provided the intervention begins at the very start of their journey.
