Vitamin B3 Notches a Win for Skin Cancer Prevention

Risk of new lesions reduced by 54% in veterans who started drug after first skin cancer

Nicotinamide reduced skin cancer risk by 14% overall in patients with a history of nonmelanoma skin cancer.

The risk reduction increased to 54% when nicotinamide was started after a first skin cancer diagnosis.

More prospective studies are needed to confirm findings and identify patients most likely to benefit.

Patients with a history of using nicotinamide had a significantly lower risk of developing nonmelanoma skin cancer, particularly when starting treatment after a first skin cancer, a large retrospective cohort study showed.

Overall, nicotinamide use for more than 30 days after a skin cancer diagnosis was associated with a 14% reduction in the subsequent rate of skin cancers, increasing to 54% in patients who started nicotinamide after a first skin cancer. In the overall analysis, the rate of new cutaneous squamous cell carcinoma (cSCC) declined significantly but not the rate of basal cell carcinoma (BCC). Among patients who started nicotinamide after the first skin cancer diagnosis, nicotinamide reduced overall rate of new cancers, BCC, and cSCC.

Use of nicotinamide did not have a significant impact on skin cancer risk in a subgroup of solid-organ transplant recipients, reported Lee Wheless, MD, of Vanderbilt University Medical Center in Nashville, Tennessee, and co-authors in JAMA Dermatologyopens in a new tab or window.

"We've known for years that the risk of new skin cancer increases with each subsequent skin cancer, but all of [the prior] studies had still been treating skin cancer history as a binary outcome," Wheless told MedPage Today. "We instead matched on the number and timing of prior skin cancers and showed that patients experienced a greater benefit when starting nicotinamide after fewer skin cancers."

"We currently don't have formal guidelines as to when to treat with nicotinamide, though in certain high-risk populations, such as those with field cancerization, it has been suggested to start after the second skin cancer or later. These results suggest that maybe we need to broaden the scope of who needs earlier intervention, while also providing some pretty strong evidence that nicotinamide is in fact effective at reducing the risk of skin cancer."

A vitamin B3 derivative, nicotinamide, repairs ultraviolet (UV) light-induced DNA damageopens in a new tab or window and reduces UV-induced immunosuppression, fueling interest in its potential for chemoprevention of skin cancer. To date, clinical studies have produced generally favorable results but not without some exceptions.

A phase III randomized trialopens in a new tab or window showed fewer new skin cancers in patients with a history of skin cancer who took nicotinamide twice daily. The results led many dermatologists to prescribe nonprescription nicotinamide for skin cancer chemoprevention, particularly for patients at high risk. A nationwide surveyopens in a new tab or window of dermatologic surgeons showed that as many as three-fourths of respondents recommended nicotinamide for skin cancer prevention.

A phase III trial in solid-organ transplant recipientsopens in a new tab or window showed no reduction in skin cancer lesions with nicotinamide supplementation.

"While that study had a number of issues, it really led dermatologists to question whether [nicotinamide] was efficacious," said Wheless. "Using the [Veterans Affairs] population, we were able to assemble a cohort with roughly 50 times the number of patients exposed to nicotinamide as had been included in the [previous] trial, and with those numbers we were able to conduct far more granular analyses."

A subsequent smaller studyopens in a new tab or window involving transplant recipients showed a decrease in keratinocyte carcinomas at 1 and 2 years after starting nicotinamide. A recent systematic review and meta-analysisopens in a new tab or window of clinical trials involving a total of 552 patients showed a 50% reduction in skin cancer risk. Other studies have shown risk reductions of 30-50%, but have been criticized for being underpowered, Wheless and colleagues noted.

The current matched-cohort study involved electronic health record data from the Veterans Affairs Corporate Data Warehouse for 33,822 patients with a history of nonmelanoma skin cancer diagnosed from October 1999 through December 2024. One cohort comprised 12,287 patients with exposure to oral nicotinamide for at least 30 days after a skin cancer diagnosis. The cohorts were matched with respect to number and year of skin cancers, as well as a variety of demographic and clinical data, including exposure to acitretin, exposure to field therapy, history of chronic lymphocytic leukemia, and history of solid organ transplantation.

The cohorts had a mean age of about 77 and mean age of 67 at skin cancer diagnosis. Women accounted for 2% of patients in each cohort and whites for 95%. Median number of skin cancers before starting nicotinamide was three.

The primary outcome was time to next skin cancer after baseline. The results showed that nicotinamide was associated with significant improvement in skin cancer-free survival (P<0.001). Patients who started nicotinamide after as many as seven skin cancers benefitted from the treatment, and the magnitude of benefit diminished thereafter. Overall, nicotinamide was associated with a 14% reduction in the rate of new nonmelanoma skin cancers. The rate of cSCC was 22% lower in the nicotinamide arm, whereas the rate of BCC did not differ between groups.

An analysis of patients who started nicotinamide after their first skin cancer showed a 54% reduction in new skin cancers, including reductions of about 50% in BCC and cSCC.

The study population included 1,334 patients with a history of solid organ transplantation. Nicotinamide use did not have a significant association with new skin cancers in that subgroup.

Wheless recommends nicotinamide to his own patients, "though admittedly I think I've been starting it too late for most of them based on these findings. For high-risk patients like organ transplant recipients or patients with clinical evidence of field cancerization but only one or two skin cancers, it makes sense to start nicotinamide earlier. For patients who do not have these high-risk features, it's much harder to know at the outset who is going to develop lots more skin cancers and would benefit from nicotinamide versus who would not develop another skin cancer even without treatment."

More prospective studies are still needed to confirm the chemopreventive benefits of nicotinamide, said Wheless. Other studies are needed to define specific patient subgroups that are more likely to benefit from the treatment.

I always find it interesting that the word "Nicotinamide" is so similar to "Nicotine." There's a reason why:

Is Nicotinamide Related to Nicotine?

Yes, nicotinamide is related to nicotine, but they are distinct compounds with different properties and uses. Both are derived from the same chemical family, sharing a pyridine ring in their molecular structure, which makes them structurally related. However, their functions and effects in the body are entirely different.

Nicotine is an alkaloid found in tobacco plants, known for its stimulant and addictive properties. It interacts with nicotinic acetylcholine receptors in the brain, leading to effects like increased heart rate, alertness, and potential addiction.
Nicotinamide (also called Niacinamide) is a form of vitamin B3, a water-soluble vitamin essential for energy metabolism, DNA repair, and skin health. It’s naturally present in foods like meat, fish, and grains and is used in supplements and skincare products. Unlike nicotine, nicotinamide is non-addictive and doesn’t have stimulant effects.

The confusion often arises because of their similar names and shared pyridine ring, but nicotinamide is not derived from nicotine, nor does it produce nicotine-like effects. In fact, nicotinamide is sometimes studied for its potential to mitigate nicotine withdrawal symptoms, but it doesn’t act like nicotine in the body.

In short, they’re chemically related but functionally unrelated—nicotine is a psychoactive substance, while nicotinamide is a vital nutrient.

Maybe I need to add Nicotinamide to my supplement regiment as I spend a lot of time outdoors, gardening, and hiking.

Can Nicotinamide Be Used Prophylactically by Healthy People?

Yes, nicotinamide (a form of vitamin B3) can be used prophylactically by healthy individuals to potentially reduce the risk of nonmelanoma skin cancers, based on evidence from studies like the one cited in the MedPage Today article by Charles Bankhead. The Bankhead findings suggest nicotinamide may have a protective effect against nonmelanoma skin cancers, particularly in individuals with a history of skin cancer. The study likely focused on high-risk individuals, but the mechanism of action suggests potential benefits for healthy individuals as well.

Mechanism of Action

Nicotinamide works by:

Enhancing DNA repair: It boosts cellular energy (via NAD+ production), helping cells repair UV-induced DNA damage, a key factor in skin cancer development.
Reducing UV-related immunosuppression: It mitigates the immune suppression caused by UV exposure, which can otherwise allow cancerous cells to proliferate.
Anti-inflammatory effects: It reduces inflammation in the skin, which may contribute to cancer prevention.

These mechanisms are relevant to healthy individuals, as UV damage accumulates over time even without a prior cancer diagnosis.

Can Healthy People Use Nicotinamide Prophylactically?

Yes, nicotinamide can be considered for prophylactic use by healthy individuals, particularly those at higher risk of skin cancer due to:

Frequent sun exposure (e.g., outdoor workers, athletes, or those living in sunny climates).
Fair skin, light hair/eyes, or a family history of skin cancer.
History of sunburns or tanning bed use.

However, there are key considerations:

Evidence Base: Most studies focus on high-risk populations. Data on healthy individuals without risk factors is less robust, but the mechanisms suggest potential benefits for anyone exposed to UV radiation.
Dosage: Studies typically use nicotinamide doses of 500 mg twice daily, which has been shown to be safe and effective for skin cancer prevention in high-risk groups. Healthy individuals might consider similar or lower doses, but this should be guided by a healthcare provider.
Safety: Nicotinamide is generally well-tolerated, with minimal side effects (unlike niacin, which can cause flushing). It’s available over-the-counter and is considered safe for long-term use at recommended doses. Excessive doses (e.g., >3 g/day) may pose risks like liver toxicity or gastrointestinal issues.
Consultation: Healthy individuals should consult a healthcare provider before starting nicotinamide prophylactically, especially to confirm appropriate dosing and rule out interactions with other medications or conditions.
Not a Substitute for Sun Protection: Nicotinamide is not a sunscreen and does not block UV rays. It should be used alongside standard sun protection measures (sunscreen, protective clothing, avoiding peak sun hours).

Broader Context

The ONTRAC trial (Oral Nicotinamide to Reduce Actinic Cancer) showed that nicotinamide reduced the incidence of nonmelanoma skin cancers by 23% in high-risk patients, supporting the article’s findings.
Nicotinamide is also used in dermatology for improving skin barrier function and reducing acne or photoaging, which adds to its appeal for healthy individuals.
Unlike topical treatments, oral nicotinamide provides systemic protection, which may benefit all sun-exposed skin.

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