Does niacinamide (Vitamin B3) reduce the risk of nonmelanoma skin cancer in high-risk individuals, such as those with a history of skin cancer, prolonged sun exposure, fair skin, or immunosuppression?

Nicotinamide for Nonmelanoma Skin Cancer Prevention

Oral nicotinamide (500 mg twice daily) reduces the risk of nonmelanoma skin cancers by approximately 23% in high-risk individuals with a history of prior skin cancers, but only while actively taking the medication—the benefit disappears after discontinuation. 1

Evidence Quality and Guideline Position

The 2018 American Academy of Dermatology guidelines acknowledge "early evidence from a small trial that oral nicotinamide may reduce the risk for subsequent keratinocyte carcinoma in nonimmunosuppressed individuals with a history of such carcinomas," but characterize the evidence as "limited." 2 For basal cell carcinoma specifically, the guidelines state there is "insufficient evidence to make a recommendation" (Strength B, Level I evidence). 2, 3

The FDA has approved nicotinamide labeling that states it "decreases the risk of skin cancer and early skin aging caused by the sun" when used with other sun protection measures. 4

The Landmark Trial Data

The pivotal 2015 ONTRAC trial randomized 386 high-risk patients (≥2 prior nonmelanoma skin cancers in 5 years) to nicotinamide 500 mg twice daily versus placebo for 12 months. 1 Results showed:

• 23% reduction in total nonmelanoma skin cancers (95% CI: 4-38%, P=0.02) 1
• 30% reduction in squamous cell carcinomas (95% CI: 0-51%, P=0.05) 1
• 20% reduction in basal cell carcinomas (95% CI: -6 to 39%, P=0.12—not statistically significant) 1
• 11-20% reduction in actinic keratoses at various time points (P<0.001) 1

Critical Limitation: No Sustained Benefit

The protective effect vanishes within 6 months of stopping nicotinamide, requiring indefinite continuation for ongoing benefit. 1 This represents a major practical limitation compared to interventions with durable effects.

Who Benefits and Who Doesn't

Appropriate Candidates:

• Immunocompetent patients with ≥2 prior nonmelanoma skin cancers 3, 1
• High-risk individuals with extensive sun damage and multiple actinic keratoses 1, 5
• Patients with coronary artery disease (nicotinamide has no cardiovascular contraindications, unlike celecoxib which carries significant cardiac risk) 3

Patients Who Do NOT Benefit:

• Organ transplant recipients on immunosuppression showed zero benefit (rate ratio 1.0; 95% CI: 0.8-1.3; P=0.96) 3
• Patients without prior skin cancer history (insufficient evidence for primary prevention) 2

Practical Implementation Algorithm

Step 1: Confirm Eligibility

• History of ≥2 nonmelanoma skin cancers in past 5 years 1
• Immunocompetent status (not transplant recipient) 3
• No contraindications to nicotinamide 3

Step 2: Prescribe Standard Dose

• Nicotinamide 500 mg orally twice daily (total 1000 mg/day) 3, 1
• Counsel that benefit requires continuous use 1
• Most common side effects: mild nausea, vomiting, diarrhea (not cardiovascular) 3

Step 3: Emphasize Adjunctive Measures

• Nicotinamide is NOT a substitute for UV protection—it must be combined with comprehensive sun protection 3, 6
• Broad-spectrum SPF ≥15 sunscreen 3, 6
• Sun avoidance 10 AM-4 PM 6
• Protective clothing and wide-brimmed hats 6
• Complete avoidance of tanning beds 6

Step 4: Surveillance Schedule

• Dermatology follow-up every 3-6 months for skin surveillance 3
• Annual full-body skin examination (Strength A, Level I evidence) 2, 3
• Patient and family skin self-examination 6

Mechanism of Action

Nicotinamide enhances DNA repair after UV damage, reduces UV-induced immunosuppression, modulates inflammatory cytokines, and restores cellular ATP levels depleted by UV radiation. 5, 7, 8 These mechanisms explain its photoprotective effects but also why continuous supplementation is required.

What Does NOT Work

The guidelines explicitly recommend against these alternatives for skin cancer prevention:

• Topical and oral retinoids (tretinoin, acitretin, isotretinoin, retinol): Not effective for keratinocyte cancer prevention (Strength A, Level I evidence) 2, 9
• Selenium and β-carotene: No protective benefit, with adverse effects including skin yellowing and GI upset (Strength A, Level I evidence) 2, 6, 9
• Celecoxib: Though some evidence exists, cardiovascular risk outweighs benefits 2, 3

Common Pitfalls to Avoid

• Prescribing for transplant recipients: Zero efficacy in this population—consider systemic retinoids or capecitabine instead 3
• Relying on nicotinamide alone without sun protection: The medication augments but does not replace UV avoidance 3, 6
• Expecting durable benefit after discontinuation: Patients must understand lifelong therapy is required 1
• Using for primary prevention: Evidence only supports use in patients with prior skin cancer history 2, 1

Melanoma Prevention

Evidence for melanoma prevention is insufficient and speculative. 8 While nicotinamide enhances DNA repair in melanocytes and reduces UV-induced damage theoretically relevant to melanoma, no clinical trials have demonstrated reduced melanoma incidence. 8 The ONTRAC trial was not powered to detect melanoma differences. 1