What is the recommended dose of Nicotinamide (Vitamin B3) for skin cancer prevention?

Nicotinamide Dosing for Skin Cancer Prevention

For immunocompetent patients with a history of non-melanoma skin cancer, nicotinamide 500 mg twice daily (1000 mg total daily) is the evidence-based dose for skin cancer prevention. 1

Recommended Dosing Regimen

• Standard preventive dose: 500 mg twice daily (1000 mg/day total) for patients with at least two prior non-melanoma skin cancers in the past 5 years 1
• Treatment duration should be continuous for at least 12 months to achieve maximum benefit 1
• Benefit is lost after discontinuation, requiring ongoing therapy for sustained protection 1

Evidence Supporting This Dose

The landmark ONTRAC trial demonstrated that 500 mg twice daily in high-risk immunocompetent patients resulted in:

• 23% reduction in new non-melanoma skin cancers (basal cell carcinoma plus squamous cell carcinoma combined) at 12 months 1
• 30% reduction in new squamous cell carcinomas specifically 1
• 20% reduction in new basal cell carcinomas 1
• 11-20% reduction in actinic keratoses throughout the treatment period 1

A subsequent meta-analysis confirmed these findings, showing a 50% reduction in all skin cancers with this dosing regimen 2

Safety Profile at This Dose

• No significant adverse effects were observed at 500 mg twice daily compared to placebo 1
• The upper safety limit for nicotinamide is approximately 900 mg/day for adults according to European Food Safety Authority guidelines, though the preventive dose of 1000 mg/day has proven safe in clinical trials 3
• Increased digestive side effects (nausea, vomiting, diarrhea) may occur but are generally mild 2, 3
• No flushing occurs with nicotinamide (unlike nicotinic acid) 3

Critical Population Distinction

This dose does NOT work in immunosuppressed organ transplant recipients. 4

• A phase 3 trial in transplant recipients using the identical 500 mg twice daily dose showed no benefit (rate ratio 1.0, meaning no difference from placebo) 4
• The trial was stopped early, but results were definitive for lack of efficacy in this population 4
• For transplant recipients, alternative chemopreventive strategies (systemic retinoids, capecitabine) should be considered instead 5

Who Should Receive This Dose

Target patients for 500 mg twice daily nicotinamide:

• Immunocompetent individuals with ≥2 prior keratinocyte carcinomas (squamous cell or basal cell) in the past 5 years 1, 2
• Patients with extensive field cancerization and multiple actinic keratoses 2
• 76.9% of Mohs surgeons currently recommend this regimen for high-risk patients 6

Practical Implementation

• Start immediately after diagnosis of second non-melanoma skin cancer 1
• Continue indefinitely as benefit ceases upon discontinuation 1
• Combine with sun protection measures (SPF ≥15 sunscreen, protective clothing, sun avoidance 10 AM-4 PM) as nicotinamide is not a substitute for UV protection 5, 7
• Monitor with dermatology visits every 3 months during the first year 1

Common Pitfalls to Avoid

• Do not use lower doses (such as the 16 mg/day nutritional requirement dose) for cancer prevention—this is 60-fold lower than the effective dose 3, 1
• Do not prescribe to transplant recipients expecting the same benefit seen in immunocompetent patients 4
• Do not stop therapy after 12 months thinking benefit will persist—protection is only maintained during active treatment 1
• Do not rely on nicotinamide alone—it must be combined with comprehensive sun protection strategies 5, 7