Is nicotinamide safe for patients with coronary artery disease (CAD) to use for solar keratosis and skin cancer prevention?

Nicotinamide Safety in Coronary Artery Disease Patients for Skin Cancer Prevention

Nicotinamide is safe to use in patients with coronary artery disease (CAD) for solar keratosis and skin cancer prevention, as it has a favorable safety profile with no known cardiovascular contraindications or adverse cardiac effects. 1

Evidence for Safety in CAD Patients

Cardiovascular Safety Profile

• Nicotinamide does not cause flushing, unlike nicotinic acid, eliminating concerns about vasodilation-related cardiovascular effects. 1

• The European Food Safety Authority has established an upper safety limit of approximately 900 mg/day for adults, while the preventive dose of 1000 mg/day (500 mg twice daily) has proven safe in clinical trials. 1

• No cardiovascular adverse events were reported in the landmark ONTRAC trial of 386 high-risk patients receiving nicotinamide 500 mg twice daily for 12 months. 2

Contrast with Other Chemopreventive Agents

This safety profile stands in stark contrast to celecoxib, which the American Academy of Dermatology specifically warns against due to significant cardiovascular risk. The AAD guidelines explicitly state that while celecoxib may reduce skin cancer risk, "the potential benefits should be weighed against the significant risk for a cardiovascular event that is associated with this medication." 3

Efficacy Evidence

Immunocompetent Patients

• In high-risk immunocompetent patients, nicotinamide reduces new nonmelanoma skin cancers by 23% (95% CI, 4-38%, P=0.02) during 12 months of treatment. 2

• Squamous-cell carcinomas were reduced by 30% (95% CI, 0-51%, P=0.05) and basal-cell carcinomas by 20% (95% CI, -6 to 39%, P=0.12). 2

• Actinic keratoses were reduced by 11-20% at various time points during treatment (P<0.001 to P=0.01). 2

Important Limitation: Immunosuppressed Patients

• For immunosuppressed organ transplant recipients, nicotinamide showed no benefit (rate ratio 1.0; 95% CI, 0.8-1.3; P=0.96), and alternative chemopreventive strategies such as systemic retinoids or capecitabine should be considered instead. 3, 1, 4

Current Guideline Recommendations

American Academy of Dermatology Position

The 2018 AAD guidelines for basal cell carcinoma management state there is insufficient evidence to make a recommendation on the use of oral nicotinamide in chemoprevention of BCC (Strength of Recommendation: B, Level of Evidence: I). 3

However, this reflects the conservative nature of guideline development rather than safety concerns. The guidelines acknowledge "early evidence from a small trial that oral nicotinamide may reduce the risk for subsequent keratinocyte carcinoma in nonimmunosuppressed individuals." 3

Mechanism of Action

• Nicotinamide enhances DNA repair of UV-induced damage by serving as a precursor to NAD+, essential for ATP production and energy-dependent DNA repair pathways. 5

• It reduces both cyclobutane pyrimidine dimers (CPDs) and 8-oxo-7,8-dihydro-2'-deoxyguanosine formation after UV exposure. 5

• Nicotinamide prevents UV-induced immunosuppression across the entire UV spectrum (UVB, UVA, and solar-simulated UV). 6

Practical Implementation for CAD Patients

Dosing and Administration

• Standard dose: 500 mg twice daily (total 1000 mg/day). 1, 2

• The most common side effects are mild digestive symptoms (nausea, vomiting, diarrhea), not cardiovascular effects. 1

Essential Adjunctive Measures

• Nicotinamide is not a substitute for UV protection and must be combined with comprehensive sun protection: SPF ≥15 sunscreen, protective clothing, and sun avoidance from 10 AM-4 PM. 1, 7

• Annual skin cancer screening by a dermatologist is recommended for all patients with a history of keratinocyte cancers. 3

Duration of Benefit

• Protection is only maintained during active treatment; benefits cease after discontinuation. 2

• This requires indefinite continuation for sustained chemoprevention in high-risk patients. 2

Clinical Decision Algorithm for CAD Patients

1. Confirm patient is immunocompetent (not an organ transplant recipient on immunosuppression). 3, 4

2. Verify high-risk status: ≥2 nonmelanoma skin cancers in the past 5 years or multiple actinic keratoses. 2

3. Initiate nicotinamide 500 mg twice daily without cardiovascular contraindications or special monitoring beyond routine care. 1, 2

4. Counsel on sun protection measures as primary prevention strategy. 1, 7

5. Schedule dermatology follow-up every 3-6 months for skin surveillance. 3

Common Pitfalls to Avoid

• Do not withhold nicotinamide from CAD patients based on cardiovascular concerns—there is no evidence of cardiac risk. 1, 2

• Do not use nicotinamide as monotherapy—it must be combined with rigorous sun protection measures. 1, 7

• Do not expect benefit in immunosuppressed transplant recipients—consider alternative agents like systemic retinoids instead. 3, 4

• Do not recommend dietary supplements like selenium or β-carotene—these are ineffective and not recommended by AAD guidelines. 3, 7