Does cemiplimab interact with antioxidant supplements (e.g., vitamin C, vitamin E, selenium, coenzyme Q10, botanical extracts) and affect its efficacy?

Cemiplimab and Antioxidant Supplements: Avoid High-Dose Antioxidants During Treatment

Patients receiving cemiplimab for advanced cutaneous squamous cell carcinoma should avoid high-dose antioxidant supplements (exceeding 100% of the Daily Value) during active cancer treatment, as antioxidants could theoretically repair oxidative damage to cancer cells and reduce treatment efficacy. 1

Mechanism of Concern

• Cemiplimab works by blocking the PD-1 receptor, stimulating an anti-cancer immune response that relies on oxidative damage to cancer cells 2, 3
• High-dose antioxidants (vitamins C and E, selenium, coenzyme Q10) could counteract the cellular oxidative stress that contributes to immunotherapy effectiveness 1
• The National Cancer Institute specifically notes that antioxidants could theoretically repair oxidative damage to cancer cells, potentially reducing chemotherapy and radiotherapy effectiveness 4

Evidence-Based Recommendations

During active cemiplimab treatment:

• Limit antioxidant supplements to ≤100% of the Daily Value to avoid interfering with treatment mechanisms 1
• The American Cancer Society guideline explicitly advises against exceeding 100% of the daily value for antioxidant-type vitamins during cancer treatment 1
• This precautionary approach is based on the theoretical concern that higher doses could protect cancer cells from treatment-induced oxidative damage 1

Prioritize dietary sources instead:

• Consume antioxidants through a variety of fruits and vegetables rather than supplements 1
• People who eat more antioxidant-rich foods may have lower risk for some cancers, but clinical studies of antioxidant supplements have not demonstrated cancer risk reduction 1
• Dietary antioxidants from whole foods provide benefits without the risks associated with high-dose isolated supplements 1

Important Caveats

The evidence is theoretical, not definitive:

• No direct studies have examined antioxidant interactions specifically with cemiplimab or other PD-1 inhibitors
• The concern about antioxidants interfering with cancer treatment stems primarily from radiotherapy and chemotherapy data, not immunotherapy 1
• Some experts argue the possible harm is only hypothetical and that antioxidants might protect normal cells from collateral damage 1

High-dose supplements carry independent risks:

• Beta-carotene at 20-30 mg/day increased lung cancer mortality in major trials 1, 5
• Vitamin E at 400 IU/day increased prostate cancer risk (HR: 1.17) and heart failure risk (RR: 1.13) 1, 5
• Systematic reviews conclude that beta-carotene and vitamin E appear to increase mortality 1, 5

Clinical Approach

Assessment:

• Review all current supplements, including multivitamins, individual antioxidants (vitamins C, E, selenium, coenzyme Q10), and botanical extracts 1
• Calculate total antioxidant intake from all sources, including fortified foods 1
• Document any nutritional deficiencies that might require targeted supplementation 4

Management during cemiplimab treatment:

• Discontinue or reduce high-dose antioxidant supplements (>100% Daily Value) 1
• If documented deficiencies exist, correct through diet or targeted supplementation to restore normal levels only 4, 5
• Encourage 5+ servings of fruits and vegetables daily for dietary antioxidants 1, 5
• Provide individualized dietary counseling to optimize nutrition without high-dose supplements 1

Communication:

• 71% of cancer patients use supplements during treatment, and 53% do not consult healthcare professionals 1
• Proactively ask about supplement use, as patients often do not volunteer this information 1
• Explain the theoretical rationale for limiting antioxidants during immunotherapy 1

After treatment completion:

• The restriction on antioxidant supplements applies specifically during active cancer treatment 1
• Post-treatment supplementation decisions should be individualized based on nutritional status and overall health goals 1

This conservative approach prioritizes treatment efficacy while acknowledging the lack of definitive evidence specific to immunotherapy interactions, erring on the side of caution to avoid potentially compromising cemiplimab's substantial antitumor activity (62% objective response rate) 6, 2.