NAD and Cancer: Clinical Recommendations
There are no established clinical guidelines recommending NAD+ supplementation for cancer treatment or prevention from any major oncology society, and NAD+ supplementation should not be used in cancer patients outside of standard nutritional support protocols. 1
Current Evidence Against NAD Supplementation in Cancer
The relationship between NAD and cancer is fundamentally problematic for therapeutic supplementation:
Cancer cells exploit elevated NAD levels to fuel rapid proliferation through enhanced glycolysis (the Warburg effect), with nicotinamide phosphoribosyltransferase (NAMPT)—the rate-limiting enzyme for NAD synthesis—frequently amplified in multiple cancer types 2, 3
Increased NAD pool size actively promotes cancer progression by suppressing reactive oxygen species (ROS) levels that would otherwise damage cancer cells, with NAMPT upregulation consistently observed in colorectal adenomas and adenocarcinomas 4
The therapeutic strategy in oncology is NAD depletion, not supplementation, with NAMPT inhibitors (FK866, CHS-828) under investigation to starve cancer cells by blocking NAD production and disrupting glycolysis, the TCA cycle, and oxidative phosphorylation 2, 5, 3
Limited Role of NAD Precursors in Cancer Care
Standard Nutritional Support Only
Niacin (a NAD+ precursor) is included in parenteral nutrition at 40 mg/day exclusively for cancer patients with intestinal failure who cannot be fed enterally, as part of comprehensive nutritional support—not as targeted NAD therapy 1
Parenteral nutrition containing niacin is recommended only when oral/enteral intake is inadequate, severe mucositis or radiation enteritis exists, or intestinal failure is present 1, 6
ESPEN guidelines explicitly acknowledge that parenteral nutrition supplies nutrients to tumors, but state this should not influence the decision to provide nutritional support when clinically indicated to prevent starvation 1
Single Exception: Skin Cancer Prevention
Oral nicotinamide 1000 mg/day is the only NAD-related intervention with cancer evidence, specifically for preventing new basal cell carcinomas and squamous cell carcinomas in high-risk patients with prior skin cancers 1
This is a preventive strategy for new skin cancers in high-risk patients, not a treatment for existing malignancies, and must be combined with sun protection as it does not substitute for UV protection 1
The upper intake level for nicotinamide is approximately 900 mg/day for adults (though 1000 mg/day has been used safely in skin cancer prevention trials), with gastrointestinal symptoms (nausea, vomiting, diarrhea) being the primary side effects 1
Critical Pitfalls to Avoid
Do Not Confuse NAD Supplementation with Evidence-Based Nutritional Support
The American Academy of Physical Medicine and Rehabilitation explicitly does not recommend NAD patches due to lack of clinical evidence 1
Cancer patients require protein intake above 1 g/kg/day up to 1.5 g/kg/day to maintain muscle mass and reduce treatment toxicity, but this is unrelated to NAD supplementation 7
Avoid long-term glutamine supplementation in cancer cachexia, as glutamine is heavily involved in metabolic pathways supporting cancer cell survival, despite being an amino acid that could theoretically support NAD-dependent processes 8
Understand the Biological Rationale
NAD serves as substrate for PARP, sirtuins, and CD38/CD157, regulating DNA repair, gene expression, and stress responses that cancer cells exploit for survival 2
Cancer cells require sustained NAD production as a hallmark of neoplastic metabolism, making NAD depletion—not supplementation—the rational therapeutic approach 5, 9
NADH fluorescence intensity measured by two-photon excitation fluorescence microscopy increases consistently in colorectal cancer cell lines and tumor tissues, serving as a potential biomarker for cancer progression rather than a therapeutic target for supplementation 4
What Cancer Patients Actually Need
Focus on Evidence-Based Nutritional Interventions
During radiotherapy (especially head/neck, thorax, gastrointestinal), ensure adequate nutritional intake through individualized counseling and oral nutritional supplements to avoid deterioration and treatment interruptions 6
For upper GI cancer patients undergoing surgical resection, provide oral/enteral immunonutrition (arginine, N-3 fatty acids, nucleotides) in the context of traditional perioperative care 6
Manage all cancer surgery patients within Enhanced Recovery After Surgery (ERAS) programs, with screening for malnutrition and additional nutritional support for at-risk patients 6
Maintain physical activity combined with adequate protein intake to support muscle mass, physical function, and metabolic patterns, including individualized resistance exercise 6, 7