Tier 3 — preclinical

Vitamin B3 derivatives support pancreatic cancer cell survival and chemotherapy resistance

Faith Nakazzi, Mehrdad Zarei, Mariana Lopes, Hallie J Graor, William C Beegan, Eric Gu, Sakineh Rezaei, Peder J Lund, Jordan M Winter
Cancer Letters 2026 645:218334

Bibliography

PubMed
PMID 41724424
DOI
10.1016/j.canlet.2026.218334
Funding
Supported by American Cancer Society grants, Gateway for Cancer Research, NCI grants, Case Comprehensive Cancer Center grants, University Hospitals support and philanthropic research funds.
Competing interests
No specific author competing-interest disclosure was identified in the accessible article text beyond the listed institutional and grant support.

Study snapshot

DesignMechanistic in vitro and in vivo pancreatic ductal adenocarcinoma study testing NAD+ precursors alongside multiple chemotherapies.
ModelHuman pancreatic-cancer cell lines and murine pancreatic-cancer models, including immunocompetent and immunodeficient mice.
SampleMultiple independent cell and animal experiments; no human participants.
InterventionNMN, nicotinamide and nicotinamide riboside tested with oxaliplatin, 5-fluorouracil and gemcitabine; NMN was the strongest pro-survival precursor in several in-vitro experiments.
DurationVaried across cell-survival and mouse tumor experiments.
EndpointsCancer-cell viability; Chemotherapy IC50; Clonogenic survival; NAD+; Mitochondrial function; Reactive oxygen species; DNA damage; Apoptosis; Tumor growth; Chemotherapy response

What the study showed, in plain terms

This 2026 study raises an important cancer-safety concern. In pancreatic-cancer models, NMN and other vitamin B3/NAD+ precursors sometimes helped tumor cells survive metabolic and chemotherapy stress.

NMN produced the strongest protective effect in several cell experiments and increased resistance to oxaliplatin, 5-fluorouracil and gemcitabine. Mouse experiments also showed reduced chemotherapy effectiveness and support of tumor growth under some conditions.

These results do not prove that NMN causes cancer in people. They do justify caution about unsupervised NAD-boosting supplements during active cancer or chemotherapy until clinical evidence is available.

Key findings

  • NMN increased intracellular NAD+ and showed strong cancer-cell survival effects in pancreatic-cancer cell models.
  • NMN increased chemotherapy IC50 values and clonogenic survival in several in-vitro experiments.
  • NMN reduced oxidative stress, enhanced DNA-repair signaling and reduced apoptosis in chemotherapy-stressed cancer cells.
  • In mouse models, NMN and nicotinamide reduced chemotherapy efficacy and supported tumor growth under tested conditions.
  • The authors specifically called for careful evaluation of NAD+ precursor use in patients with active cancer.

What this study can and cannot tell us

The study is preclinical. Cell concentrations, mouse dosing and tumor biology cannot establish that ordinary supplemental NMN causes chemotherapy resistance in humans.

Pancreatic ductal adenocarcinoma was the main cancer model; effects may differ by cancer type, treatment, immune context, dose and timing.

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Dr. Khaled Mahmoud, MBBChCritical Care Medicine, Longevity Science & Editorial Direction Dr. Amr Yasser, PhDCardiometabolic, Musculoskeletal, Gut & Bioavailability Dr. Abdulla Mostafa, PhDCellular Senescence, Neurological, Mitochondrial & Brain-Ageing Biology