Jordan Winter, MD, Co-Leader of the Developmental Therapeutics Program at Case CCC, is the senior author of a new study examining how NAD+ supplements may affect pancreatic cancer cells and their response to chemotherapy.
Published in Cancer Letters, the study examined three NAD+ precursors—nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and nicotinamide (NAM)—and their effects on pancreatic ductal adenocarcinoma cells. Researchers found that the compounds could promote cancer cell survival and reduce the effectiveness of chemotherapy, with NMN showing the strongest effect.
In laboratory experiments, NMN increased pancreatic cancer cells’ resistance to three commonly used chemotherapy drugs: oxaliplatin, 5-fluorouracil and gemcitabine. The researchers found that NAD+ precursors promoted mitochondrial function, reduced oxidative stress and suppressed DNA damage and apoptosis, mechanisms that may allow cancer cells to better withstand chemotherapy.
The findings were also observed in mouse models. Supplementation with NAM and NMN reduced chemotherapy effectiveness and supported tumor growth, raising concerns about the potential impact of NAD+-boosting supplements during active cancer treatment.
The study does not show that NAD+ supplements cause cancer or that they are harmful for everyone. However, the findings suggest that supplements marketed for energy, healthy aging and other benefits can have biological effects that may be important for patients undergoing cancer treatment.
“This research is a critical reminder that ‘natural’ doesn’t always mean safe, especially in the complex biology of cancer treatment,” Winter said.
Winter’s research focuses on how pancreatic cancer cells adapt to nutrient deprivation and other forms of cancer-associated stress. By identifying the metabolic dependencies that allow cancer cells to survive under these conditions, his laboratory seeks to uncover vulnerabilities that could be targeted therapeutically.