As a cancer-fighting organic compound, University of Iowa researchers knew vitamin C worked in cells. They knew it worked in mice. They even knew it worked in a small group of cancer patients.
What the Iowa team didn't know was how well it could work—so well, in fact, that they ended a phase 2 clinical trial early.
The trial examined the impact of adding high-dose intravenous (IV) vitamin C (ascorbate) to standard chemotherapy treatments for 34 patients with Stage 4 metastatic pancreatic cancer. The results of the phase 2 trial—published in the November 2024 issue of Redox Biology—found that the patients' survival rates doubled from eight months to 16 months, and progression-free survival stretched from three months to six.
"When we started the trial, we thought it would be successful to get to 12 months of survival. Instead, we doubled it," says Joseph Cullen (86MD, 91R), professor of surgery and radiation oncology, and the study's senior author.
Many of the patients in the study didn't just live longer—they also appeared to feel better.
"What's really cool is that if you look at the group who received the vitamin C treatment, they got higher doses of chemotherapy for longer periods,” Cullen says. “They seemed to tolerate the chemotherapy better."
Decades of research at Iowa has shown that vitamin C, when given intravenously, can build up in high levels in the blood, creating unique chemical reactions that make cancer cells more vulnerable to chemotherapy and radiation treatments. Cullen notes that with one of the research team’s phase 1 trials for pancreatic cancer—combining high-dose, IV vitamin C with radiation treatments—three patients are now long-term cancer survivors.
"They've lived nine years since their diagnosis at this point, which is far beyond the typical survival range," Cullen says.
Iowa researchers are now conducting several new trials exploring different vitamin C treatments and their effects on a wide range of cancers.
The treatment that almost never was
Improving quality of life
At Iowa, the promising vitamin C research extends beyond the pancreatic trial. A phase 2 trial in non-small cell lung cancer is nearing completion, and the results of a phase 2 clinical trial in patients with glioblastoma were published in early 2024 in the journal Clinical Cancer Research. All three trials were funded by a 2018 grant from the National Cancer Institute (NCI).
In the glioblastoma trial, participants who received vitamin C survived five months longer than those who received chemotherapy and radiation alone. For a cancer with a median survival expectancy of just 14.6 months, that's a significant amount of time, says Bryan Allen (08MD/PhD, 13R, 22MBA), professor and chair of the UI Department of Radiation Oncology, and the study's lead researcher.
High-dose vitamin C not only negatively impacts cancer cells; it also protects normal tissue from radiation and toxicity, Allen says, which is why many people who received treatment reported feeling better than those who didn't.
"This wasn't five months sick in bed. This was five months out living life," Allen says.
However, not all trial participants benefited equally. While some patients saw staggeringly positive results, Allen says, others saw small benefits, and some experienced no benefit. UI Health Care researchers are now studying likely explanations, including the role that iron stores play in patient survival.
Cancer Clinical Trials
UI Health Care Holden Comprehensive Cancer Center is offering more clinical trials than ever before.
The future of vitamin C treatments
Where vitamin C shines
Across the board, cancer treatments have become more personalized, less invasive, and more effective, saving countless lives while also improving the overall treatment experience. Consider the targeted therapies that can be tailored to specific genetic mutations in tumors or immunotherapy medications that can make it harder for cancer cells to evade the immune system.
Despite the crowded innovation field, there is still a place for high-dose, intravenous vitamin C, especially given its combination of effectiveness and low cost, says Bryan Allen, MD, PhD, MBA, professor and chair of the UI Department of Radiation Oncology.
"It's a very cost-effective treatment," he says. "Compared to immunotherapy treatments, which might cost thousands of dollars a dose, vitamin C is in the hundreds of dollars a dose."
That makes vitamin C treatments more affordable and an option to be scaled globally. High-dose vitamin C is also well-tolerated, with few side effects, Allen says. Plus, it’s a known commodity.
"People know what vitamin C is. When patients have heard of something and understand it, they're more willing to try it than something they've never heard of," Allen says.