Researchers are investigating whether restoring vitamin C levels can influence the biology of early blood disorders before leukemia develops.
A clinical trial suggests that correcting vitamin C deficiency may benefit people with certain blood disorders that can precede leukemia.
Results from the randomized, double-blind, placebo-controlled phase 2 EVITA trial found that participants who took 1,000 mg of oral vitamin C daily for one year experienced fewer adverse events during the study and follow-up period than those given a placebo.
The study, led by the Van Andel Institute-Stand Up To Cancer Epigenetics Dream Team, included 109 people with clonal cytopenia of undetermined significance (CCUS) or myelodysplastic syndrome (MDS), both of which can progress to acute myeloid leukemia (AML).
A possible survival signal
The findings, published in the American Cancer Society journal CANCER, also showed that vitamin C changed levels of cytokines, molecules involved in inflammation and immune signaling. The changes were associated with more favorable outcomes and may indicate that vitamin C affects pathways involved in abnormal blood cell growth.
Researchers did not find a significant difference between the vitamin C and placebo groups in the expansion of abnormal blood cell clones, a measure used to track progression toward leukemia.
However, an exploratory analysis found that after about three years of follow-up, participants who received vitamin C were significantly more likely to be alive than those given a placebo. Because this result came from an exploratory analysis in a relatively small phase 2 trial, it needs to be confirmed in a larger phase 3 study.
“We are tremendously excited and cautiously optimistic that our results could one day translate into a simple way to improve care and outcomes for people with pre-leukemia disorders,” said Peter A. Jones, Ph.D., D.Sc. (hon), a distinguished professor at Van Andel Institute, co-corresponding author of the study and co-leader of the VAI–SU2C Epigenetics Dream Team. “Our approach reflects a growing emphasis on cancer interception — intervening before cancer becomes established. We are working to build on the trial findings by exploring how exactly vitamin C interacts with pre-cancerous cells, including the idea that it may help restore normal epigenetic function in blood cells at risk of becoming leukemia.”
Why vitamin C may matter
More than half of the participants were vitamin C deficient when the trial began. Blood testing showed that vitamin C levels normalized in those assigned to supplementation.
Vitamin C has roles beyond immune function and wound healing. It also supports enzymes involved in epigenetic regulation, which controls gene activity without changing the underlying DNA sequence.
One important enzyme is TET2. Mutations in TET2 are common in leukemia and related blood disorders and can give abnormal blood-forming cells a growth advantage. Laboratory and animal studies have suggested that vitamin C can support remaining TET activity and may limit some cancer-related cellular changes.
Earlier studies often tested intravenous vitamin C, which produces much higher blood concentrations than oral supplements. EVITA instead examined whether a daily oral dose could correct vitamin C deficiency and affect early disease biology.
An option for patients with few preventive treatments
There is currently no approved therapy specifically designed to prevent CCUS from progressing to leukemia. MDS can sometimes be treated with stem cell transplantation, but age and other health conditions may make the procedure unsuitable for many patients.
“The standard approach for patients with pre-cancer blood disorders is to monitor their blood cell counts over time. This is, understandably, very frustrating — no one wants to hear that they have a condition that increases leukemia risk, but there’s nothing that can be done other than watch and wait,” said Casey O’Connell, M.D., FACP, the Lawrence and Jane Kelly Chair in Hematology at the University of Southern California and lead clinician for USC’s trial site. “The EVITA trial took on this challenge by exploring vitamin C’s potential to address the underlying factors that drive leukemia development.”
The international study was led by Kirsten Grønbæk, M.D., Ph.D., a hematologist, member of the VAI–SU2C Epigenetics Dream Team, and professor at the University of Copenhagen.
“These exciting preliminary findings lay the groundwork for a larger clinical trial to explore vitamin C as a possible way to improve patient outcomes,” said Grønbæk. “It is too early to make definitive recommendations based on our results, but we are hopeful that a more expansive study will provide further insights.”
Researchers are continuing to analyze the trial data, including biological mechanisms that may help explain the survival difference between the groups.
Reference: “Oral vitamin C supplementation in patients with clonal cytopenia of undetermined significance or lower-risk myeloid malignancies: Results from EVITA, a phase 2 randomized, placebo-controlled trial” by Stine Ulrik Mikkelsen, Ali Al-Mousawi, Amalie Bach Puglisi, Anders Pommer Vallentin, Astrid Østergaard Mortensen, Zachary Madaj, Toshinori Hinoue, Heidi Naomi Ottesen, Jakob Schmidt Jespersen, Linn Gillberg, Morten Tulstrup, Niels Richard Hansen, Jakob Werner Hansen, Mette Klarskov Andersen, Stacey Lyn Thomas, Christine Isaguirre, Ryan Sheldon, Marie Adams, Ryan Burgos, Stephen Baylin, Bo Kok Mortensen, Casey Lee O’Connell, Marianne Tang Severinsen, Peter William Laird, Jens Lykkesfeldt, Peter Jones and Kirsten Grønbæk, 21 September 2026, Cancer.
DOI: 10.1002/cncr.70549
Funding: Van Andel Institute through the Van Andel Institute–Stand Up To Cancer® Epigenetics Dream Team, Danish Cancer Society, Greater Copenhagen Health Science Partners
Never miss a breakthrough: Join the SciTechDaily newsletter.
Follow us on Google and Google News.