Oral Vitamin C Shows Possible Survival Signal in Precancerous Blood Disorders

A daily dose of 1000 mg of oral vitamin C for 1 year was associated with fewer adverse events in patients with clonal cytopenia of undetermined significance (CCUS) or myelodysplastic syndrome (MDS), according to results from the phase 2 EVITA trial.¹ ² The investigators found no significant difference between the vitamin C and placebo groups in the growth rates of abnormal blood cells, a common measure of progression toward leukemia.¹

No approved therapies prevent CCUS from progressing to acute myeloid leukemia, and standard care is monitoring of blood cell counts over time.¹ An exploratory analysis found participants who took vitamin C were significantly more likely to be alive after approximately 3 years of follow-up than those who received placebo, a finding that requires confirmation in a phase 3 trial.¹

"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," Kirsten Grønbæk, MD, PhD, professor at the University of Copenhagen and trial lead, said in a statement.¹

EVITA Results: Fewer Adverse Events With Vitamin C, No Change in Abnormal Cell Growth

Participants in the vitamin C group had fewer adverse events during the trial and follow-up period than those who received placebo.¹ The investigators also reported that vitamin C altered levels of cytokines, which are inflammatory signaling molecules, in ways associated with better outcomes.¹

These shifts suggest vitamin C may help regulate inflammatory pathways linked to the growth and progression of precancerous blood cells, the investigators said in a statement.¹ The growth rate of abnormal blood cells did not differ significantly between groups.¹

EVITA Trial Design: 1,000 mg Oral Vitamin C vs Placebo in 109 Patients

The trial randomized 109 patients with CCUS or MDS to 1,000 mg of oral vitamin C daily or a placebo that matched it in look, taste, and smell.¹ Participants and trial staff were blinded until the end of the trial. None of the participants were receiving cancer treatment at the time.¹

Sites included Copenhagen University Hospital Rigshospitalet, Copenhagen University Hospital Herlev, Aalborg University Hospital, and Keck Hospital of the University of Southern California.¹ Blood samples were analyzed for vitamin C levels. More than half of participants were deficient in vitamin C at baseline, and levels normalized in the vitamin C group.¹

The investigators said EVITA is the first double-blind, randomized, placebo-controlled trial of oral vitamin C in preleukemia conditions or lower risk myeloid malignancies. Earlier trials used intravenous vitamin C and focused on solid tumors.¹

Why Vitamin C and TET2 Are Being Studied in Preleukemia Disorders

Vitamin C is an essential partner to TET2, an enzyme that suppresses cancer cell growth by regulating whether certain genes are on or off.¹ Mutations in TET2 can allow malignant cells to proliferate and are common in leukemia and related disorders. In cancer models, vitamin C appeared to prevent cancer related cellular changes and impede leukemia progression, with the greatest benefit when supplementation started before disease was established.¹

The Van Andel Institute–Stand Up To Cancer Epigenetics Dream Team conducted a pilot study in 2016 showing oral supplementation was feasible for raising blood vitamin C levels, then began EVITA in 2017.¹

"This early work was critical because it offered a foundation from which to develop the present trial," Stine Ulrik Mikkelsen, MD, PhD, first author of the study, said in a statement.¹

"The EVITA trial took on this challenge by exploring vitamin C's potential to address the underlying factors that drive leukemia development," Casey O'Connell, MD, FACP, Lawrence and Jane Kelly Chair in Hematology at the University of Southern California, said in a statement.¹

Exploratory Survival Finding Needs Confirmation in a Larger Trial

The survival difference came from an exploratory analysis, and the primary comparison of abnormal cell growth showed no significant difference between groups.¹ Additional analysis is ongoing, with a focus on biological mechanisms that may contribute to the survival difference.¹

"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," Peter A. Jones, PhD, DSc (hon), distinguished professor at Van Andel Institute and co-corresponding author of the study, said in a statement.¹

References

1. Van Andel Research Institute. Phase 2 trial suggests vitamin C may benefit people with pre-cancer blood disorders. Press release. September 21, 2026.

2. Mikkelsen SU, et al. 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. Cancer. Published September 21, 2026. doi:10.1002/cncr.70549