Vitamin C Linked to Improved Survival in Pre-Cancerous Blood Disorders

Vitamin C supports immune function, wound healing, and cellular protection. Individuals with pre-cancerous blood disorders and blood cancers often have low vitamin C levels. Researchers explored whether correcting this deficiency could improve their health and treatment outcomes.

Findings from the phase 2 EVITA clinical trial indicate that vitamin C supplementation might benefit patients with pre-cancerous blood conditions and early-stage blood cancers. The randomized, double-blind, placebo-controlled study, conducted by the Van Andel Institute-Stand Up To Cancer® Epigenetics Dream Team, showed that patients taking 1,000 mg of oral vitamin C daily for one year experienced fewer adverse events. The supplement also altered immune signaling molecules, known as cytokines, in a manner associated with better outcomes, suggesting an influence on inflammation in abnormal blood cell growth.

While vitamin C did not significantly change the rate of abnormal blood cell expansion, an exploratory analysis revealed a notable finding: participants receiving vitamin C were significantly more likely to be alive after approximately three years compared to the placebo group. Scientists stress the need to confirm this potential survival benefit in a larger phase 3 trial.

“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,” stated Peter A. Jones, Ph.D., D.Sc. (hon), a distinguished professor at Van Andel Institute and co-corresponding author of the research. “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.”

The research was led internationally by Kirsten Grønbæk, M.D., Ph.D., a hematologist 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,” Grønbæk noted. “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.”

The EVITA study involved 109 patients with clonal cytopenia of undetermined significance (CCUS) or myelodysplastic syndrome (MDS), conditions that can progress to acute myeloid leukemia (AML). These disorders are more common in older adults, and currently, no treatment can prevent CCUS progression to leukemia. Stem cell transplantation is an option for MDS but not suitable for all patients.

Participants were randomly assigned to receive either 1,000 mg of vitamin C orally each day for 12 months or an indistinguishable placebo. The double-blind, randomized, placebo-controlled design minimizes bias and allows for objective assessment.

This trial is notable as the first randomized, double-blind, placebo-controlled study of daily oral vitamin C for conditions preceding leukemia or for lower-risk myeloid cancers. Previous studies often used intravenous vitamin C and focused on solid tumors.

Blood tests showed that over half of the participants had insufficient vitamin C levels at the study's outset. Supplementation successfully raised vitamin C concentrations to normal levels in the treatment group. For those at risk of developing leukemia, an accessible intervention is particularly significant, given the current "watch and wait" approach for many pre-cancerous blood disorders.

Casey O'Connell, M.D., FACP, a hematologist at the University of Southern California, commented, “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. The EVITA trial took on this challenge by exploring vitamin C’s potential to address the underlying factors that drive leukemia development.”

For over 70 years, scientists have explored vitamin C's role in cancer treatment, with inconsistent results. Recent advances have revealed vitamin C's crucial functions in controlling gene activity and directing normal cell development. It supports the activity of the TET2 enzyme, which helps prevent cancerous growth by regulating gene expression. Mutations in TET2 are common in leukemia and related disorders, and vitamin C's support for this enzyme may help maintain normal gene regulation.

Experiments with cancer models suggest vitamin C can interfere with cancer-related cellular changes and slow leukemia progression, especially when introduced before cancer is established. This research supports the concept of using vitamin C for early intervention against the biological changes preceding leukemia development.

The EVITA trial followed a 2016 pilot study that confirmed oral vitamin C could effectively raise blood concentrations. “This early work was critical because it offered a foundation from which to develop the present trial,” said Stine Ulrik Mikkelsen, M.D., Ph.D., the study's first author. “Vitamin C is important because it is involved in a range of biological functions, including the activity of enzymes that regulate normal cell function.”

Researchers are continuing to analyze the EVITA data to understand the biological mechanisms behind the observed survival improvements. While these findings are promising, further clinical studies are necessary to confirm vitamin C supplementation's ability to reliably enhance outcomes for patients with pre-cancerous blood disorders and early-stage blood cancers.