Investigators randomly assigned 55 participants to oral vitamin C and 54 to placebo. Patients entered the study with either clonal cytopenia of undetermined significance, a blood condition that can turn cancerous, or a low-risk form of blood cancer. Although participants taking vitamin C experienced changes in inflammatory signaling that aligned with better outcomes, anemia, pneumonia, acute aseptic arthritis and internal bleeding were less frequent than among those taking placebo.

Gastrointestinal problems, meanwhile, were more frequent in the vitamin C group. These differences were reported as observations from the phase 2 trial rather than definitive proof of a treatment effect. Decreased function of TET enzymes is a common driver of certain forms of blood cancer, the research team reported, providing the rationale for testing vitamin C in patients whose disorders may progress to malignancy.

The randomized trial was designed to evaluate whether supplementation could influence disease-related cellular growth and produce other changes associated with better outcomes in this at-risk population. The primary endpoint did not distinguish the treatment groups: the growth rate of precancerous or cancerous cells was similar among participants receiving vitamin C and those receiving placebo. That result means the study did not answer its main question about abnormal cell growth.

The investigators nevertheless identified several other differences between the groups, including changes in inflammatory signaling, lower frequencies of four clinical complications and more gastrointestinal problems with vitamin C. The release did not provide numerical estimates, confidence intervals or statistical significance for these individual clinical comparisons, limiting the precision with which their size or certainty can be assessed from the available report. Death outcomes provided the trial’s most prominent exploratory finding. At a median follow-up of 33.6 months, or nearly three years, 35 deaths were recorded in the intention-to-treat population: 24 in the placebo group and 11 in the vitamin C group.

An exploratory analysis found that participants assigned to vitamin C were more likely to survive during follow-up than those assigned to placebo. The survival comparison was not the primary endpoint, and the research release did not state the numerical effect estimate, confidence interval or statistical significance. The investigators consequently said the finding requires confirmation in a larger phase 3 clinical trial.

“The EVITA trial gives us a strong rationale to continue exploring if and how vitamin C might benefit people with certain pre-cancer or early-stage blood cancers,” said Peter A. Jones, co-senior author of the study and co-leader of the Van Andel Institute–Stand Up To Cancer Epigenetics Dream Team, which led EVITA. “More work is needed but we are cautiously optimistic that these findings could inform future strategies to intercept leukemia development.” The researchers presented the survival result as a reason to continue investigating vitamin C, not as evidence that the supplement prevents leukemia or improves survival for all people with blood disorders. Kirsten Grønbæk, the trial’s other co-senior author and a longtime member of the Van Andel Institute–Stand Up To Cancer Epigenetics Dream Team, also emphasized the limits of the findings.

“We are encouraged by our findings and what they ultimately could mean for people with these early-stage blood disorders,” she said. “Although it is too soon to make recommendations based on our results, we are hopeful that a larger study will give us more definitive answers.” The report did not recommend vitamin C supplementation or identify it as a clinical standard of care, and the trial did not test whether it could treat established leukemia or reverse an advanced blood cancer. Several features limit the conclusions that can be drawn from EVITA.

The intervention also involved one fixed dose of 1,000 mg per day over 12 months, while survival was assessed over a median of 33.6 months. The findings concern people with clonal cytopenia of undetermined significance or lower-risk myeloid malignancies in Denmark and the United States, so they do not directly address other blood cancers, advanced disease or the general population. The results also require careful separation of the trial’s primary, secondary and exploratory measures.

The primary cellular-growth endpoint did not differ between vitamin C and placebo. Other reported findings included favorable changes in inflammatory signaling, fewer instances of anemia, pneumonia, acute aseptic arthritis and internal bleeding, and more gastrointestinal problems in the supplement group. The apparent survival advantage emerged from an exploratory analysis and had not been established as the primary test.

The absence of a difference in the main endpoint therefore remains central to interpreting the study, even as the other observations support further research. EVITA provides a rationale for a larger phase 3 trial, but it does not resolve whether vitamin C meaningfully improves outcomes in people with these pre-cancer or early-stage blood disorders. The results were published online on September 21, 2026, in CANCER , a peer-reviewed journal of the American Cancer Society, under the title “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.” A larger study would be needed to test whether the biological, clinical and exploratory survival findings are reproducible, estimate any benefit more precisely and determine whether vitamin C has a meaningful role in intercepting progression to leukemia.

Subject of Research: Phase 2 randomized trial of oral vitamin C in clonal cytopenia and lower-risk myeloid malignancies

Article Title: Can vitamin C improve outcomes in people with pre-cancer blood disorders?

Article References: Can vitamin C improve outcomes in people with pre-cancer blood disorders?. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: vitamin C, clonal cytopenia, myeloid malignancies, blood cancer, TET enzymes, leukemia prevention, randomized trial, survival, phase 2 trial, clinical outcomes, vitamin, improve

In an exploratory analysis, participants assigned vitamin C were significantly more likely to be alive after approximately three years of follow-up, but that result requires confirmation in a larger phase 3 trial. EVITA enrolled 109 people diagnosed with clinical cytopenia of unknown significance, also called CCUS, or myelodysplastic syndrome, described in the trial as a lower-risk myeloid malignancy. These blood disorders can progress to acute myeloid leukemia, or AML, a difficult-to-treat cancer.

The investigators described EVITA as the first double-blind, randomized, placebo-controlled trial to evaluate oral vitamin C in people with pre-leukemia conditions or lower-risk myeloid malignancies. The international study was led by the Van Andel Institute–Stand Up To Cancer Epigenetics Dream Team, with trial sites in Denmark and the United States. Participants were randomly assigned to one of two groups.

The treatment group received 1,000 mg of oral vitamin C each day for one year, while the control group received a placebo that looked, tasted and smelled identical but contained no vitamin C. Participants and trial staff did not know their assignments until the end of the trial. None of the participants was undergoing cancer treatment at the time of the trial. Investigators said the design was intended to minimize bias and support objective evaluation of the supplement’s effects in a population whose disorders were being monitored rather than actively treated for leukemia.

Blood samples collected during the trial were analyzed to measure participants’ vitamin C concentrations. More than half were vitamin C-deficient at the start of the study, and participants in the vitamin C group saw their levels normalize after they began taking the supplement. Unlike earlier vitamin C trials, which used intravenous delivery, EVITA tested an oral dose matching that found in many over-the-counter supplements.

Earlier studies also focused on solid tumors rather than pre-cancer blood disorders and early-stage blood cancers. The trial therefore evaluated both the feasibility of raising blood vitamin C through oral supplementation and its possible clinical and biological effects in people at risk of leukemia progression. The reported clinical findings were not uniform across outcomes.

Participants receiving vitamin C had fewer adverse events during the intervention and subsequent follow-up, although the supplied report did not provide numerical event rates, an effect size or a statistical estimate for that difference. The investigators found no significant difference between the vitamin C and placebo groups in the growth rates of abnormal blood cells, a measure used to assess progression toward leukemia. By contrast, the apparent survival advantage came from an exploratory analysis rather than the trial’s main comparison.

Approximately three years after enrollment, vitamin C recipients were significantly more likely to be alive than placebo recipients, a finding that remains provisional until tested independently in a larger cohort. The cytokine analyses provided a biological signal accompanying the clinical observations. Vitamin C altered the levels of inflammatory signaling molecules in ways associated with better outcomes, and these shifts suggested that supplementation may affect inflammatory pathways linked to the growth and progression of pre-cancerous blood cells.

The analysis did not establish that the cytokine changes caused either the reduction in adverse events or the exploratory survival difference. Instead, it showed that the molecular response differed between treatment conditions in a manner that investigators considered relevant to the clinical results. Additional analysis of the EVITA data is under way to examine the mechanisms that could contribute to the observed survival difference.

The investigators connected the human findings to earlier work on vitamin C and epigenetic regulation. Vitamin C is an essential partner of TET2, an enzyme that regulates whether certain genes are active or inactive and suppresses cancer-cell growth. Mutations in TET2 can allow malignant cells to proliferate and are common in leukemia and related disorders.

Cancer-model studies found that vitamin C appeared to prevent cancer-related cellular changes and impede leukemia progression, with the greatest benefit observed when supplementation began before disease was fully established. EVITA extended this line of investigation to a controlled human trial in people with pre-leukemia conditions, rather than evaluating the supplement only in laboratory systems or through intravenous administration. The phase 2 trial followed a clinical pilot conducted by the same research team in 2016.

That earlier work assessed whether oral supplementation was sufficient to raise vitamin C levels in the blood and found the approach feasible. The EVITA trial began in 2017, using the knowledge gained from the pilot to conduct a larger randomized comparison. Its sites included Copenhagen University Hospital–Rigshospitalet, Copenhagen University Hospital–Herlev, Aalborg University Hospital and Keck Hospital of the University of Southern California.

Kirsten Grønbæk of the University of Copenhagen led the international trial, while Peter A. Jones of Van Andel Institute was a co-corresponding author and co-leader of the research team. The results remain preliminary and do not show that vitamin C prevents CCUS or MDS from progressing to leukemia. There are no approved therapies that prevent CCUS progression, while MDS can be treated with stem-cell transplantation, although many people—particularly older adults or those with other conditions—cannot undergo transplantation.

Monitoring blood-cell counts is the standard approach for many people with pre-leukemia disorders. Against that background, EVITA directly tested whether a simple oral supplement could affect outcomes in people who otherwise faced prolonged surveillance. Even so, the trial does not establish that clinicians should prescribe vitamin C specifically to prevent progression, and the researchers emphasized that definitive recommendations would be premature.

The current evidence supports several narrower conclusions: EVITA was a 109-participant study of oral vitamin C in CCUS and lower-risk MDS; one year of supplementation normalized vitamin C levels in the treatment group; the trial was associated with fewer adverse events; and it produced changes in cytokines associated with better outcomes. The trial did not show a significant difference in abnormal blood-cell growth, while the approximately three-year survival advantage was exploratory. Taken together, the findings justify further controlled research but do not yet demonstrate that vitamin C changes pre-leukemia disease progression or prevents acute myeloid leukemia.

Subject of Research: Phase 2 randomized trial of oral vitamin C in people with CCUS and lower-risk myelodysplastic syndrome.

Article Title: Phase 2 trial suggests vitamin C may benefit people with pre-cancer blood disorders

Article References: Phase 2 trial suggests vitamin C may benefit people with pre-cancer blood disorders. Original publication (Bibliographic details unavailable.)

Image Credits: AI Generated

DOI: Not provided

Keywords: vitamin C, pre-leukemia, CCUS, myelodysplastic syndrome, acute myeloid leukemia, randomized trial, adverse events, survival, cytokines, TET2, Phase, trial