Can oral vitamin C improve outcomes in precancer blood disorders?

Clinical takeaway: Do not change practice based on these findings alone, but oral vitamin C may emerge as a low-cost strategy worth further study in patients with clonal cytopenia of undetermined significance (CCUS) or lower-risk myeloid malignancies.

Patients with CCUS and lower-risk myeloid neoplasms have limited options beyond monitoring, despite a risk of progression to myelodysplastic syndromes (MDS) or acute myeloid leukemia. Vitamin C enhances TET enzyme activity, a pathway commonly disrupted in these disorders, raising interest in whether supplementation could slow disease evolution.

In the phase 2 EVITA trial, 109 patients in the US and Denmark with CCUS or lower-risk myeloid malignancies were randomized to oral vitamin C 1,000 mg daily or placebo for 12 months. More than half of participants had deficient or inadequate vitamin C levels at baseline, and supplementation rapidly restored levels to the normal range.

The study did not meet its primary endpoint: growth rates of precancerous or malignant blood-cell clones were similar between groups after 1 year. However, vitamin C was associated with biologic changes that investigators said were consistent with a less inflammatory disease state, including more favorable trajectories of several cytokines linked to disease progression.

Clinical outcomes also favored vitamin C. Serious adverse events occurred in 33% of patients receiving vitamin C versus 57% receiving placebo, while adverse events of any grade occurred in 44% versus 60%, respectively. Pneumonia was reported in 2% of the vitamin C group compared with 15% of the placebo group, and anemia occurred in 7% versus 15%. Gastrointestinal adverse events, including diarrhea and esophagitis, were somewhat more common with vitamin C.

Although exploratory and not a prespecified primary outcome, survival findings were notable. After a median follow-up of 33.6 months, 11 deaths occurred in the vitamin C group compared with 24 in the placebo group, translating to an estimated 65% lower risk of death. Disease progression events were also numerically less frequent with vitamin C (5 vs 9), although this difference was not statistically significant. Investigators emphasized that a larger phase 3 trial is needed to confirm these results.

“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 co-senior author Peter A. Jones, PhD. “More work is needed but we are cautiously optimistic that these findings could inform future strategies to intercept leukemia development.”

Source: Mikkelsen SU, et al. (2026 Sep 21) Cancer. 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