Phase 2 Trial Links Oral Vitamin C to Improved Survival in Pre-Cancer Blood Disorders

The standard medical consensus has long held that over-the-counter vitamin supplements cannot alter the trajectory of pre-cancerous blood disorders. But new data from the Phase 2 EVITA trial, published September 21 in the journal CANCER, challenges that assumption. While 1,000 milligrams of daily oral vitamin C did not stop abnormal blood cells from multiplying, patients who took the supplement were significantly more likely to survive over a three-year follow-up period than those given a placebo.[1][4]

The trial enrolled 109 adults across Denmark and the United States diagnosed with clonal cytopenia of undetermined significance (CCUS) or lower-risk myelodysplastic syndromes (MDS). Both conditions involve abnormal blood cell formation and carry a risk of progressing to acute myeloid leukemia, a difficult-to-treat cancer. Currently, there are no approved therapies to intercept this progression, leaving patients on a frustrating observation regimen.[1][3][4]

Researchers from the Van Andel Institute and the University of Copenhagen designed the double-blind, placebo-controlled study to test a specific biological mechanism. Vitamin C is a known cofactor for TET enzymes, which help regulate gene expression and suppress cancer cell growth. Because mutations that decrease TET enzyme function are common drivers of leukemia, the team hypothesized that restoring vitamin C levels could help restore normal epigenetic function in vulnerable blood cells.[1][3][4]

More than half of the trial participants were deficient in vitamin C at baseline, a common feature in people with blood cancers. The 55 patients randomly assigned to the active arm took 1,000 mg of oral vitamin C daily for 12 months, which successfully normalized their blood levels. The remaining 54 patients received an identical placebo.[1][4]

The trial failed to meet its primary endpoint: the median clonal growth rate of the abnormal cells was virtually identical between the two groups. "Vitamin C did not significantly slow the growth of the abnormal blood-cell clones," noted Dr. John Riches, a clinical reader in cancer immuno-metabolism at Barts Cancer Institute, who was not involved in the study.[2][4]

However, an exploratory analysis of the data revealed a stark divergence in survival. Over a median follow-up of 33.6 months, 35 deaths occurred: 24 in the placebo group and 11 in the vitamin C group. This translates to a 65 percent lower risk of death for those taking the supplement.[3][4]

The vitamin C group also experienced a lower burden of serious adverse events. Severe complications like anemia, pneumonia, acute aseptic arthritis, and internal bleeding were less frequent among those taking the supplement, affecting 33 percent of the active arm compared to 57 percent of the placebo group. Researchers also observed favorable shifts in inflammatory signaling molecules, or cytokines, suggesting the vitamin may help regulate the inflammatory pathways linked to disease progression.[1][3][4]

Hematology experts caution that because the survival benefit was found in a post-hoc exploratory analysis—meaning the trial was not originally powered to test for it—the results cannot yet change clinical practice. "The major finding of improved overall survival was an exploratory post-hoc analysis – not pre-determined, which weakens, but does not negate the finding," said Dr. Manoj Raghavan of University Hospitals Birmingham.[2]

The research team is now designing a larger Phase 3 clinical trial to validate the survival signal. If that study replicates the mortality reduction seen in EVITA, daily oral vitamin C would become the first approved preventative therapy for patients facing a CCUS or lower-risk MDS diagnosis.[1][3][4]