The trial, led by researchers from the University of Copenhagen and the Van Andel Institute, involved 109 participants diagnosed with clonal cytopenia of undetermined significance (CCUS) or a lower-risk myeloid malignancy such as myelodysplastic syndrome (MDS). Both conditions can lead to acute myeloid leukemia (AML).
Over a three-year follow-up, an exploratory analysis found that those taking daily oral vitamin C had a 65 percent lower risk of death compared with a placebo group. Fewer participants in the vitamin C group also went on to develop higher-risk, aggressive blood cancers, five versus nine, though the small total number meant this difference was not statistically significant.
"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," said epigeneticist Peter Jones of the Van Andel Institute. "Our approach reflects a growing emphasis on cancer interception – intervening before cancer becomes established."
Currently, no treatments exist to stop CCUS from turning into AML, and stem cell transplantations for MDS are not suitable for everyone. Hematologist Casey O'Connell of the University of Southern California noted the frustration of the standard approach: "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 trial builds on previous research identifying vitamin C as a helper for the TET2 enzyme. TET2 can help protect against cancer cells by controlling gene switches, and its function is often impaired in blood conditions like those studied. The thinking is that replenishing vitamin C may keep TET2 working properly, though this mechanism was not directly measured in the trial and needs confirmation.
Other encouraging signs included smaller rises in inflammatory biomarkers in the vitamin C group than in the placebo group and a return to normal vitamin C levels for those who were deficient.
"Vitamin C is important because it is involved in a range of biological functions, including the activity of enzymes that regulate normal cell function," said hematologist Stine Ulrik Mikkelsen of the University of Copenhagen.
The results are published in the journal Cancer. A larger phase 3 trial will be needed to definitively establish whether vitamin C can reduce cancer risk or extend lifespans. "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," Jones said.