What Nurses Should Tell Patients About Vitamin C in CCUS and MDS

Daily oral vitamin C did not slow the growth of mutated blood cell clones in adults with clonal cytopenia of undetermined significance (CCUS) or lower-risk myeloid malignancies. However, patients who took it had fewer serious adverse events and, in an exploratory analysis, lived longer than those given placebo, according to results from the phase 2 EVITA trial published in Cancer.¹ Investigators caution that the survival finding must be confirmed in a phase 3 trial before the supplement can be recommended.

How was the EVITA trial designed?

EVITA (NCT03682029) was the first double-blind, randomized, placebo-controlled trial of oral vitamin C in this population.^1,2 From 2017 to 2022, 109 adults with CCUS, lower-risk myelodysplastic syndromes (MDS), or MDS/myeloproliferative neoplasms who were not receiving anticancer therapy enrolled at 3 Danish hospitals and at USC Norris Comprehensive Cancer Center in Los Angeles, the only US site.¹

Patients received 1000 mg of oral vitamin C daily (n = 55) or matching placebo (n = 54) for 12 months. The primary end point was median clonal growth rate. Vitamin C is a cofactor for TET enzymes involved in DNA demethylation.¹

At baseline, 57% of participants had deficient or inadequate plasma vitamin C levels; supplementation normalized levels.¹

What did the trial find?

• Clonal growth: The median clonal growth rate was 0.030 per year with vitamin C vs 0.046 per year with placebo (P = .70).¹
• Safety: Serious adverse events occurred in 33% of patients receiving vitamin C vs 57% of those receiving placebo; any adverse event occurred in 44% vs 60%, respectively.¹
• Survival (exploratory, post hoc): At a median follow-up of 33.6 months, 11 deaths occurred in the vitamin C group vs 24 in the placebo group (HR, 0.35; 95% CI, 0.17-0.71; P = .0025).¹
• Progression: 5 vs 9 patients progressed to higher-risk disease (P = .22). Bacterial infection was the leading cause of death in both arms.¹

"Why the patients survive does not appear to have anything to do with progression of their myeloid cancer per se," Casey O'Connell, MD, FACP, lead clinician at the USC trial site, told Oncology Nursing News. "We think that it may be there were fewer serious infections in the vitamin C–treated patients that went on to lead to their demise."

Vitamin C also shifted inflammatory cytokines, including interleukin-6, in a pattern the authors associate with lower-risk disease.¹ "Reducing or controlling inflammation in a good way may be part of it," said Kirsten Grønbæk, MD, DMSc, of the University of Copenhagen, who led the trial. "But honestly, this is also still something that we're working on."

Should patients with CCUS or MDS start taking vitamin C?

"Obviously we cannot recommend this because it needs a phase 3 trial," Grønbæk said. Because the supplement is sold over the counter, some patients may take it anyway, she noted. "Please tell your doctor you're doing it because then at least we know what's going on."

Peter A. Jones, PhD, DSc (hon), a distinguished professor at Van Andel Institute and co-corresponding author, sees it differently. "I do not understand why vitamin C measurements are not taken as part of the clinical workup of patients with these diseases," he said. Given the safety profile, he added, "I do not see any downside myself … in recommending a gram a day."

What safety issues should nurses watch for?

Gastrointestinal events were more frequent with vitamin C, including diarrhea (5% vs 2%) and esophagitis (5% vs 0%). One patient with a history of kidney stones developed a stone requiring intervention; patients with stones in the prior year were excluded.¹

"There is the possibility of it causing some or exacerbating underlying reflux," O'Connell said, recommending that patients with gastritis or dyspepsia consider taking it with food. "If I have patients that have a lot of kidney stone issues, I don't recommend the vitamin C supplement."

What comes next?

EVITA was small, lacked a formal sample size calculation, and treated patients for only 12 months; survival was not a protocol end point.¹ Oncology Nursing News previously reported the trial's primary results.³ Recruiting for a placebo-controlled phase 3 trial poses a challenge: "It will be difficult because people actually have access to vitamin C," O'Connell said.

What are the key takeaways for oncology nurses?

• Present vitamin C as unproven; the survival finding was exploratory.
• Ask about and document supplement use at every visit.
• Screen for kidney stone history.
• Counsel on reflux; suggest taking it with food.
• Keep conversations open so patients disclose what they take.

References

1. Mikkelsen SU, Al-Mousawi A, Puglisi AB, et al. 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. Cancer. 2026;132(19):e70549. doi:10.1002/cncr.70549
2. Phase 2 trial suggests vitamin C may benefit people with pre-cancer blood disorders. News release. Van Andel Institute. September 21, 2026. Accessed October 23, 2026. https://www.vai.org/article/phase-2-trial-suggests-vitamin-c-may-benefit-people-with-pre-cancer-blood-disorders/
3. Oral vitamin C misses primary end point in CCUS but shows survival signal. Oncology Nursing News. October 12, 2026. Accessed October 23, 2026. https://www.oncnursingnews.com/view/oral-vitamin-c-misses-primary-end-point-in-ccus-but-shows-survival-signal