Could help in the treatment of cancer
Van Andel Research Institute
Vitamin C plays an important role in keeping the immune
system healthy, helping wounds heal, and protecting cells from damage. However,
people with precancerous blood disorders and blood cancers often have
persistently low vitamin C levels. Researchers have been investigating whether
correcting this deficiency could improve their health and treatment outcomes.
New findings from the phase 2 EVITA clinical trial suggest
that vitamin C supplementation may offer important benefits for people with
precancerous blood conditions and early-stage blood cancers. The randomized,
double-blind, placebo-controlled study was conducted by the Van Andel
Institute-Stand Up To Cancer® Epigenetics Dream Team.
The results, published in the American Cancer Society journal CANCER, revealed that patients who received 1,000 mg of oral vitamin C every day for one year experienced fewer adverse events during the study and its follow-up period. The supplement also changed the levels of certain immune signaling molecules, known as cytokines, in ways associated with more favorable outcomes. These changes suggest that vitamin C could influence inflammation-related processes involved in the growth and progression of abnormal blood cells.
Although vitamin C did not significantly affect the rate at
which abnormal blood cells expanded, the researchers identified an encouraging
result. An exploratory analysis showed that participants who received vitamin C
were significantly more likely to be alive after approximately three years of
follow-up than those who took a placebo. Scientists emphasize that this
potential survival benefit must be verified in a larger phase 3 clinical trial.
Vitamin C Shows Promise for Patients at Risk of Leukemia
"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 Peter A. Jones,
Ph.D., D.Sc. (hon), a distinguished professor at Van Andel Institute. Jones is
also a co-corresponding author of the research and co-leader of the VAI-SU2C
Epigenetics Dream Team.
"Our approach reflects a growing emphasis on cancer
interception -- intervening before cancer becomes established. 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."
The international research effort was led by Kirsten
Grønbæk, M.D., Ph.D., a leading hematologist, professor at the University of
Copenhagen, and member of the VAI-SU2C Epigenetics Dream Team.
"These exciting preliminary findings lay the groundwork
for a larger clinical trial to explore vitamin C as a possible way to improve
patient outcomes," said Grønbæk. "It is too early to make definitive
recommendations based on our results, but we are hopeful that a more expansive
study will provide further insights."
First Clinical Trial Tests Daily Vitamin C for
Precancerous Blood Disorders
The study enrolled 109 patients with either clonal cytopenia
of undetermined significance (CCUS) or myelodysplastic syndrome (MDS). Both
conditions can develop into acute myeloid leukemia (AML), an aggressive form of
blood cancer that is often difficult to treat. The likelihood of developing
CCUS and related blood disorders rises with age, making these conditions
particularly common among older adults.
Currently, no approved treatment can prevent CCUS from
progressing to leukemia. Although stem cell transplantation is an option for
treating MDS, many patients cannot undergo the procedure because of age or
other medical conditions. None of the people enrolled in the trial were
receiving cancer treatment when the study took place.
To determine whether vitamin C might offer benefits,
researchers randomly divided participants into two groups. One received 1,000
mg of vitamin C by mouth each day for 12 months. The other received a placebo
designed to be indistinguishable from the supplement in appearance, taste, and
smell, but containing no vitamin C.
Neither the participants nor the clinical staff knew who was
receiving vitamin C until the study concluded. This double-blind, randomized,
placebo-controlled approach is considered the gold standard in clinical
research because it reduces potential bias and allows investigators to assess
treatment effects more objectively.
The research was carried out at four hospitals: Copenhagen
University Hospital-Rigshospitalet, Copenhagen University Hospital-Herlev,
Aalborg University Hospital, and Keck Hospital of the University of Southern
California.
What makes EVITA particularly notable is that it was the
first randomized, double-blind, placebo-controlled trial to investigate oral
vitamin C in patients with conditions that can precede leukemia or with
lower-risk myeloid cancers. Earlier studies had primarily examined vitamin C
administered intravenously and had focused on solid tumors rather than
precancerous blood disorders or early-stage blood malignancies.
EVITA instead evaluated a daily oral dose comparable to that
available in many over-the-counter vitamin C supplements.
More Than Half of Patients Had Low Vitamin C Levels
Blood samples collected throughout the study allowed
researchers to track participants' vitamin C concentrations and determine
whether supplementation corrected deficiencies.
At the beginning of the trial, more than half of the
participants had insufficient vitamin C levels. Among those assigned to the
supplementation group, blood concentrations returned to normal after they began
taking vitamin C.
For patients living with conditions that could eventually
develop into leukemia, the possibility of an accessible intervention is
especially important. In many cases, physicians have little choice but to
monitor the disease and watch for signs that it is progressing.
"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," said Casey O'Connell, M.D., FACP, the Lawrence
and Jane Kelly Chair in Hematology at the University of Southern California and
lead clinician at USC's trial location.
"The EVITA trial took on this challenge by exploring
vitamin C's potential to address the underlying factors that drive leukemia
development."
How Vitamin C Could Influence Cancer Development
Scientists have investigated whether vitamin C could play a
useful role in cancer treatment for more than seven decades. For much of that
time, the evidence remained uncertain because studies produced inconsistent
findings and employed different experimental methods.
During the past decade, however, improved research
technologies have revealed that vitamin C has important functions beyond its
familiar roles in nutrition and immunity. In particular, scientists have
uncovered its involvement in controlling gene activity and guiding normal cell
development.
One of the most important discoveries concerns TET2, an
enzyme that helps prevent cancerous growth by controlling whether particular
genes are switched "on" or "off." Vitamin C supports the
activity of this enzyme, which helps maintain normal patterns of gene
regulation.
Mutations affecting TET2 are frequently found in leukemia
and related blood disorders. When the enzyme's normal function is disrupted,
abnormal cells can gain an opportunity to multiply and potentially develop into
cancer.
Experiments using cancer models have provided additional
evidence of vitamin C's possible protective effects. These studies found that
supplementation could interfere with cellular changes associated with cancer
and slow the progression of leukemia. Notably, the strongest effects appeared
when vitamin C was introduced before cancer had become established.
This research helped inspire the idea of using vitamin C as
a form of early intervention, potentially targeting the biological changes that
precede the development of leukemia.
Building Toward Larger Clinical Trials
Before launching EVITA, the VAI-SU2C Epigenetics Dream Team
conducted a pilot clinical study in 2016 to determine whether taking vitamin C
orally could meaningfully raise its concentration in the blood.
The initial findings suggested that oral supplementation was
a practical approach. Encouraged by those results, the researchers launched the
phase 2 EVITA trial in 2017.
"This early work was critical because it offered a
foundation from which to develop the present trial," said Stine Ulrik
Mikkelsen, M.D., Ph.D., the study's first author and a clinician researcher in
Grønbæk's laboratory.
"Vitamin C is important because it is involved in a
range of biological functions, including the activity of enzymes that regulate
normal cell function."
Researchers are continuing to examine the EVITA data to
better understand the biological processes that might explain why patients
receiving vitamin C showed improved survival.
Although the findings offer a promising direction for future
research, additional clinical studies will be essential to determine whether
vitamin C supplementation can reliably improve outcomes for people with
precancerous blood disorders and early-stage blood cancers.
Other authors include Ali Al-Mousawi, M.D., Amalie Bach
Puglisi, M.D., Anders Pommer Vallentin, M.D., Astrid Østergaard Mortensen,
Heidi Naomi Ottesen, Linn Gillberg, M.Sc., Ph.D., Morten Tulstrup, M.D., M.Sc.,
Ph.D., Jakob Werner Hansen, M.D., Ph.D., and Mette Klarskov Andersen, M.D.,
D.MSc., of the University of Copenhagen and Copenhagen University
Hospital-Rigshospitalet; Zachary Madaj, M.S., Toshinori Hinoue, Ph.D., Stacey
L. Thomas, Ph.D., Christine N. Isaguirre, Ryan D. Sheldon, Ph.D., Marie Adams,
M.S., Ryan Burgos, and Peter W. Laird, Ph.D., of Van Andel Institute; Jakob
Schmidt Jespersen, M.Sc., Ph.D., Niels Richard Hansen, M.Sc., and Jens
Lykkesfeldt, Ph.D., D.MSc., of the University of Copenhagen; Stephen Baylin,
M.D., of Johns Hopkins University and Van Andel Institute; Bo Kok Mortensen,
M.D., Ph.D., of Copenhagen University Hospital-Rigshospitalet and Copenhagen
University Hospital-Herlev; and Marianne Tang Severinsen, M.D., Ph.D., of
Aalborg University Hospital.
Funding for the study was provided by Van Andel Institute
through the Van Andel Institute-Stand Up To Cancer® Epigenetics Dream Team, the
Danish Cancer Society, and Greater Copenhagen Health Science Partners.
Journal Reference:
- Stine Ulrik Mikkelsen, Ali Al‐Mousawi, Amalie Bach Puglisi, Anders Pommer Vallentin, Astrid Østergaard Mortensen, Zachary Madaj, Toshinori Hinoue, Heidi Naomi Ottesen, Jakob Schmidt Jespersen, Linn Gillberg, Morten Tulstrup, Niels Richard Hansen, Jakob Werner Hansen, Mette Klarskov Andersen, Stacey Lyn Thomas, Christine Isaguirre, Ryan Sheldon, Marie Adams, Ryan Burgos, Stephen Baylin, Bo Kok Mortensen, Casey Lee O’Connell, Marianne Tang Severinsen, Peter William Laird, Jens Lykkesfeldt, Peter Jones, Kirsten Grønbæk. 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) DOI: 10.1002/cncr.70549