Over the years vitamin C supplementation has had a tumultuous relationship with empirical science. In 1753, James Lind, a Scottish surgeon with the British Royal Navy showed that scurvy could be treated with citrus fruit (vitamin C would be established as the necessary molecule about 100 years later). Conversely, in the late 1970s, Nobel laureate Linus Pauling threw his considerable influence onto vitamin C, suggesting that megadoses of the compound—up to 3 grams in some instances—provided protection against viral pathogens such as the common cold and influenza. The scientific community had later discovered that Pauling’s data was weak, to say the least, as he had only one test subject—his wife. Unfortunately, the damage had been done, and many vitamin C myths persist today, complicating potentially beneficial roles.
Yet now, a team of researchers has published new data showing that supplementations of the epigenetic cancer drug called decitabine (5-aza-2'-deoxycytidine) with vitamin C enhanced the drug's ability to impede cancer cell growth and trigger cellular self-destruction in cancer cell lines. Previous research has found that many cancer patients are deficient in vitamin C, and the researchers were interested testing chemotherapeutic agents with levels of vitamin C that would correct the deficiency and not overload the patients.
Interestingly, a pilot clinical trial based on this work is currently ongoing in adult patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) at Rigshospitalet in Copenhagen, Denmark. This trial combines a similar drug called azacitidine—the standard of care therapy—with vitamin C.
“If the pilot trial is successful, we plan to pursue a larger trial to explore this strategy's potential as a straightforward and cost-effective way to improve the existing therapy for AML and MDS,” explained co-senior study author Peter Jones, Ph.D., D.Sc., chief scientific officer at the Van Andel Research Institute (VARI) and co-leader of the Van Andel Research Institute-Stand Up To Cancer (VARI-SU2C) Epigenetics Dream Team. “At the same time, we must urge patience and caution. Only a clinical trial that combines azacitidine with the blinded addition of either vitamin C or a placebo will give the true answer as to whether or not vitamin C increases the efficacy of azacitidine in patients. We must emphasize that our trial is limited to a certain subset of patients with MDS or AML on a specific therapeutic regimen. We do not have evidence that this approach is appropriate for other cancers or chemotherapies.”
For the recently published article, the investigators looked at the effect of vitamin C addition could have on cancer cell lines when combined with methyltransferase inhibitor drugs.
“Here we show how this [vitamin C] deficiency may influence the use of DNA methyltransferase inhibitors (DNMTis) for the treatment of hematological neoplasias,” the authors wrote. “In vitro, when vitamin C is added at physiological levels too low doses of the DNMTi 5-aza-2′-deoxycytidine (5-aza-CdR), there is a synergistic inhibition of cancer-cell proliferation and increased apoptosis. These effects are associated with enhanced immune signals including increased expression of bidirectionally transcribed endogenous retrovirus (ERV) transcripts, increased cytosolic dsRNA, and activation of an IFN [interferon]-inducing cellular response.”
The findings from this study were published recently in Proceedings of the National Academy of Science (PNAS) in an article entitled “Vitamin C Increases Viral Mimicry Induced by 5-Aza-2′-deoxycytidine.”
In the pilot clinical study, the scientists proposed a strategy that reflects a continuing move toward combination therapies, particularly when it comes to epigenetic approaches, which target the mechanisms that control whether genes are switched “on” or “off.” In many cancers, these switches improperly activate or silence essential genes, such as those that regulate cell growth and life cycle, ultimately leading to tumors. Epigenetic therapies are thought to work in two ways to fix these errors in cancer cells—by correcting the “position” of the gene switches and by making the cell appear as though it's infected by a virus, triggering the immune system.
“This type of combination therapy is promising, but more work is needed to determine its safety and efficacy,” noted co-senior author Kirsten Grønbæk, M.D., D. Sc., chief hematologist and professor at University of Copenhagen's Rigshospitalet and a member of the VARI-SU2C Epigenetics Dream Team. “It is truly exciting to consider that there could be a simple and elegant approach to help patients fight MDS and AML. However, as a physician, I strongly urge patients to wait for the results of the clinical trial and to discuss all dietary and supplemental changes with their doctors.”
While the authors are optimistic about their findings and future results, they stressed the need for patience to wait for the results of the clinical trial. Maintaining proper nutrition is an important part of cancer therapy. Patients are strongly urged to consult their doctors before making any change to their nutrition or vitamin regimen. Use of vitamin C may preclude patients from participating in a clinical trial.