A recent paper in Cancer Research examined the impact of Vitamin C exposure on the effects of radiation in pancreatic cancer. Using cell lines and patient derived xenografts (human tissues implanted and grown in mice), these investigators showed that Vitamin C potentiated the therapeutic benefit of radiation.
This work continues earlier studies of Vitamin C in cancer that included Linus Pauling’s controversial studies in the 1970’s to more recent mechanistic studies published in the Proceedings of the National Academy of Science (PNAS) and in the Annals of Oncology in 2008.
Many sophisticated scientists have disagreed over both the theory and the substance of this work but one of the world’s greatest living biochemists, Bruce Ames, PhD former head of the Department of Biochemistry at Berkeley and now the director of the CHORI Institute in Oakland, California, among others, maintains an active interest in the scientific principles that underlie this field of investigation.
Much of the controversy surrounds Vitamin C’s possible modes of action as well as the comparatively high concentrations (in the micro-molar range) needed to achieve the desired effect.
As to the first point, it is increasingly evident that Vitamin C, known for its anti-oxidant properties, can also function as a “pro-oxidant”. Pro-oxidants actually introduce higher levels of toxic free radicals into their surroundings which can cause both harm and therapeutic benefit. It is Vitamin C’s role as a pro-oxidant that is now believed to underlie the effects seen in pancreatic cancer treatment.
The second point regarding achievable concentrations can be addressed through the intravenous administration of Vitamin C. Several studies have confirmed that IV Vitamin C can be administered safely and that blood concentrations can approximate those found in the laboratory experiments.
An examination of the literature reveals a phase I clinical trial for Stage IV pancreatic cancer patients in which the combination of IV Vitamin C plus Gemcitabine provided a mean survival for those completing 8 weeks of therapy of 13.2 months. Although direct cross trial comparisons are difficult, the results are provocative when compared with the median overall survival for FOLFIRINOX of 11.1 months and Gemcitabine/Abraxane of 8.5 months.
There are many lessons to be learned.
One is that entrenched naysayers often demonize their opponents rather than examine their data. Shakespeare’s Hamlet “The lady doth protest too much, me thinks,” reveals an individual whose faux indignation is used as cover for their unwillingness to confront an uncomfortable truth. We also realize that clinical trials must be carefully designed to correctly test hypotheses. Vitamin C tablets used in earlier studies were ill chosen as they lack the capacity to achieve the desired blood levels that can only be delivered by IV formulations. In addition the possible modes of action may not have been well understood by the earlier trialists. Most important is that “good science will out”, as smart thinkers generally trump bad testers (clinical trialists).
Despite the contemporary academic community’s overarching disapproval of metabolic medicine, the future of cancer research will almost certainly lie within the very realms of biochemistry, enzymology and metabolism that our molecular biology brethren left behind as they leapt giddily onto the genome science bandwagon.
There is preliminary data to suggest that Vitamin C, under appropriate conditions, may offer benefit to patients with metastatic pancreatic cancer. Our laboratory is engaged in these studies as we explore potential synergy and/or additivity for Vitamin C combinations with chemotherapeutics.
Pancreas cancer is an urgent, unmet need and we should use every tool at our disposal to advance therapeutics for this challenging diagnosis. The results with Vitamin C exemplify our need to expand the scope of interests beyond our comfort zones when we face such difficult problems. Our laboratory has redoubled its efforts in pancreatic cancer treatment. Perhaps Vitamin C will prove to be an unexpected ally in this important pursuit.