View Full Version : Comment re: Vitamin C Antagonizes the Cytotoxic Effects of Chemotherapy.

11-01-2009, 04:05 PM
Comment re: Vitamin C Antagonizes the Cytotoxic Effects of Chemotherapy.

Espey MG (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Espey%20MG%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Chen Q (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Chen%20Q%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract), Levine M (http://www.ncbi.nlm.nih.gov/pubmed?term=%22Levine%20M%22%5BAuthor%5D&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsP anel.Pubmed_RVAbstract).
Molecular and Clinical Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health, Bethesda, Maryland.
To the Editor: On the basis of cell and animal experiments with dehydroascorbic acid, Heaney and colleagues state, "These results suggest that supplementary vitamin C may have adverse consequences in patients receiving cancer therapy" (1). Selectively referring to dehydroascorbic acid as vitamin C throughout the majority of this work may send a clouded message to patients and their caregivers. All known actions of vitamin C are mediated by the reduced molecule ascorbate, not the oxidized molecule dehydroascorbic acid. Mice lacking the tissue transport protein specific for ascorbate (Slc23a2) do not survive because of severe vitamin C deficiency, despite having no impairments in dehydroascorbic acid transport (2). The suggestion that "...study conditions were relevant to clinical conditions" (1) should be viewed cautiously. Compared with cells devoid of any ascorbate, researchers attenuated cytotoxicity to antineoplastic agents in vitro (11-27%) by prior treatment with 500 mumol/L dehydroascorbic acid, which rapidly elevated intracellular ascorbate concentrations up to 18 mmol/L within 1 hour (1). In vivo, numerous reductive systems ensure plasma concentrations of dehydroascorbic acid do not exceed 1 mumol/L (3, 4). Although alluded to, the actual level of dehydroascorbic acid formed endogenously within the oxidative environments of tumors was not measured in either this (1) or the previous studies cited by this group (5, 6). Most cells in vivo, including cancer cells, maintain a constant intracellular ascorbate concentration of 1 to 5 mmol/L, which never decreases to zero. Data collected in vitro by comparing two extremes, 0 and 18 mmol/L ascorbate for instance, are implausible with regard to tumors and other tissues in general. The investigators conclude that "This finding could have important clinical relevance given the wide use of vitamin C as a nutritional supplement" (1). However, to produce an effect in xenografted mice, a course of 8 x 250 mg/kg dehydroascorbic acid was administered intravenously (1). This regimen does not simulate oral ingestion of vitamin C supplements. In fact, irreversible diabetes can be induced in rats after intravenous injection of 700 mg/kg dehydroascorbic acid (7). Because meaningful differences exist in regard to chemistry, bioavailability, and metabolism, it may be imprudent to connect data gathered with dehydroascorbic acid to vitamin C (ascorbate) and oral supplements. Numerous randomized human clinical trials have not shown decreased chemotherapeutic efficacy with dietary supplement usage, including vitamin C (8). Scientific dialogue on the subject may benefit from further preclinical testing of oral vitamin C (ascorbate) supplementation and cancer treatment in addition to experiments deigned solely with dehydroascorbic acid. Disclosure of Potential Conflicts of Interest No potential conflicts of interest were disclosed.

PMID: 19843868 [PubMed - as supplied by publisher]

11-02-2009, 07:12 AM
Rich, thank you for this post. It points out the importance of early research and the need for continued investigation. I am pasting one of the original articles discussing the study. I think it is too early to make a decision based on this and the research is split in both directions. It is a very interesting area of research.

October 1, 2008, 9:46 am
Vitamin C May Interfere With Cancer Treatment

Many people gobble big doses of vitamin C in hopes of boosting their immune system and warding off illness. But new research shows that in people with cancer, the vitamin may do more harm than good.
Researchers at Memorial Sloan-Kettering Cancer Center in New York studied the effects of vitamin C on cancer cells. As it turns out, the vitamin seems to protect not just healthy cells, but cancer cells, too. The findings were published today in the journal Cancer Research.
“The use of vitamin C supplements could have the potential to reduce the ability of patients to respond to therapy,” said Dr. Mark Heaney, an associate attending physician at the cancer center.
Dr. Heaney and his colleagues tested five different chemotherapy drugs on cancer cells in the laboratory. Some of the cells were first treated with vitamin C. In every case, including a test of the powerful new cancer drug Gleevec, chemotherapy did not work as well if cells had been exposed to vitamin C. The chemotherapy agents killed 30 to 70 percent fewer cancer cells when the cells were treated with the vitamin.
A second set of experiments implanted cancer cells in mice. They found that the tumors grew more rapidly in mice that were given cancer cells pretreated with vitamin C.
The researchers found that just like healthy cells, cancer cells also benefit from vitamin C. The vitamin appeared to repair a cancer cell’s damaged mitochondria, the energy center of cells. When the mitochondria is injured, it sends signals that force the cell to die, but vitamin C interrupts that process.
“Vitamin C appears to protect the mitochondria from extensive damage, thus saving the cell,” Dr. Heaney said. “And whether directly or not, all anticancer drugs work to disrupt the mitochondria to push cell death.”
Dr. Heaney measured the buildup of vitamin C levels in cells and said that the levels of vitamin C used in the experiments were similar to those that would result if a patient took large doses of the vitamin in supplement form. Earlier research at the cancer center showed that vitamin C seems to accumulate within cancer cells more than in normal cells.
Patients should eat a healthy diet that includes foods rich in vitamin C, Dr. Heaney said, but it’s the large doses of vitamin C in tablet form that are worrisome.

Ellie F
11-02-2009, 09:02 AM
It always seems to be the stuff in tablet form that causes the problems. Vitamins and minerals sourced naturally don't seem to present such a problem.I suppose once we mess with nature we change the biochemical balance with unknown effects

11-02-2009, 09:41 AM
Well said. There is a synergy in food that cannot be replicated in pill form. We know without a doubt (and backed by research) that a good diet is the best defense.

11-02-2009, 09:52 AM
I remember the big splash on this last October. my mom was hospitalized and I was just about body blocking the Onco floor nurses who were coming around with C supps.
The newer article reminds me of what a naturopath told us last November. it matches up with the quote from above:
"Because meaningful differences exist in regard to chemistry, bioavailability, and metabolism, it may be imprudent to connect data gathered with dehydroascorbic acid to vitamin C (ascorbate) and oral supplements. Numerous randomized human clinical trials have not shown decreased chemotherapeutic efficacy with dietary supplement usage, including vitamin C "

Not sure it's it's a pill vs food issue here. Sounds like Heaney may have used an unsuitable analog in questionable research. Shouldn't this be settled by now? Has there been other studies with the more typical form of C supp?

11-02-2009, 10:10 AM
I don't know of any randomized human trials that have been able to definitively determine that vitamin c did not interfere with chemo. I would be very interested in seeing these trials. I search PubMed and could not find anything. Unfortunately, it is a very difficult thing to prove in human trials because there are so many other factors that can interfere. For instance, people with the "same" cancer diagnosis receiving the same treatment can have very different response rates. If a patient taking vitamin C had a worse response than a patient not taking vitamin C one might conclude that it was the vitamin C that caused the poor response but there is no way to determine if that patient would have responded poorly despite the vitamin C. In human studies the factors of genetics, diet, activity, socioeconomic status and others all interfere. I don't know what form of vitamin C Heanly used in his studies. It is an interesting point.

11-02-2009, 10:20 AM
maybe contacting the researchers (Espey)would shed light on this

11-02-2009, 12:28 PM
I don't know about the interaction of Vitamin C with chemo, but I do know that my rads onc did not want me to take my normal vitamin C pill while having rads therapy. She said it was controversial, but she perferred I not take it until therapy was completed.


11-02-2009, 06:17 PM
In an instance of a 6 week rad period, probably not worth wrestling with the issue. In a long term scenario, still wanna know.