Undeterred, they published a follow-up study in that purported to confirm the findings of their study.
It was little better. Pauling and Cameron used many of the same patients and selected a different control group, but the patients were still not matched for stage of cancer, age, or performance or nutritional status. It, too, was a shockingly poorly-designed study, even for a retrospective study. Three decades later, I have to wonder how these studies saw print.
It turns out that they were originally published in the Proceedings of the National Academy of Sciences , which is not a clinical journal. What is not really known much outside the scientific community is that thirty years ago members of the NAS could contribute papers to PNAS as they see fit and in essence pick their reviewers. Thus, in essence a member of the Academy could get nearly anything he or she wished published in PNAS , whether written by him or herself or a friend. Normally, this ability has not been such a big problem for quality, because getting into the NAS is so incredibly difficult and only the most prestigious scientists are invited to join.
Consequently, PNAS is still a highly prestigious journal with a high impact factor, and most of its papers are of high quality.
U-I starting new trials of vitamin C treatment against cancer
Scientists know, however, that sometimes Academy members use it as a journal of last resort to publish some of their leftover findings. All they have to do is to find a couple of sympathetic colleagues to review their manuscripts and then submit them. Even so, getting a paper published in PNAS is quite easy for an Academy member and incredibly difficult for a non-member who does not have the connections that allow him to line up an Academy member willing to act as referee and thus is forced to submit his manuscript directly to the journal.
These observations largely explain how Linus Pauling could submit such shoddy studies to PNAS and have them published.
Thus endeth my chance for ever getting a manuscript of mine published in PNAS. Eventually, three different randomized trials of high-dose vitamin C used to treat cancer were carried out by the Mayo Clinic. The first study was published in the New England Journal of Medicine in , and Pauling was not pleased.
He wrote a letter to the editor complaining that most patients had had extensive prior chemotherapy, which in his view meant that they were immunologically compromised. Given that his concept was that high-dose vitamin C somehow boosted the immune system, he thought it was an unfair trial, even though his first trial had pointed out that the patients undergoing vitamin C treatment had received standard therapy, including surgery, radiation, and chemotherapy as appropriate.
This was followed by two other randomized clinical trials , which when coupled with the first trial, involved patients and failed to find a benefit from high-dose oral vitamin C in cancer. Meanwhile, some studies were pointing out that high-dose ascorbate was not without adverse reactions, including diarrhea, and even renal failure after high-dose IV administration. Since then, among conventional oncologists at least, vitamin C as a therapy for cancer has been viewed as having no value.
It is highly doubtful that the concept that vitamin C might cure cancer and other diseases would ever have been taken as seriously as it was for as long as it has been had it not been championed by a scientific figure as towering as Linus Pauling.
Unfortunately, in his zeal, Pauling popularized his ideas not primarily by publishing in scientific journals, but mostly by writing books, giving talks, and forming his own institute to do experiments designed to prove his ideas. Indeed, when data from the experiments of a colleague at his institute, Arthur Robinson, suggested that vitamin C at the doses advocated by Pauling might actually increase the rate of tumor growth in an experimental model in mice:. Robinson, a former student and long-time associate of Pauling, helped found the institute and became its first president. According to an investigative report by James Lowell, Ph.
Shortly after reporting this to Pauling, Robinson was asked to resign from the institute, his experimental animals were killed, his scientific data were impounded, and some of the previous research results were destroyed. Robinson responded by suing the Institute and its trustees. In , Robinson and two colleagues summarized the results of four mouse studies he had carried out while working at the Pauling Institute. Nearly all of the mice developed skin cancers squamous cell carcinomas following exposure to ultraviolet radiation.
Altogether, 1, hairless mice received a total of 38 different diets. The researchers found that a the rate of onset and severity of tumors could be varied as much as fold by just modifying dietary balance; b diets with the worst balance of nutrients had the greatest inhibitory effect on cancer growth; and c no cures or remissions were observed although the researchers were not looking for this. In , Robinson commented:.
The results of these experiments caused an argument between Linus and me, which ended our year period of work together. He was not willing to accept the experimentally proved fact that vitamin C in ordinary doses accelerated the growth rate of squamous cell carcinoma in these mice.
Vitamin C increased the rate of growth of cancer at human equivalents of 1 to 5 grams per day, but suppressed the cancer growth rate at doses on the order of grams per day near the lethal dose , as do other measures of malnutrition . Of course, this could just be sour grapes after a falling out among old friends, or it could be only one side of a more nuanced story. It could also be that the acceleration of growth reported by Robinson may not be the behavior of all tumors or even most tumors in response to high-dose vitamin C. The representation of Pauling as a scientist unfairly vilified for his ideas that were outside the mainstream may have an element of truth to it, but just an element.
The whole story is not nearly so flattering to Pauling, and he deserved more than a little of the vilification heaped upon him for his vitamin C advocacy and for his role in the promotion of orthomolecular medicine , which consisted mostly of recommending megadoses of vitamins and nutrients to treat disease. Of course, falling from grace as Pauling did led to wishes for that most American of stories: His triumph and vindication, even if posthumous.
However, in the case of vitamin C as a cancer therapy, one loophole in the clinical studies that did not show efficacy is that in all of well-designed randomized clinical trials, it was oral vitamin C that was studied. It turns out that emerging data showed that ascorbate was differentially toxic to some tumor cell lines at concentration in the millimolar to tens of millimolar range.
Indeed, if you told most pharmacologists that you had a new experimental compound for the treatment of cancer or any other disease, for that matter but that it required blood and tissue concentrations of 10 mM to be effective, nearly all of them would suggest that you give up in a hurry because of how difficult it is to reach concentrations that high in humans without toxicity. The PNAS study was simply an in vitro study using five tumor cell lines that showed selective toxicity due to ascorbate in tumor cells compared to normal cells at concentrations that are achievable with intravenous doses of ascorbate.
It turns out that ascorbate was four- to twenty-fold more toxic to the tumor cells tested than to normal cells, and that cell killing depended upon hydrogen peroxide generation, as it was abrogated when cells were pretreated with peroxide scavengers. Also, he only exposed the cells to the ascorbate for one hour, even though the paper itself states that it can take several hours for a large intravenous dose of vitamin C to be eliminated from the body.
Vitamin C and Cancer
At the time I thought that the paper represented an interesting in vitro observation, but, as they say, you can kill tumor cells in vitro with just about anything if you crank the concentration high enough. In vitro experiments can generate hypotheses, but they are inherently highly artificial systems. As clinicians, we want to know if this works in vivo. Many are the chemotherapeutic agents that appear to kill cancer cells selectively in vitro but fail in animal experiments. All in all, this study was hardly a stunning vindication of Pauling. Based on the concept that only intravenous dosing can produce high enough blood levels of ascorbate and that that is the reason previous trials failed to show a benefit from high-dose vitamin C, three cancer cases were reported, all of whom received high-dose vitamin C and all of whom, it was claimed, showed much longer-than-expected survival.
The first patient of the three reported, for instance, had renal cell carcinoma with putative lung metastases and received 65 g vitamin C intravenously twice a week for 10 months. The lung metastases were never biopsy-proven to be renal cell carcinoma, leaving some doubt about them. However, in oncology generally it is always better to have a tissue diagnosis than not.
High doses of vitamin C to improve cancer treatment passes human safety trial -- ScienceDaily
The problem is that renal cell carcinoma is a tumor type that is one of the more common tumor types to be reported to undergo unexplained spontaneous remissions. This led me to ask: If the authors believed that alternative therapies like high-dose vitamin C can cure certain cancers, why did they automatically assume that it had to be the vitamin C? She again opted for vitamin C treatment, but the second cancer did not respond. The second case presented was of a man who had a primary bladder tumor with multiple satellite tumors. These were all resected with apparently clear margins transurethrally using a cystoscope.
Rather than additional conventional therapy, the man chose intravenous vitamin C and was reported alive and well nine years later. Normally, this would be a pretty poor prognosis tumor without more therapy, but, as the accompanying commentary points out, long term survival has been reported with surgical therapy alone.
Indeed, this case reminds me a lot of breast cancer patients who undergo excision of their primary tumor, forgo adjuvant therapy for alternative therapy, and then attribute their survival not to the conventional therapy surgery but rather to the alternative therapy. In addition, this patient also took a variety of other alternative therapies, leading to the question again: Why did the authors assume that it was the vitamin C?
They may be correct, but there are too many confounding factors. It could just as plausibly been the surgery. Finally, the third patient had a large paraspinous mass that turned out to be diffuse B-cell lymphoma. She agreed to radiation therapy but refused chemotherapy, opting instead for intravenous vitamin C. She, too, used a variety of other alternative therapies, including beta-carotene, bioflavonoids, chondroitin sulfate, coenzyme Q10, dehydroepiandrosterone, a multiple vitamin supplement, N-acetylcysteine, a botanical supplement, and bismuth tablets.
Besides the confounding factor of using multiple alternative therapies, the patient reported only had, as far as can be told from the case report, a Stage I diffuse B cell lymphoma. Radiation therapy alone used to be a common treatment for such tumors and is well known to be able to produce long term survival in such cases. To try to show that this was something other than Stage I disease, the authors made much of the observation that the patient subsequently developed enlarged lymph nodes in numerous other nodal basins over ten years.
However, nowhere did they report that any of these enlarged lymph nodes were ever biopsied to prove conclusively that they were recurrent lymphoma, and the only pathology result reported was from the biopsy of the paraspinous mass. It would have been very easy to do biopsies of any of the superficial lymph nodes that were reported to have become enlarged. CAM advocates love such series, though, because they allow them to cherry-pick patients. The problem is this: Even if these three cases do represent legitimate tumor responses to vitamin C, we have no idea what the denominator is.
But eating lots of food containing vitamin C is unlikely to provide our bodies with the same carefully controlled levels of purified chemicals being tested in these scientific studies. It can also be consumed in high doses via supplements. But a closer look at the research reveals that neither study used food or supplements as the source of vitamin C being tested to treat cancer.
Instead, the researchers were injecting patients or mice with very high doses of vitamin C — much higher than you could get from food or supplements directly. And the difference between injecting a molecule and getting it through what you eat is vast, says Professor Anne Thomas , a Cancer Research UK-funded scientist at the University of Leicester.
This leaves us with a question: could a high dose vitamin C jab be used to treat cancer? So far, the evidence is mixed. In the most recent studies, results tentatively support the idea that high-dose vitamin C has potential as a cancer treatment. But this is far from clear-cut. The first study tested vitamin C as a treatment in mice with blood cancer, and found that injecting high doses of vitamin C slowed down the progression of the disease.
But as mice are very different to people, this has some way to go before we can say that vitamin C will help treat cancer patients. These tests would follow only if the injections are safe. This is far from the clear-cut answer some headlines would have you believe. Some studies have suggested that vitamin C may help alleviate some of the side effects of cancer treatment.
But other clinical trials had to be stopped early due to severe side effects caused by vitamin C itself. Some studies have even suggested vitamin C could interfere with some anti-cancer drugs, with one study showing it may even protect breast cancer cells from the drug tamoxifen.