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The return of the revenge of high dose vitamin C for cancer

Somehow, I’ve a feeling we’re not in Kansas anymore—except that we are, as you will soon see.

Because I’m the resident cancer specialist on this blog, it usually falls on me to discuss the various bits of science, pseudoscience, and quackery that come up around the vast collection of diseases known collectively as “cancer.” I don’t mind, any more than my esteemed colleague Dr. Crislip minds discussing infectious diseases and, of course, vaccines, the most effective tool there is to prevent said infectious diseases. In any case, there are certain things that can happen during a week leading up to my Monday posting slot on SBM that are the equivalent of the Bat Signal. Call them the Cancer Signal, if you will. One of these happened last week, thus displacing that post I’ve been meaning to write on a particular topic once again. At this rate, I might just have to find a way to write an extra bonus post. But not this week.

In any case, this week’s Cancer Signal consisted of a series of articles and news reports with titles like:

These stories, to varying degrees, miss the point. Unfortunately, I confess that I wasn’t able to help at least one of them. A reporter happened to leave me a message Tuesday morning, which is my operating room day, and I didn’t have time to read the paper and to get back to her before her deadline. That paper, by the way, appeared in Science Translational Medicine from Jeanne Drisko and Qi Chen from, yes, Kansas University Medical Center, and indicates to me that STM‘s standards are slipping. But then, STM did publish a rather credulous paper by our old friend Ted Kaptchuk on placebos; so maybe I expect too much. Clearly STM appears to be looking for more papers on “complementary and alternative medicine” (CAM) or “integrative medicine.”

Be that as it may, a typical story describes the recently published research thusly:

People with ovarian cancer who receive high-dose vitamin C injections are less likely to report toxic side effects from chemotherapy than people who had chemotherapy alone, according to the results of a small clinical trial.

The study, published today in Science Translational Medicine1, was too small to assess whether the combination of chemotherapy and vitamin C combats cancer better than chemotherapy alone. But accompanying work in mice suggests that the two treatments could be complementary.

The results are the latest salvo in long-running controversy over the use of vitamin C against cancer. Early studies championed by Nobel-prizewinning chemist Linus Pauling in the 1970s suggested that vitamin C could help to fight tumours2. But larger clinical trials failed to substantiate those claims3, 4.

With the spin, from another typical story, being:

One potential hurdle is that pharmaceutical companies are unlikely to fund trials of intravenous vitamin C because there is no ability to patent natural products.

“Because vitamin C has no patent potential, its development will not be supported by pharmaceutical companies,” said lead researcher Qi Chen.

“We believe that the time has arrived for research agencies to vigorously support thoughtful and meticulous clinical trials with intravenous vitamin C.”

Yes, indeed. The same old tropes are there, from the claim that vitamin C has usefulness in treating cancer to the old ascorbate warriors’ lament that there’s no patent potential in vitamin C, which means that pharmaceutical companies don’t want to invest money into doing science and clinical trials on it because there’s no profit potential. Of course, I’ve written fairly extensively about vitamin C and cancer before, using it as an example of how even a two-time Nobel Prize winner like Linus Pauling could fall prey to bad science when he wandered outside of his area of expertise. Every so often these stories come up suggesting that Linus Pauling has somehow been vindicated and how vitamin C is the greatest thing for cancer patients since surgeons first discovered that some cancers could be cured by cutting them out. Inevitably, I have to throw cold water on such claims. No, Linus Pauling has not been vindicated, and, no, vitamin C for cancer is not all that great.

Also, no, contrary to what critics say, I’m not close-minded about vitamin C and cancer. Unlike so many “alternative” cancer treatments, it’s actually a chemical and, at the doses used by alternative cancer practitioners, a drug. There’s even a (very) weakly plausible mechanism by which it might work. However, in vitro, the concentrations required to provide even a whiff of a hint of antitumor activity are ridiculously high, and the same is true in animal models. Let’s just put it this way. Imagine a pharmaceutical company had developed a compound with properties identical to that of vitamin C and could thus own the complete patent on it as a drug. Given the ridiculously high concentrations and doses required in preclinical models to demonstrate a hint of antitumor activity, that pharmaceutical company would probably retire that compound before even the animal model stage because, as I like to put it, getting any useful anticancer activity out of it would be such a long run for a short slide. A good drug for cancer is, at the very minimum, active at low or reasonable concentrations against the cancer cells being targeted, and vitamin C fails miserably on that count. Worse, there are at least indications that in some cases vitamin C might interfere with chemotherapy.

Vitamin C in Kansas

So does this study change my opinion? Not really. It suggests there might be some utility for ascorbate (vitamin C) against ovarian cancer, but that ascorbate therapy for cancer still remains at best a long run for a very short slide right into the gloved ball of reality to be tagged for a third out. (OK, I’ll stop with the baseball analogies.)

The dubious reasoning begins right in the first paragraph, with the authors’ justification for “re-examining” ascorbate as a cancer therapy. Basically, they point out that the pharmacokinetics of oral ascorbate dosing is different from intravenous dosing, to the point where it is possible to obtain serum ascorbate concentrations of 10 mM (millimolar). To give those of you who aren’t chemists a rough comparison of just how high that concentration is, most cancer drugs have active concentrations in the nanomolar (nM) to micromolar (uM) range, in other words, a thousand-fold to a million-fold lower than 10 mM. For example, the IC50 (the concentration that leaves only 50% of cells alive) for paclitaxel is in the 2.5 to 7.5 nM nM range, depending upon the cell line, and 50 nM is considered a good, effective therapeutic concentration. You get the idea. You need a lot of ascorbate:

By contrast, when ascorbate is injected intravenously, tight control is bypassed and pharmacologic concentrations of ascorbate are established until excess ascorbate is excreted by kidney. Plasma concentrations greater than 10 mM are safely sustained in humans for ~4 hours (10–13). When patients have normal renal function and glucose-6-phosphate dehydrogenase (G6PD) activity, toxicity is minimal even with intravenous doses as high as 1.5 g/kg, equivalent to 105 g for a 70-kg person (2, 12). These data indicate that intravenous administration of pharmacologic ascorbate doses is safe and similar to drug administration. Therefore, the effect of ascorbate in cancer treatment is worth reexamining.

These are huge doses, consistent with previous experiments in mice with a xenograft from an ovarian cancer cell line (Ovcar5) in which 4 g/kg of ascorbate was administered twice daily for a total of 8 g/kg/day. The result was an inhibition of xenograft growth of around one-third after 30 days. Results for a pancreatic cancer cell line and a glioblastoma cell line were only marginally better.

The authors did several cell culture studies in which ovarian cancer cell lines were treated with ascorbate and various chemotherapeutic agents. The authors reported an IC50 of between 0.3 and 3.0 mM, which is still incredibly high for an anticancer drug. The authors blithely write that this is “easily achievable” with IV ascorbate. Maybe so, but given the quantities involved, if you’re going to use a drug that requires such high plasma concentrations to have activity, that activity had better be awesome. None of the activity shown in this paper can be characterized as being particularly impressive. Worse, the authors, despite testing several ovarian cancer cell lines, only tested one non-tumorigenic immortalized ovarian line, HIO-80, and, finding that the IC50 to kill HIO-80 cells was much higher than all but one of the other cell lines (SHIN3), proclaimed a high degree of specificity for cancer. Moreover, HIO-80 cells are hardly “normal.” They likely contain BRCA1 mutations. Finally, the authors only used one assay for proliferation, the MTT assay. This particular assay is very popular (I use it in my lab not infrequently) because it is faster and easier than counting viable cells and also allows for large experiments using 96-well plates. However, the MTT assay depends on the metabolism of cells to produce a dye that is detected. The amount of light absorbance due to the dye is assumed to be proportional to the number of viable cells. Usually, this assumption is reasonable accurate, but lots of things can interfere with this and render that assumption incorrect. For instance, one wonders if very high concentrations of ascorbate can interfere. I’d want to see a control demonstrating that the MTT results correspond to cell number.

In other words, if I were a reviewer for this paper, not so fast, I’d have said. I want to see the results for at least a couple of more non-tumorigenic cell lines and a control validating the MTT in the presence of so much ascorbate (even if just a reference) before I’ll let you conclude that the effects of ascorbate are highly specific for cancer over normal ovarian cells. At the very least, I wouldn’t have considered it unreasonable to ask for a couple more non-tumorigenic ovarian epithelial cell lines to be tested.

In any case, the authors also did some mechanistic studies, the results of which were consistent with the activity of ascorbate in cancer requiring the production of peroxide (H2O2), as H2O2 scavengers blocked the effect. They also did a series of experiments that indicated synergy between ascorbate and carboplatin, a common chemotherapy drug used in ovarian cancer. One area that, as a reviewer, I’d have gotten on the authors’ case was the series of xenograft experiments using ovarian cancer cell lines implanted under the skin of immunodeficient mice, specifically this part:

Two-tailed Student’s t test was performed for comparison of treated groups to control group in the cell and animal experiments, as well as for toxicity comparison between chemotherapy group and chemotherapy + ascorbate group.

No, no, no, no, no! This is some pretty basic stuff here. There are eight different experimental groups, and the authors didn’t control for multiple comparisons, as far as I am able to tell. Pair-wise two-tailed t-tests are not the correct statistical test for determining statistical significance in such a case; likely some form of ANOVA would be, given that the dataset consists of tumor weights and volumes of ascites, the latter being a common estimate of ovarian tumor burden in mouse models. Some form of ANOVA, likely factorial ANOVA, would have been the proper test, given that there are combinations of three drugs being used. Whatever the correct test is (and I’ll leave that to the statisticians out there), I know that Student’s t-test isn’t it, and that using Student’s t-test will often produce “false positives” that appear statistically significant but aren’t.

All of this, however, is the warm-up to the part of the study that got it noticed, namely the clinical trial. Without the clinical trial, this would have been yet another in vitro and animal study of high dose vitamin C that provokes a collective yawn throughout the scientific community. The clinical trial itself was a randomized prospective phase I/IIa clinical trial, which means that the trial was designed to combine an evaluation of toxicity with a pilot study to evaluate efficacy and safety. Its primary objective was to “determine the safety of high-dose intravenous ascorbate when combined with first-line chemotherapy paclitaxel and carboplatin in the treatment of advanced-stage ovarian cancer,” along with evaluation for toxicity. Consequently, the two groups were (1) standard carboplatin plus paclitaxel (Cp + Pax) and (2) carboplatin plus paclitaxel plus ascorbate (Cp + Pax + AA) according to this design:

Ascorbate dose for the Cp + Pax + AA arm was established via dose escalation initiated at 15 g per infusion titrated up to a therapeutic range of 75 or 100 g per infusion, with a target peak plasma concentration of 350 to 400 mg/dl (20 to 23 mM) (12, 13). The ascorbate infusion was given at a rate of 0.5 g/min, and 400 mg of magnesium chloride (Wellness Pharma) was supplemented into each infusion. Once the therapeutic dose was established, the Cp + Pax + AA group received ascorbate two times per week in conjunction with chemotherapy for 6 months, and injectable ascorbate was continued for another 6 months after chemotherapy completion.

In addition, the authors noted:

Two subjects voluntarily withdrew from the Cp + Pax arm before treatment commenced because they wanted intravenous vitamin C, and they were excluded from data analysis. Two subjects were removed from the Cp + Pax + AA arm because they were noncompliant with tobacco use, and one was removed from the Cp + Pax + AA arm after in vitro cytotoxic assays detected that her tumor cells were resistant to all chemotherapy. These three subjects received doses of chemotherapy and ascorbate, so their adverse events were counted, but they were excluded from the survival report (table S3). Double blinding was used at enrollment and randomization, but was not maintained during the treatment because no placebo control was used.

So what we have here is a small clinical trial with a 19% dropout rate that wasn’t even blinded. It reported zero difference in overall survival (both were, as one would expect for ovarian cancer at this stage, abysmal), and zero statistically significant difference in time to relapse/progression. In all fairness, there would have had to have been an enormous effect to produce a statistically significant effect on survival or progression in such a small study, but these are the two “hard” endpoints that would be least affected by the lack of blinding, although one notes that time to progression could be affected by lack of blinding when the definition depends on interpreting scans. It’s also hard not to note that the differences in toxicities are all in the mildest reported toxicities, grades 1 and 2 (out of a scale of 1 to 5, with a score of 1, which denotes mild toxicity that requires no intervention to 5, which is death). There were no statistically significant (or even close to statistically significant) differences in toxicities graded 3 or 4, which are the most troubling kind. Take a look at the graph:

fig4a

Then, when the authors broke it down, this is what they found:

fig4b

Notice the types of complaints with the biggest difference: gastrointestinal (which usually includes symptoms such as nausea, abdominal pain; dermatology, which usually includes itching and rashes of various types); pulmonary, which often includes symptoms of shortness of breath, cough, and the like, and renal/genitourinary, which is the only one that’s less objective. So, basically, what we have is a study that found no benefit in overall survival or time to progression (not unexpected for such a small study). More importantly, contrary to the way it was trumpeted to the press, the decrease in adverse events actually observed was limited to the least serious adverse events (grade 1 = minor, causing no limitation of activity, no intervention required; grade 2 = moderate, some limitation of activities, minimal intervention indicated) with the most potential to be subject to reporting bias, which in the context of a trial that is not blinded makes the difference reported probably meaningless. In other words, this was probably a negative study, a long run for a short slide, indeed. (Sorry, couldn’t resist.)

There’s no woo like Kansas woo

I thought it might be interesting to provide SBM readers with a bit of context about the institution from which this rather pointless study emerged. The reason that this particular study rose to the level that I thought I had to blog about it was not because a reporter contacted me about it. Rather, one of the key investigators on the study, Jeanne Drisko, recently appeared on a web chat, Can Alternative and Conventional Medicine Get Along?

This chat featured, in addition to Dr. Drisko, Dr. Josephine Briggs, the current director of the National Center for Complementary and Alternative Medicine (NCCAM) as well as an associate editor from Science Translational Medicine, Yevgeniya Nusinovich, M.D., Ph.D., who served as moderator. Dr. Jeanne Drisko’s titles include Director, KU Integrative Medicine and the Riordan Endowed Professor of Orthomolecular Medicine, and, consistent with her involvement in this study, KUMC offers its patients high dose vitamin C for cancer. The video itself was standard fair, discussed by a certain “friend,” where the Trial to Assess Chelation Therapy was incorrectly touted as a success warranting further study for chelation therapy for heart disease. However, what tweaked me to write this was Dr. Drisko’s mention at the end of her “hot off the presses” study of high dose vitamin C.

Personally, I found it instructive to take a look at the website for Dr. Drisko’s home department, the University of Kansas Medical Center Integrative Medicine Program. The first thing I noticed when I perused its website was this:

Nourishing the whole person — body, mind and spirit — and stimulating the body’s natural healing response, is our mission at KU Integrative Medicine. We combine the best therapies from conventional medicine with our integrative medicine approach, to form a comprehensive system of biomedical care.

From a patient’s very first visit with us, we attempt to uncover the underlying story that set the patient on their journey from wellness to disease. We listen. Based on our findings, we tailor a plan for each individual patient based on their lifestyle, their needs and their preferences. We consider the patient an integral part of the treatment team, and encourage patients to take control of their medical care.

Practitioners at KU Integrative Medicine include physicians, a naturopathic doctor, nurses, certified neurofeedback technicians and registered dietitians. We hope that you want to learn more about us, our services, and how we can help you forge a new path to healing and wellness.

Because Integrative Medicine attempts to dig deeper, very specialized lab work is often ordered. This also enables us to personalize your care and cater to your biochemical individuality.

Yes, it’s the same old tropes. KU claims to combine the “best of both worlds”. Unfortunately, whenever I hears that phrase, there’s another “best of both worlds” that I can’t help but think of, and it involves assimilation. Sadly, in this case the assimilation appears to involve science-based medicine being assimilated by quackery. After all, there’s a naturopath there, and naturopathy is nothing more than a cornucopia of pretty much every quackery imaginable under the sun, be it homeopathy, traditional Chinese medicine, “energy healing” modalities, and, of course “detoxification.”

However, it isn’t the fact that there’s a naturopath based at an academic medical center promising to “listen” and provide “individualized care.” That’s pretty much par for the course. In fact, it’s probably hard to find an “integrative medicine” program that doesn’t claim to “listen” and provide “personalized” or “individualized” care. Nor was I particularly surprised to see “healing foods” or neurofeedback. Nor was I even particularly surprised to see that KU offers detoxification. No, what caught my interest was the fact that KU offers “oral and intravenous vitamin and mineral therapies,” as in IV vitamin C being offered at a major academic medical center.

Orthomolecular medicine? Yes, Orthomolecular medicine, a form of quackery that posits that if the body needs some vitamins and minerals that more, more, more would be better. Indeed, it’s the quackery espoused by Linus Pauling that features, in particular, high dose vitamin C as one of its favored modalities. And guess what? The integrative medicine program at KU offers high dose intravenous vitamin C to its patients. It even has a FAQ about vitamin infusions on its site. What’s really scary, however, is this:

How do I know if the intravenous vitamin C therapy will work for my cancer?:

Each individual responds differently, and we can’t predict how different tumor types will react. A PET scan is usually a guidepost. If the PET is positive, the tumor usually responds to the vitamin C. If the PET is negative but there is active tumor present, the vitamin C is less effective in most cases. Vitamin C works best in the early stages of cancer when used in conjunction with chemotherapy or radiation. They will only consult patients who are also following along with a traditional oncologist.

It’s even said that there are “no contraindications to giving intravenous vitamin C with any chemotherapy when proper protocol is followed” and that the only chemotherapy that intravenous vitamin C doesn’t work with is methotrexate “because of urine pH requirements.” Upon what evidence is this based? Well, before it was minimal. One study examined on intravenous vitamin C. It was an in vitro and xenograft study (i.e., preclinical), and Dr. Drisko wasn’t even the corresponding author. Another study was a case series involving two patients. The third was a review article. None were particularly impressive. After this study, the evidence still remains unimpressive.

But that’s not all.

It turns out that Dr. Drisko has a rather dubious honor (dubious, at least to me; no doubt she doesn’t consider it so). I’m referring to her title of Chair of the Alliance for Natural Health USA. Yes, ANH-USA is one of the premier “health freedom” organizations in this country, “health freedom” in reality meaning advocating for freedom from pesky government regulation that might interfere with the selling of supplements. She’s also an advisory board member for the Institute for Functional Medicine. Functional medicine, a nebulously defined “specialty,” is pure pseudoscience, as has been described before. Perhaps the most famous practitioner of “functional medicine” is Dr. Mark Hyman, who promotes it under the title of “Ultrawellness.” In fact, the sad thing is this:

Dr Drisko teaches a fourth-year medical student elective in integrative medicine along with other teaching duties to 1st and 2nd year students, nursing students, and practicing physicians. A fellowship program in integrative medicine for primary care physicians began in 2008 under Dr Drisko’s leadership. She was nominated by the University of Kansas Medical Student Assembly to receive the Rainbow Award for Excellence in Teaching the Art of Medicine.

Dr Drisko serves the School of Medicine at KU Med by sitting on multiple committees, provides guidance for the State of Kansas on topics in integrative medicine, and participates at the national level on CAM initiatives. Dr Drisko is a member of the Kansas Cancer Research Institute and an advisory board member of the General Clinical Research Center at the University.

Meanwhile, the website for KUMC helpfully tells patients:

Will my insurance cover the costs of the vitamin C infusions?

They will not cover them in most cases. Alternative medicine doctors must use billing codes that are not usually accepted by insurance companies. And because vitamin C infusions are not FDA approved, insurance companies are not inclined to cover costs. Vitamin C infusions range in price from $125.00 to $160.00.

Good to know.

Yes, you read that right. An academic medical center is trying to facilitate patients going to alternative medicine practitioners who administer high dose vitamin C.

Depressingly, Dr. Drisko is intimately involved in the education of the next generation of doctors in Kansas and has started an “integrative medicine” program for primary care physicians, the better to “integrate” woo into real medicine. This latest highly unimpressive study being touted as evidence that high dose intravenous ascorbate/vitamin C therapy is anything other than a long run for a short slide (oops, there I go again!) is merely part of the campaign to insinuate quackademic medicine even more firmly into the mainstream than it has regrettably already succeeded in doing.

Posted in: Basic Science, Cancer, Clinical Trials

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366 thoughts on “The return of the revenge of high dose vitamin C for cancer

  1. PMoran says:

    I had been awaiting the results of this study. I suspect that they were hoping that the IV vitamin C would have a dramatic effect upon survival, but then had to salvage what they could from it.

    One question is whether the side effects were less (if a confirmed finding) because vitamin C in those doses interferes with the activity of the chemotherapy in some way.

    I note the Riordan connection. After some decades of the use of high dose IV vitamin C his group could only find about three doubtful responses. You wonder what it takes to discourage some enthusiasts. I suppose cancer is something that encourages gambling on long odds.

    1. Andrey Pavlov says:

      You wonder what it takes to discourage some enthusiasts.

      Hmmm. Yes one does wonder, one does. It seems that diagnoses with no definitive cure such as chronic pain and particularly ones with a high likelihood of mortality such as cancer really do encourage gambling on anything that “might” work, regardless of the odds.

      1. Ed Palonek says:

        Just tlike the surgergrantees from otherapy and radiation that “might work”. The measure of efficacy of patented conventional treatment when it come to cancer survival is limited to a 10 year period. I have not heard ANY grantees from oncologists. Off the record, an oncologist friend, suggested if she ever had the misfortune of being diagnosed with cancer that she would explore every avenue of treatment.

    2. MBMD says:

      I guess you have plenty time in your hands to BASH the more useful than you. Ascorbate.

  2. Laurens says:

    I wonder whether the bad vitamin studies get all the publicity. All in all, 2014 has so far been a pretty bad year for vitamins and supplements. A Swedish study found that antioxidants (N-acetylcysteine and vitamin E in this case) actually accelerate tumor growth because they eliminate the free radicals that fight the cancer. The study was published in… Science Translational Medicine :

    http://www.ncbi.nlm.nih.gov/pubmed/24477002

    If you’re an aspiring athlete, it’s best to go easy on the vitamins, a Norwegian study demonstrates:

    http://www.medicalnewstoday.com/articles/272023.php
    http://www.ncbi.nlm.nih.gov/pubmed/24492839

    Athletes who took vitamin C and E supplements (1000 mg and 235 mg respectively) increased their maximum oxygen intake, but no more than those in the placebo group. However, markers for the production of new muscle mitochondria only increased in the placebo group. Vitamins seem to hinder new muscle build-up.

    1. Peter H Proctor says:

      No surprise. Oxidative stress (e.g., due to minor muscle injury with exercise) is an important driver of muscle development….

  3. Rachelle says:

    My friend who recently died had been receiving vitamin C injections for ovarian cancer. Made no difference to her cancer whatsoever. Neither did the mistletoe therapy or any of the many other quack therapies she so desperately tried in the last 20 months of her life. I wish these people would stop making money out of the dying and desperate. How do they sleep at night!

  4. The BBC article has been edited, presumably following complaints. The headline now reads “”Vitamin C ‘gives chemotherapy a boost’”.

    1. David Gorski says:

      Except that it doesn’t, except maybe in cell culture and one animal model.

  5. nutrition prof says:

    And here I was, thinking anti-oxidants have the potential to reduce cancer therapy effectiveness by interfering with the production of the free radicals that are supposed to destroy cancer cells.
    When a colleague’s breast cancer recurred, her doctors told her it was bc of the antioxidant supplements she was taking-she was told the pills interfered with her treatment (nothing like blaming the patient).
    If only we had a set of rules that never changed, never waivered, withstood the test of time.
    Oh, wait, then we wouldn’t be scientists/skeptics.

    1. Peter H Proctor says:

      The emerging model of oxidative stress and cancer is that by inducing mutations and positively-driving cancer growth factors, oxidative stress causes and maintains cancer, as much as anything does. In fact, increasing oxidative stress is positively selected for, e.g., by deleting protective systems such as SOD3.

      But oxidative is also detrimental to cancer cell survival, say, by physical damage to DNA, etc. and by inducing apoptosis. So typical cancer cells represent a delicate natural-selection based balance, always on the edge of oxidative-stress-induced apoptosis. Sometimes selection even selects for restoring SOD3 activity. Chemotherapy takes advantage of this by driving cancer cells over into apoptosis with an acute hit of further oxidative stress.

      Thus, in theory antioxidants can have opposite effects. They can induce apoptosis at the same time they may protect the cancer cell from oxidative stress.

      Experiment (some of it ours) indicates that both processes can happen in the same cell at the same time. Thus (e.g.) SODs and SOD-mimetics protect against chemotherapy-induced toxicity while at the same time showing significant anticancer activity. E.g., See: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0069485

  6. David Gorski says:

    I note the Riordan connection. After some decades of the use of high dose IV vitamin C his group could only find about three doubtful responses. You wonder what it takes to discourage some enthusiasts.

    Yeah, I should have thrown in a couple of sentences about the Riordan connection. As for why people cling to high dose vitamin C, I don’t know. Despite the spin, vitamin C is about as useless a cancer treatment as I can imagine. Why do so many people refuse to admit this after so many experiments that, in aggregate, clearly lead to the conclusion that, even putting the best possible spin on the body of data supporting its use against cancer, ascorbate has at best very modest antitumor activity—but only at ridiculously high concentrations that require equally ridiculously high doses to attain. A more realistic assessment is that, even if ascorbate does have that exceedingly modest antitumor activity (which it probably does not), the work and doses required to get that modest benefit are just not worth it.

    Yet vitamin C never dies. Every time there’s a study that seems to bury it, it’s never long before it rises again from the grave.

    1. windriven says:

      “Why do so many people refuse to admit ”

      Why indeed? Why, given the long, difficult, intricate effort to develop the underpinnings of science based medicine – and in light of the dramatic improvements to the human condition that it has brought – why are there so many who gleefully abandon the effort and embrace discarded ideas and just plain quackery?

      It would seem to me that anyone trying to reassert the utility of ascorbate in cancer therapy should recognize the necessity of elucidating a clear mechanism of action. Otherwise, we are just churning old water.

      This is the case with all too many pseudo-scientific claims: acupuncture, homeopathy, chiropractic; we’ve been there and done that. It is no longer enough to claim that if you squint your left eye and look at it just right it seems to work when the new moon falls on a Friday.

      Research resources are scarce. Pissing them away to prove that bicycle tires are square is reckless and wasteful.

      And stupid.

  7. Angora Rabbit says:

    David, can you help me understand some of your objections. My understanding of Mark Levine’s work (and I’m speaking of Mark, not Drisko) is that the proposed action of IV ascorbate is completely independent of *any* nutritional action. Mark did the best pharmacokinetic studies on human ascorbate requirements that we’ll likely ever get, and steady state ran ~60uM. It’s very clear that the putative pro-oxidant action of ascorbate would be 50-100-fold greater, as you say at the low mM range. That fold-change isn’t out of line with other ratios of endogenous vs. pharmacological levels, retinoic acid/Accutane being a poster child wherein we use 50-100-fold increases above endogenous levels to achieve pharamacological benefit.

    I agree that anyone claiming that this actions of ascorbate have any relationship to its endogenous or nutrient actions is feeding a line of horse poo. And my understanding of what Mark is studying – and Mark has said this to me as well – is the same. He’s no more a believer of Uncle Linus’s nonsense than I am – great chemist, failure as a nutritionist. Even Uncle Linus couldn’t be brilliant at everything.

    If it turns out that low mM serum ascorbate doesn’t have the benefit suggested from the animal work, I’m fine with that, and that’s the progression that science should take. If there are better chemotherapeutics, then I’m fine with that too. But if the objection is from the nutrient side, then it looks like one of us is missing the point, because I don’t hear Mark saying this has anything to do with its nutritional role. So please help advise here. (I can’t and won’t address Drisko, however, since I’m not convinced she thinks this way.)

    I’ve been meaning to post this question for awhile, and I guess today’s my lucky day. :)

    1. Sawyer says:

      I didn’t quite understand the concentration critique either. If mM doses are need to achieve an effect size it may be extremely impractical, but that doesn’t have anything to do with the plausibility of generating an effect. There should be huge difference in levels of ascorbic acid and “typical” chemo drugs required based on their varying pharmokinetics.

      On the other hand I don’t think Levine’s work is the primary focus of Dr. Gorski’s critique. Ma is the primary author so the quality of the paper ultimately rests on her shoulders. Chen and Drisko appear to be the ones overhyping this to media outlets. Even if the basic ideas that they are investigating are worthwhile I don’t think they can be excused for sloppiness, especially considering the history of vitamin C research.

    2. David Gorski says:

      My objections are in my post. The best possible thing you can say about high dose vitamin C is that it demonstrates only mild antitumor activity—and then only at very, very high concentrations that necessitate ridiculously high doses. A more realistic assessment is that it doesn’t work.

      In brief, high dose vitamin C, as used for cancer, is simply a really crappy drug.

      As I said before, let’s look at an example to eliminate the BS about vitamin C being “unpatentable.” Imagine a drug company that synthesized a lead compound with the same properties as ascorbate, so that the compound would be patentable as a drug. That company would screen the drug against a panel of common cancer cell lines and find its IC50 in the mM range. That would be it. The lead compound would be tossed aside as not worth developing further because it’s not sufficiently active against cancer cells. Indeed, it’s highly unlikely that the drug company would even bother to proceed with animal experiments, much less take the compound to clinical trials.

      Seemingly endless research has been done by vitamin C advocates, none of which demonstrates any of the properties desired in a good anticancer drug, other than an apparently relatively favorable safety profile. No convincing evidence of activity in humans has been presented. Even this study doesn’t provide convincing evidence that it would likely be particularly useful as an agent to potentiate the effect of chemotherapy or even to reduce side effects. For cancer, vitamin C is a bad drug, and studies like these are the equivalent of flogging the proverbial dead horse because we’ve had plenty of data to know that vitamin C is a crappy drug for cancer since the 1970s.

      The reason no drug company or reputable scientist is interested in vitamin C as a cancer treatment is not due to some conspiracy or to “scientism” or to bias, it’s because vitamin C for cancer has none of the characteristics in preclinical studies (and now clinical studies) that indicate that it would be a useful chemotherapeutic agent for cancer.

      1. Sawyer says:

        I’m on board 100% for vitamin C being a waste of time and Chen’s absurd take on drug development. My only point was that you used the example of paclitaxel to show how high the concentrations of vitamin C were, but this isn’t really a fair comparison. The reaction kinetics for these two molecules are going to be completely different so one would expect different concentrations required. Sure it’s impractical, but it sounded like you were rejecting the idea of millimolar concentrations altogether. (I think this is how AR read it too)

        Ugh, I feel like Pmoran nitpicking at such a minute detail. Maybe it’s best to just let it slide.

        1. David Gorski says:

          Yes, I am actually rejecting the idea of millimolar concentrations in general, because there is a general consensus in drug development that such concentrations are so high as to be too difficult to achieve (and too prone to causing off target effects), making such compounds poor drugs, with precious few exceptions. (Actually, I am unaware of any exception.)

          Let’s put it this way. I’m doing research using a drug that has an IC50 in the 5 micromolar range or so. Reviewers for grant submissions express—shall we say?—considerable skepticism that this will be a useful drug or that we can achieve such a concentration in the plasma. They have a point. If this next round of grant applications doesn’t convince them, I’ll probably have to drop this line of research.

          1. Sawyer says:

            Bah, I think I’ve just got my head in the clouds thinking about what can be done in a test tube versus what doses can be achieved in human beings. I should probably know better when dealing with the vitamin C crowd. They always seem quite happy exploiting misconceptions about dosage.

            On a more serious note, what the hell is going on with Nature’s news articles? I realize they provided references to a few negative studies on cancer and vitamin C, but their coverage was still way too sympathetic to the authors. Can’t they at least pretend to be critical of Science and Nature papers?

            1. Peter H Proctor, PhD,MD says:

              Nature Is only the top-rated journal in the world. True, for decades they have messed up their news articles. Here is an example from 1974:

              Nature Vol. 248 April 5 1974, p475 ( News and Views )

              Semiconductors in the human body?

              from our Solid State Physics Correspondent

              …..Now at least one biological material has been shown to have a strikingly large conductivity when correctly excited. McGinness, Corry and Proctor, of the University of Texas Cancer Center, Houston, report in Science (183, 853; 1974) that melanins can be made to ‘switch’ from a poorly conducting to a highly conducting state at fairly low electric fields (say from 10K ohm- cm to 100 ohm-cm at a field of 300 V cm-1). This remarkable phenomenon occurs both in melanin made synthetically from tyrosine and in that extracted from a human melanoma. The large conduction is not destructive in any way and is reversible;. According to some tests, conduction seems to be electronic rather than ionic……..

              Now in the Smithsonian.

              1. MadisonMD says:

                OK, Peter. I have to admit … that is cool. Nice work.

          2. Angora Rabbit says:

            David, I can totally see your view; as a reviewer I’ve shot down many a nutriceutical study wherein the compound shows efficacy at concentrations far higher than is readily bioavailable. Having said that, ethanol operates quite nicely at the mM level; 0.08mg% is 17.4mM. But it is the exception, not the rule.

            I suppose the better approach with the ascorbate is traditional pharmacology. If it really is acting as a pro-oxidant at low mM serum levels (mid-nM at the cellular level), then screening ought to identify better compounds with a higher profile in entering the interstitial fluid and generating the H2O2 that the authors propose is their underlying mechanism.

            1. Peter H Proctor says:

              It is not just ascorbate that is needed, but something to transfers electrons from ascorbate to oxygen to make peroxide. e.g. an SOD-mimetic such as Mn Porphyrn

              Myron K. et al, “Mn porphyrin in combination with ascorbate acts as a pro-oxidant and mediates caspase-independent cancer cell death” Free Radical Biology and Medicine, Volume 68, March 2014, Pages 302-314 http://dx.doi.org/10.1016/j.freeradbiomed.2013.11.031

              “Resistance to therapy-mediated apoptosis in inflammatory breast cancer, an aggressive and distinct subtype of breast cancer, was recently attributed to increased superoxide dismutase (SOD) expression, glutathione (GSH) content, and decreased accumulation of reactive species. In this study, we demonstrate the unique ability of two Mn(III) N-substituted pyridylporphyrin (MnP)-based SOD mimics to catalyze oxidation of ascorbate, leading to the production of excessive levels of peroxide, and in turn cell death. “

              1. WilliamLawrenceUtridge says:

                It’s claiming “promise” in a phase I trial. Correct me if I’m wrong, but doesn’t a phase I trial assess only safety, not efficacy? In other words, the “success” was finding out that vitamin C isn’t poisonous, even at high doses? What’s the surprise here?

                I would love to see Dr. Gorski’s assessment of the statement “The catalysis of ascorbate oxidation by an optimized metal-based catalyst (such as MnP) carries a large therapeutic potential as an anticancer agent by itself or in combination with other modalities such as radio- and chemotherapy.” Really? “Large” potential? I’ll believe it when I see promising human trials, but I predict yet another long run for a short slide. But maybe it works in inflammatory breast cancer. If so, excellent, another treatment for one type of cancer. Always happy to see promising results.

      2. Peter H Proctor, PhD,MD says:

        There is an exception to the rule that drugs must work at low micromolar levels. Interestingly, this involves uric acid, the chief natural serum antioxidant, which likely partially replaces ascorbate in humans. In ongoing phase-3 trials for acute ischemic stroke, the goal is levels of 7-800 micromolar SUA or so.

        BTW, human urate levels greatly surpass those achievable with any possible “ectopic” antioxidant. Which does not leave much room for them to work.

        We have previously suggested that this accounts for the failure of antioxidant drugs that work in animal models in human trials. Perhaps this includes low-dose (but likely not high-dose) vitamin-C.

        Serum uric acid exhibits a “J”- shaped relationship to cancer. This implies that it might promote ca at higher levels, while offering protection at lower ones. Maybe its brother vitamin-c does the same.

  8. The emerging concensus is that oxidative stress is largely responsible for maintaining the cancer process. E.g., experimentally BRCA1, CtBP1, p53, PARP, HIF-1α, VEGF, mTOR, FOXM1, etc. are all under redox control.

    So antioxidants are often anticancer agents. E.g., See, e.g., “SOD mimetics: a novel class of androgen receptor inhibitors that suppresses castration-resistant growth of prostate” at: cancer.http://mct.aacrjournals.org/content/11/1/87.long for a review and discussion.

    Likewise, maintaining the oncogenic state of oxidative stress involves things like dropout of protective systems such as SOD1′s, etc. In turn, this plus characteristic endogenous high oxidative stress renders the cancer cell more sensitive to further oxidative stress. So oxidative stressors like Adriamycin, cis-platinum, bleomycin and radiation are differentially-toxic to cancer cells. If it works, IV vitamin-C likely works by this mechanism too.

    Stated simply– decreasing oxidative stress makes cancer cells less cancerous. Increasing oxidative stress differentially kills them. How exactly this balances off is the subject of considerable present research.

    COI– I have US patents in this area.

    1. Peter H Proctor, PhD,MD says:

      Also see: “BRCA1 mutations drive oxidative stress and glycolysis in the tumor microenvironment” at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC355

      “Importantly, treatment with powerful antioxidants, such as NAC and Tempol, induces apoptosis in HCC1937 cells, suggesting that microenvironmental oxidative stress supports cancer cell survival.”

      ” In summary, loss of BRCA1 function leads to hydrogen peroxide generation in both epithelial breast cancer cells and neighboring stromal fibroblasts, and promotes the onset of a reactive glycolytic stroma, with increased MCT4 and decreased Cav-1 expression. Importantly, these metabolic changes can be reversed by antioxidants, which potently induce cancer cell death.”

    2. WilliamLawrenceUtridge says:

      Stated simply– decreasing oxidative stress makes cancer cells less cancerous. Increasing oxidative stress differentially kills them. How exactly this balances off is the subject of considerable present research.

      Stated simply, if it were that simple, all the research in the area of cancer and antioxidants would probably be a lot easier to interpret.

      Stated even more simply – bullshit.

      1. Peter H Proctor, PhD,MD says:

        Suit yourself. I published my first paper in oxidative stress research in 1970. Some of our experimental apparatus is even in the Smithsonian collection.

        Evans MK(1), Tovmasyan A(2), Batinic-Haberle I, Devi GR., Free Radic Biol Med. 2013 Dec12;68C:302314.doi:10.1016/j.freeradbiomed.2013.11.031.

        “Mn porphyrin in combination with ascorbate acts as a pro-oxidant and mediates
        caspase-independent cancer cell death.”

        “Resistance to therapy-mediated apoptosis in inflammatory breast cancer, an
        aggressive and distinct subtype of breast cancer, was recently attributed to
        increased superoxide dismutase (SOD) expression, glutathione (GSH) content, and
        decreased accumulation of reactive species. In this study, we demonstrate the
        unique ability of two Mn(III) N-substituted pyridylporphyrin (MnP)-based SOD
        mimics (MnTE-2-PyP(5+) and MnTnBuOE-2-PyP(5+)) to catalyze oxidation of
        ascorbate, leading to the production of excessive levels of peroxide, and in turn
        cell death. The accumulation of peroxide, as a consequence of MnP+ascorbate
        treatment, was fully reversed by the administration of exogenous catalase,
        showing that hydrogen peroxide is essential for cell death. Cell death as a
        consequence of the action of MnP+ascorbate corresponded to decreases in GSH
        levels, prosurvival signaling (p-NF-κB, p-ERK1/2), and in expression of X-linked
        inhibitor of apoptosis protein, the most potent caspase inhibitor. Although
        markers of classical apoptosis were observed, including PARP cleavage and annexin
        V staining, administration of a pan-caspase inhibitor, Q-VD-OPh, did not reverse
        the observed cytotoxicity. MnP+ascorbate-treated cells showed nuclear
        translocation of apoptosis-inducing factor, suggesting the possibility of a
        mechanism of caspase-independent cell death. Pharmacological ascorbate has
        already shown promise in recently completed phase I clinical trials, in which its
        oxidation and subsequent peroxide formation was catalyzed by endogenous
        metalloproteins. The catalysis of ascorbate oxidation by an optimized metal-based
        catalyst (such as MnP) carries a large therapeutic potential as an anticancer
        agent by itself or in combination with other modalities such as radio- and
        chemotherapy.”

        MnP is an SOD-mimetic. I have a US patent on the use of another sod-mimetic in the treatment of a disease (fibrocystic disease of breast) which presages breast cancer. Vitamin-C seems to make it work better….

        1. MadisonMD says:

          I published my first paper in oxidative stress research in 1970. Some of our experimental apparatus is even in the Smithsonian collection.

          OK, Peter. I smell more BS. But you can prove me wrong. Go to the Smithsonian archive and identify which item is your experimental apparatus, and which publication of yours was it used for?

          I have a US patent on the use of another sod-mimetic in the treatment of a disease (fibrocystic disease of breast) which presages breast cancer.

          You keep stating this little irrelevant factoid for some reason. Yet, strangely, it is not listed at USPTO under your name. What is the patent number?

          Also, please tell us how any of this is relevant to your discussion with WLU? It would be relevant, for example, if it supported your claim that “decreasing oxidative stress makes cancer cells less cancerous.” WLU called BS and you give us puffery and a citation… and your citation fails to support your claim.

        2. Harriet Hall says:

          @Peter Proctor:
          “a disease (fibrocystic disease of breast) which presages breast cancer.”

          The American Cancer Society says “Neither fibrosis nor cysts increase your risk of later developing breast cancer.” http://www.cancer.org/healthy/findcancerearly/womenshealth/non-cancerousbreastconditions/non-cancerous-breast-conditions-fibrocystic-changes Apparently they don’t know as much as you do: you should educate them and get them to change what they say on their website.

          1. Peter Proctor says:

            Georgescu T, et al , Chirurgia (Bucur). 1992;41(1):10-8.Retrospective studies on the relation between fibrocystic disease and cancer of the breast with therapeutic conclusions

            “On the basis of 597 cases of benign and malignant tumoral, respectively dysplastic diseases of the breast, operated at the IInd Surgical Clinic of Tirgu-Mureş during the period 1977-1983, the authors consider the fibrocystic disease (FCD) of the II and III degree as a facultative precancerous lesion. ….The 4 cases (1.94%) of mammary neoplasms which occurred late after a mammary sectorectomy performed for FCD illustrate that the risk of mammary neoplasm in FCD is 7.4 times higher than the mammary cancer rate in women without FCD…..”

            1. Peter H Proctor says:

              A caveat on the above paper. These women had FCD bad enough to require surgical excision.

              This means severe disease, not the minor stuff over half of women develop. So a better way to say it is that women with FCD serious enough to require surgical excision have over a 7-fold (!) greater probability of eventually developing breast Ca.

              That is, it probably depends on the population. Also, the diagnosis is verified by actual tissue sampling, about as verified as you can get in medicine. So I believe it.

            2. Harriet Hall says:

              If you are right, the American Cancer Society is wrong. You should contact them immediately and get them to change what they say on their website.

              1. Peter H. Proctor says:

                Likely, the extra hazard for breast cancer is zero to small for women with low-grade fibrocystic disease. This is about 50%+ of women, depending on how you count.

                E.g., this paper from the NEJM : “Risk Factors for Breast Cancer in Women with Proliferative Breast Disease” http://www.nejm.org/doi/full/10.1056/NEJM198501173120303 . Says:

                “The presence of cysts had little effect on the risk of cancer in women lacking a family history of breast cancer. For women with both a family history and cysts, however, the risk was three times higher than that for the general population.”

                This is in line with my statement that fibrocystic disease Is not per se a precursor to breast Ca, but is caused by similar factors, the microenviornment, if you like. So it can presage breast cancer.

                So why unnecessarily scare the ladies without providing the qualifier.

                Epidemiological studies often have great difficulty discerning relative risks (RR’s) of less than (say) 1.4 or so, which is what some studies show broadly. You can see this in the broad spread of the standard deviations in the NEJM paper.

                The rule of thumb is that an RR of 2 (ie., twice the hazard) is generally-credible. An RR of 7+, as shown for FCD requiring surgical excision, is right off the charts.

              2. MadisonMD says:

                @PHP:
                You are digging yourself deeper into a hole of crazy. First you cite a 1992 study published in Romanian which draws on a grand total of 4 cases to demonstrate that the RR is 7x greater for fibrocystic breast disease that required surgical excision, without consideration of the large error in this RR measurement.

                Then you quote a 1985 NEJM study which doesn’t even mention fibrocystic disease, and use it to conflate cysts with fibrocystic disease. Even though the finding of said cysts do not correlate with increased cancer risk, you somehow twist its negative results to conclude that fibrocystic disease ‘presages’ cancer.

                Finally, you use this very shaky ground to retreat to the claim that fibrocystic disease is a marker of risk rather than a precursor lesion of breast cancer, which brings up the question of Why treat it at all?* … unless perhaps it needs to be surgically excised in which case it is already treated.

                Finally, you use all this to justify your non-existent patent (“just sent off the issue fee”) which, even if real, only proves that you convinced a few lawyers (with the extra inducement of fees) that you made some sort of discovery to treat a disease that doesn’t need to be treated.

                And all this is based on your fundamentally flawed premise that you can boil down a complex disease like cancer, hair loss, of fibrocystic disease to a simple model of oxidative stress.

                Lissen up! That’s really, really wacky, dude.

                ————
                *We can’t even agree to treat DCIS which is a precursor lesion and definitely correlates with high risk of breast cancer. And incidentally, we already have FDA-approved drugs which are proven to reduce risk of breast cancer by 50%.

              3. Peter H Proctor says:

                “..Only 5% of women with fibrocystic breast condition have the type of cellular changes, namely cellular hyperplasia, which represents a risk factor for breast cancer. When compared to a “normal population” of women, these patients have a two to six fold increased risk of breast cancer. The exact risk depends on the degree of the hyperplasia and whether atypical-appearing cells are also present. ” http://www.medicinenet.com/fibrocystic_breast_condition/page8.htm

              4. MadisonMD says:

                Well, yes Dr. Proctor, atypical ductal hyperplasia (ADH) is a risk factor for cancer. And yes, sometimes you find ADH when you excise cysts. Florid hyperplasia without atypia increases risk to a lesser extent. I’ve already said all this here. (And why you find “medicinenet” to be a better source than ACS is a mystery to me; they are not materially different but ACS is more precise).

                So your finding that 5% of excised fibrocystic lesions show hyperplasia on histopathology is not strong evidence that fibrocystic disease is a risk factor for cancer.

                Also, you still haven’t made it clear whether you imagine Tempol to be useful for preventing cancer (though this is what you imply) and, if so, why you only are considering one risk factor, that is in fact only a moderate risk factor present only in 5% of excised firbrocystic lesions.

        3. WilliamLawrenceUtridge says:

          MnP is an SOD-mimetic. I have a US patent on the use of another sod-mimetic in the treatment of a disease (fibrocystic disease of breast) which presages breast cancer. Vitamin-C seems to make it work better

          It’s funny how when Big Pharma stands to make money, any research supporting their opinions is suspect and should be discounted.

          But somehow that critical scrutiny is absent when it’s an individual, and/or vitamins are involved.

          If vitamin C “works”, it doesn’t work very well. As Dr. Gorski says – a long run for a short slide. Any other compound this unpromising would have been dropped years ago, and I don’t know why this one hasn’t been.

          Dr. Proctor. If your results are as convincing and impressive as you seem to believe them – why have they not convinced your expert peers? Why haven’t you succeeeded in dredging signal from the noise?

          1. Peter H Proctor, PhD,MD says:

            Four cases? Straw argument– More like 600 And a 7-fold increase in breast ca in this group is pretty significant. Also, I provide several other refs to the same effect– that in certain populations fibrocystic disease is associated with an increased incidence of breast cancer.

            Also, you clearly do not understand what a patent entails.

            1. MadisonMD says:

              Also, you clearly do not understand what a patent entails.

              I can’t really understand your patent because I can’t read it. It doesn’t even have a number yet… more like “Patent pending.” But I have filed a patent, thank you, so I do have at least some understanding of what it entails.

              Four cases? Straw argument– More like 600 And a 7-fold increase in breast ca in this group is pretty significant.

              It is also difficult to read your citation which is written in the obscure journal, Chirurgia (Bucharest)– I’m simply not fluent in Romanian. However the english abstract says this:

              The 4 cases (1.94%) of mammary neoplasms which occurred late after a mammary sectorectomy performed for FCD illustrate that the risk of mammary neoplasm in FCD is 7.4 times higher than the mammary cancer rate in women without FCD.

              So we are dealing with 4 cases of cancer of 206 at risk (not 500; 4/206 = 1.94%; do the math) This is apparently compared with a baseline risk of 0.26; it is unclear how they reached this latter number since it was not measured in the study and might not represent a well-matched population. Moreover, the error in the measurement of risk based on 4 cases of 206 is large as I said before. So it doesn’t really matter if 7 is a big number if that number isn’t accurate.

              Other, much better evidence with superior statistical power and published in a slightly less obscure english journal, does not support your theory that FCD is a risk factor for cancer. That’s likely why mainstream sources of information say just the opposite of what you claim, including:
              1. the American Cancer Society,
              2. The Mayo Clinic,
              3.Cleveland Clinic, and
              4.Cancer Research UK

              You must excuse us for accepting the evidence and expert opinion from these sources with more confidence than we would accept your opinion based on a single obscure questionable source.

              In any case, if you concede that FCD is not a precursor lesion of breast cancer, then you commit a logical error in trying to prevent cancer by treating it. If it were a risk factor, then you could use it, in combination with many other risk factors to identify women with the highest breast cancer risk. Then you could use increased surveillance or chemoprevention. The standard for chemoprevention is tamoxifen which is proven and FDA approved for this purpose.

              If you wanted to beat tamoxifen with TEMPOL, you will require an extremely large and expensive RCT. But even to get there, you would need to convince modern specialist that this is worth doing with outstanding preliminary evidence such as an outstanding safety profile and excellent evidence of efficacy. Unless you have this, your patent has no value, other than to decorate your CV.

              So, you are out on a limb, Dr. Proctor, despite your outstanding scientific record in the 1970′s.

              1. Peter H Proctor says:

                True, antiestrogens like tamoxiphen have some efficacy in fibrocystic disease. The problem is that antiestrogen tx drives women into artificial menopause and is thus not generally-used. And yes, I know that tamoxiphen is a partial estrogen agonist. I’m a pharmacologist, after all.

                Tempol does not produce the symptoms of an estrogen antagonist. Further, it is useful in estrogen deficiency syndromes. So its action is elsewhere, likely on one of those redox-sensitive cell growth factors such as a BRCA-1, p53, etc.

                The NCI says HIF-2a (“Tempol: A Commercially-Available Nitroxide as a Cancer Therapeutic” https://ttc.nci.nih.gov/opportunities/opportunity.php?opp_id=654253004100 ). Me, I am unable to pick from the many such factors tempol is known to modulate.

              2. MadisonMD says:

                Ummm.. Dr. Peers, you still seem a bit confused.
                (1) Fibrocystic disease doesn’t need to be treated at all.
                (2) Atypia on biopsy and other risk factors could identify women who are at elevated risk of breast cancer for whom prevention with tamoxifen (or emerging evidence aromatase inhibitor) might be indicated.
                (3) Tamoxifen does not cause menopause. Menopause has already occurred in most women who have sufficient risk to warrant tamoxifen.

                Of course you are correct that tamoxifen has side effects and is a partial ER agonist. But it does not lead to the conclusion that Tempol is either safer or more effective than tamoxifen for preventing breast cancer.

                Most early drugs tested don’t pan out. It would seem about 1 million to one that Tempol would be useful to prevent breast cancer. You would have to have extremely promising preclinical and early clinical data to test this concept since phase III chemoprevention trials typically require 10,000 subjects.

              3. MadisonMD says:

                Oops. I mixed up Peers and Proctor. Lemme get this straight.

                Peers => inositol = panacea
                Proctor => Tempol/antioxidants = treatment for FCD and baldness.

                Whew, got that straight. Sorry Dr. Proctor. You seem a wee bit more science-minded than Peers. (Though you seem to be working with an old oxidation model that largely hasn’t been validated by the past 30 years of research– likely because, although true in some specifics, the additional complexities of human biology largely obviates or limits role and effect of antioxidants.)

      2. Peter H Proctor says:

        See: “Absence of manganese superoxide dismutase delays p53-induced tumor formation” Adam J. et al at: http://www.sciencedirect.com/science/article/pii/S2213231714000111

        The first figure summarizes the concept of oxidative stress causing and maintaining the cancer process. And too much killing the cancer cell

        “In summary, these results in combination with our previous work suggest that MnSOD needs to be tightly regulated for proper cellular homeostasis, and altering the activity in either direction may lead to cellular dysfunction, oncogenesis, or death.”

  9. Denise B says:

    Who exactly is making these decision to bring quackery into our medical centers? Are they doctors? Business people? Both? Do they believe in it, or is this just a cynical way to bring in money, or are they being pressured to, and if so by whom? Who, really, is behind this?

    1. Peter H Proctor, PhD,MD says:

      The mechanism given is quite consistent with that of several important antitumor agents and with the known basic science. No guarantee of efficacy, naturally. Also, the role of oxidative stress in maintaining the cancer process is quite complicated and probably varies among tumors. It may be that IV vitamin-C works sometimes…

  10. Frederick says:

    27 patient, no blinding and 19% drop out. Just that. Me, that is all need to discard those kind of studies, i’m far far far from a guy who really understands clinical trials. I don’t understand Statistic, ( give some matrix and Trigonometry, that’s i have no problem ), That’s why i trust people on SBM to do those analysis, But i know my basic : Sample size, blinding, is the protocol to complicate. And drop out.

    Nice read again, I’m happy to have learned about concentration needed for some chemo. That’s is also a article about that on scienceblogs : http://scienceblogs.com/insolence/2014/02/10/vitamin-c-for-cancer-trying-to-rise-from-the-grave-once-again/

    1. Frederick says:

      The moment you realized what the “not-so-secret-blog” Means…

      1. Chris says:

        :-)

        It happens.

        1. Frederick says:

          I read from that other blog from time to time, now i just realized it. LOL
          I look Dumb now

  11. MadisonMD says:

    It’s even said that there are “no contraindications to giving intravenous vitamin C with any chemotherapy when proper protocol is followed”

    Well, Drisko et al.’s patient information seems to be discounting published research that shows otherwise (in cell culture and xenograft models–the best we have in the absence of human non-inferiority analysis).

    So how can she be so certain that there is no harm in giving Vitamin C along with chemotherapy?

    1. Peter H Proctor, PhD,MD says:

      Key is “when proper protocol is followed”. Presumably this means not at the same time as chemotherapy. There is a lot here unsaid that presumably the docs know, but don’t tell us. This is a pretty complicated subject. E.g., searching “superoxide” and “cancer” on pubmed gives 6000+ citations. “Redox signaling” and “cancer” gives more than 1500 citations.

      Likewise, at these levels, vitamin C is not an antioxidant but rather acts as a pro-oxidant. This is like most strong reducing substances at higher concentrations and most importantly, like several important anticancer agents, which are felt to act by over-stressing the already highly oxidatively-stressed tumor cells. It may also provide reducing equivalents to such pro-oxidant antitumor agents, enhancing their pro-oxidant properties. The mind reels.

      1. MadisonMD says:

        Key is “when proper protocol is followed”. Presumably this means not at the same time as chemotherapy.

        So what exactly is the protocol? What is the evidence that it does not antagonize chemotherapy? Or is this just a “presumption?”

        1. Peter H Proctor, PhD,MD says:

          Apparently, there are various protocols, typically involving 25-50 gm of vitamin-c. BTW, I and my associates were among those who established that adria, bleo and (particularly) cis-platinum work by inducing oxidative stress over three decades ago. Also look up my name and vitamin-C on pubmed.gov. So lissen-up.

          Present theories of oxidative stress and cancer postulate that cancer is a primarily a disease of oxidative stress, which is selected for in the tumor. Thus early on, many cancers lose protective enzymes such as SODases.

          Administration of SOD or an SOD-mimetic drug such as TEMPOL may cause such cells to apoptose. BTW, this has been known since our group and (especially) Larry Oberley’s discovered it in the late 1970′s. E.g., http://cancerres.aacrjournals.org/content/39/4/1141.full.pdf . So what I am going to say is not exactly new.

          Anyway, while oxidative stress is what maintains the cancer process, it also stresses the cancer cell. Additional oxidative stress (say from adria, or bleo) over-stresses the already oxidatively-stressed cancer cell and induces its death. IV vitamin-C is alleged to work this way. Does it– beats me. Just sayin’

          Interestingly, as the cancer process advances and oxidative stress increases, clonal selection may cause restoration of protective systems such as SOD. E.g., see:

          “Manganese Superoxide Dismutase Is a p53-Regulated Gene That Switches Cancers between Early and Advanced Stages” http://cancerres.aacrjournals.org/content/71/21/6684.long

          Anyway, the fact that cancer cells need a certain amount of oxidative stress to be cancer yet too much oxidative stress kills them explains a lot of seeming paradoxes.

          All this is “druggable”. If chemo selects for the most oxidatively-stressed tumor cells. the remaining ones may respond to treatment from the other direction, e.g. with an SOD-mimetics such as TEMPOL. For more on this, use “TEMPOL” and “cancer” as search terms on pubmed.

          COI– I have a patent on the use of TEMPOL to treat fibrocystic disease of breast, which also seem to involve a lot of oxidative stress.

          1. MadisonMD says:

            My dear Doctor Proctor,
            I simply asked whether there was a protocol for vitamin C therapy for cancer and whether there is evidence that it does not antagonize chemotherapy. The only part of your response that addresses these questions are this:

            Apparently, there are various protocols, typically involving 25-50 gm of vitamin-c.

            and this:

            IV vitamin-C is alleged to work this way. Does it– beats me. Just sayin’

            So that would be enough to answer it– you don’t know.

            Anyway, then you go on to make a bunch of claims that suggest an… shall I say? Well, yes I shall… an inflated ego.

            Also look up my name and vitamin-C on pubmed.gov. So lissen-up.

            So I did. In fact I looked up all your pubmed listings. There are 18. Not all that impressive for 4 decades of research, especially since the 7 of the last 8 were letters to the editor, the 8th was a review article, and the last peer reviewed paper was 3rd author publication in Physiol Chem Phys Med NMR in 1986. But perhaps I’m missing something. Have you published under another name?

            BTW, I and my associates were among those who established that adria, bleo and (particularly) cis-platinum work by inducing oxidative stress over three decades ago.

            Really? It’s too bad you weren’t able to publish any of the work on adriamycin or bleomycin, and were only able to publish one second-author paper in 1978 on amelioration of cis-platinum nephrotoxicity by orgotein… in Physiol Chem Phys. But I’m sure you were right there making these major discoveries on mechanism of chemotherapy action in the 1970′s… (neverminding you missed the part of the mechanism that concerns direct effects of these three chemotherapies on DNA).

            COI– I have a patent on the use of TEMPOL to treat fibrocystic disease of breast, which also seem to involve a lot of oxidative stress.

            Well, perhaps you are working on filing this yet. The only patents I can find under your name at the US PTO concern hair loss remedies by topical application of Vitamin C, TEMPO and other antioxidants.

            Good day.

            1. Peter H Proctor says:

              My patent for TEMPOL and related compounds for fibrocystic disease (FCD) is approved for issue. I Just sent in the issue fee. So it should be out in the next few weeks.

              Arguando, some breast Ca’s actually develop from FCD– see citation below. For numerous reasons, I personally doubt this.

              Likely, the same microenvironmental conditions that originate and promote breast ca also promote fibrocystic disease. Rather surprisingly, nominally benign FCD seems to be under the control of the same cell growth factors as breast ca itself. Makes ya go hmmm.

              1. WilliamLawrenceUtridge says:

                Question – is a patent the same thing as a research publication?

              2. MadisonMD says:

                same microenvironmental conditions that originate and promote breast ca also promote fibrocystic disease

                Yes, certainly. That would be the systemic hormones and the breast microenvironment… which are the conditions that originate every disease of the breast, in fact. :)

                FCD seems to be under the control of the same cell growth factors as breast ca itself. Makes ya go hmmm.

                All breast tissue is hormonally sensitive. So, actually, makes me go duh.

              3. Peter H Proctor, PhD,MD says:

                “Question – is a patent the same thing as a research publication?”

                The H-index (look it up) counts them the same. Also, you have to prove a patent has “utility”. That is , it works and does something useful. The other requirements are non-obviousness and novelty, that is, nobody has done it before.

                Anyway, nobody would apply for a patent unless it works. Too expensive and a major hassle.

                “All breast tissue is hormonally sensitive. So, actually, makes me go duh.”

                Here, I am talking about the local redox microenviornment. There is no evidence that TEMPOL (e.g.) acts hormonally. Just the opposite, in fact.

                The exception is that TEMPOL reverses the expression of androgen receptors that cause prostate cancer cells to become resistant to antiandrogen treatment. This appears another manifestation of its ability to reverse the cancer-promoting properties of ROS. Ref elsewhere on this thread.

              4. Harriet Hall says:

                “The H-index (look it up) counts them the same. Also, you have to prove a patent has “utility”.”

                I looked it up and found no reference to patents. And “utility” for patents doesn’t mean it is an effective treatment.

              5. WilliamLawrenceUtridge says:

                The H-index (look it up) counts them the same. Also, you have to prove a patent has “utility”. That is , it works and does something useful.

                I didn’t ask about the H-index, I asked if it was the same thing as a research publication. Do they contain original data? Why patent rather than publishing in the peer-reviewed press? Though I guess you’ve addressed that – personal profit.

                Also, I’ve seen patents for various quack nostroms, I’ve even added them to wikipedia. Patents can rely on in vitro studies, they do not require human results.

                Is your patent about vitamin C, the original topic of the post? Because my point is, and always has been, that research consistently fails to justify vitamin C specifically as a chemotherapeutic agent. Your chain of reasoning seems to involve saying “redox-signalling molecules play a role in cancer, vitamin C is a redox signalling molecule, therefore vitamin C is (perhaps has potential to be) a chemotherapeutic agent”. That’s a chain of reasoning whose final premise has been tested, pretty thoroughly really, and failed. Repeatedly. Sure, I suppose there’s a possibility that vitamin C is chemotherapeutic in some patients, for some cancers, when the moon is right, or whatever. But those assertions have not been proven, and in several cases have specifically been refuted.

                Merely because a vitamin is a vitamin does not make it magic, and again I don’t understand why people think that it must be magic merely because it is necessary for survival.

          2. Harriet Hall says:

            “cancer is a primarily a disease of oxidative stress”

            References, please.

            1. Peter H Proctor says:

              I provide the citations above and below.

          3. WilliamLawrenceUtridge says:

            BTW, I and my associates were among those who established that adria, bleo and (particularly) cis-platinum work by inducing oxidative stress over three decades ago. Also look up my name and vitamin-C on pubmed.gov. So lissen-up.

            Yeah. Linus Pauling won two nobel prizes, and he still ended up wrong and crazy (and died of cancer). Montagnier identified HIV as the cause of AIDS, and now he believes in homeopathy. Kary Mullis developed the technology for PCR, and now he’s an alien-believing AIDS denialist.

            Past work does not obviate the need for convincing data.

            The nice thing is, if you’re right – eventually you’ll demonstrate this fact through high-quality research. Or one of your peers, the actual experts in the area who know if you’re bullshitting or not, will. Reality is great in that fact – it’s reproducible.

            So don’t try to convince us. Publish. Or perish.

            1. Peter Proctor says:

              Again, I do not know if vitamin-C works in cancer. Just trying to make the point that this would be in accord with the well-known science. So not to be easily dismissed. Do not mean to offend , but calling this BS is wrong and shows a need to educate.

              As for “Publish or perish” ? Stopped publishing and mostly started patenting years ago. The money and lifestyle are better and IP is legally-enforcible.

              Also, not my job to educate you-all, but merely to point in the right directions. Again, go to pubmed and search cancer vs words like superoxide, redox signaling, and (yes) TEMPOL.

              Stated-simply–essentially all those oncogenes, cellular signaling factors, etc. are under redox control. In fact, because of it druggability, this is arguably the hottest area in oncology right now. Some samples:

              This paper contains a graphic illustration of the role of oxidative stress in ca causation and treatment: http://www.sciencedirect.com/science/article/pii/S2213231714000111

              http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0070575

              http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3552923/

              Also See:
              smithsonianchips.si.edu/proctor First demonstration of what is now called redox signaling in macromolecules. First identifiable organic semiconductor electronic device. From a cancer hospital.

              P. Proctor, Free Radicals and Human Disease, a Review
              CRC Handbook of Free Radicals and Antioxidants, vol 1 (1989) pp 209-221. To be invited to do a review in a crc handbook is a pretty good endorsement.

              and

              “An in vivo enzymatic probe for Superoxide and Peroxide by Chemotherapeutic Agents” Pathology of Oxygen,(1982) ed. A. P. Autor, Academic Press, New York, pp.1982

              Roughly: The antitumor action and toxicity of adriamycin, cis-platinum, and bleomycin involve reactive oxygen species (ROS). Ectopic superoxide dismutase is roughly-equivalent to adriamycin as an anticancer drug. That is, ROS are cellular messengers in cancer.

              Just because all these agents generate ROS does not mean they don’t do it while DNA-bound. Oxidative stress does a lot of things, including damaging DNA. Present model is that this pushes the already oxidatively stressed ca cell over the threshold to apoptosis.

              True, tempol is hair loss agent: Here is an example of this patent being applied clinically: http://clinicaltrials.gov/show/NCT00801086

              As for trials: To date, my work with uric acid as an evolutionary replacement for ascorbate ( http://www.nature.com/nature/journal/v228/n5274/abs/228868a0.html ) has resulted in several clinical trials using urate as a neuroprotectant for Parkinson’s, acute ischemic stroke (phase-3), and MS. Not to mention that I had a piece of NXY-059 for stroke. Disappointment, that. I could go on….

              1. WilliamLawrenceUtridge says:

                Just trying to make the point that this would be in accord with the well-known science

                …except for the fact that basically every study that has been done on vitamin C as a chemotherapeutic agent has come up null, or at best a very, very small effect.

                Again, go to pubmed and search cancer vs words like superoxide, redox signaling, and (yes) TEMPOL.

                Given the blog post and the fact that I pay very little attention to the specifics of your post, I’m merely going to point out the complete lack of good-quality emprical evidence supporting vitamin C as a cancer treatment, as conducted in actual patients. Stated simply, when you give vitamin C to cancer patients, it really doesn’t seem to help.

                All the hypotheticals in the world don’t matter if the in-humans results are null.

  12. rork says:

    Maybe this will provoke some biologists:
    Using two-sample T-tests when there are more than 2 groups and you could have used an ANOVA model to model the data for all of the groups is not cheating usually – it can be inefficient is all. It’s not clear from my brief reading whether they log-transform the data for things like Fig 3 A, B, C (Tumor weight, ascites volume, # non-blood cells), and that might be why they resorted to the Welch trick in some cases (which ones, we don’t know). And by Darwin’s liver could we plot those things on log-scaled Y-axes? If we did that we wouldn’t need the silly two-scales tricks, and we could see if there is greater than additive effects or not with our own eyeballs. These “bar graphs” on non-logs are dreadfully common, folks say “that’s what everyone does”, but much of their popularity is that they are bad. I’ve even seen people plot cell numbers of growing populations on non-logs – unglaublich! In Fig 3 there are 10 or more replicates per group, so summarizing with mean and standard deviation (or error) is useful (though I might still have shown the actual data myself), but these days folks will give you just those summary statistics even when there are only 3 or 4 samples per group and they could have easily just plotted the damn data (but it “looks worse”). In RT-PCR studies folks commonly plot on anti-logs even when the statistical tests are in log-space, and it is the mean and standard deviations of the logs that matter, not the statistics about the anti-logs.

    I felt no need for them to correct for multiple comparisons – they give the p-values and I can see about how many tests interest me. My opinion about the AA+Cp vs Cp difference is not much affected by whether they bothered to test AA vs control or not.

    Perhaps the most objectionable math was for Fig 4 C and D. For C, I think they are saying (methods) they tried log-rank tests but apparently “forgot” to report the result of that – and just giving the result (e.g. “p=.41, log-rank test”) would have been shorter than the sentence they supply in methods about how to do it. For 4D there are 22 pieces of data, not 25, and I suspect they are ignoring the data in 3 cases where there is right-censoring – the proper way to deal with censored time-to-event data is to show the Kaplan-Meier plot as in 4C and to give the damn p-value from the log-rank test – they know how to do that, but didn’t. In both cases every good reader wants to know exactly that result, but author does not provide it. Perhaps reviewers weren’t good readers, since they should have demanded that be fixed. If a certain analysis of data is knee-jerk and every good reader wants it, supply that analysis.

  13. WBailey says:

    Vitamin C reappearing constantly makes sense to me, from an economic standpoint. The raw material is cheap, allowing higher profit margins. It also has universal brand recognition, without the average consumer/victim really knowing anything about it.

    1. MBMD says:

      I trust the mr Ascorbate more than I trust an traditional quacker MD

    1. windriven says:

      Love the xkcd

  14. middleground? says:

    For the past year I’ve literally studied hundreds of peer-reviewed papers on Vitamin C pharmacology and have noticed two ends of the spectrum in the belief in Vitamin C.

    One side, which I undoubtedly place Dr. Qi Chen and her colleagues’ results as biased at the believer’s end of the spectrum which attempts to wrestle science onto its side, the middle of the spectrum which is often rife with experimental error, and the side Dr. Gorski comes off as being, on the opposite side which I see often rebuke the believer’s evidence without providing any of their own (experimental or literature).

    Dr Gorski, I enjoyed your analysis of the study, but I would be pleased to see your argument against vitamin c laid out with reference.

    Also, because I don’t honestly know (I only have a BS), is there a basis to your reasoning of why we should completely dismiss a potential drug on the sole reason its IC50 is so high? I would think one would have to also consider LD10 and the maximum tolerated dose, as compared to the IC50?

    Thanks!

    1. MadisonMD says:

      Also, because I don’t honestly know (I only have a BS), is there a basis to your reasoning of why we should completely dismiss a potential drug on the sole reason its IC50 is so high?

      Regarding your IC50 question most directly, very few drugs are safe and effective at above 10 uM serum concentrations. Mechanistically, this is due to off-target effects that become common with chemicals at high concentrations. This impacts the plausibility of the drug being safe/effective.

      But the true objection here is simpler than that. I (and probably Gorski) simply think the evidence for safety and efficacy, including clinical evidence, should be present before subjecting patients to a therapy off-trial. Most drugs that are promising precinically are found to be ineffective. So this makes treating with Vitamin C and collecting cash a swindle.

    2. WilliamLawrenceUtridge says:

      You might want to go into the deep links in Dr. Gorski’s posts, as well as at his not-so-super-secret-other blog. Dr. Gorski has done myriad analyses of the vitamin C-cancer link, looking at numerous individual and review articles.

      What I find irksome about the whole thing is how unshakeably convinced quacks and their followers are that there is some signal to be found in the noise. Their protestations that vitamin C is not just a chemotherapeutic agent, but a powerful one.

      Really? Then why is it so hard to demonstrate this fact? If vitamin C cut cancer deaths by 50%, even 25%, this signal would veritably leap from the page. It doesn’t. Instead we see equivocal results that require a massive infrastructure to enact. Patients have to come in every day, get several bags worth of IV solution and all for at best what – perhaps some symptom reductions?

      Talk about a long run for a short slide. Maybe vitamin C doesn’t do a damned thing.

  15. Thomas V. Dahl says:

    Dr. Gorski, I am no medical” wizard” or authority like You, but You seem to
    forget what is called common sense and logic … :-)

    If “even a two-time Nobel Prize winner like Linus Pauling could fall prey
    to bad science” then any medical authority can fall prey to present paradigmas
    omni-knowledge or simply medical industry-corruption too !

    Not to long ago tobacco was recommended as a medical supplement and
    if we look further back the shame will perhaps become unbearable to some
    conscientious doctors . Your history of mistakes and near relations to the
    “disease-business” is far more flawed and foggy than my favourite-science
    nuclear physics where we must live with fortunately only a FEW, but VERY
    bad choices made by people considered geniuses …

    So if “even a two-time Nobel Prize winner like Linus Pauling could fall prey
    to bad science” then the logic is that You could be advocating Your vanity
    OR medical industry …

    How do I come to this elementary conlusion, my dear Dr. Watson/Gorski ?

    You are avoiding to investigate the facts about the PROFIT-interest and the
    PATENT-posessions of those who invest money . That imbalance is exactly
    what ANY REAL DOCTOR concerned about the patients, should demand in
    the name of OBJECTIVE SCIENCE !!!

    You and every medical authority should be INDEPENDENT and respect the
    Hippocratic oath of helping . You should be concerned about the TRUTH
    of medicine as well as supplements as well as alternatives …

    But You don’t challenge the medical industry, cause they are so “helpfull”;
    try questioning them/ their motives and You’re OUT !!!

    I’m glad that I’m not in the highly manipulative medicine profession, in many
    ways MEDICINE have ironically replaced RELIGIONS – twisting peoples minds
    and banning “heretics”, ridiculing “quacks” looking for new ways to heal the
    human organism – there might be many “snakeoil-sellers” yes, but You have
    become the new medical priests forgetting the change of paradigmas …

    1. David Gorski says:

      Your ALL CAPS has totally convinced me…

      1. weing says:

        “You are avoiding to investigate the facts about the PROFIT-interest and the
        PATENT-posessions of those who invest money . That imbalance is exactly
        what ANY REAL DOCTOR concerned about the patients, should demand in
        the name of OBJECTIVE SCIENCE !!!”

        I’m having trouble understanding all this. Just for a start, isn’t it obvious that those who invest money and possess patents have a profit interest? Why would that need investigation? What kind of imbalance should we, as doctors, demand?

        I don’t recall a time when I recommended tobacco as a medical supplement. What do you mean by that? Can you be specific? Nicotene has obvious effects on the nervous system. So does morphine found in opium. We don’t recommend it as a supplement.

    2. Chris says:

      “Not to long ago tobacco was recommended as a medical supplement and
      if we look further back the shame will perhaps become unbearable to some
      conscientious doctors ”

      We need to believe someone who cannot tell the difference between medical research and advertisers?

      1. Chris says:

        Second link is borked. This one is very relevant though:
        http://tobacco.stanford.edu/tobacco_main/index.php

    3. WilliamLawrenceUtridge says:

      Not to long ago tobacco was recommended as a medical supplement

      Um….[citation needed] much?

      Also, once the evidence became clear that smoking was associated with lung cancer, what happened? Don’t you see the comparable feature here? If vitamin C is ever proven, with good quality data, to be chemotherapeutic, that is when it should, and will, be embraced. Until that point – recommending vitamin C unethically subjects patients to risks for no good reason.

      The fact that vitamin C is potentially a cheap, low-profit intervention has no bearing on whether it is effective. Vitamin C has been repeatedly tested for efficacy and has repeatedly failed. Rather than accusing Dr. Gorski of being a pharma shill, or of medicine being a religion, perhaps ask yourself why vitamin C consistently shows no evidence of being a good treatment for cancer. Rather than throwing about vague accusations of bias – why not look at the actual data? It’s not Dr. Gorski’s fault that vitamin C keeps coming back as inert or at best weakly effective when tested against tumors.

      1. nancy brownlee says:

        @WLU
        In the late 19 and early 20th century, tobacco smoke was widely recommended for asthma treatment- and for what seemed to be a pretty good reason. A choking, hacking, uncontrollable bronchospasm may be stopped by inhaling tobacco (or sometimes, other) smoke, giving very temporary relief to the asthmatic. Not a good thing, obviously- it works because it briefly paralyzes the cilia. I don’t have a real citation- but here’s a link with some pretty good information-

        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844275/

        1. WilliamLawrenceUtridge says:

          …and as soon as they had an understanding of what asthma was, and effective medical interventions for it, they stopped using tobacco. Plus, I consider “late 19th/early 20th century” to be a greater temporal distance than “not that long ago”, Thomas’s initial comment. I mean, the Flexner report was still a new thing back then, American medical schools were still being closed, revamped, revolutionized, recreated. Thomas is pretending it was last week that doctors were handing out Marlboro’s and candy to go along with prescription samples.

          1. nancy brownlee says:

            That’s all very true. In fact, I’ve always thought that it was a good example of the “I’ve seen it work, it’s effective, therefore it’s good medicine” school of antiquated medical thought.

            There were, however, individual doctor’s (paid) endorsements of brands of cigarettes right through the 40s and 50s. I was there. There was also considerable hemming and hawing and equivocating on the part of many doctors, about the carcinogenic effects of smoking- through the 1960s. That doesn’t of course negate the truth or value of the surgeon general’s report of 1964. But at the time it caused a lot of doubt in ordinary people.

            1. Chris says:

              Nancy, see my second link.

              1. nancy brownlee says:

                Sorry- I can’t access the link. But of course I understand the difference between medical research and advertising, and for that matter, the difference between those things and the personal, uninformed opinions of people who just happen to be doctors. See my last paragraph! Not everyone did- or does.
                My point was, at the time- the 50s, 60s, 70s – the utter ubiquity of cigarette smoking can’t be overstated. We smoked in hospitals, and in doctor’s offices. I didn’t have a doctor who wasn’t a smoker until the 1980s. In the understanding of most people, there WAS no medical consensus. It changed, but it changed very slowly.

              2. Chris says:

                Rats! It used to open access, which is why I saved the link. Sorry about that.

                Here is the abstract:
                http://onlinelibrary.wiley.com/doi/10.1002/lary.22358/abstract

                I heard about the author on this podcast:
                http://radio.seti.org/episodes/Skeptical_Sunday_I_ll_Buy_That_

            2. weing says:

              “There were, however, individual doctor’s (paid) endorsements of brands of cigarettes right through the 40s and 50s. I was there.”

              I thought I was old, but I wasn’t there. Tobacco was a supplement? Do you have any links to endorsements?

  16. Thomas V. Dahl says:

    That certainly stirred the pot ! :-)

    Apart from Nancy Brownlees wellchosen on-the-spot information and
    formulations; I must admit the best comment is from Dr. Gorski …

    ALL CAPS :
    Yes, You’re right ! I allow feelings to “power up” my quest for truth and
    I pity those who lose that “holy” flame . You are still curious enough to
    sit back and observe; congrats to You (and Your fine sense of humour),
    BUT I hope You get my constructive criticism-point ?

    To those believing my attack was aimed at Dr. Gorski : You are wrong !

    You see it’s people like David Gorski who might make a difference in the
    future IF we convince them that WE (the patients) are worth fighting for
    and we should remember that David, they, these authorities are human
    and prone to the same uncertainties of life as the rest of us .

    Don’t lean Your head on Doctors or root Yourself in narcissistic science
    that applauds itself – there’s more miracles in the universe than priests
    who soothes our fears of death and ageing

    Actually priests (and other titles of religious authorities) were THE FIRST
    to PATENT the whole truth; so the church (and other names of religious
    structures) could harvest PROFIT and direct the way society is shaped !

    Mr. / Dr. WilliamLawrenceUtridge – I declared myself :
    __________________ no medical” wizard” or authority ____________________
    And again I’m not accusing Dr. Gorski of anything, but being comfortable
    in his views on the “investment-dilemna” where he – perhaps – could take
    a stand and ask if great discoveries in the health-area will escape us …
    just because the medical profession has flirted too long with companies .

    C-vitamin might not work against cancer or it may work in ways we have
    yet to encounter e.g. via the endocrinical system which (as far as I know)
    is so complex that noone at present can claim expertise on that matter;
    look at the ½ nobelprize of 1966 – it may turn out to be a misunderstood
    coherence .

    Or in relativistic terms : The “treatment” of Prostate Cancer could reveal
    itself as a special case, not a general law . The missing testosteron
    might be connected otherwise to the whole endocrinological process !

    But then again, there might not be enough double-blind-tests from labs ?

    Who cares ?
    The World needs growth and not a true scientific spirit, right ?

    1. David Gorski says:

      You see it’s people like David Gorski who might make a difference in the future IF we convince them that WE (the patients) are worth fighting for

      Patients are worth fighting for. That’s why I try to warn them about stuff like high dose vitamin C for cancer, Laetrile, Stanislaw Burzynski, and the like; educate them about the flaws in CAM research; and do critical posts on existing medical practices.

    2. WilliamLawrenceUtridge says:

      Thomas, you give yourself too much credit. You merely showed up and repeated the same tired tropes we here from the scientifically-illiterate conspiracy-mongerers that we get on a weekly basis. You hit a bunch of the usual paranoid ranting nails on the head – conspiracy, can’t make a profit, ALL CAPS as if it made things more convincing. Nothing new, and nothing to feel special about. You claim it’s about TRUTH as if scientific TRUTH existed – it doesn’t, merely interlocking, complex sets of data. The only people who proclaim TRUTHS exist are usually quacks trying to sell you something, sometimes an idea, sometimes a product. It’s these quacks who proclaim TRUTHS like “vitamin C cures cancer” despite the fact that their TRUTHS never manifest as higher survival rates among cancer patients.

      You see it’s people like David Gorski who might make a difference in the future IF we convince them that WE (the patients) are worth fighting for
      and we should remember that David, they, these authorities are human
      and prone to the same uncertainties of life as the rest of us .

      Goddamn but you’re a shitheel. Why do you claim Dr. Gorski doesn’t think patients are worth fighting for? Dr. Gorski spends his day either trying to cure cancer through further research, or actually curing cancer through surgery. Have you even read the study that he talks about? Did you understand it? Do you understand why the study is unconvincing? Do you have any reason to believe that vitamin C is effective when paid for out-of-pocket in a clinic in Mexico, but somehow becomes ineffective when part of a clinical trial?

      As for claiming vitamin C as a “great discovery”, it has been investigated. Many times. It has never been found to be particularly effective. Never. Merely because Linus Pauling got a Nobel prize (in a totally unrelated field, then took 40 grams of vitamin C per day, then died of cancer) does not make him somehow magical, nor does it grant him the scientific equivalent of Papal infallibility. Many have made scientific contributions then turned down a path of fruitless research, Pauling is one, Salk is another.

      Vitamin C may work in unexpected ways, it may work only for certain cancers. It may not work at all. Something you apparently refuse to even concede as a possibility. But Dr. Gorski, because he looks at the data and points out the obvious – he’s the biased one.

      Sure.

      Who pays you to hold this position? Jamieson? GNC? Webber? Or do you merely have an intellectual conflict of interest, an unwillingness to consider that vitamins might be necessary for good health only, and are not, in fact, magical? True scientific spirit involves the willingness to admit that one’s pet hypothesis is wrong – and true scientists will abandon fruitless research when it fails to pan out after over four decades.

      By the FSM your hypocrisy offends me.

      Also, not a doctor, don’t need to be one to point out stupid errors in reasoning.

    3. Angora Rabbit says:

      “C-vitamin might not work against cancer or it may work in ways we have
      yet to encounter e.g. via the endocrinical system which (as far as I know)
      is so complex that noone at present can claim expertise on that matter;
      look at the ½ nobelprize of 1966 – it may turn out to be a misunderstood
      coherence .”

      Just because you are incapable of understanding (and spelling) endocrine system, doesn’t mean that no one else does, either.

      And if you had a half-grasp of chemistry and physiology, you might begin to understand why this VC mechanism doesn’t work against cancer. Uncle Linus was a brilliant chemist but a sh*tty physiologist and nutritionist. Indeed, speaking of poo, Uncle Linus freely admitted and in public that, since starting his megadose VC, he hadn’t had a normal bowel movement in decades.

      Which says something about the power of self-deceiving belief.

      Btw, whether VC is effective is completely separable from how it works. We didn’t understand aspirin’s mechanism for decades but it was clearly effectual. We know how VC ought to work in the VC mechanism (read Levine’s introduction and then his appended references) but when push comes to shove, all that knowledge doesn’t make it magically effectual. Don’t waste time on stuff that doesn’t work – at best, that’s naivety and at worst, stupidity – and instead spend time on stuff that works.

    4. Chris says:

      “Apart from Nancy Brownlees wellchosen on-the-spot information and
      formulations; ”

      I am watching this video, and it explains some of what she said, because it is an historical account of tobacco ads starting in the late 1800s. You should give it a watch:
      https://www.youtube.com/watch?v=UL-xd_XzmF0

      “You see it’s people like David Gorski who might make a difference in the
      future IF we convince them that WE (the patients) are worth fighting for
      and we should remember that David, they, these authorities are human
      and prone to the same uncertainties of life as the rest of us .”

      Yeah, sure, ya betcha. One thing I remember about Dr. Jackler on the SETI radio podcast was how his voice broke at (as I remember it) his mother suffering from smoking induced tobacco. It is one reason for the museum display, and the above video.

      I would very much suggest that you go to the library and check out the book The Emperor of All Maladies. It is written with a great deal of heart by an oncologist. Plus it even has a detailed account of the UK epidemiology study that linked smoking with cancer.

      1. weing says:

        @Chris,
        Great link to the video. Thanks.

      2. nancy brownlee says:

        Thanks, Chris, for the links- the video and the information on otolaryngologists. You’re a peach.

        I’m undeniably oldish – 66 – but by god, not doddering yet. Although social and cultural assessments are subjective, selective, and variable, if something happened within living memory, I call it recent.

        1. Chris says:

          I’m just ten years younger, and I remember the smoking ads. In the past two decades too many members in our extended families have succumbed to smoking related diseases. This includes a cousin who was in his early 40s.

          This is why I hate the claim about “doctors recommending smoking” claims. Though, to be fair, it was a dentist who told my dad to stop smoking in the early 1960s due to seeing the beginning of mouth cancer. So my dad quit, and is still alive fifty years later, but does have some lesions removed from his mouth every few years.

          Thanks for telling me that the paper was no longer available for free. It allowed me to find that page and video from Standford Medial School.

        2. weing says:

          Just 4 years younger than you. But I grew up in Eastern Europe. Practically everyone smoked there.

  17. MadisonMD says:

    I get the sense that folks, like TVD, without actual exposure to pharmacology or cancer research have a myopic focus on a small number of “popular” chemicals .

    Consider this:
    1. The ‘chemical space’ i.e. universe of possible chemicals is 10^60.*
    2. 83 million chemicals have been registered with CAS (at least some research done)
    3. 70,509,714 chemicals are commercially available
    4. The National Cancer Institute has a national repository of 170,000 natural products, 500,000 synthetic chemicals for cancer research and discovery.
    5. The NCI Developmental therapeutics program has screened nearly 400,000 chemicals.
    6. There are 167 FDA approved cancer drugs.

    So if you select, say a handful of possible chemicals, natural or not, simple consideration of the numbers leads to the conclusion that they are extreeemely unlikely to ‘make the cut’ as an effective cancer drug.**

    If you choose something like Vitamin C that has bad pharmacology AND*** has been tested a bunch of times and found.. so far.. to not be effective, well gee whiz. Lets move on to the other (novemdecillion-1) chemicals, shall we already? We need to get going on these, if we are ever going to find new cures.

    ——————-
    *A novemdecillion (i.e. 10^60) is difficult to comprehend. Well, if you count all the atoms in the solar system, you are not there. But if you do it 1000 times, you get to 10^60.
    **To make the cut, a chemical need not only kill cancer cells to a greater extent than non-cancer cells, but it also must have favorable pharmacologic properties including lack of lethal or severe toxicity, and pharmacokinetics.
    ***ALL CAPS INTENTIONAL!

    1. Andrey Pavlov says:

      @MadisonMD:

      Excellent comment, particularly with the references. I often make the argument that the a priori likelihood of a particular compound(s) being effective is small, but it is nice to have a few actual numbers along with that.

  18. Thomas V. Dahl says:

    This is getting silly …
    I was trying to make a point about the medical profession
    should investigate their connections to financial interests …

    Maybe limited to Denmark yet, there is a network named :

    Læger uden sponsor = Physicians Without Sponsor ; which is “a network of Danish
    physicians and medical students founded in 2004 to promote independence from
    commercial influence in both clinical work, research and education.
    An important issue for the network is to raise awareness about conflicts of interest
    in health care brought about by sponsoring, research cooperation and gifts from
    commercial stakeholders.”

    So Yes , i’m STILL (ALL CAPS at proper places …) no medical wizard/authority,
    but I know that Physicists do not consider themselves next to Angels or Gods …
    maybe because we were the main frontier against the church; unlike Physicians .

    If people actually read my post they’ll notice I say :
    C-vitamin might not work (or …)” And Dr. Gorski kindly informs us upon the present
    documentation which I don’t object to . It is really irrelevant for my post

    All I’m saying is “Trust no paradigm”; a lesson well learned in Physics; but perhaps
    harder to accept when your science is close to people, sometimes in despair and
    on the edges of death . I can easily understand the psychology working here …

    #############################################################

    Oh, and Mr. / Dr. WilliamLawrenceUtridge when You tell people that Linus Pauling
    died of Cancer even when he took large doses of C-vitamin, You FUNNILY enough
    forget to mention he died of prostat Cancer at the age of 93½ years old !

    And furthermore I heard he recommended 3 grams a day, so I doubt he’d take an
    excessive dose … as he would know 40 grams is only nescessary in acute cases of
    bites from venemous insects etc.

    Finally You forget to mention Pauling died of Prostate Cancer; which I commented
    in my 2′nd post as likely connected to the complex endocrine system and maybe
    a special case (or general) where Vitamin C has no effect . Or any medical drug ?

    Looking back at Your posts Mr. / Dr. WilliamLawrenceUtridge I cannot help feeling
    sorry for Your conversational abilities; when You’re using words like “SHITHEEL” it
    makes me wonder about Your academical foundation; please explain the word …!

    ##############################################################

    MadisonMD should stop looking down on “folks” intelligense and instead actually
    read what my point is and BTW it is Dr. Gorski who has brought up & focused on
    the “popular chemical” C-vitamin … not TVD :-) Ooooops !!!

    ##############################################################

    Angora Rabbit, I didn’t know Pauling was Your “Uncle Linus” :-D And I am not into
    “magically effectual” substances, but can understand Your authoritative approach
    towards someone not grasping medicines “Holy Grails” such as endocrinology .
    And I would like to know WHO the true expert on the complex of endocrinology is …

    Please remember we are just humans, at least dr. Gorski does, and though I’m not
    a medical doctor I’m a fellow-scientist capable of deductive powers and rationality;
    something which elude a few insulted omni-knowing medical masterminds here !

    Can we land these misinterprations now ? And debate/stick to my point about the medical profession should investigate their connections to financial interests …???

    1. weing says:

      “Can we land these misinterprations now ? And debate/stick to my point about the medical profession should investigate their connections to financial interests …???”
      Physicists don’t have connections to financial interests? Interesting. Patient pays me for medical services. My financial interest is to keep patient around healthy and paying. If he/she dies, that is not in my interest. Now, if the government, hospital, or insurance and not the patient is paying me, they can try to dictate what services can be given to the patient. What if they drop the patient from coverage in the middle of a treatment regimen? What if they decide to send him to a nursing home in Mexico where he will develop bedsores, pneumonia and die? What do I do then? What does all this have to do with Vitamin C?

    2. WilliamLawrenceUtridge says:

      I was trying to make a point about the medical profession should investigate their connections to financial interests …

      What, like the conflict of interest and funding source statements that accompany most scientific articles published these days? Brilliant idea, but what else needs to be done? Hire private investigators and financial auditors for every single paper published? Perhaps we could start a registry for people proposing new clinical trials, that way we could track if researchers or companies buried data that didn’t work out for them. Maybe the government could do it. We could call it, say, clinicaltrials.gov. Man, someone should register that domain name.

      But what is actually needed is for the existing measures proposed and established to really take effect – for journals to only publish articles that were preregistered in the clinical trials database, rather than signing a declaration to do so, then forgetting about it.

      Oh, and Mr. / Dr. WilliamLawrenceUtridge when You tell people that Linus Pauling died of Cancer even when he took large doses of C-vitamin, You FUNNILY enough forget to mention he died of prostat Cancer at the age of 93½ years old !

      Yeah, and he still died of cancer. Not the Hayflick limit, not heart disease, cancer. The very disease he swore up and down could be prevented by high-dose vitamin C (which itself reveals his ignorance of the subject matter since there is no such thing as “cancer” – each tissue generates several different types of cancer with different clinical and treatment arcs, it’s like assuming all bacterial infections can be treated with a single antibiotic). Dying at 93.5 years old, when one is born in a rich country with good nutrition and a job that provides constant mental stimulation, is not particularly noteworthy. My grandmother died at 92 years old, after drinking and smoking most of her life while living in an ex-Warsaw Pact country, and she didn’t take vitamin C. What does that prove? Nothing, these are at best black swans.

      “Shitheel” is an English insult that I am using to express contempt at your reasoning abilities and your utter failure to appreciate the history of the treatment you are defending and your apparent lack of comprehension of Dr. Gorski’s initial post. Literally it would imply you have feces on the heel of your foot, but in substnative terms it’s nothing more than an insult. I could call you a stupid hypocrite instead if that would aid your comprehension, but realistically you’d get more out of re-reading the original blog post and the deep links it contains, which goes into the history of vitamin C and recent, unimpressive research on the topic. I truly don’t understand why people become convinced that vitamin C must be magic. Why? Why would this one molecule act as a panacea, when it’s so unimportant that we’ve lost our ability to synthesize it? Why this one molecule out of the nigh-unlimited potential combinations of carbon-hydrogen-oxygen atoms alone, why must it be more than a mere essential nutrient? Why insist that it does more than assist in the synthesis of collagen and act as an antioxidant, why insist it is capable of curing cancer while simultaneously being nontoxic? A feature that would make it unique among all molecules we are aware of, all of which have some degree of lethality at sufficient doses. And why insist on this despite decades of failure to show any evidence of such effects despite many, many clinical trials? Why insist that biology is easy, despite all evidence to the contrary, and that scientists just don’t appreciate the alleged miracle of this single molecule out of presumable pique or conflict of interest?

      Stupid, dogmatic and completely contrary to the evidence, and you somehow feel that all the scientists who have looked into it are missing something. And why? Apparently because Linus Pauling says so. Yeah, Pauling died a quack, his brilliance in chemistry did not translate. His legacy has a dark side.

    3. MadisonMD says:

      I wouldn’t dispute the issue of financial interests in medicine, but that doesn’t qualify Vitamin C as a cancer therapy, which is, as you point out, the topic of this post. So railing against financial interests is what would be called off topic. You can find other posts on SBM where it would be on-topic. The issue was, for example, covered very recently in the post on mammography.

      Oh, and just to be clear, I was looking down on your ignorance, not on your “intelligense.”

  19. Peter H Proctor says:

    Sarvesh Jajoo, et al, “Essential Role of NADPH Oxidase-Dependent Reactive Oxygen Species Generation in Regulating MicroRNA-21 Expression and Function in Prostate Cancer.” Antioxidants & Redox Signaling, 05/2013; DOI:10.1089/ars.2012.4820

    “…Conclusion: These data demonstrate that miR-21 is an important target of ROS, which contributes to the highly invasive and metastatic phenotype of prostate cancer cells.”

    1. WilliamLawrenceUtridge says:

      You know what’s missing? “IV vitamin C is a safe and effective chemotherapeutic agent, with a NNT of 10″. Yes, ROS are molecules that exist in cells. Yes, they appear to have a role in signaling, and probably play a role in some, if not many or even all cancers. No, that is not the same thing as “dumping a ton of vitamin C into a person’s veins cures cancer”. Not even close. Ludicrously far, in fact, particularly given the number of tests assessing this very fact that came back pretty soundly negative.

    1. MadisonMD says:

      Dr. Proctor,
      If you mean this citation to support your claim that fibrocystic breast disease confers a high risk of breast cancer, you err. In citing this article, you seem to conflate fibrocystic breast disease with usual hyperplasia or atypical hyperplasia. They are not the same. Your citation merely shows that the HR’s are:
      Usual hyperplasia w/ average breast density: HR = 1.37 (CI=1.11 to 1.69)
      Atypical hyperplasia prob higher but not in abstract independent of breast density.

      This is not in dispute. Here is what ACS says about these:

      These different types of hyperplasia affect breast cancer risk differently:

      Mild hyperplasia of the usual type: This does not increase the risk for breast cancer
      Moderate or florid hyperplasia of the usual type (without atypia), also known as usual hyperplasia: The risk of breast cancer is about 1½ to 2 times that of a woman with no breast abnormalities.
      Atypical hyperplasia (either atypical ductal hyperplasia [ADH] or atypical lobular hyperplasia [ALH]): The risk of breast cancer is about 3½ to 5 times higher than that of a woman with no breast abnormalities.

      So, my dear Dr. Proctor, you sir, are very very confused about benign breast pathologies and their roles as risk factors and precursor lesions. Perhaps you should subject your patent to peer review before filing.

  20. VitaminC says:

    How about spending your time writing about the side effects of everyday drug prescriptions and chemotherapy (the poisen people get injected into them) rather than vitamin supplement and ‘quakery’.?? How many people die from these everyday?

    And why don’t you take your ‘research’ from REAL people? I have had Medullary Sponge Kidneys for the past 14 years that make me prone to calcium-oxalate kidney stones. Despite some of the studies out there that say ‘Vitamin C causes kidney stones’, I take very high doses……and guess what? I very rarely have kidney stones anymore!

    So don’t knock it until you have tried it yourself!

    1. WilliamLawrenceUtridge says:

      Well this is a first, a sentient molecule with a kidney is posting comments.

      How about spending your time writing about the side effects of everyday drug prescriptions and chemotherapy (the poisen people get injected into them) rather than vitamin supplement and ‘quakery’.??

      SBM does on occasion, as well as “good news” success stories regarding real medicine. But this blog is dedicated to science-based medicine, so writing about drugs having side effects is not really relevant – we already know this. The purpose of the blog is mainly to provide a resource to combat the ongoing infiltration of quackery in medical schools and hospitals. But the real implication of your question is a common one – the idea that quackery doesn’t require proof of safety or efficacy until real medicine is perfect. This is stupid for a couple reasons – mainly that this is a false dilemma, real medicine should become safer and quackery should demonstrate safety and efficacy before it is used. We don’t have to choose. Quackery is also not without risks – acupuncture has lead to deaths, as has chiropractic, and all have the potential to divert people with serious health issues away from real medical care (what’s the harm? has hundreds, if not thousands of examples of both). Not to mention – if quackery doesn’t work, it is a pure waste of money and time. Why should we support it either financially or with social capital? If it does work – real medicine is deprived of a tool because the practitioners haven’t bothered to prove it works. Unproven and spectacularly unlikely proposed treatments are inherently unethical.

      How many people die from these everyday?

      As I said before – who cares who dies of medical error and adverse effects? It’s not like we have to choose one or the other. This is the kind of talking point that quacks spoon-feed their customers to distract from the fact that they’re taking your money while you get better on your own. Don’t you find it questionable that they would use such a spurious and unethical trick to try to drum up business? It’s like a mechanic slashing your tires, or a store lying about the quality of their competitors’ products to drum up business. Call me crazy, but that seems unethical.

      And why don’t you take your ‘research’ from REAL people? I have had Medullary Sponge Kidneys for the past 14 years that make me prone to calcium-oxalate kidney stones. Despite some of the studies out there that say ‘Vitamin C causes kidney stones’, I take very high doses……and guess what? I very rarely have kidney stones anymore!

      Because that’s not research. Real research doesn’t deal with the individual patient, it addresses groups. In aggregate, high-dose vitamin C does cause kidney stones, but we can’t predict who will get them. Not to mention – you’re taking vitamin C and your proof of efficacy is that you rarely get kidney stones? How do you know you wouldn’t stop getting kidney stones if you eliminated vitamin C supplementation?

      So don’t knock it until you have tried it yourself!

      I bet heroin users say that all the time!

    2. Dave says:

      The question of chemotherapy comes up frequently in posts about other unrelated issues, usually by people who fail to state whether they are talking about adjuvant, palliative or curative chemotherapy. Since the doses of palliative therapy are specifically chosen to minimize the chance of fatality from the therapy I presume you are talking about chemotherapy with intent to cure. It is obvious that this is given to people who have a lethal cancer which will otherwise kill them. As one of my teachers put it, “Drastic diseases require drastic treatments”.

      This sort of puts comparing vitamin c with cancer chemotherapy in perspective.

      1. Peter H Proctor says:

        Some recent papers from FRBM on this matter.

        Myron K. et al, “Mn porphyrin in combination with ascorbate acts as a pro-oxidant and mediates caspase-independent cancer cell death” Free Radical Biology and Medicine, Volume 68, March 2014, Pages 302-314 http://dx.doi.org/10.1016/j.freeradbiomed.2013.11.031

        Caroline Kuiper, “Intracellular ascorbate enhances hypoxia-inducible factor (HIF)-hydroxylase activity and preferentially suppresses the HIF-1 transcriptional response” Free Radical Biology and Medicine, Volume 69, April 2014, Pages 308-317
        http://dx.doi.org/10.1016/j.freeradbiomed.2014.01.033

  21. Peter H Proctor says:

    NCI antioxidant cancer treatment
    https://ttc.nci.nih.gov/opportunities/opportunity.php?opp_id=654253004100

    “Tempol: A Commercially-Available Nitroxide as a Cancer Therapeutic”

    “The National Cancer Institute’s Urologic Oncology Branch is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize the use of Tempol to target HIF-2a in cancer.

    “Elevated HIF-2a is associated with clear cell kidney cancer characterized by mutation of the VHL tumor suppressor gene and with many other cancers. A commercially-available stable nitroxide, TEMPOL, can effectively reduce the level of hypoxia-inducible transcription factor (HIF)-2a. Therefore, TEMPOL can potentially be developed into a cancer drug to treat patients with elevated HIF-2a, whether due to compromised VHL function or not.”

    COI: I have some IP here.

    1. Peter H Proctor says:

      I know what “hyperplasia” means, having done a path residency to qualify for Tox certification and having done my graduate work at MD Anderson, generally considered man’s best cancer hospital. Verifiable by the quote above from Nature. Howabout you?

      True, it was a while back. It is true that such represent only a few percent of women with fibrocystic change (perhaps a better term). But a few percent of roughly half of all women is still a lot of women. And the reported association is with fibrocystic change. Besides which, other studies (cited about) show that Tempol works on rodent explants of human breast cancer.

      I seem to be talking to a moving target here. I give cites from the scientific literature, you disapprove of those.

      Then I give a cite from the more popular medical literature written by an expert on the subject to establish this is well-known and accepted. You disagree with that too. Thousands of cites retrievable on pubmed and 30+ years of basic research and none of you LMD-types seem to have heard of any of this.

      Says a lot. Me, I get cancer, I’m going to MD Anderson, where this originated.

  22. Peter H Proctor, PhD, MD says:

    Dr Gorski– Concerning your work with mGluR1:

    “Administration of a group I mGluR agonist (DHPG) into the CeLC by microdialysis increased the responses to innocuous and noxious somatosensory (knee joint compression) and visceral (colorectal distention [CRD]) stimuli. A ROS scavenger (PBN) and a superoxide dismutase mimetic (TEMPOL) reversed the facilitatory effects of DHPG.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904214/

    Similarly: “The inhibitory effects of tempol and live-cell imaging of mitochondrial ROS production suggest that superoxide plays an important role in the mGluR5-IP3-ROS cascade..” At: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073477/

    Ya learn something new every day. If you keep an open mind.

    For fun, use “Tempol” and each cell-signaling system you work with as search terms on pubmed.gov . E.g.,”nuclear factor-kB”, “p21WAF1″, etc.. All redox modulated and readily druggable.

  23. Peter H Proctor, PhD, MD says:

    Dr Gorski– Concerning your work with mGluR1:

    “Administration of a group I mGluR agonist (DHPG) into the CeLC by microdialysis increased the responses to innocuous and noxious somatosensory (knee joint compression) and visceral (colorectal distention [CRD]) stimuli. A ROS scavenger (PBN) and a superoxide dismutase mimetic (TEMPOL) reversed the facilitatory effects of DHPG.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2904214/

    Similarly: “The inhibitory effects of tempol and live-cell imaging of mitochondrial ROS production suggest that superoxide plays an important role in the mGluR5-IP3-ROS cascade..” At: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3073477/

    Ya learn something new every day. If you keep an open mind.

    For fun, as search terms on pubmed.gov , use “Tempol” combined with each cell-signaling system you work with. E.g.,”nuclear factor-kB”, “p21WAF1″, etc.. All redox modulated and readily druggable.

  24. Jude says:

    It is very frustrating to hear learned professionals so sure of themselves that they refuse to open their minds to various and plentiful evidence of many relatively mundane product that prove to be powerful. Vit c is one such product and I have had first hand success with oral vit c that my vet could not achieve with orthodox drugs. With oral vit c I beat a cold in less than 24 hours and my horse goes from a dreary flaky coat to having a shiny one within a week. Our cat had a chronic cough and after months and a considerable amount of money paid to the vet who achieved no results whatsoever, I decided to use plain old ascorbic acid in his food (taking into account his weight), twice a day and within 3 days his cough had ceased, never to return.

    I wonder if learned professionals such as yourself are blinkered due to your academic upbringing – you learn from a particular set of books, information and from others who have done the same; so It is hardly surprising. In fact it appears more like brain washing rather than teaching individuals to be strong enough to think outside the accepted protocols or use their common sense. When there are many of a like mind it can be Very restrictive and breed arrogance. An open mind, accompanied with common sense and unfettered intelligence is the most honest and productive approach to anything in life.

    1. WilliamLawrenceUtridge says:

      With oral vit c I beat a cold in less than 24 hours and my horse goes from a dreary flaky coat to having a shiny one within a week. Our cat had a chronic cough and after months and a considerable amount of money paid to the vet who achieved no results whatsoever, I decided to use plain old ascorbic acid in his food (taking into account his weight), twice a day and within 3 days his cough had ceased, never to return.

      Three points:
      1) Vitamin C is an antihistamine, in large doses. You didn’t “beat a cold”, but you might have had a clearer nose. Like you would get from taking a regular antihistamine.

      2) So…you gave a horse some vitamin C, then a week later the coat was shinier. What else happened in that week?

      3) So…you saw a vet, presumably for at least several days, then gave your cat vitamin C, and three days later the cough went away. So that’s, say, a week, of a cat having a cough, roughly? How long does it take for a cat to clear a cough normally? Would you say, perhaps, a week?

      you learn from a particular set of books, information and from others who have done the same; so It is hardly surprising. In fact it appears more like brain washing rather than teaching individuals to be strong enough to think outside the accepted protocols or use their common sense.

      You do realize what goes into acquiring the information to write those books, don’t you? Fine-grained, detailed research into the biochemistry of the body, cells, their organelles, etc. The actions of single molecules flowing through chains. The convergence of results from multiple labs, the results of hundreds of people, all of whom arrive at the same conclusions, build from those conclusions, predict the results of future experiments (successfully), and build even further, ultimately producing things like vaccines, antibiotics, monoclonal antibodies, the ability to re-attach severed limbs, stop anaphylactic shock in less than a minute, allow diabetics to live beyond their teens, etc.

      But yeah, those books are dumb.

      When there are many of a like mind it can be Very restrictive and breed arrogance. An open mind, accompanied with common sense and unfettered intelligence is the most honest and productive approach to anything in life.

      So…before the development of the scientific method, there were no open minds with common sense?

      Doesn’t your common sense suggest that the sun revolves around the earth? That heavy objects fall faster than light objects? That the earth is flat? You might have excessive respect for common sense.

      Also, common sense does suggest that if a small amount of something is good, lots must be better. I don’t suggest you try it for vitamin D. Gary Null did, and it didn’t work out so well.

      1. Peter H Proctor, PhD,MD says:

        Minor chide: It is certainly worthwhile to take shots at the anti-vaccine people, etc. But you better make sure that you know your stuff when you take cheap shots at stuff that comes out of major cancer hospitals, etc. It is very easy to look foolish.

        One defense mechanism physicians use is the delusion of omniscience. “These people are talking about something I never heard of. Thus, it must be wrong”. Cutting thru such denial can be a bitch.

        Very likely, the people involved know what they are doing and have plenty of scientific backup. Maybe even in your own area of research. None of us know everything. Working 60 to 80-hour weeks, sometimes it is difficult to stay up with a field.

        1. WilliamLawrenceUtridge says:

          Ah, because you believe vitamin c can cure cancer, right? Great.

          1. Peter H Proctor, PhD,MD says:

            No, because compelling evidence (6K or so papers) says that “cancer” is under redox control. Been known since the late 1970′s in one form or another. As I note, some of this work originated at MD Anderson and some at the University of Iowa. Further, this is druggable.

            Yet, astonishingly, nobody here seems aware of this entire body of research. This is true even where it touches directly on the narrow field of research in (say) glutamate receptors on cancer cells.

            That is, the trial of vitamin-c as an anticancer agent is entirely consistent with the science and it is an error to claim that it is not. Further, taking legitimate researchers to task simply because you are unacquainted with this well-established field sounds (well) cultish.

            As for whether Vitamin-C works or not, I do not know. More numbers are needed.

            1. Peter H Proctor, PhD,MD says:

              Rereading the papers. It seems that they are more concerned with Vitamin-C cutting the toxicity of chemotherapy, and that there may be indications of anticancer activity. That drugs such as adria, bleo, etc. exert their toxicity by means of oxidative stress and that antioxidants cut this toxicity has been known since the 1970′s. E.g., our work at MD Anderson with with SOD and cis-platinum, Adriamycin, and bleomycin toxicity. Hundreds of papers to the same effect subsequently.

            2. Peter H Proctor, PhD,MD says:

              Rereading the papers. It seems that they are more concerned with Vitamin-C cutting the toxicity of chemotherapy, and that there may be indications of anticancer activity. That drugs such as adria, bleo, etc. exert their toxicity by means of oxidative stress and that antioxidants cut this toxicity has been known since the 1970′s. E.g., our work at MD Anderson with with SOD and cis-platinum, Adriamycin, and bleomycin toxicity. Hundreds of papers to the same effect subsequently.

            3. WilliamLawrenceUtridge says:

              So what you’re saying is:

              a) Cancer involves redox signalling.
              b) Vitamin C is a redox signalling molecule.
              c) Therefore vitamin C cures cancer.

              Huh. If that’s the case, it’s curious that the studies of vitamin C and cancer keep coming up null.

              How do you know that vitamin C doesn’t spur tumor growth? Or that tumors can’t repurpose or evolve to use high-dose vitamin C to, say, oxidize chemotherapy?

              See, to me, it sounds like a matter of “a little vitamin C is good, therefore tons should be amazing”, which I put into the same category as “people need a temperature of around 100F to live, therefore lighting them on fire cures all disease.” Which has its own degree of truth.

              Question – your work on redox signalling, did it involve a) redox signalling in cancer cells or b) vitamin C redox signalling in cancer cells? I’m not disagreeing that vitamin C is important, or that redox signalling occurrs, or that vitamin C is a redox signalling molecule. I’m disagreeing that it is a cure for cancer.

              Also, they probably are looking at vitamin C reducing chemotherapy toxicity because there is so much evidence that vitamin C doesn’t cure cancer and for some reason a group of people seems bound, dedicated to and obsessed with the idea that vitamin C must do something for cancer.

              Why, I don’t understand. It’s necessary for life, that doesn’t make it magic.

              1. Peter H Proctor says:

                “Redox signaling” is the concept that reactive oxygen species (ROS) and the like are cellular messengers. Nothing more. True, it provides a conceptual framework for explaining a lot of experimental results. One example is the ability of Tempol to modulate CNS glutamate receptor activity. It is also very “druggable” in certain circumstances.

              2. WilliamLawrenceUtridge says:

                Redox signaling exists. That doesn’t mean vitamin C cures cancer, and it doesn’t make evidence for this assertion magically appear. Nor does it make the evidence that vitamin C doesn’t cure cancer disappear.

                Many tests have been done regarding cancer being a chemotherapeutic agent. None have come back showing it to be particularly effective.

            4. MadisonMD says:

              Peter Proctor, you’re still here? I was too busy rubbing OJ on my head to notice–just kidding.

              I know you think redox is the center of all biology, especially in cancer. But redox is an old and incomplete model. The chemotherapies you name have specific mechanisms related to DNA damage that occur, in some, by oxidation. However, newer and more successful therapies are targeted to specific oncogenes activated in cancer with cognate biomarkers that let you select patients most likely to benefit. There are a number of successful therapies of this class in the past 15 years which are far superior to DNA-damaging agents.

              But in a sense, I am surprised that you, a scientist, think that all biology can be boiled down to molecules that simply alter the redox state in a part of the body. In the most fundamental sense, redox reactions are about the transfer of electrons in chemical reactions. Biology is all about chemical reactions– oxidation of glucose for example, to release energy. Without any oxidation, you’re dead, which simply sets a limit on how reductive an environment you can provide. Thus homeostasis prevents you from making large changes in redox states within cells. Doing so with radiation and certain chemotherapies have significant consequences.

              In short your short and bright scientific career in the 1970′s left you with blinders to much else that has been learned since. It is not that redox is not real or is not important, but that it is fundamentally not a useful concept to make major changes in cancer. Vitamin C, in particular, has been beat like a dead horse, but you somehow advocate flogging away and ignoring more promising lines of research.

              And that is why you are patenting Vitamin C for baldness these days instead of publishing new papers in high-profile journals– or any scientific journals for that matter.

              1. WilliamLawrenceUtridge says:

                I was curious to see the gaps in publishing. And was the initial Nature paper from 1978 an actual letter to the editor, or is “Nature Letters” a sub-journal or code for an actual article.

                But no matter what – don’t try to convince us, we don’t care. Convince the scientific community. And find a reason why vitamin C hasn’t worked so far, despite decades of testing. A real reason, that can be tested – not a made-up handwave dodge like “oh, you didn’t use IV vitamin C from fresh nuns’ farts”.

              2. MadisonMD says:

                Hi WLU,
                So here’s the scoop. Peter Proctor worked in the lab of John McGinness, a physicist at MD Anderson in the early 1970′s. They published this paper in Science in 1974. Nature news mentioned it in a couple lines of text the same year. Later, these scientists were not so successful. McGinness apparently left the institution and went on to get a medical degree in 1985, then ended up in psychiatry and was in practice for a few years. Peter, on the other hand, went on to work on superoxide dismutase, publishing a few low-profile middle author papers and some reviews related to his 1974 Science paper. Finally, Proctor turned his genius to hair loss remedies and wrote letters to the editor only sporadically, mostly in response to articles on redox.

                Over the past decade Proctor has worked on rehabilitating his scientific profile, but not by actually doing science. Instead, he apparently has edited Wikipedia articles about what a landmark discovery the 1974 Science paper was. Meanwhile, other Wikipedia editors note that it was cited only 168 times, and is not actually mentioned in major reviews. of the topic (168 is not bad, but also not what would be expected from a landmark paper.) Moreover, they note that Peter seems to be using sockpuppets to edit”>sockpuppetry to magnify the importance of his early worke:

                There are a few editors who all edit the same topics, make the same spelling mistakes and have the same writing style and attitude. They gravitate around Peter Proctor, John McGinness, Conductive polymer,…

                (Hilariously, there is a photo of the device used in the experiment with the label “this image is everywhere.” Who uploaded it? Who else? Proctor.)

                Meanwhile, in 2003, Proctor managed to donate the actual device to the Smithsonian “The Chip Collection” which took it into its with a description given by Proctor himself, and not actually edited or reviewed by a curator. It’s listed in the archives between “Microelectronics news,” a weekly newsletter known as the industry’s tabloid from 1975-1986, and an electric fry pan control device donated by Texas Instruments (you know, the dohickey that plugs into your large electric griddle).

                All this allows Proctor to crow about his greatness due to publishing in Science in 1974, studying at the greatest cancer hospital in the Universe… in 1974, and about having an object in the Smithsonian. After annoying the Wikipedia editors for a while, he turns to SBM to now tell us how great he is. How dare we question him?

                Why does Proctor try argument from authority? I don’t really give a sh!t what Proctor did 40 years ago. I wouldn’t care if he was Pauling himself with two Nobel Prizes in his pocket and 800 landmark papers to his name (hint: he’s not). He still needs to back up claims with evidence to be credible, just like everyone else.

                Yet, the history above shows Proctor is all about an outsized ego trying to cover up an undersized…………………………………………………………………………………….scientific output.

                Proctor MD Phd should perhaps stick to this line of business.

              3. MadisonMD says:

                Incidentally, WLU, you should know that Proctor and McGinness were cheated out of the Nobel prize. Despite this, you might be surprised that Dr. John McGinness, MD, PhD, psychiatrist is faculty at Northwood College, which is an independent day school for girls in the UK. Perhaps it is a typo. Northwood University is a small business school with campuses in Florida, Texas, and Michigan. Either place is unusual for a psychiatrist-physicist since there is no medical school or department of physics at either school.

              4. WilliamLawrenceUtridge says:

                Does he have a cause of baldness? I hate getting my hair cut. I would pay many fine dollars for such a cause, perhaps as high as 40.

              5. MadisonMD says:

                Maybe since chemotherapy-oxidation causes baldness, Proctor would infer that reduction reverses it.

                This is why Proctor has spent the last 28 years rubbing antioxidants into the scalps of balding middle aged men.

  25. Peter H Proctor, PhD,MD says:

    It is true that I have comercialized certain of my discoveries. Live with it– every other academic I know wishes they could do the same and historically many have.

    As for general relevance– e.g., the hair cycle is under the same redox control, using the same redox-sensitive cell-signaling systems as cancer cells. Which is why cancer treatment with chemo or radiation causes hair loss. That is, the hair cycle is a model for the cancer process. The same drugs can even work on one as the other. E.g.:

    1. “Chronic Restraint Stress Inhibits Hair Growth via Substance P Mediated by Reactive Oxygen Species in Mice” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637209/

    “Furthermore, antioxidant Tempol (a free radical scavenger) also restored hair cycle, reduced SP protein expression and mast cell activation.”

    2. “A Phase I Study of Topical Tempol for the Prevention of Alopecia Induced by Whole Brain Radiotherapy” http://clincancerres.aacrjournals.org/content/10/19/6411.long

    “Evidence of protection against radiation-induced alopecia was observed. A phase II study that uses a gel formulation to increase the exposure of scalp to Tempol has been initiated.”

    3. “Topical application of nitroxide protects radiation-induced alopecia in guinea pigs.” http://www.ncbi.nlm.nih.gov/pubmed/1544853

    4 “Radiation-induced Alopecia” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107958/

    “Use of nitroxides tempol and tempo, vitamin D3 and 16, 16-dimethyl prostaglandin E2 (PGE2) prior to radiation have been shown to protect against radiation-induced alopecia”

    1. Peter H Proctor, PhD,MD says:

      Since you-all brought it up— The fact that the hair cycle and “cancer” both seem to be mediated by the same redo-sensitive systems and the following patent are additional reasons why I think Vitamin-C just might work as an anticancer agent. True, more patients are need, but there are certain interesting implications.

      Patent US6150405 – Hair loss treatment with ascorbates.

      “A method for treating hair loss by repeated topical application of a ascorbate compound, a flavine or another hydroxyl radical scavenger. Original Assignee, Proctor; Peter H

      Quite a valuable patent, BTW. I just love patents– the money is better and intellectual property rights are enforcible in court.

      Once more, current theories of the etiology of “cancer” say it is almost entirely a disease of oxidative stress. cites above. At one extreme– driven to apoptosis by antioxidant treatment, at the other extreme driven to apoptosis by additional oxidative stress. All mediated by redox-sensitive factors and not so much by damage per se.

    2. WilliamLawrenceUtridge says:

      I’m sorry, is alopecia the sole cause of baldness? I was under the impression that alopecia was an autoimmune condition. But mostly – god, who cares? Vitamin C has been tested and shows minimal evidence of being an effective chemotherapeutic agent. Your beautiful theory has been killed by an inconvenient fact.

      1. Peter H Proctor, PhD,MD says:

        Straw. The papers merely say that there are suggestions that ascorbate may help with cancer, but that minimally it helps patients on chemo feel better. We have kown antioxidants help with the toxicity of antitumor agents since the 1970′s, first with SOD and later with flavonoids and vitamin E.

        As for the fact that the same redox-sensitive cellular control factors operate in the hair cycle as in cancer. On http://www.pubmed.gov Cross “wnt” first with “hair” and then with “cancer”.

        1. MadisonMD says:

          Dude,
          Wnt signaling plays a key role in stem cell regeneration in hair follicles and has little to do directly with redox.
          Do you cure any middle aged men of baldness with OJ? Or do you just tell them they would have lost more without your tonic?

  26. weing says:

    “I’m sorry, is alopecia the sole cause of baldness?”

    Alopecia is the general term for baldness. You may have alopecia areata, totalis, generalisata, etc.

  27. Peter H Proctor, PhD,MD says:

    Perhaps Dr.Gorski can comment on the role of wnt in cancer…..

    A search of “ros” and “wnt” on pubmed comes back with 89 cites. Definitely under redox control.

    As with many other cellular control elements, tempol modulates the action of wnt: http://www.ncbi.nlm.nih.gov/pubmed/24328990

  28. Peter H Proctor, PhD,MD says:

    Title says it all.

    “Redox Regulation of Canonical Wnt Signaling Affects Extraembryonic Endoderm Formation.” http://www.ncbi.nlm.nih.gov/pubmed/24471440 \

    If a clinical oncologist, surprisingly uninformed about your field. Anyway, nerve to criticize others. Try talking like this at a meeting. At least in the big cancer centers, everybody knows this stuff, much of which originated at MD Anderson.

  29. MadisonMD says:

    If a clinical oncologist, surprisingly uninformed about your field. Anyway, nerve to criticize others. Try talking like this at a meeting. At least in the big cancer centers, everybody knows this stuff, much of which originated at MD Anderson.

    You are so funny. Nobody ever criticizes at big oncology centers? Nobody criticizes at an oncology meeting? Yes, you wouldn’t know if you haven’t stepped into such a cancer center in 40 years or sent out a grant proposal or publication for peer review in decades.

    While you are at the bizarro AACR parades and hugs next week, I’ll be at the real meeting across the street. Maybe I’ll run into you on the way there.

    Cheers.

    1. Peter H. Proctor, PhD, MD says:

      Contrary to your statements, this field even has its own forum at the 2014 AACR meeting. Check it out:
      FO08. “Antioxidant to Pro-Oxidant Therapy for Cancer” Mon, Apr 7, 5:00 – 6:30 PM

      Session summary: “Cancer cells produce high levels of reactive oxygen species (ROS), primarily superoxide and hydrogen peroxide. Oncogene activation, coupled with the loss of tumor suppressors, promotes ROS production at mitochondria, endoplasmic reticulum, and NADPH oxidases. The tumor microenvironment, characterized by low glucose, hypoxia, and inflammatory infiltration, further increases ROS levels in cancer cells. Elevated ROS levels can hyperactivate multiple pathways (PI3K, MAPKs, NF‐KB, HIFs) that are known to be protumorigenic. However, uncontrolled oxidant production is incompatible with cellular viability. Thus, cancer cells have enhanced antioxidant function which allows them to maintain a balance between the growth-promoting and damage-inducing properties of ROS. We will discuss the current thinking regarding disabling cellular antioxidants to increase ROS levels in cancer cells to levels that elicit damage and thus reduce tumor burden.”

      Like I’ve been sayin’. Similarly, a search on “redox” on the meeting schedule brings back 53 abstracts. In turn, “superoxide” shows 24 abstracts. Again, the complete lack of knowledge here concerning the role of redox-signaling in cancer is most surprising for clinical oncologists.

      1. Peter H. Proctor, PhD, MD says:

        AACR 2014 meeting abstract:Presentation 3179:
        “Redox signaling to nuclear respiratory factor-1 proteins by reactive oxygen species contributes to the estrogen-induced breast tumor development,” Deodutta Roy, et al

        Abstract: “We have investigated the molecular mechanisms by which reactive oxygen species (ROS)-mediated redox signaling regulates estrogen-dependent growth of breast tumorigenesis and prospects for targeting these signaling pathways for therapeutic prevention and control of tumor growth. We present here for the first time that ROS generated by E2 exposure were responsible for in vitro MCF-7 cell tumor formation. This is evident from the inhibition of E2-induced ROS formation by ROS scavengers. H2O2 and O2•− seem to play important role in estrogen-mediated tumor growth redox signaling by inactivation of PTPs, such as, CDC25A, PTEN to prolong signaling through kinases, such as ERK and AKT. We observed a novel link between ROS-generated by estrogen, redox regulation of ERK and AKT-mediated signaling to nuclear regulatory protein, nuclear respiratory factor-1 (NRF-1) and ERα responsive gene expression in breast cancer cells and their involvement in the growth of estrogen-dependent breast tumor. NRF-1 serves as a nucleating factor to recruit signaling proteins involved in regulating estrogen-responsive cell cycle genes, and oxidative stress regulatable proteins. Findings of this study not only identify the new redox signaling pathway critical to the estrogen-dependent growth of breast tumors; but also provides important information for the design of redox signaling based therapeutic agents for the prevention and treatment of breast cancer. ”

        Which might be related to the efficacy of tempol in fibrocystic disease (estrogen-dependent) and, just maybe, to preventing breast cancer.

        Also see: abstract 2258 “Tempol diet provides chemoprotection against UV-induced skin cancer in mice with epidermal Smad4 deletion.” Monday, Apr 07, 2014, 1:00 PM – 5:00 PM

  30. Peter H. Proctor, PhD,MD says:

    AACR meeting, 2014
    Session Title: “Antioxidant to Pro-Oxidant Therapy for Cancer”
    Session Type: Forum
    Session Start/End Time: Monday, Apr 07, 2014, 5:00 PM – 6:30 PM
    Location: Room 11, San Diego Convention Center

    Description: “Cancer cells produce high levels of reactive oxygen species (ROS), primarily superoxide and hydrogen peroxide. Oncogene activation, coupled with the loss of tumor suppressors, promotes ROS production at mitochondria, endoplasmic reticulum, and NADPH oxidases. The tumor microenvironment, characterized by low glucose, hypoxia, and inflammatory infiltration, further increases ROS levels in cancer cells. Elevated ROS levels can hyperactivate multiple pathways (PI3K, MAPKs, NF‐KB, HIFs) that are known to be protumorigenic. However, uncontrolled oxidant production is incompatible with cellular viability. Thus, cancer cells have enhanced antioxidant function which allows them to maintain a balance between the growth-promoting and damage-inducing properties of ROS. We will discuss the current thinking regarding disabling cellular antioxidants to increase ROS levels in cancer cells to levels that elicit damage and thus reduce tumor burden.”

    Be there or be square…..

    1. MadisonMD says:

      Cool, Peter. Will you be presenting your work on ROS and hair loss?

      1. Peter H. Proctor, PhD,MD says:

        Researchers depend on all sorts of models. E.g., “The name Wnt is resultant from a fusion of the name of the Drosophila segment polarity gene wingless and the name of the vertebrate homolog, integrated or int-1.1.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2634250/ Now what do fruit flies possibly have to do with cancer?

        Similarly, the hair cycle is a handy model for exploring the same cellular control elements that modulate the cancer process. E.g. AARC meeting:

        “A novel topical candidate for chemotherapy and radiotherapy-induced alopecia (CRIA) through local modulation of apoptosis” Wednesday, Apr 09, 2014, 8:00 AM -12:00 PM Location: Hall A-E, Poster Section 16

        Author: Jiawei Liu, et al
        Abstract: “Chemotherapy- or radiotherapy-induced alopecia (CRIA) is a common side effect of adjuvant and metastatic chemotherapy regimens or radiotherapy treatments. The likelihood of alopecia depends on the types and modes of treatment modalities. In cancer patients undergoing chemotherapy, the hair loss incidence is estimated to be 65%. Although CRIA is often assumed to be an unavoidable and transient side effect that can be dealt with using wigs, it is considered by the sufferers the most visible and emotionally distressing consequence of cancer therapies, giving negative repercussions on various aspects of quality of life (QOL). There are no approved pharmacologic treatments available for CRIA, and the outcome from scalp cooling devices are of variable quality.
        Normal hair cycle mainly consists of growth phase (anagen), regression phase (catagen), shedding phase (telogen) and resting phase (telogen). In the course of CRIA, the rapidly growing and dividing cell populations in anagen phase are damaged by the systemic chemotoxic agents and undergo unwanted premature apoptosis, consequently inducing premature onset of catagen. Apoptosis is finely tuned by endogenous and exogenous factors. The extrinsic pathway is principally mediated by an apoptosis stimulus factor, Fas. The intrinsic pathway is essentially mitochondria dependent and executed by members of Bcl-2 (B cell lymphoma-2).
        Bcl-2 level is depressed in the scalp of balding subjects, indicating a key role of apoptosis. A previous study using mouse model revealed that certain chemo-agent (e.g. cyclophosphamide) caused up-regulation of the pro-apoptotic protein p53 in root sheaths and hair matrix, sensitizing hair follicular cells to apoptosis. In contrast, p53-deficient mice showed neither hair loss nor abnormal apoptosis in hair matrix keratinocytes, most likely as a result of down-regulation of Fas and increased expression of the anti-apoptotic protein Bcl-2.
        As Bcl-2 level in non-alopecia subjects has not been documented so far, we conducted a scalp biopsy study in order to measure the “normal” Bcl-2 level in non-alopecia subjects. We then compared the “normal” Bcl-2 level in non-alopecia subjects with the level of Bcl-2 in androgenetic alopecia (AGA) volunteers, before and after topical application of a GMP-grade botanical extract (“the Product”). It turned out that, after Product application, the level of scalp Bcl-2 was restored, towards normal level, consequently preventing early onset of the apoptosis-driven catagen phase.
        Pharmacological inhibition of apoptosis pathways has been proposed to prevent chemotherapy induced alopecia. The outcome obtained from our studies have now made it possible to study the potential benefit from positive modulation of hair follicular cell apoptotic process in cancer patients suffering from unwanted hair loss due to chemo- or radiotherapy. “

      2. MadisonMD says:

        OK, Peter, seriously. Yes, redox is connected to all biology. DNA is connected to all biology. Methionine is connected to all biology. Oxygen is connected to all biology. Glucose is connected to all biology. Lipids are connected to all biology. p53 is connected to all biology. So what? What does posting a bunch of citations on redox prove?

        Yes, I’ve heard Elaine Fuchs speak about the stem cell niche for hair follicles. Yes, there is some fundamental biology here that connects to cancer biology. And yes, redox is indirectly connected to notch signaling and, judging form the total of 220,518 pubmed articles on redox, indirectly connected to just about any aspect of biology you can name (re-read what I wrote about directness of the link). Yes, some cancer therapies, notably radiation operate by ionizing radiation, creating free radicals and DNA double-strand breaks. Yes, some chemotherapies also function by damaging DNA by a similar redox reaction.

        What I don’t understand is:
        (1) Why you think that reducing agents can generate hair follicle stem cells anew, from basically nothing?
        (2) Why you think high-dose Vitamin C would somehow be a more specific or a better oxidant than cisplatin or hundreds of other oxidants that failed in clinical trials?
        (3) What major advance is likely to be accomplished by developing new cancer therapies that modify redox states when existing chemotherapies do this already? (Targeted therapies don’t do this and are safer, more effective)
        (4) Why, even admitting that a scientist could consider these hypotheses, you are appear as a strong proponent of their use without clinical evidence of efficacy?

        My point is that redox is a useful and real concept, but it is not likely very useful to make major advances in curing cancer– or baldness for that matter. You can prove me wrong with your clinical evidence showing how they work. If you do, I will change my mind.

        1. Peter H Proctor, PhD, MD says:

          You seem to miss the main point– ROS, etc, are primarily cellular messengers and (except for DNA-damage) their role in cancer is mainly messenger-mediated. This includes inducing apoptosis.

          Dr. Gorski’s antiexcitotoxic drug, riluzole. is a good example of the applicability of this to cancer treatment. Used in the treatment of ALS, this antiexcitotoxin acts on release, uptake, and binding of glutamate. Significantly, ALS and excitotoxicity in general have a significant redox element. Well-known and established– e.g., a pubmed.gov search on “redox” and “glutamate” shows 4K+ cites.

          BTW, the role ROS play in neuropsychiatric and neurodegenerative diseases was my original area of research. So I was quite excited to see that this might also be directly relevant to cancer. Imagine, glutamate receptors on melanoma.

          E.g., my favorite antioxidant antiexcitotoxin, uric acid, is felt to be a major endogenous neuroprotectant in ALS. I have even suggested that the general failure of both antioxidants and antiexcitotoxins to be neuroprotecive in stroke and other neurodegenerative diseases is because uniquely-high endogenous human levels of urate leave little room for such agents to work, even after working in animals. (http://stroke.ahajournals.org/content/39/8/e126.full.pdf).

          Urate is antiexcitotoxic, e.g., by enhancing glial glutamate uptake by redox-modulated EAAT’s. Makes ya wonder about glutamate, urate, and cancer. Interestingly, uric acid levels do show a J-shaped relationship with cancer incidence.

          Turning around your argument about vitamin-C– uniquely high human levels of the similarly-acting antiexcitotoxin urate may similarly not leave much room for riluzole in human cancer, replicating its apparent failure in (say) stroke. But the only way to tell is just to try it. The fact it works in ALs is encouraging.

          Significantly, IV uric acid is the only antiexcitoxic neuroprotectant to work in stroke and is currently in Phase-2 trials, . Similar trials are underway in Parkinson’s and MS. There is talk of trials in ALS. All based ultimately on my Nature paper. I am told that the Parkinson’s results are “interesting”.

          In sum, Rizulide works on a target system well-known to be redox-modulated in brain and apparently also in cancer. Makes ya wonder what would happen if Dr Gorski tries tempol (which is also antiexcitotoxic) in his system. As I note above, Tempol works in human breast cancer explants. Just maybe, we have figured out why.

          BTW, why does ischemic (e.g.) brain tissue insist on killing itself? Makes no sense. Perhaps the real function of ischemic reperfusion injury is to make incipient cancer cells apoptose.

          1. Peter H. Proctor, PhD, MD says:

            Paganoni S(1), et al, “Uric acid levels predict survival in men with amyotrophic lateral sclerosis”. J Neurol. 2012 Sep;259(9):1923-8. doi: 10.1007/s00415-012-6440-7. Neurology Clinical Trials Unit, Massachusetts General Hospital, Harvard Medical
            School,

            “Elevated uric acid levels have recently been found to be associated with slower disease progression in Parkinson’s disease, Huntington’s disease, multiple system atrophy, and mild cognitive impairment….. This is the first study to demonstrate that serum uric acid is associated with prolonged survival in ALS, after adjusting for markers of disease severity…”

            Recall that uric acid is antiexcitotoxic….

  31. Doug Peacock says:

    so as cancer & cvd kill another 1.3 mill Americans this year, what is your answer? Or do you not have one & that is why you make fun of people trying?

    Doug Peaock
    Health Teacher
    Mt. Vernon HS
    Fortville, IN

    1. Harriet Hall says:

      @Doug Peacock, “so as cancer & cvd kill another 1.3 mill Americans this year, what is your answer? Or do you not have one & that is why you make fun of people trying?”

      Our answer is to continue to study cancer and CVD with the scientific method. We never make fun of anyone who is doing that.

    2. weing says:

      “so as cancer & cvd kill another 1.3 mill Americans this year, what is your answer? Or do you not have one & that is why you make fun of people trying?”

      What kind of a question is that? It sounds to me, that you are JAQing off.

    3. Windriven says:

      Health teacher? Really? If I believed in a god I’d do a novenna giving thanks that my kids don’t go to Mt. Vernon HS. Do they teach science at your school? Critical thinking?

      First off, everybody dies of something. Are you of the belief that conquering cancer and CVD = eternal life?

      Second, and echoing Dr. Hall, only the laughable are laughed at here. If you pull something lacking evidence out of the air and proclaim it profound, you’re going to have a rough ride. If flecks of spittle fly from your mouth while extolling it, you’re going to get laughed at.

      Third, thousands of researchers dedicate their lives and public and private wallets fund many millions of dollars researching cancer and cardiovascular diseases. Cancer ain’t gonna get fixed by titrating one’s ascorbic acid intake. Ibid CVD. Vitamin C has been looked at. Carefully.

      Fourth, many cancers and many forms of CVD are managed much better today than just a decade ago – and both are likely to achieve additional gains in the coming decades. But these gains come incrementally. Both of the disease labels you mention encompass a wide range of pathologies with multiple causes. There isn’t going to be a silver bullet that ‘cures’ either one.

      Meaningful answers are rarely simple answers. Those who offer simple solutions only appeal to simple minds.

      1. Peter H. Proctor, PhD,MD says:

        Back on topic. I was at MD Anderson when Pauling came out with his vitamin-C stuff. There was a lot of turf-defense among the cancer docs, even though Pauling had a pretty good history in medical research. E.g., he was the first to chemically-define a human hereditary disease, cycle cell anemia.

        By chance, I had published a paper on how uric acid might limit the human requirement for vitamin-C. Somewhere around here, I even have a letter from Pauling. One of my papers at the time notes that vitamin-C can act as a pro-oxidant, the proposed mechanism for its putative anticancer properties So this is nothing new.

        Anyway, all this towel-snapping aside, a quick look at the studies published at the time does show some apparent efficacy from IV infusion, which can result in vitamin-C levels many time that for oral administration. The more recent work merely provides a possible mechanism for this finding, which has never been properly explored.

        This mechanism is the same as for several well-known anticancer drugs. I wrongly believed this was common knowledge, but the point be a little subtle, unless this is ones actual field.

        1. Peter H. Proctor, PhD,MD says:

          Re: Riluzole, melanoma, and oxidative stress—
          Pigment Cell Melanoma Res. 2014 Mar;27(2):263-274. doi: 10.1111/pcmr.12207..

          Disruption of GRM1-mediated signalling using riluzole results in DNA damage in melanoma cells.l BA1, et al.

          Abstract
          “……In this study, we investigate the mechanism of an inhibitor of glutamate release, riluzole, on human melanoma cells that express metabotropic glutamate receptor 1 (GRM1). Various in vitro assays conducted show that inhibition of glutamate release in several human melanoma cell lines resulted in an increase of oxidative stress and DNA damage response markers.”

          1. Peter H. Proctor, PhD,MD says:

            Speaking of melanoma
            “The function of melanin or six blind people examine an elephant.” Hill HZ. Bioessays. 1992 Jan;14(1):49-56 Abstract:

            Re: Melanin: “…Aside from camouflage, its other roles can be brought together by a unifying hypothesis as first proposed by Proctor and McGinness nearly 20 years ago. Melanin is envisaged as an energy transducer with the properties of an amorphous semiconductor. It can absorb many different types of energy and dissipate them in the form of heat. However, if the energy input is too great, the output can be expressed in the form of activated chemical species that can damage cellular macromolecules resulting in cell death, mutations and cancer. ” at: http://www.ncbi.nlm.nih.gov/pubmed/1546980

            These days, it is expressed as redox signaling…

            1. Peter H Proctor, PhD, MD says:

              Some presentations featuring vitamin-c at the 2014 AACR meeting. From some prtty heavy-hitting places. Note the role of the well-known concept of “redox-signaling”. That is, the targets are cellular growth and apoptosis factors.

              2951 – “Vitamin C is selectively toxic to cancer cells harboring KRAS or BRAF mutations by targeting GAPDH ” Jihye Yun1, et al, Weill Cornell Medical College, New York, NY; Tufts Medical Center, boston, MA; 3The Johns Hopkins Institutions, Baltimore, MD; Beth Israel Deaconess Medical Center, Boston, MA

              240: “Natural antioxidants exhibit chemopreventive characteristics through the regulation of CNC-bZip transcription factors in estrogen-induced breast carcinogenesis”, Anwesha Chatterjee.et al UMKC, Kansas City, MO

              229/6 – “Restoring physiological levels of ascorbate alleviates HIF-1 activation and reduces tumour growth in Gulo-/- mice” Elizabeth J. Campbell, et al

              494/9 – “Tumor ascorbate content is associated with extended disease-free survival and decreased hypoxia-inducible factor-1 activation in patients with colorectal cancer”

              1. MadisonMD says:

                So to you, the presence of 4 abstracts about lab-based Vitamin C research at a meeting of 6000 presentations is evidence that we should be using it already to treat cancer and prevent baldness?

                If we review the other 5996 abstracts, then we’ll have another thousand or so compounds with preliminary evidence. But, I’m still holding out for proof that they are useful therapies before administering them to patients.

                Vitamin C is not implausible, just well studied compared to many of those other compounds and not yet found to be useful. The place to look for possible utility is in the lab, not in patients.

        2. WilliamLawrenceUtridge says:

          What I’m curious about, is why vitamin C, despite apparently being incredibly effective as you believe, consistently fails to show any efficacy despite numerous scientific trials.

          How do you explain that?

          Oh, that’s right, they always did it wrong.

          1. Peter H Proctor says:

            Again, you miss-state my position. Which is that there are plenty of good scientific reasons to try Vitamin-C in cancer. Or, more likely, some kinds of cancer. Just as there are plenty of good reasons to try (e.g.) riluzole, Dr. Gorski’s antiexcitotoxic drug.

            1. WilliamLawrenceUtridge says:

              Again, you miss my point – vitamin C has been tested for many different types of cancer and it has failed repeatedly. There has never been good evidence for vitamin C being a mediocre chemotherapeutic agent, let alone a good one, so the ongoing assertion that it is, baffles me. All of the protestations that somehow we’ve missed the point are not evidence. Many brilliant theoretical arguments are based on flawed premises or simple errors in understanding, and the best way to determine if you’re brilliant or wrong is empirical tests. Well, as far as I can tell, the empirical tests of vitamin C versus cancer simply show no reason to believe it’s effective for anything. So why keep defending the idea?

      2. Peter H. Proctor, PhD, MD says:

        Modulating cellular control elements such as PI3K, MAPKs, NF‐KB, HIFs, etc. holds the greatest promise for improvements in cancer treatment. As the above session abstract notes, many of these are under redox control. This is readily druggable and thus an area of much current activity in cancer research.

    4. Peter H. Proctor, PhD,MD says:

      We can often cure cancer, but there ain’t no cure for the dumbass..

    5. WilliamLawrenceUtridge says:

      so as cancer & cvd kill another 1.3 mill Americans this year, what is your answer? Or do you not have one & that is why you make fun of people trying?

      Exercise, get enough sleep, eat a good diet (the recommendations of the USDA are quite reasonable), don’t smoke.

      Don’t take massive doses of vitamin C, or any vitamins. Get your vitamins from foods, not pills.

      Millions of Americans are going to die every year – even aside from accidents, one must contend with the Hayflick limit. People die. People will always die. They have to die of something, and it’s now cancer because most major infectious causes of death have in large part been controlled.

  32. -peter H Proctor, PhD,MD says:

    Homocysteine-lowering vitamins (B12, folate, B6) also make sense. e.g.,: “Hyperhomocysteinemia as a risk factor for the neuronal system disorders.” at:
    http://www.ncbi.nlm.nih.gov/pubmed/24622826

    Similarly, people a Free Radical Biology and medicine meetings like lipoic acid and acetylcarnitine. Many people develop a relative deficiency in B12 uptake as they grow old.

    And if you just it in mom’s basement posting to chat-groups or work all day in some hospital, you are also likely to develop a vitamin-D deficiency. All easy and cheap to fix, just in case.

    1. Harriet Hall says:

      @ Proctor,
      “Homocysteine-lowering vitamins (B12, folate, B6) also make sense”

      Elevated homocysteine is a risk factor for heart disease, and B vitamins lower homocysteine levels, but they don’t reduce the incidence of heart disease. Ideas from basic science have to be tested before we can assume clinical applications.

      1. Peter H Proctor, PhD,MD says:

        Uh, the cite I give is for neuropsychiatric disorders. Follow the link. This, and the likely correlation of hyperhomocystinuria with cancer are currently hot topics.

        As for cardiovascular diseases– the big correlation is with homocystinuria itself as well as (IIRC) with heterozygotes. The treatment for these is b12, etc. The big dispute is whether moving homocysteine levels from (say) 12 down to 7 does much.

        Like other powerful reducing substances such as uric acid and vitamin-C, homocysteine is a “conditional pro-oxidant”, being an antioxidant at low concentrations and a pro-oxidant at higher ones. There is also an interesting correlation between cancer an homocysteine.

        1. Harriet Hall says:

          @Proctor,
          “Uh, the cite I give is for neuropsychiatric disorders. Follow the link. This, and the likely correlation of hyperhomocystinuria with cancer are currently hot topics.”

          Uh, I think you missed my point: that correlation doesn’t prove causation and that assumptions must be tested with clinical studies.

          1. Peter H Proctor says:

            Naturally. Unfortunately, that costs a lot of money. So you need to get as close as you can.

            BTW, sometimes a good scientific idea is enough to justify using a treatment. Best example is statins for cardiovascular disease. These were originally-approved just because they improve the lab numbers on (e.g.) cholesterol. Only fairly recently have they been clearly shown to have any effect on cardiovascular disease.

            The alternative was letting a lot of people die unnecessarily while you waited for the proper trials. IIRC, took about 15 years.

            Paradoxically, other data suggests that the original rationale for using statins may not be connected to their efficacy. Interestingly enough, this may be connected with their free radical scavenging activity.

            1. MadisonMD says:

              BTW, sometimes a good scientific idea is enough to justify using a treatment.

              This is where you part ways with most denizens on this website. Yes you can pick statins which were approved on a surrogate endpoint. But it was still a clinical endpoint with very strong evidence (mechanistic and clinical) that it was a true surrogate. Drugs are provisionally approved on surrogate endpoints even today, although it is required that there is confirmation with the ultimate endpoint (survival, cardiovascular survival, etc).

              Most preclinical data does not work out in clinical trials. One in-house study by Amgen suggests that that most published preclinical data are not reproducible. This jives with what we know about confirmation bias and publication bias.

              In fact these failures explain the high attrition rate of pharmaceuticals. Thus it is folly– and a disservice to patients– to adopt new standards of care based on preclinical evidence alone.

              The alternative was letting a lot of people die unnecessarily while you waited for the proper trials. IIRC, took about 15 years.

              But the time is well spent if 80% of preliminary findings are ultimately rejected and then the answer is known to hjumans forevermore.

              1. Peter H Proctor, PhD,MD says:

                True, often animal studies do not work out in people. Likely, this is because people are different, e.g., our main extracellular antioxidant is uric acid.

                Or, the drug formulation changes in mid-stream. My favorite example is AstraZeneca’s NXY-059 for acute ischemic stroke. NYY-059 is a derivative of a drug (pbn) that I held the primary patent on. Had already picked out the Bentley. and ya wonder why I patent…

                The first half of the phase-3 trial showed significant efficacy, particularly for tpa-induced hemorrhagic stroke. The subsequent trial crashed and burned.

                Subsequent inquiry strongly suggested that AZ had stabilized their drug formulation between the first and second trials, the active agent with this class of drugs being a hydrolysis product.. See: “SAINT-I Worked, But the Neuroprotectant Is Not NXY-059″ at: http://stroke.ahajournals.org/content/38/10/e109.full

                Interestingly, NXY-059 is now undergoing development as an anticancer agent. Why is left as an exercise for the reader…

          2. Andrés says:

            Dr. Hall said:

            assumptions must be tested with clinical studies

            At least in connection to mild cognitive impairment it has already taken place. From de Jager et alter paper:

            The mean plasma total homocysteine was 30% lower in those treated with B vitamins relative to placebo. B vitamins stabilized executive function (CLOX) relative to placebo (P=0.015). There was significant benefit of B-vitamin treatment among participants with baseline homocysteine above the median (11.3mmol/L) in global cognition (Mini Mental State Examination, P<0.001), episodic memory (Hopkins Verbal Learning Test–delayed recall, P=0.001) and semantic memory (category fluency, P=0.037). Clinical benefit occurred in the B-vitamin group for those in the upper quartile of homocysteine at baseline in global clinical dementia rating score (P=0.02) and IQCODE score (P=0.01).

            1. Andrey Pavlov says:

              You really should learn to read more than just abstracts, Andres.

              In the intention-to-treat cohort of participants with
              MCI who completed the trial, B-vitamin treatment
              did not improve performance in tests of global cognitive
              function (MMSE), episodic memory (HVLT-DR)
              or semantic memory (category fluency) or on measures
              of clinical status (CDR and IQCODE). However, Bvitamin
              treatment did stabilize performance on the
              CLOX test of executive and planning function, and this
              effect was independent of baseline tHcy, perhaps indicating
              a direct effect of one or more of the B vitamins.

              So multiple comparisons finds one effect.

              On the other hand, when analysis was done according
              to predefined subgroups based on the baseline
              tHcy concentration, there were clear beneficial effects
              of B vitamins on tests of episodic memory, semantic
              memory and global cognition in participants with
              baseline tHcy ≥11.3mmol/L.

              Different analysis shows only one subgroup with benefit. Could be real benefit because that subgroup is different in their biochemistry or could be an artifact of doing multiple comparisons. The fact that it is a different set of benefits means it could well be the latter.

              A similar result was found for the clinical outcomes
              (CDR and IQCODE), where B-vitamin treatment actually
              improved the clinical outcome, but only in participants
              with baseline tHcy ≥13.1mmol/L.

              Maybe it is that subgroup of people with biochemical differences that make treatment actually beneficial. Either way that is not relevant to the discussion per se and:

              Our results contrast with several negative trials on
              homocysteine-lowering treatment and cognition or
              dementia

              And, not that it proves anything, but:

              A. D. Smith is named as an inventor on three patents
              held by the University of Oxford on the use of folic
              acid to treat AD or MCI (US6008221; US6127370;
              PCT/GB2010/051557); under the University’s rules,
              he could benefit financially if the patent is exploited.
              Drs Refsum and Smith report having in the past received
              speaking honoraria from Recip AB, the company
              that donated the vitamin tablets, and from
              Axis-Shield, who make the equipment used to assay
              homocysteine.

              Furthermore they themselves say:

              Although the sizes of the effects of B-vitamin treatment were relatively modest, the fact that they were
              highly significant and were found in several cognitive
              domains and also in clinical assessments is consistent
              with an effect of the intervention on disease progression.

              Single center trials are known to have larger effect sizes than multi center trials. So this already a modest effect that is likely actually smaller than reported. Plus, when authors use terms like “highly significant” it is clear that they don’t really know how statistics actually work, what P-values actually mean, and no correction for multiple comparisons used.

              Overall, this is, at best, a bit of preliminary data showing that people with the highest levels of homocysteine could be worthwhile investigating further. It does not provide any sort of compelling evidence that VitB supplementation can provide any meaningful clinical benefit. It is paltry evidence at best, particularly in context.

              But definitely on par with the sort of evidence you like to provide for VitC.

            2. Harriet Hall says:

              @Andres,

              I don’t find that study convincing. For one thing, they themselves say they got different results than several previous studies. For another thing, the only differences they found were for patients who had high pre-treatment homocysteine levels. It’s quite possible that they were seeing the results of treating vitamin B deficiency, and that homocysteine was not involved at all.

              1. Peter H Proctor,PhD,MD says:

                At FRBM meetings is the usual reaction is “True, all we may be doing is producing expensive urine. But the scientific rationale is persuasive and do you want to find out too late that it really works?”

                That is, balanced against the low costs and minimal hazard, most knowledgeable experts that I know will take the chance, just in case. YMMV, naturally.

            3. Andrés says:

              First a personal disclosure. As far as I know cognitive impairment doesn’t run in my family (nor in that of my other half) so my interest in this subject is scant. I take a high in pantothenic acid B-complex supplement twice a week (another of my interventions that as with gluten avoidance I don’t know if has contributed to my acne disappearance).

              Dr. Pavlov said:

              You really should learn to read more than just abstracts, Andres.

              My fault this time. Corrected. I have just read the original paper about the RCT by Smith et alter too. This one focuses directly on measuring brain atrophy.

              Dr. Pavlov said:

              Plus, when authors use terms like “highly significant” it is clear that they don’t really know how statistics actually work, what P-values actually mean, and no correction for multiple comparisons used.

              I don’t think that there are so many people/researches using p-values correctly.

              Dr. Hall said:

              It’s quite possible that they were seeing the results of treating vitamin B deficiency, and that homocysteine was not involved at all.

              Unlikely. From Smith et alter:

              The overall B vitamin status was very good in the whole cohort of 266 participants. Only 7 participants (2.6%) had plasma folate concentrations of <7 nmol/L and 6 (2.3%) had vitamin B 12 concentrations of <150 pmol/L at baseline. Since the vitamin analyses were done after the trial ended, these subjects, although classified as vitamin deficient, were not treated medically unless diagnosed by their GP.

              Although they say too:

              In contrast, in the group on active treatment there was no relationship between baseline tHcy and the rate of atrophy. It is tempting to suggest that this finding is consistent with the view that raised homocysteine is a direct cause of the atrophy. However, it does not exclude that tHcy is only a marker for low-normal levels of the vitamins, which are themselves the causal factors.

              On the other hand the adequacy of a given vitamin dose must be dependent on one own genes as it was stated around here elsewhere when citing Ames et alter.

              Dr. Proctor said:

              That is, balanced against the low costs and minimal hazard, most knowledgeable experts that I know will take the chance, just in case. YMMV, naturally.

              I am certainly not an expert. Nevertheless I will check my homocysteine level in the future just in case it is higher than 9.5μmol/L. If affirmative I will proceed as if the intervention is effective while waiting for refutation (I am not optimistic about it happening soon).

              1. Harriet Hall says:

                “the vitamin analyses were done after the trial ended”
                So the vitamin status before the subjects were given vitamins is not known. So as I said, it’s quite possible that they were seeing the results of treating vitamin B deficiency, and that homocysteine was not involved at all.

            4. Andrés says:

              Dr. Hall said:

              “the vitamin analyses were done after the trial ended”
              So the vitamin status before the subjects were given vitamins is not known.

              You have misread it. Blood samples were drawn at baseline and at two years. Yes, they measured vitamin levels at the end of the trial but from both samples as you can check on Table 2 from Smith et alter. They are explicitly talking about lack of poor vitamin status at baseline.

              1. Harriet Hall says:

                You are correct. I missed table 2.
                Nevertheless, Andrey Pavlov’s criticisms of the study are valid, and a causal role for homocysteine has not been established.

            5. Andrés says:

              Dr. Hall said:

              Nevertheless, Andrey Pavlov’s criticisms of the study are valid,

              Dr. Pavlov’s criticisms are about the second paper of the Oxford group, not the first one. They are mainly quotes from it. Main outcomes are discussed on the first one. A more complete view is attained by reading both papers and also the last published paper about the intervention of the Oxford group (I haven’t read this last one yet).

              Dr. Hall said:

              and a causal role for homocysteine has not been established.

              I have not said it was settled. There is enough recent research such as Hooshmand’s thesis that I haven’t read yet that seems to support it though.

              1. Andrey Pavlov says:

                Dr. Pavlov’s criticisms are about the second paper of the Oxford group, not the first one. They are mainly quotes from it.

                Yes, with, you know… criticisms inserted between. Criticisms that the paper doesn’t actually demonstrate what you are trying to claim. I just don’t waste my time on more detailed responses with you anymore.

                You do realize that all of your arguments not only hinge entirely on cherry picked data with a hugely speculative bent, but that your argumentation style can only be considered either cherry picking for a conclusion already decided by you (i.e. the antithesis of scientific inquiry) or so vague as to be meaningless prattle (JAQing off). You are either asserting a conclusion exists which is not justified by the data or just saying “more research needed. Anti-science or pointless prattling.

  33. Peter H Proctor, PhD,MD says:

    “So to you, the presence of 4 abstracts about lab-based Vitamin C research at a meeting of 6000 presentations is evidence…”

    You made such a point about the AACR meeting and how you were going there. Seems fair to feed you back papers from the meeting.

    Likewise, it is significant that researchers at places like Johns Hopkins report at AACR meetings in this area. BTW, there are other papers, search “vitamin-C” and “ascorbate” on the site. Perhaps the big boys know something.

    BTW, when somebody keeps making straw arguments and ad hominems, and deliberately wrongly misstates my arguments, I assume that they don’t have anything else to offer. Again, many researchers are in agreement that there might be something that justifies trying ascorbate. Nothing more.

  34. Peter H Proctor, PhD,MD says:

    3211. “Citral is the major component of ginger-derived terpenes to mediate p53-dependent apoptosis in cancer cells” Lucas Fass, Mildred Felder, Manish S. Patankar, Arvinder K. Kapur. Univ. of Wisconsin-Madison, Madison, WI AACR, meeting, Apr 08, 2014, 8:00 AM -12:00 PM

    “…Treatment of cancer cells with citral results in a rapid increase in intracellular Reactive Oxygen Species (ROS). The cellular stress resulting from ROS generation leads to phosphorylation of the Ser-15 residue of p53. Activation of p53 via this phosphorylation event leads to apoptosis in cancer cells.

    “….Our on-going efforts will identify sensitivity of commonly found p53 mutations to activation by citral and also the specific p53 kinases triggered subsequent to the ROS surge mediated by this terpene.”

    Which is the same pro-apoptotic mechanism postulated for another small molecule, Vitamin-C.

    1. Angora Rabbit says:

      “Which is the same pro-apoptotic mechanism postulated for another small molecule, Vitamin-C.”

      Mebbe. Mebbe not. First off, did Arvinder show that blockade of ROS itself directly prevented Ser-15 pylation? Just as an example, disruption of ribosome biogenesis also activates p53 and that’s independent of ROS, though I don’t recall if there’s a role for pS15 there.

      Major point – citral is a multimechanism compound. It is a polyisoprene and can be (a) incorporated into prenylation sites in proteins like p53 to alter their cellular localization; (b) inhibits conversion of retinal to retinoic acid, which in of itself has antitumor activities that focus on gene expression and not ROS,; (c) can inhibit cholesterol synthesis; (d) could inhibit a number of other isoprene-dependent events. I don’t think they are proposing citral affects ROS directly – there’s no structural reason to think it would unless you’ve got a demonstrated target better than these.

      The problem with ROS (I have hitherto avoided dragging myself into this) is that its proponents see it everywhere and assume it is mechanistic. I’ve seen so much bad work invoking ROS but, when push comes to shove, the investigators fail to show a mechanistic role. It isn’t enough to show it’s there – it has to be shown to be mechanistically relevant. And in something like apoptosis and cell death, it’s hard to buy because it jumps in so late into the apoptotic pathway, well after that train is already on the apoptosis track.

      1. Howabout the hard, undeniable fact that SOD’s are anticancer agents.. I was part of the one of two research groups that originally showed this, BTW. SOD1 is one of the most specific enzymes known.

        See: “An in vivo enzymatic probe for Superoxide and Peroxide by Chemotherapeutic Agents” Pathology of Oxygen,(1982) ed. A. P. Autor, Academic Press, New York, p191. By John McGinness and the rest of us. From MD Anderson, where this work still continues. See figure 2, where we show SOD is as effective as cis-platinum in our animal ca model. Over three decades ago.

        The next chapter in the book is entitled “The Use of Superoxide Dismutase in the Treatment of Cancer”. Oberly, et al., from the University of Iowa. Hesitatingly, since we thought nobody would believe it, we showed one case, but they really blow it out of the water.

        Things have come a lot further since. To the point that it seems that ROS sit at the very center of the cellular control mechanism This efficacy also extends to SOD-mimetics. How otherwise can you explain the anticancer effects of (say) tempol.

        As for “apoptosis”. This statement makes me urge you to read a review article or two. As the AACR session abstract above notes, ROS modulate a lot of cancer-related cellular control elements. In fact, the list they give is rather incomplete. It is becoming more and more apparent that cancer is a disease of oxidative stress more than anything else…

        And “redox-signaling” is a pretty broadly-applicable concept these days. Look it up. Also see: http://www.redoxsignaling.com .

        1. MadisonMD says:

          Nobody here said that ROS isn’t important. However, it is your peculiar tunnel vision which leads you to view it as the center of the biologic universe. You say:

          To the point that it seems that ROS sit at the very center of the cellular control mechanism

          What does that even mean? It’s not even wrong. The same can equally true be said about:

          DNA (sits at the very center of the cellular control mechanism!)
          the centrosome
          histones
          transcription factors
          the citric acid cycle
          KRAS
          p53
          NFkappaB

          BTW. SOD1 is one of the most specific enzymes known.

          Really? More specific than Ras for GTP? Is specificity the sine que non of being somehow the most important enzyme? Are you bragging “my enzyme is better than yours!” How odd. Well, a geneticist who wanted to play this schoolyard game might point out that SOD1 isn’t even essential. It seems that loss of cytoplasmic SOD only makes motor nerves more susceptible to injury.

          Funny that you can actually have a mouse born without any cytoplasmic SOD, given that it sits at “very center of the cellular control mechanism.” You would think that the control mechanism would be all catywompus without SOD, no?

          1. Peter H Proctor, PhD,MD says:

            In retrospect, I have made a terriible mistake in trying to explain a set,of well-known scientific concepts to people who don’t have the proper knowledge base. My bad.

          2. Peter H Proctor, PhD,MD says:

            In retrospect, I have made a terriible mistake in trying to explain a set,of well-known scientific concepts to people who don’t have the proper knowledge base. My bad.

            1. MadisonMD says:

              Yeah, that’s it. Some fools think the nucleus is the center of cellular control because you actually need it to be born alive. You can’t reason with them.

              1. Peter H Proctor, PhD,MD says:

                “Redox control of enzymatic functions: The electronics of life’s circuitry.” Bonini MG1, et al, IUBMB Life. 2014 Mar 26. doi: 10.1002/iub.1258.

                “Formerly regarded as bi-products of the aerobic metabolism exclusively involved in tissue damage, reactive oxygen species (ROS) are now recognized as active participants of cell signaling events in health and in disease. In this sense, ROS and the more recently defined reactive nitrogen species (RNS) are, just like hormones and second messengers, acting as fundamental orchestrators of cell signaling pathways.” http://www.ncbi.nlm.nih.gov/pubmed/24668617

        2. Angora Rabbit says:

          “As for “apoptosis”. This statement makes me urge you to read a review article or two. ”

          Guess what I actually *study* and publish on for a living. Instead of just reading other people’s papers. I think the phrase is “teaching one’s grandmother to suck eggs” though I’ve never understood the phrase. I stand by my statement.

          “Stop HIF-1 from working and the cancer cell often doesn’t just quit growing, it dies.”

          Sometimes but not always, and not in the way one intends. Example: the cancer promoting chemical TCDD (dioxin, generically) binds its AhR receptor, in heterodimer with ARNT. ARNT is also the cooperative partner for HIF1a, as you know. Pull the ARNT away and HIF1a signaling drops. Yet the cell doesn’t apoptosis. By your logic, TCDD would be a cancer-fighting agent, not one of the more potent carcinogens.

          I’m with MadisonMD. Saying ox stress is “central” is about as useful as saying that glucose or oxphos or proton pumps are central. A lot of what you say is true and I’ve no quarrel. But a lot of it glosses over nuances or overstates the situation, which in science is fatal.

          1. Peter H Proctor, PhD,MD says:

            Yes, I know, being a toxicologist and all. This context does not lend itself to detailed matters. For one thing, we have posters here who clearly don’t have much of a knowledge base. So I have to talk down.

            Again, when I say that oxidative stress is central to the cancer process, what I mean is that large parts of the promotion and maintenance of the cancer process are under redox control. This is clearly established, so far has not been falsified, and is the subject of research at many major cancer centers. Unless you are looking for straw arguments, it should be obvious that I do not mean this is the only control they are under.

            As noted in the AACR session abstract, this includes some very fundamental cellular control process that it would take much more than a sentence or two to detail. For that reason, I give links to relevant papers, review articles , etc.. Read them.

            As for papers, etc. I patent and only rarely publish. E.g., in the last few months, I have had one patent approved for issue and applied for three more, all for significant human disorders. Most importantly, no drug gets developed without good IP protection.

            True, I do sometimes comment on matters, in essence giving away valuable proprietary information. E.g., why antioxidant drugs work in animals and then fail human trials. Over the past decades, this has cost billions of dollars and lots of frustration.

            1. Windriven says:

              “This context does not lend itself to detailed matters. For one thing, we have posters here who clearly don’t have much of a knowledge base.”

              Inasmuch as you recognize this, I’m again wondering why you are here. Dazzling us with your brilliance? Casting pearls before swine? An ego thing?

              “As for papers, etc. I patent and only rarely publish.”

              So … Slumming for a venue to trot out your theories without all the muss and fuss of peer review? Or maybe trolling for investors?

              ” in essence giving away valuable proprietary information”

              Or you’re our benefactor, giving away the keys if only we’re clever enough use them?

              The original question was along the lines of whether or not there is good evidence supporting the clinical use of high dose vitamin C.

    2. WilliamLawrenceUtridge says:

      Which is the same pro-apoptotic mechanism postulated for another small molecule, Vitamin-C.

      Emphasis on the vital point – postulation isn’t proof, and it isn’t justification to hook patients up to a daily vitamin C drip or make them swallow gram-doses of the stuff. Ongoing failures to find any benefit also argue against throwing more research funding at the idea in the absence of preclinical evidence.

      1. Peter H Proctor,PhD,MD says:

        The same can be said of (e.g.) antiexcitotoxic drugs verses glutamate-receptor-bearing cancers. A good scientific rationale, some evidence of efficacy, but mostly in vitro cellular work.

        My personal opinion is that this is a very promising area of research. In fact, because it ameliorates the CNS effects of the same system, I’d like to thro some tempol at this system. Betcha $5 it works…

        1. WilliamLawrenceUtridge says:

          Have antiexcitotoxic drugs verses glutamate-receptor-bearing cancers been tested in humans? Have they proven to improve survival time or quality of life?

          Because vitamin C has been tested in humans and has failed repeatedly. If vitamin C were still at the stage where it were showing promise in bench work, you might have a point. But repeatedly it has failed, in both bench and people, and never showed much promise in the first place. Endorsement by Linus Pauling, who died of cancer, isn’t enough to overcome the weight of all this negative evidence. Many brillaint scientists have been wrong, and many have descended into quackery. Pauling was one of them.

          1. Peter H Proctor, PhD,MD says:

            “Have antiexcitotoxic drugs verses glutamate-receptor-bearing cancers been tested in humans? ”

            Yes

            “Have they proven to improve survival time or quality of life?”

            No.

            See: “A Phase 0 Trial of Riluzole in Patients with Resectable Stage III and IV Melanoma” at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2812866/

            Also see: “Metabotropic Glutamate Receptor-1 as a Novel Target for the Antiangiogenic Treatment of Breast Cancer” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898178/

            The very kind of thing that the usual suspects here would fault. But definitely worth a shot…

            Combines my two favorite areas–neuroprotection and melanoma…. The mind reels…

          2. Peter H Proctor, PhD,MD says:

            “How Vitamin-C stops cancer”. Johns Hopkins http://www.sciencedaily.com/releases/2007/09/070910132848.htm

            “Nearly 30 years after Nobel laureate Linus Pauling famously and controversially suggested that vitamin C supplements can prevent cancer, a team of Johns Hopkins scientists have shown that in mice, at least, vitamin C — and potentially other antioxidants — can indeed inhibit the growth of some tumors, just not in the manner suggested by years of investigation.”

            “Some rapidly growing tumors consume enough energy to easily suck out the available oxygen in their vicinity, making HIF-1 absolutely critical for their continued survival. But HIF-1 can only operate if it has a supply of free radicals. Antioxidants remove these free radicals and stop HIF-1, and the tumor, in its tracks.

            The authors confirmed the importance of this “hypoxia protein” by creating cancer cells with a genetic variant of HIF-1 that did not require free radicals to be stable. In these cells, antioxidants no longer had any cancer-fighting power..”

            1. Harriet Hall says:

              Prevent is not the same as inhibit growth. Mice are not the same as humans.
              This does nothing to support Pauling’s suggestion.

              1. Peter H Proctor, PhD,MD says:

                Stop HIF-1 from working and the cancer cell often doesn’t just quit growing, it dies. This process is called “ischemic injury” and is the same mechanism that causes cell death in heart attack and stroke.

              2. Harriet Hall says:

                I repeat: killing a cancer cell once it has developed is not the same as preventing cancer. And mice are not people.

              3. Windriven says:

                This is all very interesting, Dr. Proctor. But where are the human studies of reasonable power that demonstrate that high loadings of ascorbic acid or any other antioxidant reduce tumors and prolong life?

                This blog is not really an appropriate vehicle for debating prospective research. So far as I can see there is little data to get excited about clinically or even translationally. Am I mistaken about this?

            2. WilliamLawrenceUtridge says:

              …and again, ignoring the fact that vitamin C has been tested in humans with no good evidence of efficacy. Sure, vitamin C might work, but the randomized, controlled trials keep rolling in as negative. There’s no reason to believe that vitamin C is a good chemotherapeutic agent. You can throw up all the analogies, preliminary data and broad comparators you want, but that doesn’t erase all those trials that failed to find any increase in lifespan.

              1. Peter H Proctor, PhD,MD says:

                Vitamin-C (ascorbate) levels do tend to correlate with cancer in epidemiological studies. Whether this translates to anticancer efficacy is currently unclear. But there is lots of animal and in vitro data that says it should.

                Citing my own work to contradict this assertion– Humans are different in that we run uric acid levels 5-10X that of (say) mice. In humans 200-400 mcm uric acid, vs 20-40 mcm ascorbate, about.

                Both are roughly equivalent as antioxidants. This 5-10-fold excess of urate does not leave much room for ascorbate to work. This may account for the repeated failure in human trials of antioxidants which work fine in animals.

                Thus, in humans, urate infusion works in acute ischemic stroke, while ascorbate does not. The same may be true for ascorbate and human cancer. Only trials can tell.

                Interestingly, the Johns Hopkins paper cited below essentially says that ascorbate suppresses the same system that Dr. Gorki’s glutamate receptors stimulate and that this system is under strong redox control. Something we already knew from the same receptors in brain.

                Anyway, if it works, none of this stuff works very well, nor should it be expected to do so. But the tradeoff of low cost and toxicity for any clinical improvement makes it a good thing to investigate.

              2. WilliamLawrenceUtridge says:

                Whether this translates to anticancer efficacy is currently unclear.

                It makes sense that vitamin C would be correlated with the prevention of cancer (in reasonable doses, the idea that megadoses will prevent cancer is one to be independently tested, and one that hasn’t bourne out so far), but that has no bearing on treating cancer. Once the DNA damage is done, there’s no reason to expect that antioxidants will reverese the damage or otherwise assist in dealing with it. You can’t resurrect someone ejected from a vehicle by belting them back into the wreckage.

                But there is lots of animal and in vitro data that says it should.

                And there’s many human trials saying it doesn’t. There are many, many, many glass and animal drugs that turned out to be useless in humans, an order of magnitude more, if not two.

                But the tradeoff of low cost and toxicity for any clinical improvement makes it a good thing to investigate.

                By that rationale, water (or apples, or sterilized pigs blood, or sawdust, or snow) would also be good chemotherapeutic agents to investigate. It’s actually quite hard to identify anti-cancer drugs, and there’s little reason to expect that merely because something is readily accessible that it must therefore cure cancer.

              3. MadisonMD says:

                We are not even getting a straight story about whether Vit C is an oxidant or an antioxidant. The 2007 Hopkins Cancer Cell paper suggests it could prevent cancer by virtue of being an antioxidant. The Kansas folks claim it operates by being an oxidant at high doses.

                Also, lead author of the 2007 study, Chi Dang, is now director at Penn. He would have had plenty of resources to follow up, if he believed it was a promising line of inquiry. Odd that he hasn’t published subsequent studies on Vitamin C in the past 7 years, nor has Penn opened a clinical trial. Why not? Well the conclusion of the a href=”http://www.sciencedirect.com/science/article/pii/S1535610807002334″>Cancer Cell paper (cited by Proctor’s press release) is somewhat revealing:

                Hence, our findings not only uncover a basis for the antitumorigenic effect of antioxidants, but they also suggest the potential application of antioxidants for adjuvant therapy to prevent progression or recurrence of HIF-dependent tumors. We caution, however, that the doses of antioxidants used in our mouse studies exceed those currently used in the clinical setting, which may require a much higher dose to affect tumors.

                So it could work in renal cell cancer (HIF-dependent), but very high doses needed, antioxidant (not pro-oxidant). But apparently not promising enough for the Penn Cancer Center Director to get a grant, run a study or even follow up on in his lab in the past 7 years. Ah, well.

  35. Again, the role of ROS in cancer is complicated. See:, e.g., “Upsides and Downsides of Reactive Oxygen Species for Cancer: The Roles of Reactive Oxygen Species in Tumorigenesis, Prevention, and Therapy” At: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3324815/

    Roughly: A mutational event, say that causes expression of glutamate receptors (extremely oxidatively stressing in the CNS), gets the ball rolling.

    Early-on, ROS are cancer promoters, largely by turning on cellular growth factors (including vascular neogenesis) and turning off apoptosis factors, etc. ROS are also mutagenic. They can also be anticancer, e.g., by setting off apoptosis.

    The combination sets off Darwinian selection in the tumor for increased oxidative stress, e.g., by deleting mitochondrial SODs. And thus further unchecked growth. This in turn selects for even more oxidatively-stressed clones, further stimulation of growth factors, metastasis, and so forth. All by reasonably well-known mechanisms.

    At some point, the degree of oxidative stress becomes too much and less oxidativily-stressed clones get selected. This can cause the cancer cell to again start expressing protective enzymes such as mitochondrial SODs. That is cancers tend to be at a knife-edge between the degree of oxidative stress required to be (well) cancer and oxidative stress killing them..

    Treatment with adria, bleo, and platinum-style drugs further oxidatively-stress the tumor cell, forcing it over into apoptosis. OTOH, sod-mimetic drugs such as tempol. or SOD itself lower oxidative stress and thus drive the cancer cell in the direction of niceness– maybe even into apoptosis as (e.g.) antiapoptotic mechanisms get switched off.

    Paradoxically, SOD’s and anticancer drugs can both work at the same time. E.g., see our 1982 paper above and “Mito-Tempol and Dexrazoxane Exhibit Cardioprotective and Chemotherapeutic Effects through Specific Protein Oxidation and Autophagy in a Syngeneic Breast Tumor Preclinical Model .” at: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3734284/ . This may be because sod’s make peroxide and can thus also be oxidative stressors, but nobody really knows.

  36. Peter h Proctor, PhD,MD says:

    1. It is the “therapeutic index” that is important. That is, the ratio of the toxic dose to the effective dose. This is very high for vitamin-C. Combine this with low cost and ease of use and you have a winner, even if the overall activity is not particularly great.

    2. Don’t know of any anticancer agents that reverse DNA damage. More typically they force the cancer cell into apoptosis. Some may force cell death by ischemic injury, a la the description of what vitamin C does to HIF-1 described above. Some agents (perhaps including tempol) may force redifferentiation by shutting off whatever factors are making the cell act “bad”.

    1. WilliamLawrenceUtridge says:

      …and again, clinical trials in humans have been underwhelming. No change in cancer level, no change in death rates, at best a small increase in quality of life (at the expense of ongoing IV infusions). So all that theory, all the bench work and animal work that you’re invoking that should have been done before clinical trials took place? Right now it looks to be basically as useful as the thousands of other examples of bench work and animal work that were the lead-up to a compound that is not a good chemotherapeutic agent in humans. You can keep talking about how this molecule or that pathway shows that vitamin C might, could, maybe, perhaps be an anticancer agent – but that doesn’t change the fact that actual trials in humans, the apex of the pyramid, the peak of the mountain, the whole point of all that preliminary work, have not shown any evidence of efficacy.

      How do you explain this? To date, I don’t think you have except to slide out the usual trope of “they tried it on the wrong type of cancer”. Also known as “moving the goalposts”.

  37. Peter H Proctor, PhD,MD says:

    Thiol-based redox switches.Biochim Biophys Acta. 2014 Mar 19. pii: S1570-9639(14)00057-0. doi: 10.1016/j.bbapap.2014.03.007 ,Groitl B1, Jakob U2. http://www.ncbi.nlm.nih.gov/pubmed/24657586

    “…Redox regulation of phosphatases and kinases is used to control the activity of select eukaryotic signaling pathways, making reactive oxygen species important second messengers that regulate growth, development and differentiation.”

    1. Peter H Proctor, PhD,MD says:

      “Hydrogen peroxide sensing, signaling and regulation of transcription factors” Redox Biol. 2014; 2: 535–562. H. Susana Marinho,et al

      “The regulatory mechanisms by which hydrogen peroxide (H2O2) modulates the activity of transcription factors in bacteria (OxyR and PerR), lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4) and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1) are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1) synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii) stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii) cytoplasm–nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and (iv) DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes.”

    2. Peter H Proctor, PhD,MD says:

      “Hydrogen peroxide sensing, signaling and regulation of transcription factors” Redox Biol. 2014; 2: 535–562. H. Susana Marinho,et al

      “The regulatory mechanisms by which hydrogen peroxide (H2O2) modulates the activity of transcription factors in bacteria (OxyR and PerR), lower eukaryotes (Yap1, Maf1, Hsf1 and Msn2/4) and mammalian cells (AP-1, NRF2, CREB, HSF1, HIF-1, TP53, NF-κB, NOTCH, SP1 and SCREB-1) are reviewed. The complexity of regulatory networks increases throughout the phylogenetic tree, reaching a high level of complexity in mammalians. Multiple H2O2 sensors and pathways are triggered converging in the regulation of transcription factors at several levels: (1) synthesis of the transcription factor by upregulating transcription or increasing both mRNA stability and translation; (ii) stability of the transcription factor by decreasing its association with the ubiquitin E3 ligase complex or by inhibiting this complex; (iii) cytoplasm–nuclear traffic by exposing/masking nuclear localization signals, or by releasing the transcription factor from partners or from membrane anchors; and (iv) DNA binding and nuclear transactivation by modulating transcription factor affinity towards DNA, co-activators or repressors, and by targeting specific regions of chromatin to activate individual genes.”

  38. MadisonMD says:

    It is the “therapeutic index” that is important. That is, the ratio of the toxic dose to the effective dose. This is very high for vitamin-C.

    Really, now? What, exactly is the therapeutic index for Vitamin C, Dr. Proctor? You’ve defined it and you would do well to be precise. I doubt you can tell, because it seems that no effective dose has ever been established.

    But if you try, please provide the citation to the human study showing effectiveness of Vitamin C. Please verify that the authors actually concluded that Vitamin C was an effective cancer therapeutic. Even better, also cite the review, drug package insert, or clinical guideline that agrees with the interpretation and list the appropriate type of cancer, clinical situation (prevention/early stage/metastatic), dose and schedule of this effective therapeutic.

    1. Peter H Proctor, PhD,MD says:

      Again, straw. We are all in agreement that vitamin-C hasn’t been studied to these standards. So why do you keep asking? And why when I come up with literature support is the first reaction an ad hominem on me and the authors of the paper?

      But vitamin-c is worth a shot. As is (say) riluzole. Difference is– a drug company has a patent on riluzole and is apparently willing to pay for trials.

      But primarily, I object to impinging the motives of fellow physicians without knowing the particular area. This thread shows that some clearly do not even know their own areas very well. And on major items, not trivial stuff. So how can they criticize others?

      Might be OK for, say, the antivaccine fanatics, not for docs at a recognized cancer center. If a doc at a major cancer center does something, chances are there is some rationale for it. Understand what that is before attacking. Otherwise, you look petty and ridiculous.

      1. Windriven says:

        “So why do you keep asking?”

        Perhaps because that is the subject of the post at hand.

      2. WilliamLawrenceUtridge says:

        But vitamin-c is worth a shot.

        Why? Why go through the inconvenience of swallowing dozens of pills, or venipuncture for IV vitamin C, with no evidence of efficacy even in humans? Even if I had fatal cancer – I’d rather spend my days eating pizza and flying to Rome (and eating pizza in Rome) than sitting in an easy chair every day getting useless vitamins dripped into my arm.

        As is (say) riluzole. Difference is– a drug company has a patent on riluzole and is apparently willing to pay for trials.

        Drug companies are quite capable of making money from off-patent medications. Have you ever heard of “aspirin”?

        1. Peter H Proctor, PhD,MD says:

          “Drug companies are quite capable of making money from off-patent medications. Have you ever heard of “aspirin”?”

          Uh, Aspirin’s development costs were made back a century ago. Which is why a bottle of 1000 costs $10 or so.

          NCE’s (New chemical entities) must undergo a development process that typically costs about a billion dollars. No drug company is going to pay out this cash unless they have a marketing monopoly, e.g., a patent.

          Otherwise, all their competitors will market the drug without the development costs. Typically, within a year of a drug going off-patent, the cost decreases 5-10-fold.

          E.g the antiexcitotoxic Dr. Gorski works with, Riluzole, is covered by patents. So the drug company is willing to pay for its development. Alas, the same is not true for Vitamin-C. We see this with regularity in the drug trade.

          1. Windriven says:

            “Alas, the same is not true for Vitamin-C. We see this with regularity in the drug trade.”

            What development? Ascorbic acid is already FDA approved and very widely available as a supplement. Yes, studies would have to be done at that dosing for that indication* but as vitamin C is and has been used since Limeys sucked limes the costs should not be anything like those to bring, say, Riluzole to market.

            If there is solid evidence that vitamin C has a powerful effect on some tumors there are any number of funding agencies that would help. Congresspersons would be stepping all over each other to press for funding.

            *Maybe. My field is devices, not drugs. I’m not convinced that a huge amount of testing would be required as physicians would simply be ordering up IV bags with the desired concentrations. Any compounding pharmacy could do it.

          2. MadisonMD says:

            True that pharma won’t pay for it. But it is certainly possible to do a RCT on Vitamin C. With some promising preclinical data on it, you write an NIH grant and, if you convince the review panel that it is promising, you get a clinical trial done.

            It’s been done for Vitamin E. Twice. It’s been done for Vitamin D. Again, more than once.

            And, just to show you that it certainly is possible to do a randomized controlled trial on Vitamin C, here is irrefutable proof. And, gosh, 10,000 patients randomized! A huge trial–gets done. In fact, it is fairly inexpensive to do a Vit C trial because tox is well established*. It’s just efficacy that is lacking**.

            ————-
            *Your billion dollar figure is the price to develop one approved drug. Which means it includes the cost of the development of many failed drugs. Moreover, it includes cost of preclinical tox, phase I testing, etc. that is not needed for Vit C.
            **Incidentally, Vit C efficacy is clearly lacking in the NEJM RCT I linked. Surprising that you can’t cite a positive one given the many that have been done– even assuming null hypothesis for all Vit C trials, 1 in 20 should nevertheless meet the pre-specified primary endpoint by chance alone.

          3. WilliamLawrenceUtridge says:

            Rather missing my point again. Yes, aspirin is cheap, but is also effective, and profitable in both name brand and generic versions. Unless you think Bayer is selling it at a loss? if vitamin c worked, it could profitably be sold as chemotherapy. In fact, the big pharma companies who currently manufacture it would be ecstatic as the demand would be huge and production cheap.

      3. MadisonMD says:

        We are all in agreement that vitamin-C hasn’t been studied to these standards. So why do you keep asking?

        Uh, you claimed:

        It is the “therapeutic index” that is important. That is, the ratio of the toxic dose to the effective dose. This is very high for vitamin-C.

        I asked you what exactly was the therapeutic index for Vitamin C because you claimed it was very high.

        And why when I come up with literature support is the first reaction an ad hominem on me and the authors of the paper?

        I must have missed it. What exactly is the ad hominem argument and straw man argument you are referring to? (Incidentally, pointing out that Chi Dang’s evidence is preliminary does not, in any way, impugn his status as a scientist or the quality of the evidence in his publication. He himself wrote that the Vitamin C levels were impractical. He himself then turned to more promising lines of research inquiry. There is nothing wrong with him or his science. In fact this discernment is characteristic of an outstanding scientist worthy of U Penn leadership.)

        But primarily, I object to impinging the motives of fellow physicians without knowing the particular area.

        Do you mean impugn? In which post was there a discussion of your motives? All I recall is windriven wondering what your motives were for posting here.

        This thread shows that some clearly do not even know their own areas very well. And on major items, not trivial stuff.

        To which statement specifically do you refer? What is the evidence that the statement is factually incorrect?

        If a doc at a major cancer center does something, chances are there is some rationale for it.

        Glad you think so. I am a doc at a major cancer center. I trained at another major cancer center. So if I write something, then you would argue there is some rationale for it. Do you now wish to lay your argumentum ab auctoritate at my feet?

  39. Peter H Proctor, PhD,MD says:

    Wrong. The specific issue raised by the Science medicine paper is whether Vitamin-C is worth a further look. I happen to agree with this and have said so repeatedly. Asked and answered. That is, you-all keep making a straw argument.

    But the real issue with me personally is maliciously questioning the personal motives and actions of fellow physicians and other cancer centers. This is clearly without properly investigating what it is they are doing and why. Very reckless. This is not Dr. Bryzinsky or the antivaccine people.

    1. Windriven says:

      “Wrong. The specific issue raised by the Science medicine paper is whether Vitamin-C is worth a further look.”

      Yeah, huh? Maybe we’re talking about different “Science medicine papers.” I’m talking about Dr. Novella’s blog post: “The Return of the Revenge of High Dose Vitamin C for Cancer.” I’ve scanned through the blog again to see if I missed anything the first time. But gaw-lee, I’m just too fricking dense to recognize that as “the specific issue” addressed by Dr. Novella. So I’ll just smile and take your word for it, you being an MD PhD and all.

      “But the real issue with me personally is maliciously questioning the personal motives and actions of fellow physicians and other cancer centers.”

      Yeah, well, I took the first part on faith but that stops here. There is a common expression to the effect that facts talk and bullsh!t walks. Dr. Novella has always struck me as quite receptive to new evidence. Evidence.

      Now I haven’t followed every word of every one of your threads but I don’t recall Dr. Novella engaging in personal attacks against you or anyone else (well, maybe a few totally whack-o commenters). Linus Pualing has been dead for 20 years. Vitamin C has been studied every day since he died. After 20 years there ought to be some interesting translational work, no? Something to make one sit up and take notice?

      I normally don’t get involved in specialist discussions of molecular biology and biochemistry because those aren’t my fields. But I’ve gotten involved here because you insinuate that you have powerful insights into the relationship between vitamin C and cancer yet you’ve published little in the last 20 years and seem to spend your days trying to grow hair on alopecic heads. How you spend your days is your business. But if you have something profound to say about vitamin C and cancer the peanut gallery at SBM doesn’t strike me as the best venue.

      1. WilliamLawrenceUtridge says:

        Gorski, not Novella :)

        Yeah, the real issue is how Proctor keeps talking about how it COULD work, ignoring that it DOESN’T.

        1. Windriven says:

          @WLU

          “Gorski, not Novella”

          Indeed. Domo arigato. These MD PhDs* all look alike ;-)

          It is interesting how Proctor returns – like a computer program stuck in a recursion loop – to the same tropes while generally avoiding the questions put to him.

          In his latest comment he notes:

          “Some of [the new evidence regarding ascorbate] everybody here seems surprisingly ignorant.”

          But he ignores my repeated questioning of why he chooses to present his highly specialized arguments in the comments gallery of a generalist website. Could it be that some pearls only glisten in the eyes of mostly unspecialized swine?

          The specialized swine in these pages including Madison, Angora, Gorski, and others seem largely unimpressed with the pearls. But then the pearls seem to keep changing. To my recollection they started out as, if not the grail, the map pointing the way. The latest comment seems a much more modest Cochranesque ‘deserves more study.’ Seems like an awful lot of spilled verbiage to get there.

          Anyway, it is Saturday in the PNW. The sky is clear (!), the temperature moderate, and the earth dry. My garden awaits. I have a crisp clean Jackson that says my garden will be a lot more productive than this ‘conversation’ has been.

          * Yes, I know Dr. Novella isn’t an MD PhD. Just go with the joke.

      2. Peter H Proctor, PhD,MD says:

        Uh, when you read the Science medicine paper, it mainly calls for a reconsideration of Vitamin-C in view of new science. Some of which everybody here seems surprisingly ignorant. Perhaps misled by old prejudices. A proported academic clinical oncologist who never heard of oxidative signaling. At Anderson, common knowledge over thirty years ago. The mind reels. Again, this is no basis to question the motives and integrity of fellow physicians…

  40. Leslie says:

    I actually came onto this site to see if there was anyone who had actually done the Vitamin C IV therapy like I have – and what their results were. I was diagnosed with Stage 4 Ovarian cancer April of last year (I was 48 and totally healthy, or so I thought) and given 13 months to live. After 2 surgeries, 4 months of chemo (carboplatin and paclitaxel), completely changing my diet to cut out processed foods and getting Vitamin C IV therapy (twice a week during chemo, once a week now), my tumor marker tests have consistently been between 4 and 6 (under 35 is considered normal) and I just had my 3rd CT scan which was all clear. Chemo was physically draining but I never threw up and was able to keep working (chemo on Friday and back to work on Monday) although I pretty much cut out doing anything else during that time and had a lot of help from friends and family. My hair has grown back now, my stamina is almost back to where it used to be and looks like I won’t be dying next month after all. Now I’m not sure if it’s the Vitamin C that made the difference or not but I do know I’m glad that I was open to try something new (even if it wasn’t “evidence-based” enough to be officially recommended). I consider myself to be fairly skeptical; however, this particular treatment struck me at the time as having enough credible science behind it to give it a chance (after all, didn’t really have much to lose). Just wanted to weigh in from someone who’s actually been there.

    1. Andrey Pavlov says:

      Leslie,

      Dr. Gorski is much more qualified to respond to this than I am, and I am certainly sorry to hear of your diagnosis but glad that things are currently looking up.

      However, everything other than the VitC is nothing to scoff at. Given the evidence it is by far the most likely answer that it was everything else that lead to your current remission.

      One thing I remember from my gynecological oncology surgical rotation was that ovarian cancer is somewhat unique; the vast, and I do mean vast, majority of the outcome is dependent on the first surgery and how well “de-bulked” the original tumor and metastases were. Everything else – the chemo/radiation and even the 2nd surgery – is a drop in the bucket compared to that. We still do it because it does add some value in outcomes and helps with recurrence (though I seem to recall that in ovarian cancer this is somewhat questionable, but I am not expert enough in the field to comment fully; perhaps someone else like Dr. Gorski or MadisonMD will).

      The point being is that it is truly unlikely that the VitC did anything at all – good or bad. However, there is a tiny bit of evidence to say that anti-oxidants can actually increase the risk of cancer, but that is a tiny signal in a lot of messy data so I wouldn’t get too hung up about it. However, if someone in my family developed ovarian cancer (or any cancer) I would certainly vigorously admonish against VitC therapy.

      Once again, continued best wishes for a complete recovery.

    2. WilliamLawrenceUtridge says:

      2 surgeries, 4 months of chemo (carboplatin and paclitaxel), completely changing my diet to cut out processed foods and getting Vitamin C IV therapy (twice a week during chemo, once a week now),

      Hi Leslie. So on the basis of the post, you had:
      1) Surgery twice
      2) 4 months of chemotherapy
      3) A radical change in diet
      4) Vitamin C IV therapy

      Why do you attribute your survival solely to the final element of that list? How do you feel about your experiences being at odds with the scientific research.

      Also, as far as I understand it, high-dose vitamin C works by oxidizing the contents of cells through extremely high levels of H2O2. Are you concerned that such high doses of pro-oxidation might have an effect on the DNA of the non-cancerous cells? Are you concerned about the potential for all that pro-oxidation damaging the DNA and possibly leading to more cancer later on in your life?

      Why is “trying something new” more important than “trying something proven”? And it’s not a matter of vitamin C being not “officially recommended”, it’s a matter of vitamin C having little proof of efficacy such that it will probably never be recommended unless new research is unexpectedly positive.

      Are you still getting vitamin C intravenously? How long will you continue to do so? Is the high concentration impacting your blood pressure? Have you been informed of any possible increased risk of stroke due to higher than normal blood volume? Are you paying for this out of pocket? Are you part of a clinical trial?

      How would you feel about being given a drug produced by Pfizer that requires dosing this high, and has this little proof behind it?

  41. Hank Nickerson says:

    George Carlin once quipped about doctors, “They don’t know what they’re doing, it’s all guesswork in a white coat.” After reading this blog post and the thread of comments underneath it I cannot help but feel what Carlin said is true.

    I keep reading comments here saying that studies have proved Linus Pauling wrong. This claim is clearly false. Pauling always claimed that to treat Cancer Vitamin C needed to be administered intravenously. Yet no large clinical trials have been performed on this basis. And, the trials that have been performed have all used orally administered Vitamin C. You cannot claim that Pauling is wrong, if you have not conducted the trials using the methods he laid out. This is the equivalent to the Church refusing to look into Galileo’s telescope.

    Knowing that you cannot conclude that Pauling was wrong without using his prescribed methods is just simple logic. Is that not taught in Med Schools? Now when IV infusion of Vitamin C is brought up, it is ridiculed. Something was said about “Angels and Nuns”. I do not know what place ad hominem argument plays in medicine. But I do know that is has no place in rational discourse.

    Could it be that advocates of IV Vitamin C as a treatment for Cancer are the Galileo’s of their day and the Oncologists the Church? Why don’t we look through his telescope and conduct the IV trials to find out?

    P.S.
    Leslie it could be the case that the Vitamin C did all the work. Now that is something the doctors cannot face or fathom.

    1. MadisonMD says:

      Your post is rather strong on the Galileo Gambit, and shifts the burden of proof, to prove the negative. Typical of drive-by posters here.

      Anyway, if you want evidence that high dose Vitamin C is ineffective, review this phase I/II trial where there were no responses in 24 patients treated and there was grade 3 toxicity (nephrolithiasis). Usually standard drugs are dropped at that point. At least you should tell us why it didn’t work in these 24 and tell us specifically what type of cancer and situation it is more likely to work for.

      Nothing is stopping these proponents or you from doing the follow up study. NCCAM funds this type of work. No unproven therapy should be sold to people.

    2. Dave says:

      You’re doing the same thing you accuse other posters of doing – having an opinion. Now you need to back it up with evidence. Do you have any evidence that high dose intravenous vitamin C works? If so, I’d like to see it for the benefit of my cancer patients. Standard chemotherapy regimens are ungodly expensive, and have numerous unpleasant and dangerous side effects. The only reason anyone would use them is that they improve outcomes in diseases which are generally uniformly fatal. It would be great to have a cheap, nontoxic alternative.

      What you are saying is that large studies have not been done to prove IV vitamin C is effective. That is not the same as saying that IV vitamin C is effective, it is still unproven. So many posters here are leery of therapies for which there is evidence of effectiveness but so willing to accept other therapies without evidence of effectiveness. The mantra in medicine is that any positive study should be repeated, and surveillance needs to be ongoing even after approval of the therapy to assess the therapy for effectiveness and unforeseen side effects. The same standard should hold for alternative treatments.

    3. WilliamLawrenceUtridge says:

      Hank, intravenous vitamin C has been studied. In fact, Dr. Gorski’s post is about intravenous vitamin C, finding it to be of no use for actually treating cancer, and only providing an equivocal benefit in quality of life. In addiiton, there’s very little theoretical basis for which vitamin C would work, and many studies finding that it doesn’t at high-oral doses; not a jot or tittle difference in mortality or survival, suggesting a lack of dose-response relationship.

      So quite possibly, probably even, Linus Pauling was wrong. Simply, flat-out wrong. Totally wrong. Completely making shit up and getting it wrong. Merely because he won two Nobel prizes (in fields unrelated to medicine) does not make him in falliable. Merely because Pauling said something, does not make it true, and bypassing all of the preclinical work and ignoring contradictory data merely because Linus Pauling descended into quackery doesn’t make sense given the scarce funding of current times and the previous evidence of lack of effect.

      Incidentally, you know who wasn’t taught anything in med school? Linus Pauling, because he wasn’t a doctor. Much as we can’t discredit someone based on ad hominem, nor can we credit someone because of halo effects. Pauling didn’t have, and never developed, the data necessary to support his hypothesis.

      Three final points:

      1) Galileo; you know why Galileo is respected? Because he attacked the claims of the times, at great personal risk, and was right. How do we know he was right? Because he had great data. The during the Albigensian crusade the Church also persecuted the fuck out of Cathars in 13th century France. While we might respect them for their endurance in the face of suffering, nobody takes their ideas about health (or even theology) seriously – because persecution does not equal correctness.

      2) Would you pay money for, or accept as a practice, any drug peddled by Pfizer or GSK with the record of vitamin C? If the CEO of GSK said “You should take this drug as an adjuvant chemotherapy agent; it’s failed a dozen times in oral dosing protocols, but that’s because it’s supposed to be taken intravenously. Trust me. A really smart guy that works here thinks it works, even though we’ve never seen any actual evidence of objective improvements.” If you wouldn’t accept that from GSK, why accept it from the loons who promote vitamin C?

      3) As Andrey and I said to Leslie – she undertook four treatments for cancer, and appears to attribute all improvements to vitamin C. Why? Surgery is often curative of solid cancers, chemotherpay agents are used because they are proven to prevent recurrence, but unproven vitamin C is claimed to be the silver bullet? Doesn’t that reasoning seem odd and wrong?

  42. Hank Nickerson says:

    I read the study that was linked. One thing I noticed was the patients were not all given the same dosage. They all were not receiving the same treatment. So, really several studies were being conducted. Each study had a sample size of a handful of people. It did seem to stabilize one patient though. So to the contrary to your assertion there were “no responses”. There was one. Now before you go arguing that Vitamin C was not the cause of this patients stabilization. I will point out if you can assert that the treatment was the cause of their kidney stones. We can certainly assert that Vitamin C was the cause of this patients stabilization.

    This patient is one of those 9 patients with colon cancer that received a 400mg per kilo dosage recommend by advocates of IV Vitamin C. That is a one out of nine stabilization rate for those that received the recommended dosage. If we assume that 430mg per kilo is the right dosage then it comes out to 1 out of 6 stabilization rate. If we narrow it down to just the patients with colon cancer that received the 430mg dose now it is a 1 out of 4 stabilization rate. Does this count as evidence of some efficacy?

    There could be several reasons why the treatment did not work in the other patients. The dosage that was given in some cases was not high enough. The dosage is too high in other cases. It may also have been too late for any therapy to work. The sample size was so small in this case I do not know how anyone can come to any solid conclusions one way or another.

    Some of the other evidence that I know of are Pauling’s initial studies. The results of those studies claim to have produced a 30% increase in longevity and an 8% survival rate after eight years in terminal patients. If true, that is pretty impressive to a layman like myself.

    The point I am making still stands. And claiming that you are being asked to prove a negative is no argument. We prove negatives all the time. For example I can certainly prove the moon is not made out of green cheese. Linus Pauling still has not had his day. Large scale trials with statically valid sample sizes need to be conducted before we can say one way or the other. Such trials would prove a negative namely that Vitamin C is ineffective as a treatment for cancer. You certainly cannot claim it is ineffective until such studies have been done.

    This is all I am objecting to and it is a major flaw in your reasoning. The jury is still out until the needed experiments are conducted.

    1. Dave says:

      If I read the study correctly, it was done to establish the safety of vitamin C on patients with advanced disease. All but one of the 24 patients had progression of disease, and that one with colon cancer and liver mets had stabilization but not improvement. As an aside I am now caring for an individual who has colon cancer with liver mets who was initially diagnosed in 2006 and has had long periods of stability. Some of this is undoubtedly due to the various chemo regimens he has gotten and is getting but I think some of it has to do with the biologic behavior of his individual cancer. Perhaps as you say a study should be done at your recommended dose but the fact remains this is still unproven therapy and should not be done outside a clinical trial setting. You should still have evidence that something works before it becomes mainstream therapy – this goes for all treatments, not just vitamin C. The history of medicine is littered with instances where this was not done, to much later regret. The use of postmenopausal estrogens to prevent coronary disease is an example. (I mention this to save you the trouble of coming up with a reply that mainstream medicine doesn’t always follow this dictum – true, but that’s not science based medicine)

    2. MadisonMD says:

      Yes, it is true to state that the primary purpose of a phase I trial is to establish tolerable dose and toxicity. However, if no responses are seen, that is usually a sign that the drug shouldn’t be developed further (sorry, Hank, stable doesn’t mean much as shown by Dave). In the 21st century, we are looking for phase I trial results like this and this or this.*

      In the opinion of most scientists, and patient advocates, it’s just not worth developing drugs that have, at best, marginal benefits. We can do better with improved knowledge of the disease, specific mechanism, and matching a drug to a particular cancer type.

      If you, the Riordan clinic or anyone thinks the phase I is terribly promising, you can send application for funding from NIH through NCI or NCAAM. I’d advise you to get a biomarker to predict who will benefit. (Cancer is not one disease but many, so you would do well to get specific mechanism beforehand.) I doubt you will get funding with this type of prelim data when other drugs have mechanism, specific target, and promising phase I or early clinical data.

      You all seem to think someone is saying Vitamin C can’t work, will never work, is useless therapeutic. Well, hey, maybe someone will find a particular and very rare cancer with a tremendous response to Vitamin C. But maybe not. Until then, Vitamin C therapy for research should be relegated to the laboratory, and not sold to patients. If, in the future, promising and suitable specific evidence exist suggesting it would work for a particular cancer, I would change my mind. I doubt this evidence is forthcoming given that the ascorbate field is rather well-trod territory. There are so many other compounds we have never tested… so very many other opportunities. Shall we move on?

      We prove negatives all the time. For example I can certainly prove the moon is not made out of green cheese.

      No you can’t. You just haven’t looked in the right place. Have you checked in Mare Moscoviense? Have you looked in the center?

      Says Proctor:

      Further, the concentration of vitamin-c reached are lower than those shown to work in guinea pigs.

      Bravo. My moon cheese analogy seems apt for the both of you.

      —————
      *Please note that all these trials tested a specific drug, cancer type and mechanism extensively validated in preclinical models by multiple investigators. The NIH scientific review panel will be looking for this in your proposal, gentlemen.

    3. WilliamLawrenceUtridge says:

      There was one. Now before you go arguing that Vitamin C was not the cause of this patients stabilization. I will point out if you can assert that the treatment was the cause of their kidney stones. We can certainly assert that Vitamin C was the cause of this patients stabilization.

      Yeah…no. See, we know that vitamin C causes kidney stones. We understand the mechanism. There is prior probability and other experimental results that build towards this conclusion of “high dose vitamin C = kidney stones”. We have very little of that in cancer; to kill cancer cells, even in petri dishes, takes near-lethal doses of vitamin C. So even if vitamin C is an effective form of chemotherapy, it’s not promising. Nearly anything – salt, water, sugar, oxygen – is lethal to all cells in high enough concentrations.

      You then chain together a series of speculations. Speculations are not evidence. Sure, at X dose it might be effective (and again – is anything not effective at X dose, if it’s high enough?) but it might not be effective – and there are far more promising compounds, and far more effective medicines, than vitamin C.

      For example I can certainly prove the moon is not made out of green cheese.

      Um…no. We can prove the moon is not made of green cheese because we’ve landed on the moon and proven it’s made of fucking rocks. Anyone who wants to prove that there’s a chunk of green cheese on the moon – it’s incumbent on them to overturn the massive evidence that the moon is made of fucking rocks. Evidence wins – and there’s no promising evidence here that vitamin C is a particularly good chemotherapeutic agent. Do you seriously think it’s a good use of money to spend millions of dollars, years of researchers’ lives, and the actual lives of patients exploring every possible permutation by which vitamin C might cure cancer?

      At a certain point, it might be better to simply admit that there’s no good reason to expect vitamin C to cure cancer, there’s no good evidence it cures cancer, and there’s no real reason to believe that Linus Pauling was a magical truth machine. Vitamin C is necessary for life. We can’t manufacture it ourselves. That doesn’t make it magic, and the continuous goalpost-moving just proves how weak the case and the evidence is.

  43. Hank Nickerson says:

    Will,

    Galileo is respected now. He certainly was not in his life time. Pauling may very well be a Galileo. The thing they both share is they confront the orthodoxy. No one has radically changed science by standing with the orthodoxy. My point still stands you cannot claim he is wrong till you perform the clinical tests the way he prescribed. Until that day you are just, as an other poster here has alluded to, constructing Strawmen.

    I understand that you stand with the orthodoxy and you want to declare Pauling wrong without any statistically significant evidence. This just what one would expect from a scientist.

    You want to fault me for “stringing together speculations”? Well when I am engaged in a debate I try to directly answer questions given to me. I was asked to speculate so I did.

    So, you know that kidney stones were caused by the Vitamin C in this case? This patient had a prior history of kidney stones. How do you know that it was the Vitamin C?

    So you are arguing that we do not know the moon is not made of green cheese? We cannot prove that negative? We prove negative statements all the time. Here is another one. Four does not equal Five. We certainly know that somethings are not the case. If you want to falsely believe that you cannot prove a negative. You have to explain how we know that somethings are not the case. Why do we have the concept of negation at all? Are you really that big of a skeptic? Do you really believe that we never know if something is not true?

    Your website is really bizarre to me. You argue using school boy informal fallacies. You declare something is not the case when no statically valid tests have been done. Exactly what you would expect from a site with the moniker “sciencebasedmedicine”. And you have some serious acronyms next to your name. How in the hell did you make it this far?

    Lastly it would certainly do a lot of good, that is what medicine is supposed to be about? if a statistically valid experiment using exactly the methods laid out by Linus Pauling were conducted on Vitamin C. Why? You might ask. Because it would shut people up. If you truly cared about people and wanted to stop them from being treated with “quack” therapies. You would conduct the statistically valid experiments. People would be convinced the therapy does not work, if they were told “We conducted a statistically valid experiment using the methods exactly what Linus Pauling prescribed for Vitamin C treatment on 10K people. We found nothing”.

    Most sane people would believe that and not pursue the therapy. Meanwhile we have many people with cancer seeking out alternative therapies which you think are quackery. If you really cared about these people and wanted to stop them you would perform the experiment. This way you would have some real evidence in your hands. The thing is you don’t care it is all grandstanding on your part. Personally I think you like arguing without having any conclusive evidence. It’s not like we cannot have such evidence all we have to do is conduct the experiment.

    1. Bruce says:

      Hank,

      It is funny that you accuse someone here of “You argue using school boy informal fallacies”.

      When you try to pull one of the most basic of fallacious argument tools in the Galileo Gambit:

      http://rationalwiki.org/wiki/Galileo_gambit.

      The rest of your posts show your lack of understanding of formal logic and science in general.

      Your statement that four does not equal 5 is TRUE. We can also say that four equals five is FALSE. These are not, however, proofs; they are merely a statements. Science works by putting forward hypotheses and then presenting evidence to prove that the hypothesis is valid.

      Scientifically speaking, all evidence we have currently points to the moon not being made of cheese. If you were to make the hypothesis that it is made of cheese then the onus would be on you to prove that it is in fact made of cheese despite all the evidence against the case.

      You ask us to do the experiment to prove that Pauling is right, when in fact the onus is on him to prove his case. Using the analogy above, NASA is not going to fund a trip to the moon to disprove a claim that the moon is made of cheese, it would be on the person making the claim to fund the evidence finding.

      Until such time as Pauling proves his therapy works we can quite safely claim that “there is no evidence that Paulings claims are true.”

    2. weing says:

      “My point still stands you cannot claim he is wrong till you perform the clinical tests the way he prescribed.”

      That’s not exactly right. You cannot claim he is right until you perform the clinical tests and show the effect.

    3. MadisonMD says:

      Lastly it would certainly do a lot of good, that is what medicine is supposed to be about?

      Scientific research is not about trying to falsify every hypothesis to the smallest limits of residual possibility. It’s about pursuing the most promising leads to have the maximal improvement in medical care.

      if a statistically valid experiment using exactly the methods laid out by Linus Pauling were conducted on Vitamin C. Why? You might ask. Because it would shut people up.

      Wrong. Proctor already demonstrated that the goalposts will move, remember. Reread this:

      Further, the concentration of vitamin-c reached are lower than those shown to work in guinea pigs.

      This is why a clinical trial cannot convince everyone of lack of efficacy. And you can’t prove to us that there is no cheese on the moon. Although the idea that cheese is on the moon is rather unorthodox, right? So we should consider it, Galileo?

      We conducted a statistically valid experiment using the methods exactly what Linus Pauling prescribed for Vitamin C treatment on 10K people.

      Why 10,000? So you think it is ethical if, after the first 1000 or so have no benefit we should continue with the remaining 9000? Do you know about biostatistics?

      If you really cared about these people and wanted to stop them you would perform the experiment.

      Do you care about the the 10000 patient who by your clinical trial design would receive this therapy if no effect in the first 9999?

      You’ve avoided the question about what type of cancer is likely to benefit and why. But you can explain this when you put in your NIH proposal. I’m pursuing things that look a hell of a lot more promising myself.

    4. WilliamLawrenceUtridge says:

      Galileo is respected now because he produced good data to support his iconoclasm; data that was impossible to argue with, once you looked through his telescopes you had to admit that the Earth was not the center of the universe. One isn’t right because one challenges the orthodoxy, one is right because ones observations align with reality and one provides evidence for that. Pissing off authority figures doesn’t make you right (otherwise teenagers would be right), and nor does being laughed at make you right (otherwise comedians would be the doctors). So, where’s the good data showing vitamin C cures cancer at reasonable concentrations in humans? It’s not there. There does not seem to be any evidence that vitamin C has any special chemotherapeutic properties. While I can’t definitively say that vitamin C doesn’t, and can’t, cure cancer, it’s incumbent on the claimants that it does to provide evidence and do the kind of preclinical work we expect of other compounds. That people want to short-circuit this process on the basis of Pauling’s word alone (who died of cancer let’s not forget).

      Vitamin C would do a lot of good if it were shown to be a powerful, safe form of chemotherapy. But you could say that about anything without it being true. It would be great if yogic flyers could fly. It would be great if by wishing hard enough we could cure cancer – but we can’t. Further, resources are scarce, and there are far more promising avenues of potential cancer research, both in terms of prior probability, past evidence and conceptually (even the idea of a universal cure for cancer doesn’t make sense). Seriously, do you know how much money it would cost to run a double-blinded trial of 10,000 cancer patients? How much better use that money could be put to – for instance, repairing bridges and tunnels, researching the mating habits of frogs, etc. I mean, you do realize that there aren’t enough cancer patients in America to do a study like that, right? Because there’s not enough people with the requisite cancer type and staging to achieve proper groups. And again, the evidence to date just doesn’t paint vitamin C as a reasonable cancer treatment – you would be blowing hundreds of millions of dollars on a treatment that today shows, at best, equivocal results, whose most impressive claim to fame is that a two-time Nobel scientist (who wasn’t a doctor, whose Nobel prizes were not related to medicine) who died of cancer despite taking gram-quantities of vitamin C daily, thought it was a good idea. And it wouldn’t convince or drive patients away from vitamin C, since the patients seeking it in the first place aren’t making this decision rationally. Because the rational decision is – maximize your chances with proven treatments.

      If you care about patients, you give them the best information and treatment available. You don’t sell them false hope or ignore contrary evidence merely because some guy, even a smart guy, said it. Asking for conclusive evidence would accomplish little and retard progress because conclusive evidence is very difficult and expensive to acquire. We have good enough evidence that it’s a waste of time without further basic research.

      If you really care about cancer patients – you put that money and effort into testing promising agents.

  44. Peter H Proctor, PhD,MD says:

    “Vitamin C may boost chemotherapy” at http://www.medicalnewstoday.com/articles/272408.php

    Again, the article does not claim clinical efficacy for Vitamin-C in cancer and it is a straw argument to claim it does. What it does do is say this might be worth looking at again, which I and many others knowledgeable in redox control of the cancer process happen to believe.

    Since you-all clearly have not a clue about this field (6000+ cites on pubmed) or even its existence until I pointed it out to you, you simply have not the expertise to make such pronouncements. Educate yourself so we can discuss this matter on the basis of the extensive science and not with ad hominems and straw arguments….

    1. MadisonMD says:

      You appear to think very highly of yourself, Dr. Proctor. Well, if you know more than everyone else, you should be able to provide some specifics. Exactly what type of cancer has the most promising preclinical evidence, Dr. Proctor? Based on the known pharmacology of Vitamin C and mechanism of action, what dose/schedule is expected to be efficacious? What are the expected effects (tumor response, prolonged survival, etc.)? Does Vitamin C operate as an oxidant or antioxidant under these circumstances?

      Specifics are required, Dr. Proctor, not just random abstracts, writing “straw,” and repeated claims that you know more than everyone else.

      1. Peter H Proctor, PhD,MD says:

        Whatever. Fact is, were ignorance bliss, I’d be very happy. However, clearly, I know more about redox control of the cancer process than you, Me and my posse at MD Anderson having partially originated the field. “The race may not always go to the swift, nor the contest to the strong, but that’s the way to bet.”

        And I give lots of cites above. Read them….

        1. MadisonMD says:

          That’s what I thought. You don’t have any specifics. But thanks for saying you know more than everybody else yet again. That was very enlightening.

          1. Peter H Proctor, PhD,MD says:

            Again, I clearly know a lot more about the role of redox signaling in the cancer process than anyone here. Not difficult, since nobody here seems to have heard of it, though the field has more than 6K or so citations. For one thing, I and my cohorts share discovery credit. e.g.,

            “Role of Active Oxygen Species in Ocular and Neurological Diseases” Conference on Active Oxygen and Medicine, Honolulu, Hawaii, March 3-4 (1979)
            “…active oxygen metabolites act as specific intermediary transmitter substances for a variety of biological processes including inflammation, fibrosis, and possibly, neurotransmission.”

            “An in vivo enzymatic probe for Superoxide and Peroxide by Chemotherapeutic Agents”
            Pathology of Oxygen,(1982) ed. A. P. Autor, Academic Press, New York, pp.

            The antitumor action and toxicity of adriamycin, cis-platinum, and bleomycin involve reactive oxygen species (ROS). Ectopic superoxide dismutase is roughly-equivalent to cis-platinum as an anticancer drug. That is, ROS are cellular messengers in cancer.

  45. Hank Nickerson says:

    Hmm the mind boggles this site gets stranger and stranger citing of the “Galileo Gambit”. It is a way to dismiss an argument without even hearing the person out. It is certainly not a “fallacy”. If Pauling is right. The gambit is way of dealing with people that believe they have invented perpetual motion machines in their basements. It does not deal with people like Pauling who have bona fide scientific credentials. The thing about people like Galileo is that people do not know they are right until sometimes hundreds of years later. Aristarchus of Samos conceived of the heliocentric view of the solar system nearly 1700 years before Copernicus. It took another few hundred years before the idea became accepted.

    I have yet to read a logic text book with said “fallacy” inside it. If it is a fallacy no logician I know knows about it. Anyhow on the face of it at the wiki page. No where in any of my posts do I assert that Pauling is a Galileo. I say he maybe. Of course the skeptics here are not serious about proving Pauling is not a Galileo. God forbid they actually back up their claims with evidence. But wait no one here actually wants evidence in the form a statically valid experiment.

    They claim that there is no proof that Vitamin C works. To claim this is to ignore Pauling’s original work with Cameron. Actual they go into denial mode claiming Pauling, a Nobel Prize winning scientist, did not know how to conduct research. Not only is there evidence there are plenty of places actually pursuing the therapy. Look at University of Kansas among others they actual offer the therapy. They are not some clinic in Mexico. They certainly believe that there is some efficacy there.

    http://www.kumed.com/medical-services/integrative-medicine/faq/iv-vitamin-c-faq

    Now I asked some questions about negative statements I will reiterate here. Because no one has answered my questions.
    “If you want to falsely believe that you cannot prove a negative. You have to explain how we know that somethings are not the case. Why do we have the concept of negation at all? Are you really that big of a skeptic? Do you really believe that we never know if something is not true?”

    1. MadisonMD says:

      Actual they go into denial mode claiming Pauling, a Nobel Prize winning scientist, did not know how to conduct research.

      Uh, no. Even a Nobel prize winner can be wrong, can’t he? See here, for example.

      “If you want to falsely believe that you cannot prove a negative. You have to explain how we know that somethings are not the case. Why do we have the concept of negation at all? Are you really that big of a skeptic? Do you really believe that we never know if something is not true?”

      We know somethings are more or less likely given the evidence available. Some things are less likely than others. For example, given what is known, homeopathy is less likely a useful cancer therapy than Vitamin C. Vitamin C is less likely a useful therapy than cisplatin for lung cancer. Cisplatin is less likely a useful therapy then vemurafenib for certain types of melanoma. We could re-evaluate these likelihoods in light of new evidence in the future, but we can be most confident that new knowledge will not upset the fundamental 150 years of physics, chemistry, and medicine to conclude that homeopathy works. It is a hierarchy of knowledge not all/none, proof/disproof, and is always subject to re-evaluation.

      Now, please answer my question: What type/subtype of cancer is Vitamin C most likely useful for and why? As Proctor points out, it’s well-trod territory in research with over 6000+ cites (far more than vemurafenib with 676 articles only). So you should be able to provide an answer.

    2. Sawyer says:

      Since you’re harping on the Galileo Gambit, I’ll do your homework for you. I don’t thin it would be considered an informal logical fallacy, but it certainly falls under the umbrella of the availability heuristic. People can readily recall the story of Galileo and a handful of other scientists that have underwent a similar treatment. Anyone interested in science here’s these stories on a regular basis. However, most people are NOT familiar with the thousands of scientists that get burnt out in the last decade of their career, pick a project outside their area of expertise, and do terrible, terrible work. Yet statistically this is the far more likely scenario.

      We don’t know which present day scientists will be heroes of the 22nd century, but we know which ones won’t. People wasting time on the vitamin c hypothesis are in the “won’t” category. There’s a lot more that could be said about this, but it looks like you’ve already made up your mind on this topic.

    3. WilliamLawrenceUtridge says:

      Yeah…you’re the one who brought up Galileo Hank, not us. And you brought him up in the context of “persecution = correctness”, which is wrong. The true equation is “evidence = correctness”, the persecution, which everyone focuses on, is tangential to whether or not GG was right. Galileo had evidence at the time of his trial, it was noted that church fathers were extremely reluctant to engage with it because it would prove their model of the universe wrong, unambiguously. It didn’t take 300 years for people to realize he was wrong, that’s how long it took the church to admit it was wrong. Scientists had moved on, well, about 299 years ago.

      Pauling’s credentials were not in medicine by the way. A related field, but not medicine.

      The fact that vitamin C is offered for sale is not proof of efficacy, it’s proof of the weakness of the regulatory regime used to protect patients. Homeopathy is for sale, it’s quite popular in some areas, and rakes in billions of dollars. Do you think homeopathy works? There are people who will sell you perpetual motion and free energy machines, but there’s a reason they can’t be patented and a reason NASA won’t use them to launch rockets.

      Skepticism is about asking for evidence, and in particular asking for high-quality evidence when extreme claims are made. Vitamin C is such a claim. We simply can’t know if something is true until we do the work, but doing the work requires resources and decisions about where to invest those resources are made on the basis of prior evidence. The prior evidence for vitamin C is very, very poor, and not helped by studies like these.

      I mean seriously, if “vitamin C” were replaced with “substance X, made by Pfizer”, and Linus Pauling hadn’t endorsed it, would you give it a second thought with this kind of evidence?

    4. WilliamLawrenceUtridge says:

      The thing about people like Galileo is that people do not know they are right until sometimes hundreds of years later.

      I don’t know if you’ve noticed, but the pace of evidence accumulation has changed since Galielo’s time. They went from not knowing what AIDS was, to having an effective treatment in what, a decade or so? Galileo and his peers existed in a time when all science and knowledge was derived from ancient authority and scripture. To prove something right, you merely had to prove that someone old holy said it. It took Galileo centuries to be proven right (which actually I doubt but don’t have specifics on) but it took less than a century to go from Pluto being discovered to being considered not a planet. Plus, you simply can’t point to Pauling and say he was right because Galileo was right, in a totally different situation, several centuries in the past, in a different field of science. You aren’t helping your case by continually bringing up Galileo, because scientists are proven right by evidence, not historical analogy. For every Galileo there are thousands of forgotten scholars who were wrong. How do you know Pauling isn’t one of them?

      Then you bleat about how we aren’t providing statistically significant evidence – well, Dr. Gorski examined the evidence, and linked to other blog posts about vitamin C and cancer, with a consistent finding – vitamin C hasn’t been proven effective. Experiments have been conducted. The best they’ve found is “hey, it doesn’t make your cancer worse!” Well, colour me unimpressed.

      And if you’d read a bit more, you’d find that Cameron’s contributions have been examined and found wanting. He did record longer survival times – but his “vitamin C” patients were categorized as terminal before his non-vitamin C patients. Two patients have cancer. Both will die in five years. Patient A is declared incurable by Cameron after one year, and is given vitamin C. He survives four more years. Patient B is declared incurable by someone else (the controls were patients of doctors other than Cameron) after four years of chemo, and does not get vitamin C. He survives for one more year.

      Upon review, that is how vitamin C “cured” more people in Cameron’s study. Which is to say – it didn’t.

      And as someone else pointed out – an integrative cancer center offering (and charging) for vitamin C treatments doesn’t prove it is effective, only that they are willing to charge people money for it. That’s rather our objection – that a double standard exists for CAM therapies, including vitamin C treatment. Any real chemotherapy drug that was tested and sold to desperate patients like vitamin C is, would have been shut down by the FDA. But because of the CAM double-standard, cancer patients get to have their pockets rifled before dying. Hooray.

      See, what you need to do is show peer-reviewed studies that vitamin C increases cancer survival in humans, not that someone is willing to sell it. I’m not sure why you fail to grasp that mentioning Galileo and sales locations aren’t evidence of efficacy.

      It’s not up to us to prove that vitamin C doesn’t cure cancer. It’s up to you to provide evidence that it does. I haven’t seen any.

  46. Windriven says:

    “The thing about people like Galileo is that people do not know they are right until sometimes hundreds of years later.”

    Don’t be a horse’s ass. Science in the 17th century was quite a bit different than science today. Pauling’s conjecture about ascorbate is easy enough to prove. So shut your hole and go prove it. Others have tried.

    “I have yet to read a logic text book with said “fallacy” inside it.”

    How many logic texts have you read? Perhaps zero? Name them for us?

    “But wait no one here actually wants evidence in the form a statically (sic) valid experiment.”

    You’re dead wrong. Everyone here is waiting for exactly that: statistically valid evidence. We do not have to prove that ascorbate has no utility any more than we have to prove that moonbeams have no utility in managing cancers. The ascorbate crowd has made a claim. Now it is time for you to belly up to the bar and provide some evidence of clinical effectiveness in humans.

    “If you want to falsely believe that you cannot prove a negative.”

    I won’t pretend to understand that sentence. Conditional reasoning requires both an ‘if’ and a ‘then.’ But implicit in that crippled melange of words is the notion that someone can prove a negative. Lay out for us the logical process by which a negative might be proven.

  47. Hank Nickerson says:

    You would not know logic, if Quine slapped you in the face.

    University of Kansas claims on their website thae Vitamin C has efficacy. Did you miss that? This is a quote from their website:
    “Research shows that intravenous vitamin C at high doses, used in conjunction with chemotherapy or radiation, kills cancer cells in the early stages of cancer. For those in the later stages of cancer, the intravenous vitamin C protocol may improve the quality of life. – See more at: http://www.kumed.com/medical-services/integrative-medicine/faq/iv-vitamin-c-faq#sthash.pzSiFGNr.dpuf

    Here is a Modens Ponens to help you on the logic front.

    IF the moon is made of rock. Then the moon is not made of cheese.
    The moon is made of rock.
    Therefore the moon is not made of cheese.
    WOW I just proved a negative.

    1. Chris says:

      I see that link claims “Research shows that intravenous vitamin C at high doses, used in conjunction with chemotherapy or radiation, kills cancer cells in the early stages of cancer. For those in the later stages of cancer, the intravenous vitamin C protocol may improve the quality of life. ”

      But it is missing a crucial bit of information: links to the PubMed indexed papers on that research.

      Could you please provide the PubMed Identification Numbers of that research, please?

    2. Bruce says:

      “IF the moon is made of rock. Then the moon is not made of cheese.
      The moon is made of rock.
      Therefore the moon is not made of cheese.
      WOW I just proved a negative.”

      In order to prove something you must have a hypothesis. In order to have a hypothesis you need to have something more than a series of statements that do not contradict each other.

      Perhaps you need to read a bit more on what a hypothesis is. Merely making two statements does not make a hypothesis. Wikipedia is a good place to start:

      http://en.wikipedia.org/wiki/Hypothesis

    3. weing says:

      Here is a Modens Ponens to help you on the logic front.

      “IF the moon is made of rock. Then the moon is not made of cheese.
      The moon is made of rock.”

      Can you prove it is made of rock? Then, I’ll buy it. If vitamin C works in curing tumors, then vitamin C is not quack therapy. That vitamin C works, needs to be proven.

      “University of Kansas claims on their website thae Vitamin C has efficacy.”
      Yes the integrative, aka unproven, medicine department makes that claim. That is not science based medicine. They do not back up their claim with research. You are just supposed to trust them. This here is Science-based Medicine. We need the actual research backing it up, so it can be critically evaluated.

    4. Dave says:

      I looked at the link above and it said research shows vitamin c worked when given with chemo or radiation. It also said you could look at the research articles in “this section of the website” but try as I might I cannot find those research articles. Could you please link them or post them?

      1. WilliamLawrenceUtridge says:

        I wonder what happens of those patients do not get chemotherapy and radiation, and what would happen if they got both – but no vitamin C? Would we see any difference? I bet the former group would die quickly and in pain. The latter – either saved, or with longer lives and greater comfort.

    5. Windriven says:

      “You would not know logic, if Quine slapped you in the face.”

      How long did it take you to find Quine? It is clear you’ve never read him.

      “The moon is made of rock”

      WOW I just proved a negative.

      No, you’ve only reiterated that you’re a horse’s ass. You haven’t demonstrated that the moon is absent cheese. You have no evidence to prove that. You can reasonably say that evidence to date suggests that the moon is made of rock. That, Henry, does not prove a negative. You really should seek remediation.

  48. MadisonMD says:

    University of Kansas claims on their website thae Vitamin C has efficacy. Did you miss that?

    WTF? Did you read Gorski’s blog post you are commenting on? It’s about U. Kansas selling unproven Vitamin C to cancer patients based on hypothesis and inconclusive evidence!

  49. Hank Nickerson says:

    Wow the Amazing Randi has really warped some minds around here. People do not know the difference between inductive and deductive reasoning around here. There is not a single Logician that believes you cannot prove a negative. It would be news to Kurt Godel. You do not know what a valid deductive argument is as well.

    I cannot prove a negative? SO I do not not know something is the case? So you guys do not not know that your hand is in front of your face? Are you not not sure that is a scalpel in your hand before you start cutting? Wait you can’t right? Because you cannot prove a negative!

    Here is a paper on proving negatives. I see you don’t need to know logic to cut into people. Are surgeons just butchers with an advanced degree? Hales does a real good job of taking apart the absurdity of your you cannot prove a negative point of view.

    You might know something about cancer but you do not know anything about logic. Please read this it is short and get educated on logic.
    http://departments.bloomu.edu/philosophy/pages/content/hales/articlepdf/proveanegative.pdf

    1. Windriven says:

      Go here:

      http://xkcd.com/1052/

      Pay close attention to the first cell.

    2. Windriven says:

      From the article that you linked:

      “1. If unicorns had existed, then there is evidence in the fossil record.
      2. There is no evidence of unicorns in the fossil record.
      3. Therefore, unicorns never existed.”

      Are you clever enough to find the logical fallacies here? Nearly everyone here could pick up one in less than a second and a second a second later. How ’bout you?

      1. Hank Nickerson says:

        I see nothing wrong here. It is a completely kosher inference. Do you really believe that there is a undiscovered unicorn somewhere in the fossil record?

        1. Windriven says:

          “I see nothing wrong here. It is a completely kosher inference. Do you really believe that there is a undiscovered unicorn somewhere in the fossil record?”

          Do you really believe in unicorns?

          Do you believe that all fossils extant have been discovered?

          Do you believe that all species for which fossils exist have already been found in the fossil record?

          Hank, you would not make a good scientist. Me? I don’t believe in unicorns. But if an apparent unicorn fossil was found it wouldn’t spoil my day. I would reorder my thinking to allow that something resembling a unicorn once apparently existed and would follow the ensuing research with interest.

    3. MadisonMD says:

      Interesting article on logic, Hank. After the odd unicorn demonstration, it makes this argument:

      Someone might object that that was a bit too fast…after all, I didn’t prove that the two premises were true. I just asserted that they were true. Well, that’s right. However, it would be a grievous mistake to insist that someone prove all the premises of any argument they might give.

      Really now? We should’t worry about whether the premises are true? Why not? It continues…

      Here’s why. The only way to prove, say, that there is no evidence of unicorns in the fossil record, is by giving an argument to that conclusion. Of course one would then have to prove the premises of that argument by giving further arguments, and then prove the premises of those further arguments, ad infinitum. Which premises we should take on credit and which need payment up front is a matter of long and involved debate among epistemologists.

      So you don’t have to prove the premises true because you can’t using pure logic! Maybe this is the precise reason you don’t do medical research with logic alone. Perhaps that’s why Aristotle didn’t make too many medical advances. When applying deduction in science, the verity of the premises is quintessential.

      More from your link:

      But one thing is certain: if proving things requires that an infinite number of premises get proved first, we’re not going to prove
      much of anything at all, positive or negative.

      Yeah, no kidding. That’s why you don’t advance medical science with pure logic. Dr. Hales is admitting this is not possible. Yet, science can get pretty close to certain in some things, and remains rather uncertain in others.

      The final conclusive sentence from your link:

      You can prove a negative — at least as much as you can prove
      anything at all.

      Yeah, basically, with the qualification, that’s what I am saying. (Yet this philosophy professor from Bloomburg U. ignores that it is more difficult to use observation to reject a hypothesis with a high degree of certainty than it is to accept a hypothesis with the same degree of certainty.)

      1. Windriven says:

        Well done, Madison. I bailed after the unicorns because of the unfounded assertions: that unicorns would have necessarily existed at a time and place conducive to fossilization, that because no fossils have been found to date that none exist.

      2. Hank Nickerson says:

        Madison, the whole point of the article was to show that “you can prove a negative”. It is wrong to think that you cannot. I am not saying you can advance medical science on the basis of pure logic alone. Of course actual experimentation has to be done. I realize that science suffers from the problem on induction. There is no certainty in science.

        There are observations that you can be practically certain of. Such as this is my hand in front of my face. I try not to be a total skeptic though. I believe that induction is a fairly reliable way at arriving at knowledge. It’s funny how some of us here want to turn into total skeptics and deny that the moon is made of rock.

        1. MadisonMD says:

          Madison, the whole point of the article was to show that “you can prove a negative”.

          And, Hank, the conclusion of the article was:
          You can prove a negative — at least as much as you can prove
          anything at all.

          There is no certainty in science.

          Yes, agreed, that’s what I am saying.

          There are observations that you can be practically certain of.

          If you mean there are facts that you can be practically certain of, I also agree. One is that homeopathy doesn’t cure cancer.

          My point is we can demonstrate to your satisfaction, wherever you set that bar, that Vitamin C is not useful to treat cancer. However, it’s not possible to prove it. Maybe we haven’t looked at the right cancer, haven’t used the right dose, schedule, etc. etc. See Vitamin A example below, demonstrating how laboratory observation can resolve the issue.

          1. Hank Nickerson says:

            Well this is where we differ. From what I have read on the subject which I admit is not a lot. I am not an oncologist nor do I want to be one. That being said it is my understanding that Linus Pauling has not had his day. Because protocols that he had set forth in an experiment have never been adhered to in any way. For example in the 70′s he did research on using Vitamin C to treat cancer with Doctor Ewan Cameron. They administered the Vitamin C both orally and intravenously. The reported results from those experiments supposedly extended the life of patients 33% and 8% of the patients treated were still alive 8 years later. From what I have read the Mayo Clinic then tried to look into these results they also conducted experiments into Vitamin C.

            They did not use the protocols laid out by Pauling though. And when the results came out negative they declared that Vitamin C had not anticancer properties. Pauling of course objected to what happened in a letter to the Mayo Clinic. So in this case Pauling said the experiments have to be carried out according to Y protocols. The Mayo Clinic carried out the experiments according to Z protocols. Well if the Mayo Clinic was supposed to do Y, but did Z instead they cannot declare Vitamin C untherapeutic on that basis. That is called a Strawman in Logic.

            How can they declare Pauling wrong when they did not follow his protocols? Please explain to me how they can do that? It is my understanding in science when you try to duplicate someones experiment you follow the steps they took. The Mayo Clinic has never done that. Now I do think a statically valid experiment can prove Pauling wrong but it has to be performed along the lines he laid out until that happens the jury is still out.

            Now there are some doctors out there that have been treating Cancer patients with Vitamin C claiming to have produced the same results that Pauling and Cameron did. Some people claim they are quacks. But how do I know this if no one has tried to replicate what Pauling and Cameron did following their methods using a statistically valid sample?

            When it comes to you Vitamin A example I think that it does show that it does not cure cancer. Now using the basic taxonomic rankings. We are using the word cancer as a family diseases. In this case it is a word that picks out a family of diseases. Leukemia would be a genus. And the species of cancer you laid out would be a species. Now it did cure the species of cancer that you brought out. So what we have here is a category error. We can say Vitamin A cures a species leukemia. But it does not cure Cancer. Your example does point out the limitations of trials. The larger they are the better and potential treatments should not be taken off the table if they have never been used to treat a certain species of cancer.

            1. Windriven says:

              Let’s presume for just a moment that you are correct. Why do you suppose that after the initial trials, Pauling’s protocols were discarded in favor of something else?

              1. Hank Nickerson says:

                I have no idea why they changed the protocols. I am just telling the story as I have read it argued by the proponents of Pauling’s position. Pauling claimed conspiracy in his letter. I am just a layman here. Who has had several family members die from cancer. I don’t know what to think. It seems fantastic to me that vitamins play such a vital role in our health. From the lectures I have seen given by Pauling he makes what seems like a convincing case to me.

                Pauling’s credentials are very impressive to me. He did win two Nobel Prizes and should have won a third for his work on the sickle cell. Now if it had been the psychic reiki healer down the street proclaiming I would not give Vitamin C a second thought. Pauling is a lot harder to dismiss as a kook. I have seen his critics claim he was a megalomaniac. But in the interviews and talks I have seen he does not come off that way at all. He says things like “I maybe right on Vitamin C” or “I think I am right on Vitamin C”. So he was by no means certain. Megalomaniacs do not claim they might be right.

              2. MadisonMD says:

                We cannot assume Linus was always right. He also thought he was right about the structure of DNA (a topic, unlike cancer therapy, directly related to his area of expertise). But he was dead wrong. Remember?

              3. MadisonMD says:

                Why do you suppose that after the initial trials, Pauling’s protocols were discarded in favor of something else?

                Linus didn’t know how to design clinical trials. Even if he did design them to the best standard of the early 1970′s, we now know there were various biases and conceptual errors in the trial designs of the 1960-1970′s (e.g. comparing survival of responders versus nonresponders). Researchers today expect trials today to be designed to eliminate these errors. Researchers today would expect the past 45 years of preclinical research would provide strong evidence to actually support doing the trial.

                45 years is a long time ago in oncology. We know a hell of a lot more than we did at that time. Scientists don’t worship at the altar of ancient geniuses. They builds on the shoulders of these giants, and consider more recent knowledge before laying down future plans.

              4. Windriven says:

                I don’t know why they haven’t pursued his protocol either. But the obvious answer would be because earlier work on ascorbate pulled researchers in a different direction.

                Peter Proctor, an ascorbate activist and researcher, has appeared prominently in this comments section. It would be interesting to hear his answer.

                No one doesn’t want to cure cancer. Well, a few psychos maybe. Researchers pursue the avenues that they believe will be most productive. The aforementioned Dr. Proctor claims confidence in ascorbate in the treatment of cancer but has spent much of his professional life on baldness. I say this because there is likely a Nobel for someone making a dramatic breakthrough in cancer treatment. If ascorbate is the grail I struggle to understand why it isn’t being chased.

                Cancer, as I’m sure you know, isn’t a single disease. Worse, each form is devilishly complex – even when the underlying genetics of a particular type of cancer is understood.

                Medical research is a scarce resource. There are too few researchers and too few research dollars. So research tends to follow avenues of greatest potential. I suspect this is the fulcrum on which your ire regarding ‘proving a negative’ pivots. We (they really, I am not a cancer researcher) cannot prove that purée of ant testicles doesn’t cure cancer – for all the reasons I mentioned in an earlier comment. In a world of infinite resources we could pursue it. But would it be ethical to pursue a treatment possibility that I pulled out of my butt rather than one with established potential?

                I’m not suggesting that ascorbate is a butt pull. But I am suggesting that it has been judged less promising than other possibilities by the very people with the most to gain and with the best expertise to make the judgment. And Hank, that includes the ascorbate fans. Getting the money for a major trial isn’t trivial but neither is it impossible.

                Action speaks louder than words.

            2. MadisonMD says:

              When it comes to you Vitamin A example I think that it does show that it does not cure cancer.

              Really? It cures Acute Promyelocytic Leukemia but you would say it does not cure cancer? So you would define “cure cancer” as a substance that cures ALL cancer? If, so you would only need to test in one person. The Riordan paper above did this. Question answered.

              If you would define “cure cancer” as randomly curing a fraction of cancers selected from a diverse population of species and subtypes without any predilection for one subtype, then you should know this concept contravenes all prior experience in oncology. It also contradicts what we know about the biology and pathophysiology of cancer. Did Linus claim this? What fraction would be worthwhile? 10% 1% 0.1%?

              You are ignoring that clinical trials are built on strong preclinical evidence. That has been lacking for Vitamin C, with, in fact, some concerning preclinical evidence that it could make other medicines ineffective.

              Now there are some doctors out there that have been treating Cancer patients with Vitamin C claiming to have produced the same results that Pauling and Cameron did. Some people claim they are quacks.

              They are quacks. You are ignoring that University of Kansas, the Riordan clinic and others are selling Vitamin C to cancer patients based on claims without evidence. Can you admit this is unethical? And if were really effective why don’t they publish a few case reports, at least, showing unexpected and miraculous cures on the thousands of patients to which they already sold Vitamin C?

              Linus was brilliant, he deserved his Nobel Prizes. Like any human, he could be wrong–he was certainly wrong about the inside-out DNA triple helix. He was wrong about Vitamin C and the common cold. He was wrong about Vitamin C and cancer. If you consider all the evidence instead of requiring only clinical evidence on 10,000 patients, you would conclude the same… well about as much as you can prove that anything doesn’t work. (But I still think it could possibly be useful perhaps in a particular rare cancer type or situation–if discovered to do so in the laboratory).

              Look again at some of the phase I trials I posted and tell me if you think the best investment of limited resources is a Vitamin C clinical trial instead of a drug that shows those effects.

              1. Hank Nickerson says:

                Not saying that Pauling can’t be wrong.His history does show that he was right more than he was wrong. I am saying that the experiments need to be run according the protocols he laid out before we can declare he is wrong. This is the argument that Pauling laid out. And I do not see any of his detractors responding to it.

              2. Windriven says:

                ” And I do not see any of his detractors responding to it.”

                Ask not why his detractors have moved in other directions*, ask instead why his supporters have not followed the protocols.

                * because it has been explained repeatedly that the evidence has led them in other directions.

              3. weing says:

                “Not saying that Pauling can’t be wrong.His history does show that he was right more than he was wrong.”
                Is that logical? Was he really right more than wrong? Can you really make that claim? Of course you can. You just did. But my spider senses tell me something is wrong. I wish I could understand what Gödel’s Theorems say about strong and weak arguments.

              4. Hank Nickerson says:

                @weing When it comes to Godel’s Incompleteness theorem you just wish you could understand it. When it comes to Pauling being right more than he has been wrong. That is an observation. It is not an argument. Do you see me deriving any conclusions from that? No you don’t. Do you see me claiming that he is right on Vitamin C because he was more right than he has been wrong? The very fact that you ask the question “Is that logical?” Shows how little you know about logic. You Spidy sense is tingling because you would not know logic, if we rectally infused a logic book into you. Do you really think he could of got as far as he did in science if he was wrong more than he was right? He did through his work on sickle anemia basically create molecular medicine. It is not like the man had no understanding of disease on a biochemical basis. Please tell me you are not a doctor. God I pity your patients if you are.

                @winddriven I am just laying out the story as I have read it. I concentrate on the detractors because their claims against Pauling have all the earmarks of being a Strawman argument. If it is the case as Pauling has claimed that the Mayo Clinic did not perform their Vitamin C anticancer trials according to his protocols. So, they did not get the same results. Then claimed that Pauling was wrong on that basis. If that is true then he most certainly was the victim of a Strawman assault. I do not see any of his detractors dealing with that argument. I find this troubling. Could there be something to what Pauling is saying? I do not know. Now what I see on this site is a bunch of guys with acronyms at the end of their names saying, “Trust me I am an expert.” I say this assuming what Pauling was saying is true. None of his detractors have tried to duplicate his experiments.

                Now if I am going to go on credentials alone who do you go with? Do you go with the man who was a CALTECH professor, wrote the book on chemical bonds, founded Quantum Chemistry, founded Molecular Biology, founded Molecular Medicine, discovered the alpha helix and won two Nobel Prizes. OR do you go with the guy that screams QUACK!!! the loudest on the internet? I honestly do not know. But, if what Pauling has claimed is true. I think I might just might try IV vitamin C, if were diagnosed with cancer. Now it would be nice if Pauling detractors would respond to the strongest argument in his favor. One can only scratch their head wondering why they don’t.

              5. Windriven says:

                “One can only scratch their head wondering why they don’t.”

                Pauling has his supporters, former colleagues, and an eponymous institute. In science the burden of proof lies with those making the claim.

                One would expect to see a series of impressive case reports followed by a small trial which, if successful, would then lead to an appropriately powered trial.

                You say you wonder if there was something to Pauling’s claim. I wonder why no one has attempted to prove it. And that leads me to wonder if the real culprit isn’t publication bias; researchers tend not to submit and journals tend not to publish negative studies.

              6. Sawyer says:

                When it comes to Godel’s Incompleteness theorem you just wish you could understand it.

                I keep seeing people ranting about how terrible mainstream medicine is, killing tens of thousands of people every year. I could never wrap my head around how this happens. What’s causing all these horrible mistakes in healthcare?

                But now we know. It’s because doctors don’t understand Godel. All these idiot hospital administrators are wasting their time with hand washing initiatives, careful restrictions on opiate prescriptions, and new rules about antibiotics. The real solution is to plop doctors into graduate level mathematics courses. And more Linus Pauling, of course.

                Thanks Hank, you’ve been extremely helpful for both the math nerds and the doctors on this site.

                /sarcasm

              7. weing says:

                @Hankie
                “You Spidy sense is tingling because you would not know logic, if we rectally infused a logic book into you.”
                I hope that is not the way you learned logic. Rectal infusions of logic books are as effective in learning logic as vitamin C is in treating cancers.

        2. Windriven says:

          Weing, Madison, and O have all tried to get you to recognize that you are trying to fit a square peg in a round hole. Your notion of proving a negative is true – in a very narrow and specific sense that has little applicability to translational research.

          One cannot prove that ascorbate doesn’t cure … Pick your disease. There are too many biological variables, too many environmental variables too many dosage variables. One can’t even prove that ascorbate does not cure the disease in African-American females with a BMI between 25 and 30 when dosed at 10 grams per kilogram. Because it might be that Froot Loops stimulate another factor that blocks the bioavailability of ascorbate but nobody knew and nobody asked the subjects about their Froot Loop consumption. When you work through the almost infinite range of variables it becomes clear to all but those as dense as depleted uranium that it is Impossible in any meaningful sense to prove that negative.

          So crawl off to whatever warren you emerged from and amuse yourself with the magnificence of your argument. Ignore the fact that it is useless in the context of the blog post that you felt compelled to inject yourself into. Useless. Theoretically accurate. But useless.

          1. Hank Nickerson says:

            Wow that must have taken a lot for you to admit. I see you still cling to this idea that we cannot prove a negative.

            So here is a question for you can we cross cyanide off the list of possible cancer therapies? What if you are eating fruitloops that morning?

            1. Windriven says:

              It took nothing for me to admit, you nitwit. In a narrow theoretical way you are absolutely right. But in the context of this blog – the place you brought it – it is useless sh!t. So you’re all warm and runny? Jesus. If I’d thought it would have helped you understand the specific context of science I’d have confessed to the Lindbergh kidnapping. As it happens you’re as dense as Rodrigues. Great company. You should be proud.

              1. Hank Nickerson says:

                You are not answering my question. Can we cross cyanide off the list of possible cancer treatments? Yes or No?

              2. Windriven says:

                “Can we cross cyanide off the list of possible cancer treatments? Yes or No?”

                I’ve no idea, have you? Cyanide is a large family of compounds both organic and inorganic. Making the blanket statement that cyanide is useless in the treatment of cancer – or anything else – is not possible.

              3. MadisonMD says:

                So here is a question for you can we cross cyanide off the list of possible cancer therapies?

                No good preclinical evidence for cyanide. Unlikely to be useful due to inhibiting cellular respiration at very low concentrations. Maybe there could be a therapeutic window in some rare cancer type. Perhaps cyanide can be delivered specifically to cancer cells. So I don’t think we could rule it out completely. But fairly unlikely to be useful. A bit less likely than Vitamin C.

                Incidentally, if you selected Arsenic as the poison, the answer would be that it is useful for cancer treatment as a trioxide.

              4. WilliamLawrenceUtridge says:

                Laetrile, a proposed quack cancer remedy, relies mainly on cyanide for its claims of efficacy. Upon testing, it didn’t help with cancer but did tend to kill patients through cyanide poisoning.

                So in the absence of compelling data showing cyanide to be effective (indeed, because of the Warburg effect, one could assume it would be more toxic to regular cells than cancer cells) and evidence of toxicity well beyond its benefits, we can assume it is not a good treatment for cancer.

                Read a book.

    4. weing says:

      “Here is a paper on proving negatives.”
      That works in deductive reasoning and assumes the premises are true. Induction doesn’t have that certainty.

    5. WilliamLawrenceUtridge says:

      Hank,

      All this discussion of logical fallacies, Galileo and the University of Kansas’ integrative cancer center distracts from one crucial fact – there are no randomized, double-blind controlled trials showing that vitamin C improves cancer survival.

      Until you have that, you have nothing.

      And vitamin C research is actually a step behind that of comparable cancer treatments in that it lacks an adequate preclinical basis.

      U of K’s integrative treatment center is allowing its greed and ideology override the ethics of patient care. The double standard applied to CAM wastes resources and lives. Without positive evidence that vitamin C helps, it shouldn’t be sold or offered as treatment.

  50. Hank Nickerson says:

    A couple of points on the “Galileo Gambit” and the assertion that “Galileo; you know why Galileo is respected? Because he attacked the claims of the times, at great personal risk, and was right. How do we know he was right? Because he had great data.”

    Here is my point. While the “Galileo Gambit” is a great use of alliteration. It is a complete misnomer. Moreover Galileo did not have “good data”. Well it was not good data in the sense that it showed the Earth moved around the sun. But it was good in the sense that the data showed that Aristotelian conception of the universe could not be the case.

    Oh wait I forgot around here we believe that you can not prove a negative… Shh don’t tell that to Galileo… It took the work of Newton on the tides to show the earth was moving. The conclusive evidence did not come until 196 years after the death Galileo when stellar parallax was finally observed in 1838.

    So this quote from rationalwiki is completely wrong.

    “In reality, taking up the mantle of Galileo requires not just that you are scorned by the establishment but also that you are correct.[1] — that is, that the evidence supports your position.”

    It is wrong because at the time of Galileo there was no evidence supporting Galileo’s position. The fact of the matter is he was not proved right until nearly 200 years later. This “gambit” business is totally ignorant of the history.

    Here is an interesting short history on Galileo
    http://muse.tau.ac.il/museum/galileo/did_galileo.html

    1. Windriven says:

      “Oh wait I forgot around here we believe that you can not prove a negative… Shh don’t tell that to Galileo…”

      Jesus Hank, where the hell did you go to school? Galileo did not prove a negative, he demonstrated that his astronomical observations were not consistent with the geocentric model.

      Remediation. Really. You should.

    2. Harriet Hall says:

      “It is wrong because at the time of Galileo there was no evidence supporting Galileo’s position.” But that’s exactly the point. Lots of people had and have positions that are not supported by evidence. Galileo was the exception: he turned out to be right when the evidence was found. The Galileo gambit says “You should believe my unsupported opinion because it might be supported by evidence 200 years from now.” It “might,” but it would not be sensible to bet money on everyone who says that.

      1. Copernicus concepts was the basis for Galileo’s idea a generation earlier, so the evidence was under everyone’s nose or over the nose with a telescope.

        It was the Roman Catholic church that threatened Galileo with the torture from the rack that put a lid on all of the scientific truths. This was a conspiracy based in in ideology and religion. No one in his or her right mind would go up against the church or get their legs pulled!!!

        The only way to apply the scientific methods is real time in the lab or with patients, something Travell did for almost a century. I trust her observations because they are still valid today in the lab or my office.

        1. Harriet Hall says:

          “The only way to apply the scientific methods is real time in the lab or with patients”

          You left something out: systematic observations using controls.

          1. Yep, I have a type of control, but it requires logical thinking and not narrowed views.

            1. MadisonMD says:

              What factors exactly do you control for?

              1. Windriven says:

                The Sotweed Factor? or maybe the X factor? He tracks them in the X Files.

            2. WilliamLawrenceUtridge says:

              Bloodletting, as derived from its premises, is absolutely logical, and follows absolutely from its premises. The thing about logic is – if one of your premises is wrong, then your conclusion is wrong. Logic requires empirical evidence for corroboration and attachment to reality, otherwise it is worthless.

        2. Harriet Hall says:

          If you have good evidence that Galileo had good evidence that was suppressed by a conspiracy, to compare yourself to Galileo you would have to have equally credible evidence that your own evidence is equally good and has been suppressed by a conspiracy. It’s easy to blame a conspiracy when you are in the wrong.

          1. My or our situation does not compare to that time. But I can tell you that people are prone to believe what they believe beyond a shadow of a doubt.

            Since our views and experiences are differnt … we are too.

        3. weing says:

          “Copernicus concepts was the basis for Galileo’s idea a generation earlier, so the evidence was under everyone’s nose or over the nose with a telescope.”

          A few things. The evidence was lacking. Copernicus was wrong. He thought the earth’s orbit was circular when in fact it is elliptical. It took the careful observation and data-keeping done by Tycho Brahe, who BTW was in the Ptolemaic camp, to provide the actual evidence. Then it took Kepler’s analysis of this evidence to support the heliocentric view.

          1. The idea was conceived the details are always or most time for the future to clarify.

        4. WilliamLawrenceUtridge says:

          Geez, read a book. Galileo was sentenced to house arrest, not torture. It was an example of political power being shown up by simple evidence. If Travell’s interventions work, then they will work in the lab or the office. The error is not that Travell’s intervention’s don’t work – it’s that they haven’t been tested or published appropriately, we’re expected to simply take her word for it. But observations can deceive, because the brain is not good at identifying objective evidence, but it is great at self-confirmation.

          And THAT is why neither Travell nor yourself are taken seriously here.

      2. WilliamLawrenceUtridge says:

        Actually, Galileo was right because he looked at the evidence rather than the dogma; everyone else was focused on dogma and didn’t bother looking for disconfirming information.

  51. Hank Nickerson says:

    Winddriven,

    The fact still stands you know jack about logic. We prove negatives all the time.

    Cute cartoon btw.

    1. Windriven says:

      “The fact still stands you know jack about logic”

      Is that how you learned debate, Hank? Caught with your foolishness hanging out and the best you can manage is an ad hominem?

      The “negative proof” your paper offered and the Galileo quip are demonstrably sh!t. We’ve seen better thought out arguments from stanmrak and Steve Rodrigues. If you want to grapple in these pages you’re going to have to kick it up a notch or two.

  52. Hank Nickerson says:

    Is this not proving a negative? “he demonstrated that his astronomical observations were not consistent with the geocentric model.”

    Let me get this straight he showed that something was NOT consistent with something? Sounds exactly like what I was saying. Galileo showed that the “Aristotelian conception of the universe could NOT be the case.” You are aware that Aristotle believed in a geocentric universe? You are also aware the the scholastic movement of the Catholic Church held to his views. Aristotle was ultimately who Galileo was battling.

    1. Windriven says:

      “Is this not proving a negative? “he demonstrated that his astronomical observations were not consistent with the geocentric model.””

      Are you frigging kidding me?

      You should have learned this by about tenth grade. In science we start with a hypothesis – in this case the hypothesis is the geocentric model. We then try to find data that is inconsistent with this ‘null’ hypothesis. If we are able to find significant inconsistent data, the null hypothesis falls. This is the fundamental exercise of the scientific method.

      In which alternate reality does this equate with ‘proving a negative?’

      1. Hank Nickerson says:

        You really do not know anything about logic. Do you happen to know that one of the greatest discoveries in science, logic and mathematics was Godel’s incompleteness theorm which proved a negative?

        Do you not understand that one of the LAWS of logic proves a negative?

        And seriously you do not understand what Galileo did. You are ignorant of the history.

        1. Windriven says:

          I’m a physicist, chunky. I know quite well what Galileo did. As to Godel’s theorem, calling it one of the greatest discoveries in science is rather an overstatement. It is an interesting observation largely isolated to formal logic.

          And speaking of science, stick to the subject at hand. You are being a weasel, trying to shelter your silliness in Jesuitical mincing. Rhetorical games have nothing to do with scientific proofs. This site isn’t Navel Gazing for Sophomores it is Science Based Medicine.

          This started with your absurd comparison of Pauling’s vitamin C hypothesis and Galileo’s takedown of the geocentric model. Do you suffer ADHD as well as scientific illiteracy?

          1. Sawyer says:

            It’s all setup for the ultimate revelation: that the Milky Way revolves around a giant agglomeration of ascorbic acid. Galileo and Pauling were getting too close to the truth so they had to be censored. By the Catholic Church and Big Pharma combined. With their time machine. Powered by vitamin C.

          2. Hank Nickerson says:

            What you are a failed mathematician? Is that why you do not know the implications of Godel’s Theorem for your own area of expertise or Mathematics? Godel’s theorem will be true eons from now when Einstein and Newton are forgotten and mere footnotes in the current Physics textbooks of the time replaced by a completely new paradigm. The fact that you do not know the implications of the theorem is a testament to how little you know. And when it comes to Godel you don’t know what you are talking about.

            Care to prove that comparing Pauling to Galileo is an “absurd comparison”?

            Rhetorical games? Does Logic have anything to do “scientific proof”? I see here on this site that logic plays very little part in how conclusions are arrived at. And, while the this site is named “sciencebasedmedicine” it certainly has not inoculated anyone here from believing some wacky things like “you cannot prove a negative”. This is just a cop out, an excuse not to back your own assertions with evidence.

            1. Windriven says:

              “What you are a failed mathematician?”

              In a sense. A mathematician who wanted to eat. Back in the day the market for pure mathematicians isn’t what it is today. The rest of your rant about Godel is, for purposes of medical research, useless.

              “Care to prove that comparing Pauling to Galileo is an “absurd comparison”?”

              The comparison stands until substantial clinical utility of ascorbate in humans is demonstrated. The corridors of science are littered with Galileo wannabes.

              “Does Logic have anything to do “scientific proof”?”

              Absolutely. But not in the rigidly formalistic construct of a 2nd year philosophy student. In the realm of science, those who make a claim are expected to provide evidence. Do try and focus on the subject at hand. The claim has been made that ascorbate has important utility in the treatment of cancer. Several thousands of words have been spilled in these comment pages to that effect. Paulingistas have been making this claim (and a variety of others) for several decades. They have immense zeal. But no goddam evidence.

            2. Windriven says:

              “What you are a failed mathematician?”

              In a sense. A mathematician who wanted to eat. Back in the day the market for pure mathematicians isn’t what it is today. The rest of your rant about Godel is, for purposes of medical research, useless.

              “Care to prove that comparing Pauling to Galileo is an “absurd comparison”?”

              The comparison stands until substantial clinical utility of ascorbate in humans is demonstrated. The corridors of science are littered with Galileo wannabes.

              “Does Logic have anything to do “scientific proof”?”

              Absolutely. But not in the rigidly formalistic construct of a 2nd year philosophy student. In the realm of science, those who make a claim are expected to provide evidence. Do try and focus on the subject at hand. The claim has been made that ascorbate has important utility in the treatment of cancer. Several thousands of words have been spilled in these comment pages to that effect. Paulingistas have been making this claim (and a variety of others) for several decades. They have immense zeal. But no goddam evidence.

        2. MadisonMD says:

          Godel’s incompleteness theorm … proved a negative

          Yes, sure, in pure mathematics and logic you can accomplish this. You can prove the pythagorean theorem definitively. Natural science, on the other hand, depends on observation. Newton could propose that F=ma, and show that this is consistent with every observation made. But he did not prove it. (And now we know that it is not quite true–though F=ma is very very close until things get moving close to the speed of light.)

          Back to cancer, let’s say you propose Vitamin A cures cancer. You run your proposed trial and enroll 10,000 volunteers* with no tumor responses. But then, someone actually notices that a certain vitamin A analog can induce differentiation of leukemia cells in the lab. It seems to work only in cells from patients with one quite rare form of leukemia (so rare none were among the 10,000 volunteers above–really!**). Finally, a research group in China performs a phase II trial on 24 patients with this one very rare type of leukemia. All 24 have complete remission. The experiment is repeated worldwide. It becomes standard of care for this type of leukemia. Scientists later discover that there was a broken gene involving a receptor for this Vitamin A metabolite.

          Sounds like a strange story, but everything except the N=10,000 trial is true. See here and here.

          This is why your proposed trial doesn’t prove Vitamin A or C doesn’t work. This is why lab-based research that seeks new therapy and specificity for a particular cancer is the best way forward prior to engaging in clinical trials.

          ————
          *Imagine saying: “Yes, Ms. Jones, never mind that Vitamin A didn’t work for the previous 9,000 patients on the study. We are going to give it to you!” Ms. Jones, no fool, walks out. Wouldn’t you?
          **APL really is so rare that if you randomly select 10,000 cancer patients you are very very unlikely to get one– only 1400 cases in US in 30 years. Compare 46 cases of APL per year with 1.6 million cases of cancer per year in US.

        3. Bruce says:

          No, logic has nothing to do with proving positives and negatives. Formal logic is about deducing logical structure from a series of statements made on TRUE and FALSE premises.

          Formal logic does not give give you anything you already have, you are confusing formal logic with scientific proof. I have suggested a few times that you go back and re-evaluate your assumptions, but it seems you are wedded to these assumptions. You will get nothing further from me on this.

          1. Bruce says:

            “does not give you anything you do not already have”

          2. Hank Nickerson says:

            Bruce does anyone that is a Logician know this? I am certain that we prove affirmative and negative propositions all the time in logic. The Law Of Excluded Middle for example is a negative proposition. We actually have a proof for it. Logic does have something to do with proving positive and negatives.

            1. weing says:

              @Hank,

              Let’s say I make a claim that if you eat a teaspoon of my excrement 3 times a day, it will cure your cancer or whatever ails you. Go ahead and try to prove that it doesn’t. This reminds me of what someone wiser than me once said. “One should not murder sh!t-eaters. Just don’t go to their parties.”

              1. Windriven says:

                I think you’re on to something, weing. My dog has a taste for cat sh!t. AND she appears to be free of cancer. Nickersonian proof!

                As to parties and poophiles the adventurous might go here. But this is not for the dainty-minded. You’ve been warned.

              2. brewandferment says:

                this is for windriven but there’s no reply for his comment about dogs who like cat poop: google “Sad Dog Diary” by zefrank (a youtube video). Although I think the “Sad Cat Diary” by the same guy is way funnier…or maybe you have to google Diary of a Sad Dog. And I recommend “Teddy has an Operation” too.

  53. john marden says:

    I have experienced a self administered therapy of emusldified VItC ( Vit C – Soy Lecithin mix in water : 42gms ascorbic acid; 60 grams lecithin – blended into 1 liter water) for over 10 months now and have averaged 14+ grams perday with several periods of going up to 40 grams a day.

    Yes my experience was motivated by an “alternative medical practisioner”. a full medical MD with and interest, and business, in applied nutrition. She gave me several 25 gram IVs, at your mentioned price range – and the resultant herxheimers and curiosity of her motrivation set me off on my own research.

    The press is full of articles like yours discrediting Vit C therapy, but there is no actual evidence that any one has ever been harmed by too much vitamin C. ZERO.

    There is the recent legendary case in New Zealand of the critical patient, on his way to be unplugged, reviving from 60 gram Vit C Ivs every 6 hours for 2 1/2 days. Then ther is Dr. F. R. Klenner and his exerience curing over 60 patients from polio with only VIT C.

    *********************
    My “success” or ” failure” with high dose VItr C continues, but I can tell you that the suggestive expereince of the observable symptoms, of course easily discredited by your FDA drug trial methodology, is that what ever the viruses and parasites and fungei or whatever that made my life miserable with eczema and hives are aparently real and do respond to a boosted imune system with Vit C therapy.

    It is fact that a certain level of AA (ascorbic acid) kills cancer cells pitri dishes; that topical AA cream kills skin cancer cells.

    When I started with high dose oral Vit C/Lecithin, I lost my voice for 2 weeks while my stumach/throat system cleaned out. I watched strep looking red spots on the back of my throat as stuff leached out. Over the next ten months the symtoms have shifted again and again, with gradually a lifetime of old injuries being revisited. The areas with recurent low grade infections irrupting, once or twice and then quieting down while other zones get cleaned.
    Even my childhood polio vaccine spot on my right shoulder appeared for a few days as swollen tissue.to regress after a few days.

    I still have stuff coming out of the cervical spinal fluid zone, and my eyes and eyelids, and, when challenged with antagonists (oregano and lavendar oil; turpentine) old polyps of staph or what not.

    Vitamin C works, probably also for cancer.

    1. WilliamLawrenceUtridge says:

      John, you do know that the reason they have been forced to test IV vitamin C is because oral vitamin C has a ceiling for absorption, right? You can’t keep increasing your blood-levels of vitamin C by eating more, once you reach saturation you simply piss and shit out the rest. So your gram-level consumption isn’t doing a damned thing to change your blood levels of vitamin C.

      But the Big Pharma company that produces the vitamin C you buy is ecstatic, it costs them almost nothing to produce and you’re buying several kilograms every year.

      I’ll also note, with some amusement, “I took vitamin C and 10 months later something happened”. I’ll assume you spent that full 10 months locked in a room with a mirror and a magnifying glass, doing nothing but scouring your body inside and out looking for something different you could attribute to your huge number of ascorbic acid pills.

    2. simba says:

      If you take something, anything, and then pay close attention you will find all kinds of interesting symptoms. The longer you pay attention the more interesting the symptoms will get. Look at the ‘provings’ of homeopathy tablets, for example. Part of the reason clinical trials are so giant and expensive to do is because they have to have control groups, because people respond to being given treatment whether or not that treatment actually has a ‘real’ ingredient that has an effect.

      My childhood memory of this was when some kind adult brought us soda at a party and told us it was ‘experimental’: two of the children vomited, a good few of the rest had very queer things happen to them. Of course it was ordinary soda.

      Have you had this ‘stuff’ that comes out tested independently by a reputable laboratory?

      There is no good evidence for the ‘cleaning’ or detox of old injuries, diseases, systems etc. If this stuff worked it would be routinely used for poisoning, for example, to clean out the liver.

      A lot of what you feel is simply because you know you’re doing something to help yourself- it’s perfectly normal, and a useful effect.

      Detoxing, and boosting the immune system, are attractive concepts which don’t actually exist. If they existed they would be very useful, and the researcher who could demonstrate them would be rich and famous. Instead people have to sell things that claim to do them, unsupported by the evidence.

      Here’s a suggestion, made in all sincerity- go to your doctor, and get her to contact actual researchers to study, confirm, and publish your reactions and your boosted immune system. If it’s actually happened you will be famous and your doctor will become rich.

  54. weing says:

    “Do you really think he could of got as far as he did in science if he was wrong more than he was right?”
    Yes. I do. I think that would be the only way. What is the batting average of the best baseball player? More than 50% as you imagine?

    1. Windriven says:

      @weing

      Excellent point that hadn’t occurred to me! The ratio of conjectures and hypotheses to scientifically accepted theories must be huge (the batting average low) even among the giants. That, I think, is lost on many of the commenters here and is a point worth repeating from time to time. Scientific brilliance does not equal omniscience. Babe Ruth led in home runs. Also in strike outs.

  55. weing says:

    @ Hankie,

    BTW, for all his mistakes. Pauling remains one of my heroes.

  56. Peter H Proctor, PhD,MD says:

    Retail, a 25 gm vial of sterile infusible vitamin-C solution costs less than $9. Infusion set, bag of saline, etc. might bring the total cost up to $20, more or less.

    Nobody has been able to show any particular side-effects. The in vitro and in vivo results are (uh) interesting and the scientific basis soundly-established. If you wait around for the proper clinical trials, you will be dead or your cancer too far advanced for it to work, if it works.

    So why not, just in case? Do it in a minute myself. YMMV, naturally.

    1. Harriet Hall says:

      Why not? Why not try everything that is similarly advocated as non-mainstream medicine? The answer is simple: because there would be little rational basis for choosing among the many different remedies, and history shows us that the probability of harm from similarly advocated remedies outweighs the probability of benefit. It’s a gamble, and an individual’s willingness to accept that gamble depends on his perceptions, belief systems, and willingness to take risks. Feel free to gamble on your own health, but don’t try to persuade me to gamble on mine. Some people like to bet on horse-races; I don’t.

      Other considerations: an inexpensive treatment is too costly if it doesn’t work; and putting anything into a vein carries a small risk of infection.

      1. Peter HProctor, phD,MD says:

        Lay-people might not be able to make such distinctions, but physicans can and do. It is one reason they pay us the big money. It is called “clinical judgement” and it often operates in the absence of full information.

        That aside, I was just pointing out to me as an MD, PhD clinical pharmacologist with a strong background in this very area, the reasons for using IV vitamin-C “just in case” are ample and the cost and hazard low. As I note, YMMV.

        Perhaps all it does is produce the classic “expensive urine”, often a topic at FRBM meetings. But if we are wrong, little economic or physical damage, If you are wrong, it may have significant consequences. Your choice.

      2. Peter H Proctor, PhD,MD says:

        This is different. Physicians make such choices all the time. It is called “clinical judgment” and often operates in the absence of full information. It is why they pay us the big bucks and make us stay so long in training.

        That aside, to me, with all my experience and training, Vitamin_c seems a natural thing to try “just in case.”, although the actual case is somewhat better than that. The toxicity is low and the expense minimal. There is a good scientific basis for any activity, etc.

        In short, all the usual and customary criteria. True, at FRBM conferences we are always talking about “expensive urine”, which may be all we are making. But if we are wrong, no big deal. If you are wrong, the possible consequences are much greater. If this were anything else, there would be no issue at all.

  57. Brian OReilly says:

    Great article and I love your approach of looking into each of the pros and cons and extracting what I call the kernel of truth.

    I recently read an article about the levels of vitamin C for commonly available foods being less than what was available 30 years ago (and I am sure other vital minerals); as a pretense that we should eat more organic food, but it posed an interesting question about the levels that we are absorbing now when compared to our past?

    I am wondering if anyone has re-baselined our common understanding?

    1. Peter H Proctor, PhD,MD says:

      My understandings
      1. There is a significant role for redox processes in the initiation and control of the cancer process. If you-all do not understand this by now, you have not been paying attention.

      2. Unquestionably, at physiologically-relevant levels, vitamin-C differentially kills cancer cells in vitro and in some animal models. Presumably, this is from C’s proxidant properties (which I noted in a 1972 paper, just to give you some idea).

      3. Decades ago, Pauling and his associates reported significant anticancer activity in infused Vitamin-C trials. The mechanism they gave is not the currently-accepted one.

      4. Oral vitamin-c does not exhibit such activity…

      5. Having two Nobel prizes, Pauling didn’t need a third. etc. So it seems reasonable that he saw what he saw.

      6. Pauling was no stranger to medical research, e.g., having figured out cycle-cell anemia in the late 1940′s and almost discovering the structure of DNA. Vitamin-C is just one more in the series.

      7. The cost of treatment is about $20. The hazard low.

      1. MadisonMD says:

        Dr. Proctor, you again post in generalities. Why do you keep avoiding my questions about specifics? Given your vast knowledge of redox, vitamin C pharmacology, and cancer, you should be able to answer.

        Can you explain exactly what cancer types you expect Vitamin C to work for and why?
        Given what you know about its pharmacology, what is the appropriate route/dose/schedule for vitamin C administration when administered for cancer therapy?

        Nobody could take your (bad) advice without these specifics.

        1. Peter H Proctor, PhD,MD says:

          1) Kinds of cancer ? Beats me. True, the proposed mechanism implies fairly broad activity.

          2) Dose– IIRC, typically 25 gm, more or less, infused IV over a period of hours.. Do not know the exact details. If you are interested, you can look them up yourself…..

          1. MadisonMD says:

            (1) Kinds of cancer– So for example, you would recommend it for acute pediatric leukemia, for CNS lymphoma, and for adult metastatic pancreatic cancer? In combination with other therapies or alone?

            (2) “25gm more or less IV over hours”? You know this won’t do for a physician ORDER. Exactly what dose do you prescribe, doctor? The pharmacist and the patient reading your recommendations must know. Is the dose adjusted by weight or body surface area? What is the frequency of administration? Given what you know about the ascorbate half-life (~2hours) will you maintain effective levels at this dose and frequency?

            … you can look them up yourself

            I looked up the phase I study and gave you the reference. You said the dose was too low. You said you know more than anyone posting here from your vast knowledge and experience in this field. Based on your vast knowledge, you recommend here that it is worth trying despite the lack of clinical evidence. Now you tell me to look up a dose/schedule? How rich? How can I look up clinical evidence for a dose/schedule when such a study has never been published? Or is there one that I am unaware of, but you, in your vast experience, know about? No, I do think you clearly said there is no such study showing such efficacy. So what exactly do you want me to look up?

            1. Peter H Proctor, PhD,MD says:

              I don’t write orders for vitamin-c. Look up the details yourself. Start with the sci-med paper.

              As for which cancers. beats me. Again, if the proposed mechanism is correct, the action should be fairly broad, a la other oxidative stressor drugs such as adria. Time will tell, or not.

              1. MadisonMD says:

                My Dear Doctor Proctor, you have repeatedly told us you know more about it than anybody here, and thus you are right.

                Now, faced with a specific question about what dose/schedule should be used to treat cancer, you refer me to the Science Translational Medicine paper covered in Dr. Gorski’s blog? This, as you must know provides a dose/schedule for vitamin C that purportedly reduces symptoms of cancer treatment. It has nothing to do about anti-cancer efficacy.

                What can you mean by this, sir? Am I to understand you have been blowing smoke here for nearly two months?

                That’s quite enough tomfoolery, hey?

    2. simba says:

      My understanding is that the size of fruit and vegetables, as well as the yield per acre and per plant, has grown and that certain minerals aren’t being produced or taken up faster than they were previously. So per plant you have the same amount of xyz micronutrient, but it’s now in 5 large strawberries rather than 2 small ones (the dilution effect). If you are practicing monoculture farming you get more mineral depletion, and if you get quicker harvests the plant has less time to take those things up. Carrots, though, have supposedly got higher in vitamin A because they’re being bred to be darker orange.

      Never heard it for vitamin C though (except Patrick Holford saying there’s no vitamin c in an orange.)

      1. n brownlee says:

        No… nutrient amounts are, roughly, equal for the same type vegetable- that is, the same cultivar of squash, potato, broccoli, etc. will have the same amounts of each nutrient per pound or ounce or whatever weight- when the water weight is subtracted. “Organic” fruits and vegetables are NOT higher in nutrients, and have never tested as higher in impartially conducted tests. And, any crop grown with a significant shortage of ANY nutrient will be unsalable. Stunted, yellowed, hollowed, blackspotted, whatever. They will show their deficiencies externally, because they need the nutrients to grow well.

        1. simba says:

          Oh, I know organic isn’t higher in nutrients, and that plants won’t grow with a significant shortage of nutrients- I didn’t say there was one.

          I’m not a botanist, I’ve just read that the supposed nutrient deficiency is due to the dilution effect- we have bigger harvests now. If there is a decrease it doesn’t mean it’s in any way significant.

          Mineral concentrations do vary in plants depending on growth, environment and variety (Riviero et al, published in Food Chemistry in 2003, looked at the mineral profile of different types of potatoes, for example).
          Some have even been altered to have more of particular nutrients, like golden rice.

          Reading the above I realise it sounds like I’m coming from a position of “Plants have no vitamins any more so take supplements.” I was responding to the specific question about supposedly declining levels of vitamin C and minerals in plants.

          1. simba says:

            Augh, misread your comment, missed ‘cultivar’. Sorry about that. Here is a slightly more relevant reference: http://www.ncbi.nlm.nih.gov/pubmed/20954162

            1. n brownlee says:

              The study was about different nutrient levels in different genotypes:

              “The mineral profile was significantly affected by genotype, head fraction, location and season. Great variation was found among studied genotypes.” Artichokes, in this particular study. Which is of course true.

              Modern monocropping, by the way, does not deplete soil of minerals – or any other necessary component for good plant growth. Nutrients used up by a crop must be replaced, and growers know it. Farmers can’t produce good quality crops on poor soil, or more likely, any crops at all. Any grower who’s sunk a fortune in bank loans and tens of thousands of acres of land into a single crop is going to use every tool and technique at his disposal to grow a good crop. He can’t afford to misuse or deplete the soil- he can’t grow anything without it.

  58. MadisonMD says:

    Hank asks why nobody is pursuing Vitamin C therapy. Windriven speculated that preliminary data may have been disappointing. Well, lets cut the data, shall we?

    Here are two additional phase I trials of interest:
    Stephenson et al.
    15 patients in cohort escalations with no response observed.
    Hoffer et al.
    24 patients with no responses observed.

    Moreover, both studies reveal the disappointing fact that halflife is only 2 hours. So basically, the Vitamin C is gone in a few hours. If you think bathing cancer in vitamin C might be useful, this means you will need to continuously infuse blisteringly large amounts a la Burzynski to maintain these levels (The Stephenson trial already reported hypernatremia as toxicity, so this might not be a good idea).

    Bad pharamacology, limited preclinical data (so far lacking specificity), and no responses in a total of sixty-three patients in three phase I trials all adds up to a dead drug in the ordinary oncology world. c.f. promising phase I trials I cited by me here.

    This is all terribly disappointing, no? This can only be argued when viewed through rose-colored glasses of a “true believer,” who completely lacks perspective on how cancer therapies are discovered and developed.

    1. Windriven says:

      “This is all terribly disappointing, no?”

      One would think so. But now some moron will fold us back on a variant of: they didn’t do it right. The dosage was wrong, the interval was wrong, the moon was in the wrong phase, they were supposed to use Minute Maid not Tropicana. And this in turn brings us back to the impossibilities* practical difficulties of proving negatives in translational research. So when all the shouting is over we find ourselves back at baseline science: let’s see the evidence that supports the claim. Come to think of it, I seem to recall you having made that request some thousands of words ago.

      * we really don’t want to revisit that nonsense, do we?

      1. MadisonMD says:

        …. or we didn’t do the trial exactly as Pauling did it, which is apparently the only way to prove that Vitamin C didn’t work. (i.e. use a retrospective control arm with patients that are not properly matched to the treatment arm.)

        1. Peter H Proctor, PhD,MD says:

          Multiple gene lesions are involved in the cancer process, particularly as clonal selection starts to work. A typical tumor cell may or may not have a particular one or set. It may be that Vitamin-C only affects specific redox-sensitive elements, as noted in the citations above.

  59. Paul says:

    Here where I am from, I saw results on both sides, for using vitamin C in cancer treatment. That means that some of them died (for example, stage IV, breast, all body methastasized, after chemo, what do you want…), and some of them lived, after using IV vit C, especially combined with the (other unproven substance, hehe…) amygdalin. So, neither vit C, amygdalin, or however what other panacea, is not a … panacea, and it is normal to be so, but sometimes it workes. A friend of mine, let say… in the nutrition field had pointed to me some of his similar observations too.

    Now, cancer is (in my opinion) an epigenetic disease, and this is why vit C, amygdalin, and who knows what other possible remedies, cant and will not work every time, and because of this mechanism involved (epigenetic I mean), I don’t even understand the real mechanism, but because I am not even truly qualified for this, I don’t care.

    But this conflict remainds me of another, and this is about silver nanoparticles (aka colloidal silver). Now, because I am working in the field, I tested such products on common cold or even flu, and it works, like it should, in uM range of ingested silver nanoparticles, depending on some factors.

    All the “industry” says: it is an unproven treatment, it is a quackery, it will turn you blue (wich it might be at enormous quantities) and also it is a quackery, and so on. But it works, and it works great (even if not for all of the diseases for wich the so named colloidal silver is, unfortunately) promoted by many sellers/manufacturers. I was amazed first time I used it (maybe a total of 20-50mg of silver nanoparticles, electrically manufactured), when I had only an easy 4 day illness, instead of the regular 4 weeks hard fight with a common cold/flu, whatever it was.

    So, should I ask myself about how much the “science based medicine” is right in stating: “this is good and this is bad, or not”?

    Just asking.

    1. n brownlee says:

      You don’t even know what you had, yet you believe that colloidal silver “works”, regardless? You do realize that four days is about right for a cold, don’t you?

  60. Paul says:

    Hmmm… How many people run their virale tests to see what strain they have, even when they have a flu, not to speaking a common (or less common) cold? In my case, before this first time, all “common cold” periods lasted at least 4 weeks. All. So please, let it out, for me this is a statistic.

    However, there were times when it lasted only one day, for me. Also, we tested further on volunteers, and we had hundreds of cases wich behaved in thesame way. We tested on infections, some of them bad, some of them not so bad, at (amazingly) it worked in some noninfectious cases where we thought it shouldn’t. Maybe it was placebo then, but again, maybe not.

    Of course, we had fails too, like in a case when we tested again HIV (oral, not IV), even in a ARV association it boosted the ARV efficiency a lot. That particular product has a median size unfitted for this, and HIV1 is a fairly bad guy ouside the Petri dish, but that is another story. Anyway, you should have read between the lines that I kinda know what I am talking, and I am not a snake oil seller, and even I am not a top scientist, I am a fairly good engineer, knowing the difference between a battery and a zeta potential, If I may have a joke.

    Also, they are so many articles about nanoparticles (silver) efficiency in viral and bacterial infections, on mainstream scientific journals (I think only me read almost a hundred, and buyed maybe half of them), so I can easily say about some wikipedia like articles that they are BS. Big BS.

    If you are willing and have the possibilities to run a trial, we are willing to help you with the products, hehe… We have even functionalised nanoparticles, gold and silver, for cancer treatment, if you are interested, but I am sure that you find such products near you, and you will find much more of them years to come.

    However, the subject of the forum is vit C, and I posted this because I thought that having final and strong determined oppinions about a subject is not quite… openminded.

    Sorry for my english language. As it is obviously, it is mainy derived from Star Treck :)

    1. Windriven says:

      “Anyway, you should have read between the lines that I kinda know what I am talking, and I am not a snake oil seller, and even I am not a top scientist”

      I don’t have to reed between the lines to know that you are full of crap.

      http://www.sciencebasedmedicine.org/homeopathy-and-nanoparticles/

      http://www.sciencebasedmedicine.org/hi-ho-silver/

    2. n brownlee says:

      “Sorry for my english language. As it is obviously, it is mainy derived from Star Treck”

      And so, it appears, are your ideas about adequate scientific trials and testing, and about how we should evaluate the plausibility and efficacy of drugs and treatments. “Hey, I swallowed some and it worked!” is not evidence.

  61. Paul says:

    P.S. Almost all the common colds (?) of my friends, in the last two years, were, untreated with silver nanoparticles, at least two weeks in duration. So maybe your four day statement it is not a general rule, or I am taking like common cold (respiratory viral affection) something what it is not a so… common cold.

    1. Windriven says:

      Self-treating the common cold anything with silver is just plain stupid.

  62. Paul says:

    @windriven: My point was that maybe we need a broader view at anything, even at vit C, and hence my example. If you don’t want to talk, I am sorry, I posted in the wrong place, and your answer, let hust say…is yours. And I know, all those who are researching about antiviral effects of silver nanoparticles, are stupid people. Well, not everybody is perfect.

    @n brownlee: and is I would have been saying that my english language is derived from looking at Oliver Hardy’s movies, then what? You are a little impolite, but not so much like windriven. And yes, I agree, swallowing something wich worked, it is not yet a scientific proof. When 1000 are doing it, and it works, you may think that it is time to make some tests, to see why is working. Now, wich is the true test: the 1000 people validating, or my tests to see why it is working? Eh, again, it was only an example wich meant something else, but suit yourself…

    I will not interfere anymore with the discussion, because it is about vit C, not silver nanoparticles, and here I have said already: I saw positives, and negatives, so taking parts seems to me being futile. Oh, or maybe the positives were from the tap water,or it would happened anyway. Maybe…

    1. n brownlee says:

      “Oh, or maybe the positives were from the tap water,or it would happened anyway. Maybe…”

      Or maybe the moon was waxing. or waning. Or you danced a little nano-dance before you swallowed, and that made it work. Doesn’t matter, your observed “effects” and “results” don’t matter, because nobody knows what they are effects and/or results from. You seem to already know this. The point?

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