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Chemotherapy doesn’t work? Not so fast…

“CHEMOTHERAPY DOESN’T WORK!!!!!”

“CHEMOTHERAPY IS POISON!!!!”

“CHEMOTHERAPY WILL KILL YOU!!!!”

I’ve lost count of how many times I’ve come across statements like the ones above, often in all caps, quite frequently with more than one exclamation point, on the websites of “natural healers,” purveyors of “alternative medicine.” In fact, if you Google “chemotherapy doesn’t work,” “chemotherapy is poison,” or “chemotherapy kills,” you’ll get thousands upon thousands of hits. In the case of “chemotherapy kills,” Google will even start autofilling it to read “chemotherapy kills more than it saves.” The vast majority of the hits from these searches usually come from websites hostile to science-based medicine. Examples include Mercola.com, the website of “alternative medicine entrepreneur” Dr. Joe Mercola and NaturalNews.com, the website of Mike Adams, where you will find cartoons like this one, which likens the administration of chemotherapy to a Nazi death camp:


Here’s another example, entitled The truth about chemotherapy and the cancer industry:

Note how Adams portrays screening for cancer and chemotherapy as a deadly scam designed solely to enrich the “cancer industry” as it kills patients.

As my final example, there’s this cartoon:

An article by Mike Adams entitled Chemotherapy Stickup that accompanies the cartoon above makes this astounding claim:

There is not a single cancer patient that has ever been cured by chemotherapy. Zero. They don’t exist. Not a single documented case in the history of western medicine.

And why is that? Because conventional medicine operates from the false belief that there is no cure for cancer! Thus, anyone offering a cure (or assisting in the body’s own natural reversal of the disease) is immediately dismissed as a quack. Meanwhile, the real quackery is found in the pushing of toxic chemotherapy chemicals that are injected into the bodies of patients and called “treatment” when they should really be called “torture.” (Nancy Pelosi, by the way, was never briefed on the fact that chemotherapy is torture…)

When I first encountered that cartoon a few years ago, I was a bit surprised that even Mike Adams would go so far as to make such an absolutist statement that not a single person has ever been cured of cancer by chemotherapy in the entire history of “western medicine.” All it would take is a single example to prove him wrong, like—oh, you know—Lance Armstrong, the patients cared for by my pediatric oncology colleagues, or the patients I saw during my training cured of anal cancer by the Nigro protocol. The Nigro protocol, by the way, consists of combined chemotherapy and radiation and is still the standard of care for anal cancer. That doesn’t even count all the patients with leukemia or lymphoma cured primarily by chemotherapy.

Unfortunately, this attitude isn’t just limited to cranks. There are legitimate scientists, even those who have published in magazines devoted to skepticism, who make very similar statements, although perhaps not quite as absolutist. Not quite, but close. For example, there’s Reynold Spector, whom Mark Crislip and I took to task for his article earlier this year in Skeptical Inquirer entitled Seven Deadly Medical Hypotheses. One of his “seven deadly medical hypotheses” read thusly:

From a cancer patient population and public health perspective, cancer chemotherapy (chemo) has been a major medical advance.

In other words, to Dr. Spector, the very idea that chemotherapy is a notable advance in the treatment of cancer is a “deadly medical hypothesis.” Of course, his statement is not a hypothesis at all, deadly or otherwise, as what one means by a “major medical advance” is very subjective (Dr. Spector really needs to get himself hence to a medical dictionary) and the weasel words of “from a patient population and public health perspective” give Dr. Spector wiggle room, but it’s very clear what his intent is. He doesn’t think chemotherapy works very well, if at all, even as he admits:

However, it cannot be denied that there are a few populations for which chemotherapy is marvelously effective, as noted above, and must be used.

So which is it?

In previous posts, such as Why haven’t we cured cancer yet? and Skepticism versus nihilism about cancer in science-based medicine, I explored some of these questions. In the former article, I pointed out just how complex the problem is, with cancer being hundreds of different diseases and using the example of just how messed up the prostate cancer genome is to provide an idea of the magnitude of the problem. In the second article, I pointed out an example of a specific cancer for which advances in chemotherapy have made a meaningful difference in both survival and quality of life outcomes. What I haven’t yet done is to look at the arguments cancer cranks use to try to convince people that chemotherapy doesn’t work.

Attacking chemotherapy

Any rational assessment of the efficacy of chemotherapy must be forced to include an admission that chemotherapy is only rarely curative in solid malignancies, particularly advanced solid malignancies. Notable exceptions include testicular cancer (which is what Lance Armstrong was cured of) and anal cancer. In contrast, for hematological malignancies, such as leukemia and lymphoma, chemotherapy is usually the mainstay of therapy. However, not being curative doesn’t mean that chemotherapy is useless anymore than the fact that beta blockers don’t cure hypertension and metformin doesn’t cure diabetes makes them “useless” drugs. Before we take a rational look at what chemotherapy can and can’t do, let me just point out that there are three studies that are frequently used by cranks to try to argue that chemotherapy is useless.

The first one is easily dismissed, but you’ll see it a lot anyway. It’s frequently cited in articles with titles like 75% of MDs Refuse Chemotherapy Themselves and the claim will go something like this:

Several full-time scientists at the McGill Cancer Center sent to 118 doctors, all experts on lung cancer, a questionnaire to determine the level of trust they had in the therapies they were applying; they were asked to imagine that they themselves had contracted the disease and which of the six current experimental therapies they would choose. 79 doctors answered, 64 of them said that they would not consent to undergo any treatment containing cis-platinum – one of the common chemotherapy drugs they used – while 58 out of 79 believed that all the experimental therapies above were not accepted because of the ineffectiveness and the elevated level of toxicity of chemotherapy. (Source: Philip Day, “Cancer: Why we’re still dying to know the truth”, Credence Publications, 2000)

Wow! This sounds really damning, doesn’t it? What hypocrites those oncologists are! Right?

Wrong.

It turns out that this survey is over 25 years old and was about a specific kind of chemotherapy, cisplatin for non-small cell lung cancer, which was a new therapy at the time and didn’t have a lot of evidence for it. As Anaximperator describes, a followup survey was conducted in 1997 at a session on the National Comprehensive Cancer Network (NCCN) clinical practice guidelines. Participants were asked to respond to the same question regarding chemotherapy:

You are a 60-year-old oncologist with non-small-cell lung cancer, one liver metastasis, and bone metastases.

Your performance status is 1. Would you take chemotherapy? Yes or no?

The results? Let Anaximperator tell the tale:

The overall results of the 1997 follow-up survey show that 64.5% would now take chemotherapy – which is almost a doubling from 34% to 64.5% of those willing to have chemotherapy and radiotherapy and a quadrupling from 17% to 64.5% of those who would take chemotherapy alone.

Anaximperator adds:

The study from 1991, “Oncologists vary in their willingness to undertake anti-cancer therapies,” pertains to many kinds of cancer and cancer stages, from early stage to terminal, as well as to experimental therapies. It shows percentages as high as 98% of doctors willing to undergo chemotherapy, while the remaining 2 % were uncertain, and none answered “definitely no” or “probably no” to chemotherapy.

Should another survey be conducted today, there’s a good chance the results would be even higher in favour of chemotherapy, given that over the years chemotherapy has shown enhanced clinical benefit and less side effects.

Indeed. One should also note that this question was constructed such that the clinical presentation of the cancer was incurable. Participants were presented with a scenario in which they are diagnosed with stage IV metastatic disease, a situation where opting for palliative care rather than aggressive treatment often makes sense, which makes the results even more striking. Also, I know from personal experience that it is not true that oncologists tend to turn down chemotherapy, even for advanced disease. having known oncologists who developed various cancers and underwent standard-of-care chemotherapy. Indeed, just this week, I was saddened to learn that an oncologist I used to know at my old job recently developed cancer and is currently undergoing chemotherapy. He’s also lost all his hair, just like many of his patients. In the end, this particular ploy serves two purposes. First, it implies that oncologists are hypocrites who don’t believe that the treatments they are giving patients are worthwhile. Second, it feeds into the conspiracy theories beloved of quacks with the implication that oncologists are hiding something about chemotherapy effectiveness. They’re not.

My favorite example of the use of the next study beloved of anti-chemotherapy cranks is by Andreas Moritz, who describes himself as “a medical intuitive; a practitioner of Ayurveda, iridology, shiatsu, and vibrational medicine; a writer; and an artist.” The article is entitled Can you trust chemotherapy to cure your cancer? and in it Moritz cites a study from Australia published in 2004:

An investigation by the Department of Radiation Oncology, Northern Sydney Cancer Centre, Australia, into the contribution of chemotherapy to 5-year survival in 22 major adult malignancies, showed startling results: The overall contribution of curative and adjuvant cytotoxic chemotherapy to 5-year survival in adults was estimated to be 2.3% in Australia and 2.1% in the USA.” [Royal North Shore Hospital Clin Oncol (R Coll Radiol) 2005 Jun;17(4):294.]

The research covered data from the Cancer Registry in Australia and the Surveillance Epidemiology and End Results in the USA for the year 1998. The current 5-year relative adult survival rate for cancer in Australia is over 60%, and no less than that in the USA. By comparison, a mere 2.3% contribution of chemotherapy to cancer survival does not justify the massive expense involved and the tremendous suffering patients experience because of severe, toxic side effects resulting from this treatment. With a meager success rate of 2.3%, selling chemotherapy as a medical treatment (instead of a scam), is one of the greatest fraudulent acts ever committed. The average chemotherapy earns the medical establishment a whopping $300,000 to $1,000,000 each year, and has so far earned those who promote this pseudo-medication (poison) over 1 trillion dollars. It’s no surprise that the medical establishment tries to keep this scam alive for as long as possible.

Here is the study to which Moritz refers and which is the origin of the claim that “chemotherapy only provides 2% benefit,” a favorite talking point used by cancer quacks. I’ve seen it on websites ranging from Moritz’s website to NaturalNews.com, to Mercola.com, to Whale.to (my favorite), to I forget how many others. Always it’s the same thing, a variant of a statement claiming that chemotherapy only contributes 2% to five year survival in adult malignancies, followed by conspiracy-mongering of the sort above in which chemotherapy is portrayed as a huge scam designed to enrich big pharma. Indeed, so common is this particular favorite that I proclaim it “The 2% Gambit.” It turns out that this is not such an impressive study. Indeed, it appears almost intentionally designed to have left out the very types of cancers for which chemotherapy provides the most benefit, and it uses 5 year survival exclusively, completely neglecting that in some common cancers (such as breast cancer) chemotherapy can prevent late relapses. There were also a lot of inconsistencies and omissions in that leukemias were not included, while leukemia is one type of cancer against which chemotherapy is most efficacious. Indeed, the very technique of lumping all newly diagnosed adult cancers together is guaranteed to obscure benefits of chemotherapy among subgroups by lumping in patients for whom chemotherapy is not even indicated. A letter to the editor listed these problems and several really egregious errors and omissions, too:

The authors omitted leukaemias, which they curiously justify in part by citing the fact that it is usually treated by clinical haematologists rather than medical oncologists. They also wrongly state that only intermediate and high-grade non-Hodgkin’s lymphoma of large-B cell type can be cured with chemotherapy, and ignore T-cell lymphomas and the highly curable Burkitt’s lymphoma. They neglect to mention the significant survival benefit achievable with high-dose chemotherapy and autologous stem-cell transplantation to treat newly-diagnosed multiple myeloma [4]. In ovarian cancer, they quote a survival benefit from chemotherapy of 11% at 5 years, based on a single randomised-controlled trial (RCT), in which chemotherapy was given in both arms [5]; however, subsequent trials have reported higher 5-year survival rates. In cancers such as myeloma and ovarian cancer, in which chemotherapy has been used long before our current era of well-designed RCTs, the lack of RCT comparing chemotherapy to best supportive care should not be misconstrued to dismiss or minimise any survival benefit. In head and neck cancer, the authors erroneously claim the benefit from chemotherapy given concomitantly with radiotherapy in a meta-analysis to be 4%, when 8% was in fact reported [6].

The authors do not address the important benefits from chemotherapy to treat advanced cancer. Many patients with cancers such as lung and colon present or relapse with advanced incurable disease. For these conditions, chemotherapy significantly improves median survival rates, and may also improve quality of life by reducing symptoms and complications of cancer.

Of course, those using this particular gambit almost invariably never include the criticism of this particular article. Another aspect of this particular study that always bothered me is that it appeared to lump patients undergoing adjuvant chemotherapy in with those undergoing chemotherapy for cure or palliation. Adjuvant chemotherapy is given after surgery in order to decrease the rate of recurrence, but the truly curative modality is the surgery itself. In early stage cancer, the absolute benefit of chemotherapy in terms of prolonging survival tends to be modest, often single digit percentages. Lumping adjuvant therapy in with other uses of chemotherapy again appears custom-designed to minimize the survival benefit due to chemotherapy observed.

The second study frequently cited by cancer quacks as evidence that “chemotherapy doesn’t work” is, not surprisingly, also cited by Moritz:

In 1990, the highly respected German epidemiologist, Dr. Ulrich Abel from the Tumor Clinic of the University of Heidelberg, conducted the most comprehensive investigation of every major clinical study on chemotherapy drugs ever done. Abel contacted 350 medical centers and asked them to send him anything they had ever published on chemotherapy. He also reviewed and analyzed thousands of scientific articles published in the most prestigious medical journals. It took Abel several years to collect and evaluate the data. Abel’s epidemiological study, which was published on August 10, 1991 in The Lancet, should have alerted every doctor and cancer patient about the risks of one of the most common treatments used for cancer and other diseases. In his paper, Abel came to the conclusion that the overall success rate of chemotherapy was “appalling.” According to this report, there was no scientific evidence available in any existing study to show that chemotherapy can “extend in any appreciable way the lives of patients suffering from the most common organic cancers.”

I looked for this study. In fact, I went to The Lancet’s website and looked up the August 10, 1991 issue. I could find no study by Ulrich Abel or anything about chemotherapy other than this study on stroke after chemotherapy for testicular cancer. So I went to PubMed and searched on Ulrich Abel’s name for 1991. All I could find were two articles, one on common infections in chemotherapy patients and another on Crohn’s disease. Nor was I the only blogger who couldn’t find this ethereal Lancet paper by Dr. Abel. So I started searching other years, and then I found what appears to be the paper to which Moritz referred, only it wasn’t published in 1991 but rather in 1992 and it wasn’t published in The Lancet but rather in Biomedicine & Pharmacotherapy, a much lower tier journal. Somehow, through the magic of playing “telephone” over the Internet, this article has morphed from being in a lower tier journal to having been in The Lancet—even published on a specific date!

It turns out that the Dr. Abel’s article is rather odd. It’s not really a study, and it’s definitely not a meta-analysis. Nor is it really a particularly good systematic review, given that the methodology of selecting papers isn’t exactly transparent, and the larger “review” to which he refers readers appears to be in German and not readily available on the web, as far as I can tell. In the abstract, Dr. Abel states that “as a result of the analysis and the comments received from hundreds of oncologists in reply to a request for information, the following facts can be noted.” More importantly, Dr. Abel was addressing a fairly limited situation that excludes two of the most effective uses of chemotherapy, as described in this English translation of a Der Spiegel article describing his work:

  • Abel’s verdict against the medicinal treatment of cancer is emphatically untrue for various kinds of lymph cancer, Hodgkin’s disease, leukemias, sarcomas, and testicular cancers in the male. These kinds of malignancies can be cured by chemotherapy with a high degree of probability, especially in children — an undisputed success. But these are, in any case, only a very small part of the new cases of cancer diagnosed every year.
  • Abel’s doubts are not directed against chemotherapy when it is used in support of a curative operation, in order to shrink the tumor beforehand; nor do they apply to chemotherapy used prophylactically after an operation, to prevent a relapse (as an adjuvant).

These are, of course, the two most effective uses of chemotherapy that there are. I’ll grant critics that the types of tumors that can be cured with chemotherapy with a high degree of probability are a minority of tumors, but, contrary to what is implied in many uses of Dr. Abel’s work, they are not insignificant. For example, leukemias and lymphomas (Hodgkins and non-Hodgkins) add up to almost 10% of newly diagnosed cancers every year, and they are cured primarily with chemotherapy. Sarcomas and testicular cancers are much less common, but add them in and the total exceeds 10%. A distinct minority, yes, but the fact that many of these cancers can be cured with chemotherapy puts the lie to statements like the one by Mike Adams quoted above, which, not surprisingly, is parroted in Andreas Moritz’s little screed.

The second indication left out of Dr. Abel’s analysis, adjuvant chemotherapy, can, depending on the circumstance and tumor, be highly effective. Admittedly in early stage breast cancer adjuvant chemotherapy adds on an absolute basis only low single digit percentages to five and ten year survivals, but in more locally advanced breast cancer, particularly so-called “triple negative” breast cancer, the benefit is much more substantial. For instance, using Adjuvant Online, it’s possible to use the latest literature to estimate the benefit of chemotherapy in specific clinical situations. Here’s an example of a hypothetical 40 year old woman with an estrogen receptor negative tumor measuring between 3 and 5 cm with 1-3 axillary lymph nodes positive for metastatic disease:

Note that standard chemotherapy increases this woman’s chance of survival by 18% on an absolute basis and by 35% on a relative basis. Either way, the survival benefit is substantial. These are women who otherwise would have died but did not, thanks to chemotherapy. These women could be your mother, your wife, your sister, or even your daughter. The bottom line is that, even though I wasn’t particularly impressed with his methodology, Dr. Abel was actually reasonably nuanced in his discussion in that he discussed overdiagnosis and stage migration as confounders that can make a treatment seem more effective than it is, as I myself have discussed many times on this blog, starting with this post.

Besides, few oncologists would disagree with this statement at the end of Dr. Abel’s abstract, “With few exceptions, there is no good scientific basis for the application of chemotherapy in symptom-free patients with advanced epithelial malignancy.” And, indeed, most oncologists do not recommend chemotherapy for patients with stage IV epithelial malignancies who are asymptomatic, because at that point all treatment is palliative, and you can’t palliate symptoms that don’t exist. That’s why chemotherapy is, in most cases, reserved for when tumor progression leads to symptoms. Moreover, this study only examined epithelial malignancies. These are cancers for which surgery can be curative if the tumor has not metastasized. Since 1991, also, we have made significant advances in improving survival using chemotherapy. I’ve used the example of colorectal cancer before, where, thanks to newer and better chemotherapy regimens developed over the last couple of decades that have improved survival in patients with liver metastases from 6 months to close to two years.

I also note that since 1992, Dr. Abel has been co-author on a number of studies involving chemotherapy, for instance, a trial in nephroblastoma and a clinical trial of high dose chemotherapy in aggressive lymphoma. As recently as 2009, Dr. Abel was co-author on a randomized multicenter study comparing two different chemotherapy regimens in pancreatic cancer. Yes, pancreatic cancer, that most intractable of cancer problems with a five-year survival rate of only around 20% in the most favorable cases; i.e., the ones that can be completely resected surgically. Clearly, Dr. Abel buys into the evil big pharma propaganda that chemotherapy can cure at least some forms of cancer and, as far as I can tell, has never written a followup to his 1992 paper.

The bottom line is that the “evidence” used by cranks and quacks to prove that “chemotherapy doesn’t work” is most often based on intellectually dishonest tactics. They either misrepresent studies, as they frequently do with the McGill study claiming that oncologists won’t use chemotherapy. True, thanks to the way these studies have been misrepresented over the years, many of these quacks probably honestly think they’re accurately representing them, but that just goes to show how lazy they are about going back to the primary sources to back up their claims. As for the rest, the Australian study was custom-designed to minimize the apparent utility of chemotherapy, while Dr. Abel’s study intentionally left out the types of situations where chemotherapy is most useful and looked at primarily advanced malignancies. In this latter case, there’s nothing wrong with that approach; the problem comes when the quacks either intentionally or unintentionally fail to disclose that qualification, lose any hint at nuance, and use the results to imply that chemotherapy doesn’t work for anything.

Framing the question

Considering the question of whether chemotherapy “works” or not is very similar to asking the question, “Why haven’t we cured cancer yet?” The reason is that it’s a question that’s so vague as to be almost meaningless. Cancer is, as I have pointed out, hundreds of diseases, each driven by a plethora of different combinations of disruptions in cell growth control mechanisms. A more appropriate question is whether we’ve cured this cancer or that cancer, not whether we’ve cured cancer. Similarly, asking the question of whether chemotherapy “works” is similarly vague and meaningless. The real questions are (1) whether this specific chemotherapy regimen “works” for this cancer, although there are some examples that in aggregate we can make some conclusions about and (2) whether specific chemotherapy regimens can cure specific cancers. As noted above, even some “skeptics” of chemotherapy admit that chemotherapy can be “marvelously effective” for some cancers; the argument that usually follows is that the cancers for which chemotherapy is effective are so few as not to matter. The other issue is that few cancers are treated only with chemotherapy. Multidisciplinary and multimodality therapy are more the rule than the exception, particularly for solid malignancies and includes chemotherapy, radiation therapy, surgery, hormonal therapy, and a variety of other less common therapies.

What needs to be understood is that chemotherapy is very good for some things. For instance, it’s very good for treating and curing leukemias and lymphomas. For certain cancers, it’s also very good at decreasing the chance of relapse after curative surgery. When given before curative surgery, chemotherapy can also make organ-preserving surgery possible. Prominent examples include using neoadjuvant chemotherapy (chemotherapy before surgery) to shrink breast cancers so that they can be removed without mastectomy and shrinking rectal cancers so that sphincter-sparing surgery is possible (i.e., surgery that leaves the anal sphincter intact and thereby spares the patient having to have a permanent colostomy). For specific tumors, chemotherapy has also contributed to significant increases in survival, but it is not a panacea. For example, chemotherapy usually does very little for pancreatic cancer, and metastatic melanoma laughs at most chemotherapy (although there are newer agents that provide hope that this will no longer be the case). For all its uses and advantages, chemotherapy alone is not very good at prolonging survival in advanced epithelial malignancies, and it’s not at all unreasonable to ask whether it is overused in such patients, who are, for the most part, currently incurable.

This reasonable skepticism devolves into nihilism or crankery, however, when tactics such as those used by Mike Adams, Andreas Moritz, or, yes, even the esteemed Reynold Spector are used to “prove” that chemotherapy is “useless.” Moreover, such “skepticism” completely dismisses as worthless survival benefits of a few months, which certainly aren’t “worthless” to many patients. Such briefly lengthened survival times can mean the difference between seeing a child graduate from college or not, seeing a child get married or not, or seeing the birth of a grandchild or not. It must also be remembered that the measured improvements in survival due to chemotherapy are usually medians. Not uncommonly, buried in that median are “outliers” who derive a huge survival benefit from the chemotherapy and survive many more months than expected, sometimes many more years than expected. Moreover, it does patients no favor to try to use the observation that chemotherapy has at best relatively modest benefits in patients with advanced epithelial malignancies to try to imply that chemotherapy doesn’t work for all patients. In particular, patients have to remember that just because chemotherapy doesn’t do that well against advanced malignancies does not, as the quacks would have you believe, imply that “alternative medicine” can do better.

Posted in: Cancer, Science and Medicine

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64 thoughts on “Chemotherapy doesn’t work? Not so fast…

  1. Khym Chanur says:

    If you’re going to use Google to count hits for a certain term or phrase, you should put it inside of double quotes. Googling for chemotherapy doesn’t work without quotes will return hits for any document that has the words “chemotherapy”, “doesn’t”, and “work” anywhere in the document, regardless of whether or not they’re next to each other, in the same sentence, or even in the same paragraph. Putting double quotes around the phrase reduces the number of hits from around 10 million to 33,100.

  2. David Gorski says:

    I made a minor alteration. Now that I’ve done that, I was just curious: Do you have anything to say about the actual content of the post rather than a minor point that has little or nothing to do with the vast majority of the post? :-)

  3. Earthman says:

    I can put my hand up and say, after an operation, two rounds of chemotherapy and two of radiotherapy, I have been in remission for 27 years. I think that counts as a cure.

  4. S.C. former shruggie says:

    There should be an internet abbreviation for “long enough to be worth reading.” It would capture the necessary attitude for discussing cancer.

  5. superdave says:

    No offense to you Dr. Gorski, but this one was just too depressing to even think about let alone read.

    Vaccines don’t work, chemotherapy doesn’t work, what’s next? Does mike Adams think anything works?

  6. Calli Arcale says:

    My first thought on seeing the cartoons was “is Mike Adams doing a Jack Chick?” Same sledgehammer approach.

    About Google, Khym Chanur raises an interesting point, because frequently journalists, alties, and more will use “Google brings up x hits for y” as a way of claiming that y is popular, or something people are worried about, or even that y is true. Yet because of the way Google processes the input string (which, to the techies out there, is actually very typical of such interfaces), each token in the string (the words) is taken as a separate entity in constructing the actual search query. I find this particularly frustrating when looking for information on my favorite TV show, “Doctor Who”, because it is not at all unusual to find those two words in the same document. ;-) Google is smart enough to favor pages with the words strung together or in close proximity, but the full eleventy billion links will include a great many that are totally irrelevant but which happen to include the search terms somewhere in there.

    This is, of course, only part of the “argumentum ad Google” fallacy. The other is that even if all of those links really did contain the complete search string, there’s no way of telling what fraction of them are positive, negative, meta-tag spam, or totally irrelevant; the number of hits really doesn’t tell you very much, yet it gets cited a great deal. Dr Gorski isn’t using an argumentum ad Goole, of course; he’s using it to illustrate how pervasive a particular idea is within the Internet, and even before the correction, I think his use was sufficiently nuanced.

  7. Esteleth says:

    I think that that’s the thing that the woo-meisters have to offer – certainty. The word “cancer” is something that still strikes terror in people, makes them feel lost and small. Doctors offer help and do help, but there is an unwillingness amongst scientists to offer certainly. We say things like “90%” or “substantial” when many people want to hear “yes” or “this will work.” I think it is very important to push back against the claims of the woo-meisters, to point out the flaws in their arguments.
    I also think that many times we ask too much of people, the patients, their families. We need to not say, “This treatment yields a 65% chance of remission in 5 years” and instead say, “This treatment is your best shot.” If we just say the former, the patient is vulnerable to the liar who says, “This cleanse will fix you.” We talk about informed consent – but many patients aren’t informed. Obviously, the best fix is better science education, but in the short term we need to make the science more approachable. I hate to say “dumb down,” but what can we do in the face of trying to explain graduate-level biology to someone who never went to college? Somewhere along the line, people lost their faith in science, that it is best to just listen to those that understand. Part of that is the fault of scientists, for failing. Part of that is the fault of the liars, for sowing doubt.
    I say this both as a scientist, and as someone who is approaching her 5-year anniversary of remission.
    I remember how hard my doctors and nurses worked on me, to help me, and I’m very grateful.
    I also remember how utterly alone and afraid I felt. Vulnerable. How much energy it took to swat away the well-meaning people who suggested this cleanse or that herb. How shocked I was when some of this bullshit came from someone wearing scrubs with the logo of the hospital on them.
    I remember winning, and I remember watching others lose. Against the disease, against the fear, against resisting the lies and trusting their doctors.

    We need to do better. We must do better.

  8. Geoff says:

    Not questioning that chemotherapy works, it can certainly be effective. However, I suspect that effectiveness of chemotherapy drugs via their proposed mechanisms are severely overblown, as I have not seen chemotherapy intervention trials controlled for weight loss. This is significant because weight loss means the metabolizing of fat tissue for a large proportion of calories, and most cancers feature damaged mitochondria, making them incapable of metabolizing fatty acids.

    So it is possible that one of the primary mechanisms by which chemotherapy works is: make patient sick –> reward value of food goes down –> fatmass setpoint in the brain normalizes –> body recognizes that it has excess fatmass and downregulates appetite –> proportion of calories from fat expended goes up –> cancer is starved of glucose –> cancer cells die.

    The rub of course is that if this is one of the primary mechanisms of action, there are better ways to starve cancer cells than injecting chemotherapy drugs into people. Would be interested to know what you think of this, particularly if you have any counter-examples that would invalidate this hypothesis.

  9. Harriet Hall says:

    @Geoff,

    “Cancer is starved of glucose” doesn’t follow.
    Blood sugar levels are maintained. Why would you expect cancer cells get less glucose?

  10. Vera Montanum says:

    Long but excellent article on many levels. An important principle illustrated by Dr. Gorski is that research articles (sometimes only the abstracts) are often misinterpreted or interpreted in biased ways and then cited as evidence to serve a particular purpose. This is then ‘re-cited’ in future articles building upon the false evidence, which serves the purposes of those who would build myths about particular treatments or even a whole area of science.

    Most readers, and certainly the mass media, do not take the time to cross-check original resources (as did Gorski). And, even if they did, relatively few persons (inside and outside of medicine) have the skills needed to correctly interpret research reports and critically appraise them. At least, that’s my observation.

  11. Geoff says:

    @Harriet

    Because on high fat diets (as well as during fasts, which is an extremely high fat diet), the entire body becomes insulin resistant in order to spare glucose for the brain. A similar phenomenon occurs during pregnancy.

    In any case, take a look at the nutrient usage during a 30-day fast here: http://healthcorrelator.blogspot.com/2010/10/amounts-of-water-carbohydrates-fat-and.html. Once the liver glycogen is used up, the entire body runs on fat, with the exception of a small amount of protein being broken down via gluconeogenesis in order to feed the brain.

    1. Harriet Hall says:

      Fasts are a high fat diet??!! And what relevance does a 30-day fast have to chemotherapy? And why would you think insulin resistance would lead to destruction of cancer cells?

  12. Geoff says:

    Yes, fasts are a high fat diet. Almost all of the calorie expenditure by the body (all of it less the 300 calories for the brain) come from fat. Actually, all calorie restricted diets are metabolically high fat for the same reason. Chemotherapy is often a calorie restricted diet, which is why intervention studies should be controlled for weight loss.

    Insulin transports glucose into tissues. The body becomes insulin resistant in order to prevent glucose from getting into the tissues for the sake of saving it for the brain. The rest of the body runs on free fatty acids, but cancer cells cannot metabolize free fatty acids. This results of them starving and dying, or so the hypothesis goes.

  13. ConspicuousCarl says:

    Geoff on 12 Sep 2011 at 3:04 pm
    The rest of the body runs on free fatty acids, but cancer cells cannot metabolize free fatty acids. This results of them starving and dying, or so the hypothesis goes.

    I am no expert, but from a quick googling I can find many descriptions of cancer cells consuming fatty acids, and in fact many such references imply that some cancer cells are quite good at it.

  14. Harriet Hall says:

    @Geoff,

    You can’t just make up your own definitions: diet refers to what is eaten, while the utilization of body fat is a response to fasting. Likewise, chemotherapy is not “a calorie restricted diet,” although chemotherapy-induced nausea may result in decreased calorie intake. If you want to recommend studying the influence of weight loss you can say that without using unacceptable terminology.

    Cancer cells can’t metabolize free fatty acids? References, please.

  15. Calli Arcale says:

    Geoff:

    The rest of the body runs on free fatty acids, but cancer cells cannot metabolize free fatty acids.

    Just curious, but why would they be fundamentally different from other human cells? And from the way you put this, you seem to be saying the hypothesis is for all cancers. That seems like a bit of a stretch to me, though as I’m a software engineer, I’m not equipped to argue the point.

  16. JPZ says:

    @Geoff

    How colon cancer cells metabolize fatty acids:

    http://www.ncbi.nlm.nih.gov/pubmed/21757690

    I would honestly suggest that you read a really good chapter on metabolism and energetics. I don’t recall if the Leninger one was very good, and my Energetics course in grad school was taught from the original papers. You have some information correct, some completely incorrect, some incorrect terminology (thanks HH), and you’ve kind of fit it all together slightly wrong. A good framework chapter could help you strighten it all out (not some blog). Honestly, I think it would be pretty easy to fit the pieces you have right together properly considering where you are right now.

  17. JPZ says:

    @Calli Arcale

    You can check the reference I just posted. Years ago, there just wasn’t all that much evidence that cancer cells did use fatty acids.

  18. nybgrus says:

    honestly I am mind boggled.

    Geoff is once again trying to ply his “paleo-low-carb-high-fat-ketogenic-diet-will-cure-cancer” spiel. He couldn’t manage to actually demonstrate any validity the last couple of times he tried – as both myself and Dr. Hall quite easily demonstrated his claims to be suprcilious. Now he is trying this tack to see if it has a go.

    No Geoff it doesn’t work that way.

    @Calli Arcale: He is referencing the fact that in many, but not all, cases cancer cells end up having dysfunctional mitochondria and are reduced to substrate level phosphorylation for energy demands – i.e. they cannot utilize the acetyl-CoA derived from fatty acid breakdown since their TCA cycle is arrested.

    However, he still hasn’t managed to address one amazingly fundamental point. That is the concept of blood glucose, as Dr. Hall raised above. Even if you are ketogenic, your blood glucose is still relatively normal. He seems to think that because you become insulin resistant, to shunt glucose to the brain (which is correct) that somehow means that all glucose is shunted away from cancer cells specifically. Yet there is absolutely no reason to assume this. And plenty of data that show it isn’t true. He also completely neglects the concept of gluconeogenesis seeming to think that the only way our bodies can get glucose is either from diet or glycogen stores. Never mind glucogenic amino acids. Never mind the fact that the brain can only survive on a maximum of about 50% ketone bodies and the rest must be glucose.

    Sorry Geoff, but it still falls flat and I am not about to let you try and keep pandering the same tired and wrong notions. You still even conflate terms, as Dr. Hall pointed out – but missed the fact that you say “insulin transports glucose into tissues.” No Geoff, it doesn’t. It stimulates kinase activty to bring pre-formed GLUT transporters to the membrane and allows the passive flow of glucose into the cells. A minor point, to be fair, but it is one of the facets that belies the fact that Geoff doesn’t understand or know basic cell biology let alone cancer biology.

    Did you actually read “The Emperor of All Maladies” yet Geoff?

  19. Thank you very much, Dr. Gorski, for putting in the time and effort to illustrate the lack of substance to these common arguments.

    I find that CAM proponents have a vested interest in portraying conventional cancer therapy as ineffective in that it opens a door in people’s minds to sell unproven or simply useless alternatives. And I agree that simplicity and certainty are much better marketing tools than the truth when the truth is complex and sometimes ambiguous. But this is a very useful analysis to offer in response to the simplistic untruths you have dismantled here.

  20. Geoff, someone else may have already pointed this out… But, one of the hallmark symptoms of some cancers is a rapid and unexplained weight loss. It seems to me, If you are correct that it is the weight loss cased by chemo that is the actual mechanism in curing or controlling the cancer, then you would see the same results in people with cancer who have experienced weightless due to their cancer. Do you?

  21. pmoran says:

    Many years ago I operated on a relatively young chap with bowel cancer, removing the primary cancer in the colon and taking a biopsy of small nodules in both lobes of the liver.
    They sadly proved to be metastases.

    He was not suitable for hepatic resection, and with colorectal cancer being notoriously resistant to chemotherapy (in those days only 5FU was considered to have any effect and even that was disputed by many) I advised him to get on with his life while we kept an eye on things, considering the options when forced to.

    However, he took himself off to see a medical oncologist — actually one that I regarded as being generally too aggressive in his use of chemo.

    Blow me down, if he didn’t return some months later with good news! He had been treated with 5FU and the liver metastases were shrinking, also starting to calcify (as dead tissue is prone to do).

    When I lost contact with him four years later, he was perfectly well, but still with small calcific nodules in his liver. Without the treatment he would probably would have lasted 18 months or less.. I suspect he is cured .

    The moral of my story is this, that the oncologist’s problem is not so much when to use chemotherapy, but when NOT to use it. Its results are rarely 100% predictable. It is also not easy to withhold even low-yield treatments when someone is suffering the privations of advancing cancer. Doctors are under the very same pressures that drive people to seek CAM.

    Remember also that those studies demonstrating an unimpressive few months’ better overall survival with certain uses of chemotherapy can conceal considerably more worthwhile results for some (as well as less so for many, of course).

    There are thus good reasons why chemotherapy may be over-used under circumstances where it is not likely to help.. There is indeed the potential for a tremendous wastage of resources.

    Without outside intervention from payers and insurers, there is no easy answer to this. Certainly chemotherapy should be stopped if after a few cycles there is no obvious effect. We should seek solid data on which to base patient advice. I don’t think the medical profession can be faulted regarding the latter.

  22. daedalus2u says:

    I suspect that the reason glucose is spared during ketosis is not so much to shunt glucose to the brain, (the brain can do just fine on ketone bodies and the brain is such a large fraction of metabolic load that it would rapidly exhaust glucose derived from amino acids), but rather to preserve glucose for immune cells which must function in anoxic regions such as abscesses where only glycolysis is going to work. Also red blood cells only use glycolysis because they don’t have mitochondria.

    Glucose is only made from 3-carbon substrates. In ketosis, these are only from glycerin released from lipids, 3-carbon tail ends that are left over from odd number fatty acids (very rare), and from amino acids catabolized from lean tissue. Some acetone is made during ketosis but that is not a significant substrate for gluconeogenesis.

    Also, the weight loss in cancer is usually from cachexia, which is usually the loss of lean tissue, to make amino acids to make glucose. Trying to reduce blood glucose via a low carbohydrate diet would likely accelerate cachexia and accelerate death from cachexia.

  23. nybgrus says:

    All of this, including D2U’s latest comment, got me doing some research. And I found a few interesting things (which one often does when perusing a 1,000 page text on biochemistry). Including a few facts that will definitively shut down Geoff’s notions (well, it should, if he listens). Also, I apologize, but this will be a long and technical post – I figure those that are keen will read it, and those that aren’t can just skip it, but this will help me consolidate some of the biochemical and metabolic knowledge I have just gained, since my mind was sort of just blown. So my apologies in advance.

    First, from Lehninger’s Biochemistry, 4th ed, 2005, page 533:

    Glucose uptake and glycolysis proceed about ten
    times faster in most solid tumors than in noncancerous
    tissues.
    Tumor cells commonly experience
    hypoxia (limited oxygen supply), because they initially
    lack an extensive capillary network to supply the tumor
    with oxygen. As a result, cancer cells more than 100 to
    200 m from the nearest capillaries depend on anaerobic
    glycolysis for much of their ATP production. They
    take up more glucose than normal cells, converting it to
    pyruvate and then to lactate as they recycle NADH.
    The
    high glycolytic rate may also result in part from smaller
    numbers of mitochondria in tumor cells; less ATP made
    by respiration-linked phosphorylation in mitochondria
    means more ATP is needed from glycolysis. In addition,
    some tumor cells overproduce several glycolytic enzymes,
    including an isozyme of hexokinase that associates
    with the cytosolic face of the mitochondrial inner
    membrane and is insensitive to feedback inhibition by
    glucose 6-phosphate.
    This enzyme may monopolize the
    ATP produced in mitochondria, using it to convert glucose
    to glucose 6-phosphate and committing the cell to
    continued glycolysis. The hypoxia-inducible transcription
    factor (HIF-1) is a protein that acts at the level of
    mRNA synthesis to stimulate the synthesis of at least
    eight of the glycolytic enzymes. This gives the tumor
    cell the capacity to survive anaerobic conditions until
    the supply of blood vessels has caught up with tumor
    growth.

    Essentially what I have been saying from the outset. The TL;DR version is basically that tumor cells have constantly increased levels of glucose uptake to suck it up from the whatever is available since their very genesis requires it. Furthermore, the hypoxia actually induces the mRNA expression of glucose metabolizing proteins which makes the neoplastic cells more able to process glucose. Therefore, if there exists any glucose in the blood, it can be essentially certain that cancer cells will make use of it.

    This is further reinforced by the bit that blew my mind – a frame shift, if you will, on how I had been viewing insulin and blood glucose. We are taught that insulin increases expression of GLUT4 transporters at the surface and that this is how blood sugar ends up dropping and getting into peripheral tissues. This is partly true. It seems though, that the primary motivator driving the decrease in blood glucose levels (BGL) is actually that insulin inhibits the export of glucose from the liver. Since the liver always has heaps of GLUT2 transporters that are completely independent of insulin and are extremely high capacity, it is actually the shift in influx/efflux that drops blood glucose – the liver has the capacity to change BGL almost instantaneously as a result. The part that makes all this really interesting is that this is integral to understanding how ketosis comes about.

    Peripheral cells (fat and muscle primarily) always have some GLUT4 transporters in their membranes. In fact, this paper demonstrates that the metabolic needs of all cells can and are met without the need for insulin at all. So in fact, in diabetes, glucose uptake by cells is increased relative to normal physiological insulin states because the glucose concentration is so much higher. I thought this was quite suspect, so I cracked open my Lehninger’s and started reading. After all, the common understanding amongst med students is that cellular starvation leads to increased fatty acid metabolism for energy with a saturation of the TCA cycle and thus spillover of acetyl-CoA into ketone bodies. Turns out that this is not quite right, but that the shortcut we use comes up with the same results.

    It is obviously very complex, but according to my reading, what is essentially happening is that the low insulin states leads to a predominant counter-regulatory effect of glucagon and epinephrine. Through the GLUT2 transporters, the liver is essentially like a giant sieve for glucose – since the entire blood volume goes through the liver ever minute or two, altering the efflux/influx ratio can produce rapid and dramatic changes in BGL. Thus, when insulin is low (whether because you actually are starving or because you have no insulin) the liver thinks it needs to pump out more glucose and will thus break down glycogen and undergo gluconeogenesis (using amino acids and TCA cycle intermediates). This cannot happen in extrahepatic cells since they don’t have the machinery for gluconeogenesis. The lack of insulin also means that a shift in fatty acid metabolism occurs – acetyl-CoA is no longer shuttled through malonyl-CoA to produce fatty acids, and so fatty acid breakdown begins to predominate (insulin directly affects the protein for fatty acid synthesis). In the liver, the TCA cycle intermediates are rapidly depleted, so there is a huge amount of acetyl-CoA that cannot be utilized to make energy and is just left hanging around. Combined with the increased extrahepatic breakdown of fatty acids leads to ketosis. However, even in the latest stages, protein breakdown and other minor gluconeogenic pathways still produce glucose – so even at time of death from starvation (and this is key here Geoff) blood glucose levels remain above 2.2mM. You die from organ failure due to protein catabolism, not from hypoglycemic coma.

    @D2U: According to this article protein catabolism is actually the primary source of gluconeogenic subsrates, and would indeed rapidly destroy your body if it weren’t for ketones substituting. By the way, I was wrong – the brain can take up to 66% of its energy from ketones, not 50% like I had said earlier. So the ketones slow down the catabolism of muscle, but will not stop it, so it is necessary to maintain adequate blood glucose, it’s just that “adequate” drops from ~4.5mM to ~2.5mM because ketones make up the rest. But that takes acclimation, which is why rapidly induced hypoglycemic states will lead to mental confusion and coma.

    As for why glucose is shunted – yeah, I think it is just a general tissue response. The brain needs glucose, so to RBCs, and leukocytes in certain situations. So those tissues that need it less (like muscle) forgo it for whichever tissue can grab it. I think we tend to say it is for the brain because we are so used to thinking of the high glucose consumption of the brain and our own concept that it is the organ most highly preserved. But in reality, it is just an “I need it less so you can have it” sort of thing. According to that article I linked, the brain would still need 40g of glucose per day, which translates to 20g of muscle breakdown per day so it is still most certainly needed for brain function, but I agree that the other tissues mentioned need it as well.

    As for the cachexia – that is actually mediated by TNF-alpha which is a product of immune cells. It is due to the apoptotic nature of TNF which leads to generalized cell death in later (i.e. massive tumors or disseminated) stages of cancer. I agree that going ketotic would thus necessitate the further catabolism of protein to maintain “adequate” BGL, and thus accelerate death. And of course, to tie it back into the beginning, cancer cells would still have the means to take in enough glucose to survive. So indeed, I think a ketogenic diet would likely be quite bad for late stage cancer and would do essentially nothing in early stages.

  24. majkinetor says:

    Looks like there is truth in that. One of the problems of ketogenic diet is for people with fungal infections which could get worst. It seem to impair immune cells who use glucose to produce respiratory bursts. So, some people experience worsening of fungal infections with such diets. It could be attributed to additional food resource for fungi as they can also use ketones. It could be combination of both. The additional problem is that of RBCs like you mentioned.

    Harriet, although body keeps glucose levels in check, its fact that after high CHO meal blood levels stay elevated for several hours. If you add soft drink between meals, it could easily translate to pre-diabetic levels most of the day. On the other side, low carb/paleo diets may produce higher blood glucose fasting levels.

    If low carb diet is effective with cancer, and there is evidence that it probably is, its effects are probably mediated by improved immune system (as glucose competition with Vitamin C is removed; after high carb meal immune system is diminished 50% for several hours), higher animal fat/meats means higher amounts of Vitamin K2 (combination is similar to Apatone) and since malnutrition may be a factor, higher amounts of Vitamin D from paleo diet [eggs/liver] may contribute. Plus ketogenic diet improves many brain conditions which can’t hurt at all, as it is the one who orchestrates all.

  25. majkinetor says:

    2 nybgrus

    Yes, its true that primary action of insulin is to reduce hepatic output, base levels of GLUT4 transporters are enough for normal functioning. Could we use that for our advantage ?

    What is known on ketogenic/low carb diets is that fasting insulin is lower. This promotes gluconeogenesis but liver has its production limits. I cant dig up numbers right now but I think its in optimal scenario something like 400g per day. Most of the body switch to burn fat on ketogenic diet to spare glucose for demanding cells.

    So, depending on behavior there are biological reasons for curative effects of such diets. For instance, if you do HIIT style trenning which promote anaerobic muslce pathways, muscle will upregulate GLUT4 in non-insulin dependent way competing with cancer cells. Brain also competes, RBCs and immune cellls. If cancer cells suck it up a lot so that brain doesn’t have enough, it will degrade some of the muscle proteins hence its good idea to build those and higher protein paleolithic type diet is good suited for that. So you can basically produce “glucose deficiency” which will probably heart cancer cells the most as they don’t use ketones and fat as much as glucose [I presume because mitochondrial disorders].

    Anyway, my opinion is that effect of low carb diets are probably most effective to prevent cancer formation rather then cure it. Such diet should probably be used along any cancer treatment since I don’t see how extra sugar could help.

  26. nybgrus says:

    If you add soft drink between meals, it could easily translate to pre-diabetic levels most of the day

    Except that wouldn’t really make sense and would completely invalidate the point of a glucose tolerance test. If you look at the curves of glucose following oral ingestion you find that it returns to baseline within about two hours. Same goes with IV glucose except that happens even faster.

    Your reference was a bit suss, so I looked it over and found some of the primary sources. Basically, all they are going off of is that hyperglycemic states decrease phagocytic activity of leukocytes. But that is reasonably well known. So you don’t need a low carb or ketogenic diet – you just need to be euglycemic. They did find that fasting for some time increased phagocytic activity but that is likely due to counter-regulatory hormone stimulation. But more to the point, immune responses to cancer have nothing to do with phagocytosis – it is direct cytotoxic action. So the concept doesn’t bear any relevance to low-carb/keto/paleo diets being useful for cancer.

    Plus ketogenic diet improves many brain conditions which can’t hurt at all, as it is the one who orchestrates all.

    The brain does not orchestrate immune responses.

  27. nybgrus says:

    I am having serious issues with link HTML, my apologies

  28. nybgrus says:

    This promotes gluconeogenesis but liver has its production limits.

    Not really. The liver will catabolize protein until you die because you have no more structural proteins to survive. That was part of my discussion and referenced above.

    Most of the body switch to burn fat on ketogenic diet to spare glucose for demanding cells.

    Considering that most of the body is muscle, fat, and both those and the heart and brain can run on ketones for a significant portion of energy, sure. I agree.

    If cancer cells suck it up a lot so that brain doesn’t have enough, it will degrade some of the muscle proteins hence its good idea to build those and higher protein paleolithic type diet is good suited for that.

    This actually isn’t bad reasoning, but all you’ve done is demonstrate that we need to feed the cancer somehow. If the cancer cells are sucking it up (which they do, at vastly higher levels than muscle can “compete” with), thus leaving the brain wanting and creating a glucose deficiency, then all that will happen is the liver will catabolize more protein. So whether that glucose for the cancer is coming from protein or carbs in your diet doesn’t really matter.

    So you can basically produce “glucose deficiency” which will probably heart cancer cells the most as they don’t use ketones and fat as much as glucose [I presume because mitochondrial disorders].

    Except that my long post above demonstrated that you cannot create a glucose deficiency. Yes, you are correct about the mitochondrial issues and the fact that cancer predominantly needs to use glucose for fuel. But no matter what you do, you simply cannot reduce blood glucose levels below about ~2.5mM – they will stay at least that until you die. So there will always be glucose available for the cancer cells.

    Anyway, my opinion is that effect of low carb diets are probably most effective to prevent cancer formation rather then cure it.

    Oncogenesis (the creation of cancer) has nothing to do with glucose levels. In fact, as my post above made note of:

    Tumor cells commonly experience hypoxia (limited oxygen supply), because they initially lack an extensive capillary network to supply the tumor with oxygen. As a result, cancer cells more than 100 to 200 m from the nearest capillaries depend on anaerobic
    glycolysis for much of their ATP production.

    In other words, no matter what you glucose levels are, the microenvironment at an oncogenic focus (place where cancer is starting) makes cancer cells go down the pathway of glucose use because it has to. So in order to actually become cancer in the first place, it already has to thwart those limitations. And as I’d said, no matter how paleo or keto or low carb your diet is, your blood glucose will always be relatively normal, so there is plenty enough for the cancer cells.

    Such diet should probably be used along any cancer treatment since I don’t see how extra sugar could help.

    Well, I answered that in the last paragraph of my long post:

    I agree that going ketotic would thus necessitate the further catabolism of protein to maintain “adequate” BGL, and thus accelerate death. And of course, to tie it back into the beginning, cancer cells would still have the means to take in enough glucose to survive. So indeed, I think a ketogenic diet would likely be quite bad for late stage cancer and would do essentially nothing in early stages.

    In general extra sugar is bad for you because people are generally well fed enough that it just makes them fat. In cancer, as I’ve been trying to say, there will always be enough sugar for the cancer to survive. So in prevention, it won’t do anything one way or another. However, adding a ketogenic diet to cancer cures (especially late stage) would probably make things worse. So having sugar there would actually act to spare muscle tissue so I think it would be a good thing and actually would help.

  29. daedalus2u says:

    nybgrus, do you have a link for the percentage of brain metabolism that can be supported by ketosis? The brain can also use acetate which can be made from 2-carbon substrates.

    It is good that you have gotten past the facile explanation that insulin lowers blood glucose in type 1 diabtes by increasing glucose removal from the blood.

    The problem with the liver explanation is that the time constants for glucose delivery to peripheral tissues are tens of minutes (it is via lymph). Raising blood glucose very fast is ok, but lowering it very fast may very well cause hypoglycemia due to the different time constants of the addition and consumption of glucose to the blood and delivery to peripheral tissues.

    The liver is a big source and sink of blood glucose, but the regulation of the transition from sourcing to sinking (delivering vs taking up) has to reflect energy status of peripheral tissues. I think it is trying to do this too quickly is what causes the increased adverse effects of “tight” glucose control.

  30. nybgrus says:

    d2u: I am always amenable to learning and changing my views based on evidence, you know that! It’s just tough to do with everything, since as you well know there is a LOT to know out there. And in med school, we have to learn a lot of different things, so I just can’t get into the depth I’d like with everything. But when I get a wild hair…. ;-)

    As for the percentage utilization – it was actually linked, but I screwed up the HTML. It is from this article specifically the section just below table 30.2:

    After several weeks of starvation, ketone bodies become the major fuel of the brain. Acetoacetate is activated by the transfer of CoA from succinyl CoA to give acetoacetyl CoA (Figure 30.18). Cleavage by thiolase then yields two molecules of acetyl CoA, which enter the citric acid cycle. In essence, ketone bodies are equivalents of fatty acids that can pass through the blood-brain barrier. Only 40 g of glucose is then needed per day for the brain, compared with about 120 g in the first day of starvation. The effective conversion of fatty acids into ketone bodies by the liver and their use by the brain markedly diminishes the need for glucose. Hence, less muscle is degraded than in the first days of starvation. The breakdown of 20 g of muscle daily compared with 75 g early in starvation is most important for survival. A person’s survival time is mainly determined by the size of the triacylglycerol depot.

    I was taught 50% in my lectures. I’ve seen sources stating 75%. But this is the most robust source I’ve found so far, and it puts it at 66%.

  31. majkinetor says:

    See http://goo.gl/8OAC7 topic What limits the liver’s capacity to convert amino acids to glucose?

    Let me paste relevant part here:

    We have data about the total extent of the oxygen supplied to the human liver. Calculations based on this (and assuming that all of this oxygen goes to support conversion of amino acids to glucose) suggest that the maximum capacity of hepatic glucose synthesis from amino acids lies around 400 grams/day. This is the equivalent of approximately 1600 kcal, close to the basal metabolism of a bed-ridden person and hardly enough to support an active life.

    then all that will happen is the liver will catabolize more protein. So whether that glucose for the cancer is coming from protein or carbs in your diet doesn’t really matter.
    So you are probably wrong about protein, as I already said it has limits. Since there is a lot more muscle then cancer cells, muscles are more effective pump of glucose then cancer cells. Don’t say now that cancer can magnetically attract glucose and that diffusion stops functioning once you have it. Competition is real, it limits available fuel for cancer. If you add Vitamin C, it will have another competitor since the same receptors are used. High protein diet, which mean high Lysine and Prolin content along with C will make collagen stronger so cancer will have hard time expanding.

    Why do you think that ketogenic diet may be harmful to late stage patients. Is it because of glucose deficiency induced by cancer metabolism ?

    2 dae

    Ketone bodies are utilised by brain proportional to their arterial concentrations (Hawkins et al. 1971; Robinson and Williamson 1980; Blomqvist et al. 2002) and in humans, can provide as much as 60% of brain substrate requirements during prolonged starvation (Cahill 1983)

  32. majkinetor says:

    Sorry for messy reply, backquote tag is not working here

  33. LovleAnjel says:

    In a fit of naughtiness I googled “chemotherapy kills stupid people” and “chemotherapy doesn’t work on stupid people” and all the same naturalnews links came up. Of course, I clicked on them.

  34. Geoff says:

    This is a good discussion, I’m glad I posted the comment. After all of the knocks on me, I’m not going to be able to respond to them all, but nothing stated here even comes close to invalidating the proposed hypothesis.

    Gluconeogenesis is expensive. The body really doesn’t want to give up its muscle mass. Referring back to the fasting chart, once adapted, the body only converts 60-70g a day of protein into glucose, and gluconeogenesis is only about 60% efficient last I checked.

    Would that be different in someone with a tumor? I don’t know, but based on what I’ve seen of Dr. Seyfried’s research, my guess is that it would not. Granted, most of his research is on brain tumors (for example: http://www.ncbi.nlm.nih.gov/pubmed/20804725), which may be a unique case, but I don’t think so. There are animal models showing success in prostate cancer, breast cancer and other endocrine organ epithelial cancers. There are also a couple of small trials on people with extremely advanced cancers that have shown some minor successes.

    These are all clues that point to the possibility of the hypothesis being accurate. Not proof, but possibly suggestive. Again though, let’s not get off topic. It’s easy to measure weight, and it’s easy to add one extra variable into the statistical analysis. Doing this would improve the quality of these studies, and the results might be surprising.

    We all have the same goals here, to keep researchers honest for the sake of improving the quality of the science and making people healthier. It is plausible that one mechanism by which chemotherapy works is by causing nausea which results in calorie restriction, particularly in overweight individuals (these are the ones for whom normalizing the setpoint would result in the largest calorie restriction). This needs to be corrected for in evaluating the efficacy of treatment for precisely the same reasons that the placebo effect must be accounted for.

  35. Harriet Hall says:

    @Geoff,

    “It is plausible that one mechanism by which chemotherapy works is by causing nausea which results in calorie restriction, particularly in overweight individuals (these are the ones for whom normalizing the setpoint would result in the largest calorie restriction). This needs to be corrected for”

    If it is plausible, the next step is to test whether it is true, not to jump to correcting for it in studies.

  36. daedalus2u says:

    The only time that a tumor can be “starved” for glucose is when the capacity of the liver to make glucose or release glucose is exceeded. Unless the liver is generating glucose at its maximum metabolic rate, as the tumor takes more glucose out of the blood stream, the liver will compensate by putting more glucose back in.

    This “competition” can only occur during time periods that are short compared to the time constant of the liver putting more glucose into the blood stream. This is very short, minutes or less. Once the liver has time to respond, it will respond and will supply what ever level of glucose the rest of physiology calls for.

    If the consumption of glucose exceeds the capacity of the liver to produce glucose (lets say by exhausting glycogen stores), then blood glucose will acutely fall and there are pretty dire consequences of that. If the acute shortage is survived, then cachexia sets in as the liver increases its glucose production capacity.

    Inducing a state of cachexia is not something I would expect to improve survival from a tumor, or from anything. I think trying to avoid a state of cachexia would be beneficial. I think that is one of the drawbacks of conventional treatment for sepsis. During sepsis a state of cachexia is induced to generate vast quantities of glucose so that most of metabolism can be run on glycolysis. This is necessary during sepsis because the very high NO levels from iNOS have turned off O2 reduction by cytochrome c oxidase. Without O2 reduction, ATP can’t be made by oxidative phosphorylation and so ATP production is limited to glycolysis. Mitochondria in the liver are shut down too, so the lactate can’t be recycled back into glucose, so it gets turned into fat.

    I think the way to treat sepsis is by infusing lots of glucose, giving lots of insulin to get the glucose inside of cells where it can be utilized, and dialyze with urea containing fluid to remove lactate. I think if you can do that, you would reduce cachexia and reduce the metabolic load on the liver. I think that organ failure occurs when the ATP level falls (it is regulated high by the high NO) because of insufficient glucose for glycolysis, and the mitochondria turn on. In a high NO environment, mitochondria turning on causes their irreversible turning off via nitration of MnSOD (first) which inhibits it, and then by nitration of the respiration chain. If too many mitochondria are irreversibly turned off, then the cell, tissue compartment, and organ fails.

  37. nybgrus says:

    @majkinetor:

    So you are probably wrong about protein, as I already said it has limits.

    I didn’t say there is no actual limit. I said “not really” in that the limit is sufficiently high enough that taken into account with the rest of physiology the liver will produce enough glucose to survive. This is accomplished both by increasing the gluconeogenic output and ketone body utilization by extra-hepatic tissues.

    Since there is a lot more muscle then cancer cells, muscles are more effective pump of glucose then cancer cells.

    Glucose is not pumped into cells. It passively diffuses across the concentration gradient via the GLUT transporters. This is vital to the understanding and not a minor point. The GLUT2 transporters are very high capacity and always expressed in large numbers in the liver. The GLUT4 are lower capacity and always expressed in small numbers in all cells and insulin increases expression. In a ketogenic state (i.e. low insulin) you will only have that basal level of GLUT4 expression.

    Don’t say now that cancer can magnetically attract glucose and that diffusion stops functioning once you have it.

    There is no magnetism involved here. As I pointed out from the biochem text, cancer cells express a much higher level of GLUT4 – the text says 10 times the level of glucose intake. It is a diffusion game. If, for example, a normal cell has 10 GLUT4 transporters and a cancer cell has 100 the cancer cells will always take up more glucose than the normal cell for each and every possible BGL you can imagine. There are simply more channels for the glucose to flow through down the concentration gradient. So no matter how much you lower the BGL, the cancer cell will always outcompete. If you give insulin, that will increase the number of GLUT4 transporters in all other tissues, but it will also increase it in the cancer cells, so that still wouldn’t help.

    And no, it doesn’t matter if there are a thousand times more normal cells than cancerous. Since the BGL must be kept at a steady state throughout the entirety of the blood volume, there will always be blood with glucose in it passing by the cancerous cells so they will always take up the glucose. The only way to prevent that would be to make sure no glucose gets to the cancer cell. That means either a BGL of zero (which means pretty much instant death) or cutting off blood supply to the cancer. The latter is accomplished through anti-angiogenic drugs and surgery.

    Competition is real, it limits available fuel for cancer.

    So, as I described above, competition means that the extra-hepatic tissues would have to soak up all the glucose in the blood before it reaches the cancer. The only way to accomplish this would be to have a BGL of zero (or alternately, so low as to starve the cancer cells which, since they constitutively express more GLUT4 than normal cells, would always starve normal cells first) which is impossible. So competition cannot be a clinically useful notion here.

    If you add Vitamin C, it will have another competitor since the same receptors are used

    What receptor for vitamin C? Vitamin C is an anti-oxidant – in other words it absorbs the radical by products of biochemical reactions. It doesn’t compete with glucose or insulin receptors – unless you would care to link me to a journal article that describes what you are referring to.

    High protein diet, which mean high Lysine and Prolin content along with C will make collagen stronger so cancer will have hard time expanding.

    That’s actually not a bad thought on the surface. And certainly you have the biochemistry right – you need vitamin C for hydroxylation of proline and lysine for collagen cross-linkages. But it doesn’t quite work that way. Unless you have clinically deficient levels of vitC then your collagen synthesis will be just fine and at a maximum – you can’t make it even stronger by adding more vitC. So I agree that if a cancer patient was deficient that would most certainly make it easier for the cancer to spread and that should be corrected ASAP. But in a non-deficient person you are already at max. Plus, by definition, for a cancer to become metastatic, it must be able to secrete collegenase to burrow through basement membranes. So even if you could strengthen collagen past 100%, and even if that meant fibroblasts would lay down thicker layers around the tumor, it would hardly be much of an impediment since the tumor secretes enzymes that will just break it down.

    Why do you think that ketogenic diet may be harmful to late stage patients. Is it because of glucose deficiency induced by cancer metabolism ?

    Because the body will do whatever it takes to maintain that minimum BGL. In late stages of cancer, when you are already cachectic, that means burning protein. So if you starve the body of glucose, that means there is only fat in the diet (and whatever may be left in your body) and protein to get glucose from. So best case scenario is the fat intake you have will cover the costs of gluconeogenesis and the protein intake will supply the subsrate. But then it is a wash – you are just maintaining status quo. If you don’t have enough fat, then you won’t be able to produce the glucose even if you have enough substrate from the diet. Since, as we’ve seen, tissues like the brain need a minumum amount of glucose, that will lead to a clinically hypoglycemic state and you’ll die quicker. If you provide enough fat but not enough protein, then you will just be giving energy for the liver to convert your own proteins to glucose, which is already going on and will only worsen the cachexia induced by TNF-alpha, and once again hasten your death. So giving carbs/glucose will simply skip that step and make less of a toll on your liver.

    Ketone bodies are utilised by brain proportional to their arterial concentrations (Hawkins et al. 1971; Robinson and Williamson 1980; Blomqvist et al. 2002) and in humans, can provide as much as 60% of brain substrate requirements during prolonged starvation (Cahill 1983)

    I agree – the paper I referenced comes up with roughly 66% of brain requirements can be met with ketone bodies. But it is the remainder that must be glucose. That is why you must have a minimum BGL at all times to live – the paper demonstrates that to be roughly 2.5mM. There is just no feasible way to keep enough glucose away from cancer cells without starving your brain.

  38. ConspicuousCarl says:

    Geoff on 13 Sep 2011 at 11:07 am

    After all of the knocks on me, I’m not going to be able to respond to them all, but nothing stated here even comes close to invalidating the proposed hypothesis.

    02/07/2011
    “Cancer Cells Use an Enzyme that Breaks Down Stored Fats to Fuel Aggressive Growth and Spread”
    http://www.cancer.gov/aboutnci/servingpeople/cancer-research-progress/advances/MAGL

    17th May 2011
    “Breast cancer cells consume fatty acids to generate energy when they are deprived of their usual diet, glucose and oxygen, a new study has revealed.”
    http://www.figo.org/news/breast-cancer-cells-turn-fatty-acids-when-deprived-glucose-003647

    24 August 2011
    “Failure refers to the state or condition of not meeting a desirable or intended objective, and may be viewed as the opposite of success.”
    http://en.wikipedia.org/wiki/Failure

  39. nybgrus says:

    @geoff:

    After all of the knocks on me, I’m not going to be able to respond to them all, but nothing stated here even comes close to invalidating the proposed hypothesis.

    They aren’t knocks on you. They are knocks on the hypothesis you postulate. And yes, despite what you seem to think, my in depth reading and citation of human biochemistry does make the basic principles of your hypothesis highly unlikely. Does it prove unequivocally that it is wrong? Of course not. But the a priori likelihood from a basic sciences point of view is quite low.

    Gluconeogenesis is expensive. The body really doesn’t want to give up its muscle mass. Referring back to the fasting chart, once adapted, the body only converts 60-70g a day of protein into glucose, and gluconeogenesis is only about 60% efficient last I checked.

    I fail to see the point. Of course the body doesn’t want to give up its muscle mass. But it will. And it does. And the lack of efficiency doesn’t mean the body will magically stop doing what it needs for basic survival. Converting 60-70g/day into glucose means that is either enough for the body to survive (and thence the cancer as well) or you die.

    Would that be different in someone with a tumor? I don’t know, but based on what I’ve seen of Dr. Seyfried’s research, my guess is that it would not. Granted, most of his research is on brain tumors (for example: http://www.ncbi.nlm.nih.gov/pubmed/20804725), which may be a unique case, but I don’t think so. There are animal models showing success in prostate cancer, breast cancer and other endocrine organ epithelial cancers. There are also a couple of small trials on people with extremely advanced cancers that have shown some minor successes.

    I agree that it wouldn’t necessarily be different with other tumors. In general they lack oxidative level phosphorylation capacity. The issue here is whether they lack constitutive glucose uptake capacity. At best this hypothesis might pan out for a very specific subset of tumors that lack this capacity. Based on my reading, and the quote I made a few comments above from Lehninger, that will be very much a minority of cancers.

    Moreso, I actually read the original article you linked from Seyfried in full. I am unimpressed. He references a total of about 4 or 5 case studies and some animal data. He even states quite clearly:

    It is important to recognize, however, that the physiological response to DR is not the same in mice and humans due to differences in basal metabolic rate.

    He extrapolates that this may be achieved using extreme dietary restriction and/or ketogenic diet but there is nothing to back up this assumption.

    Small trials, as Dr. Hall pointed out, can make one think that maybe there is something there. Which is exactly what we have been saying all along – maybe something, but unlikely. You keep insisting on putting the cart before the horse.

    It is plausible that one mechanism by which chemotherapy works is by causing nausea which results in calorie restriction, particularly in overweight individuals (these are the ones for whom normalizing the setpoint would result in the largest calorie restriction).

    That really isn’t very plausible and certainly not something that needs correcting for. We know how chemotherapeutic agents work. So even if the nausea/lack of appetite somehow did contribute, it would be so minor compared to the actual action of chemo agents as to be insignificant and extremely difficult (and IMO pointless) to suss out.

    Seyfried goes on to talk about the anti-angiogenic and pro-apoptic facets of KD and DR. This is perfectly true and reasonable. The problem is that in late stage cancers, people are literally wasting away and just the overload of TNF-alpha will lead to cachexia with a normal diet. Further restriction won’t aide in anything. In early stages there is plenty enough energy store available that a DR or KD won’t make a lick of difference for a 2cm mass trying to grow.

    So in sum, I’ll repeat what we have been saying all along. The basic sciences make this highly unlikely. The data so far is very sparse and of poor quality from which to draw conclusions. And while there may indeed be something there, it would only apply to a certain subset of cancers, would be of relatively small clinical effect, and the interactions on a large scale level are something we can’t even guess at. But history has taught us it most likely won’t pan out. Nobody here is saying not to pursue the science of it. But you are leaps and bounds ahead of where you should be based on what we know.

  40. nybgrus says:

    thanks for the references Carl. It further reinforces my stance that if it worked, it would only be for a subset of cancers. And I reckon a small one at that.

  41. nybgrus says:

    And in reading the track back to the Brain Tumors forum, and then back to the thread, I picked up on this that Geoff wrote that I missed previously:

    The body becomes insulin resistant in order to prevent glucose from getting into the tissues for the sake of saving it for the brain.

    No. No. And um, no. The body does not become insulin resistant in ketogenic/starvation states. It stops producing insulin. In fact, if you were to take someone who is in DKA and give them even a small amount of insulin, you could kill them pretty darned quickly. I’d go through the whole mechanism, but I think it is suffice to say that is simply an incorrect statement.

  42. nybgrus says:

    wowza… missed it so bad that I used it myself. Thanks to my 1st year counterpart Brian for pointing that one out to me.

  43. ryannagy says:

    I have not read any of your work in quite some time. I am glad to see that you are blogging under your own name. Thanks for a great post.

    You wrote that:

    I’ll grant critics that the types of tumors that can be cured with chemotherapy with a high degree of probability are a minority of tumors…

    I am curious, do treatments given reflect those statistics? That is, are chemotherapy treatments only used in those cases in which they have demonstrated efficacy? Stated differently, are there cancer types that are routinely treated with chemotherapy even when the probability of a cure is low?

    Thanks – Ryan

  44. Artour says:

    I believe that chemotherapy works by stimulating the immune system, but it does not address the cause of cancer that is low body oxygen levels caused by chronic overbreathing (or breathing more than the medical norms). Numerous studies proved that cancer patients are heavy and fast breathers, and the faster they breathe, the sooner they die:
    http://www.normalbreathing.com/diseases-cancer.php

    Furthermore, this controlled metastasized breast cancer trial showed 5 times reduction (a stunning result) in mortality in women who, apart from standard treatment with chemotherapy, practiced breathing exercises:
    http://www.normalbreathing.com/diseases-cancer-1-clinical-trial.php

  45. nybgrus says:

    oh go away Artour. You’re so batty it’s not even entertaining. Just annoying.

  46. majkinetor says:

    2nybgruson
    “The brain does not orchestrate immune responses.”

    You are now seriously delusional:

    http://pharmrev.aspetjournals.org/content/52/4/595.short
    http://goo.gl/Pkl7n

  47. majkinetor says:

    “Glucose is not pumped into cells”

    I didn’t mean to imply there is actually an active transport. I definitely used wrong words, but since muscle will upregulate GLUT4 no matter insulin when you do specific exercise, the diffusion will be bigger.

    “What receptor for vitamin C? Vitamin C is an anti-oxidant – in other words it absorbs the radical by products of biochemical reactions. It doesn’t compete with glucose or insulin receptors – unless you would care to link me to a journal article that describes what you are referring to.”

    LOL ?
    I am sure you can find it yourself. DHAA uses GLUT4, AA uses SVCT1/2 (pump). DHAA uptake by GLUT4 is thought to be main mechanism of C uptake by the cells and particularly brain which only expresses GLUT4 on BBB. There are so many papers about it, but if you still need reference I will be pleased to send hundreeds of them to you.

    So this is the main point for competition = Vitamin C.

    “So I agree that if a cancer patient was deficient that would most certainly make it easier for the cancer to spread and that should be corrected ASAP. But in a non-deficient person you are already at max”

    This is about chemotherapy, right ? Also, hospitalized patients are deficient in number of vitamins, most importantly C. If there was surgery, add +1. Add 1 for high carb diet which competes with C (hence paleo diet benefits). Also, in collagen synthesis C is actually used up and not used enigmatically.

    Anyway, I agree with you, after your elaboration that it would be very hard to beat cancer for sugar uptake, but like I said, its not only low carb diet, but diet with carefully crafted supplements like gram doses of C, specific proteins (Lysin, Prolin), perhaps some anti-angiogensis natural stuff like tomatoes etc… Synergy of all will probably make a big difference, maybe not cure cancer but life will be better and ladonger for sure.

  48. majkinetor says:

    spelling errors

    enigmatically = enzymatically
    landonger = longer

  49. majkinetor says:

    “[body] stops producing insulin”.

    Could you provide some reference for this ?
    That can’t be true.

    Here is just the first picture I found about insulin response for starvation.

    http://goo.gl/wCYLe

    Body never stops making basal levels of insulin. Its essential hormone. No insulin = death.

  50. nybgrus says:

    @Majkinetor:

    I am glad I have demonstrated to you why trying to starve cancer cells of sugar would most likely not work.

    You have also educated me a bit – I was not aware that VitC (well, the DHA – not DHAA – form of it) is transported into cells via GLUT transporters.

    However, VitC is not transported using GLUT4 transporters – it is transported via GLUT1 transporters which are constitutively expressed and have nothing to do with insulin. So the competition here would not matter in regards to our conversation.

    As for the brain orchestrating an immune response – you are correct. I spoke too loosely. Sympathetic changes can indeed change immune responses. However, my response was to your reference of ketogenic diets helping brain function thus helping immune function. That link is extremely tenuous at best. The only data relating to ketogenic diets and positive outcomes on the brain are helping with higher functions. Autonomic responses are decidely very low function and there is indeed little direct control there. So the assertion that the brain orchestrates the immune response is only nominally correct since it doesn’t really orchestrate it – it merely influences it. I was being nit-picky without being clear, so I apologize for that. But to orchestrate the immune response, especially in the sense you were using it, is simply incorrect. To have pretty significant influence via autonomic innervation of various end organs and thus hormone production – sure. But I still don’t see how a ketogenic diet would help regulate that in any way.

    but since muscle will upregulate GLUT4 no matter insulin when you do specific exercise, the diffusion will be bigger.

    What do you mean muscle will upregulate GLUT4 no matter insulin? If you are referring to trained athletes having a higher baseline level of constitutively expressed GLUT4 I would agree and say that is very likely (though I don’t know of any data offhand to suport that). If you mean that it would somehow generate insulin even in a starved state, then you are indeed incorrect. The mechanism by which insulin is released into the bloodstream is directly linked to blood glucose levels. Drop them low enough and you get no insulin release.

    Also, hospitalized patients are deficient in number of vitamins, most importantly C. If there was surgery, add +1. Add 1 for high carb diet which competes with C (hence paleo diet benefits). Also, in collagen synthesis C is actually used up and not used [enzymatically].

    As I said, those deficient should have supplements. I did not say that most hospitalized/chemo patients would not be deficient. I was saying that your assertion and insinuation that extra levels of VitC would be beneficial beyond replacement for deficiency. It won’t be.

    its not only low carb diet, but diet with carefully crafted supplements like gram doses of C, specific proteins (Lysin, Prolin), perhaps some anti-angiogensis natural stuff like tomatoes etc… Synergy of all will probably make a big difference, maybe not cure cancer but life will be better and [longer] for sure.

    Gram doses of vitC are not helpful, as I’ve established above. Beyond replacement of deficiency there is no added benefit. I’ll just assume you mistyped as lysine and proline are amino acids, not proteins, but once again that is an essentially pointless statement. Give someone a steak or, if they cannot stomach it, a multi-supplement. But additional amounts beyond need will not help. In fact, in many cancer/chemo patients there is decreased renal function so a protein restricted diet is necessary. But they still need all their amino acids, so focusing on a few is once again pointless. Also, why bother with “natural” anti-angiogenics? We have synthetic ones that actually work quite well. Even if tomatoes were anti-angiogenic, the effect size would have to be so small as to be pointless. Otherwise I would have died a long time ago – I eat 3-4 tomatos a day, on most days of the week. And I work out quite a bit. So when I put on 15lbs of muscle last year, eating 25 tomatoes a week, it would have been pretty bad if I hadn’t been able to make new capillaries for all that muscle growth. Of course that’s an anecdote, but there is also no good data out there showing a significant effect size.

    The point is that yes, of course, a good nutritious, healthy diet will most certainly help you live longer – period. Whether you have cancer or not. But the specific components you cite, really don’t have any particular value above and beyond basic good nutrition.

    “[body] stops producing insulin” Could you provide some reference for this ? That can’t be true.

    Interestingly enough, you provided the reference for yourself. Look at the graph again. It shows the insulin levels right at about 0mM – i.e. no production. There is almost certainly a basal level of production that will never stop, but it is very low and since glucagon is a direct antagonist to all the functions of insulin and is in much higher concentration than normal, there is effectively no insulin. And you will not die if you do not secrete any insulin. At least, not for a fair while. Type 1 diabetics do not secrete insulin and they can live for weeks before going into DKA and dying. And you can also starve for a few weeks before dying.

  51. majkinetor says:

    “However, VitC is not transported using GLUT4 transporters – it is transported via GLUT1 transporters”

    Not true.

    Dehydroascorbic acid uptake is via the facilitated-diffusion glucose transporters, GLUT 1, 3 and 4, but under physiological conditions these transporters are unlikely to play a major role in the uptake of vitamin C due to the high concentrations of glucose that will effectively block influx.

    Read More: http://informahealthcare.com/doi/abs/10.1080/09687680110033774

    Here are the brain pathways:
    http://www.biocarta.com/pathfiles/h_vitCBPathway.asp

    There is also GLUT10 in muscle, recently discovered.

    Its not strange given the similarity of AA and Glucose (C6H12O6 vs C6H8O6) and that C is made from glucose in 4 steps.

    Furthermore RBCs have somatin switch that shifts preference from glucose to C which is thought to be adaptation to losing GULO gene function. So RBCs PREFERE C over glucose, due to absent mytohondria (for its AO role) and to fastly deliver C where its needed in inflamation.

    Insulin does boost C absorption as protein meals are known to give highest plasma levels (since there is no glucose to inhibit it).

    “What do you mean muscle will upregulate GLUT4 no matter insulin?”

    With anaerobic exercise muscle will stay without glucose very fast as glycogen supply is very limited, so they upregulate GLUT4 transporters. Very well known and seems reasonable given how physiology of receptors work in entire body. Its also known that Glut4 is not insulin-dependent in adipose tissue during prolonged fasting. One of the ways cells react to absence of resource is to up-regulate receptors and for muscles this happens with anaerobic exercise since fats can be used for aerobic type.

    But you could educate yourself a bit more about it, you seriously lack info about pathways of essential substances body needs. I am sure you know how to use search engines (mhm… you may need to be better at it IMHO, perhaps spending to much time with anti-vaccine lunatics or hanging too much with Maybe Mike Adams ? )

    “I was saying that your assertion and insinuation that extra levels of VitC would be beneficial beyond replacement for deficiency. It won’t be.”

    It will be. Deficieny is characterized by scorbut which is final level of tissue destruction. Subclinical scruvy apperas far before that, and is seen in reduced wound healing, gingivitis, arherosclerosis etc. There is also evidence that IV doses of high C amounts, simulating liver optidosing provide better outcomes for cancer patients in both life expectency and life quolity. There are well known case studies about complete remisions too. Negative studies used very small oral amounts which are meaningless given that its absorption is 5-15%. Liposhperic vitamin C (LET) can provide IV benefits with oral usage.

    “Look at the graph again. It shows the insulin levels right at about 0mM – i.e. no production”

    Incorrect. That means that its not meassured, not that its 0. If it was 0, we would see triangles on X-ordinate after 20th day. Basic math. Let me google that for you.

    Anyway, we have plausible mechasnim and biology here. It should be tested, not ignored. Its not like current cancer protocols provided with EPIC results, far from that [no matter what you throw at cancer, it will evolve fast enough to survive so you need to boost the system]. I know, its hard disese, but still… its evident that current medicine about it is in dead end. Thats not without value however. Everybody saying otherwse don’t know anything about history of science. The value of current practices are tremendous in our cancer understanding, just not on indivual level most of the time. My personal beleif (which is just that, beleif), is that cancer is consequence of bad immune system due to nutritional deficiences which were always there to control ‘misbehaving’ cells. Cells were probably always like that, however, system is weakend enough in our urban style of life using toxic industrial foods that it allows deliquents to survive and destroy the system :) Its well known that cancer is disease of civilisation. Maybe fantasy, maybe not but I like it and is very cool and along all the lines I talked here:

    See Cancer tumors as Metazoa 1.0: tapping genes of ancient ancestors for fun and open mindness.

    Thx for the discussion. It was enlightening.

  52. majkinetor says:

    BTW, the following link contains some interesting references:

    http://ramblingsofacarnivore.blogspot.com/2011/09/carbs-and-cancer.html

  53. nybgrus says:

    @majkinetor:

    So, I try and be civil and have a scientific discussion and you go ahead with heaps of ad hominem and go ahead and give me absolutely nothing that supports what you say? Perhaps you have been spending too much time with the Mike Adams types – but on the other side from me.

    Dehydroascorbic acid uptake is via the facilitated-diffusion glucose transporters, GLUT 1, 3 and 4, but under physiological conditions these transporters are unlikely to play a major role in the uptake of vitamin C due to the high concentrations of glucose that will effectively block influx.

    Feel free to continue nit-picking details that have no bearing on the discussion. Both links you sent me delineate GLUT1 as the primary passive diffusion mechanism for VitC intake and specifically mention, as you quoted, that at physiological levels are essentially not used as such. Considering that “physiological levels” are the levels at which we are alive, I have yet to see any evidence that megadoses of vitC could outcompete glucose. Since your google-fu is so strong, why don’t you find an article that demonstrates that you can outcompete glucose in that manner in vivo? It seems that the primary method of cellular uptake has nothing to do with GLUT transporters at all, since the papers both say: ” Svct2 imports reduced ascorbate from the plasma into very active tissues like the brain.” Interesting that you would posit those papers as evidence of your assertion that it would.

    Its not strange given the similarity of AA and Glucose (C6H12O6 vs C6H8O6) and that C is made from glucose in 4 steps.

    Please, endeavor to actually make sense when you respond to my posts.

    AA (amino acids) are indeed used to make glucose. That is the basic biochemistry of gluconeogensis. Where on earth does vitC come in? Humans cannot synthesize vitamin C. So no, vitC is not made from glucose or anything else for that matter. Not that I can even understand the point of your statement there beyond that.

    Furthermore RBCs have somatin switch that shifts preference from glucose to C which is thought to be adaptation to losing GULO gene function. So RBCs PREFERE C over glucose, due to absent mytohondria (for its AO role) and to fastly deliver C where its needed in inflamation.

    You insult me with some ad hominem and then toss out this statement of absolute garbage? It is becoming clear you really don’t have a clue of what you are talking about.

    First off, RBCs don’t prefer glucose – they can only use glucose.

    Secondly, the only reference I can find for somatin is a drug form of somatastatin, which has nothing to do with RBCs nor any “switch” in them.

    Third, GULO is a gene that is lost and non-functional in primates – it codes for a protein that is the first step in vitC synthesis. It is an excellent reference for evolutionary biology, since it is a conserved non-functional gene that maps to lower mammals and other animals, demonstrating our common descent. But is has no bearing on human physiology whatsoever. So once again, no RBC’s have no way to utilize vitC for energy ergo cannot prefer it over glucose.

    With anaerobic exercise muscle will stay without glucose very fast as glycogen supply is very limited, so they upregulate GLUT4 transporters. Very well known and seems reasonable given how physiology of receptors work in entire body.

    Exactly what I’d said. What’s your point? It changes nothing in regards to what I have been saying.

    Its also known that Glut4 is not insulin-dependent in adipose tissue during prolonged fasting.

    Citation please? In starvation states GLUT4 is downregulated – and pointedly so. This has no bearing on the conversation.

    One of the ways cells react to absence of resource is to up-regulate receptors and for muscles this happens with anaerobic exercise since fats can be used for aerobic type.

    The only thing I can say is, “Duh!” So what’s the point? Once again this does not relate to the conversation.

    But you could educate yourself a bit more about it, you seriously lack info about pathways of essential substances body needs.

    Says the person who just asserted that somehow humans use the non-functional GULO gene which is, when operational, used to synthesize vitC as a gluconeogenic pathway that is not only used but preferred by RBCs. Yes, I am clearly that one that needs to educate myself more.

    Subclinical scruvy apperas far before that

    Even if it is subclinical it is still a deficiency, and does not in any way negate what I’d said about it being useless beyond replacing deficiency. And on top of that…

    and is seen in reduced wound healing, gingivitis, arherosclerosis etc.

    seeing such signs is by definition clinical deficiency!. If I can see it, clinically, then it cannot be sub-clinical, now can it?

    There is also evidence that IV doses of high C amounts, simulating liver optidosing provide better outcomes for cancer patients in both life expectency and life quolity. There are well known case studies about complete remisions too.

    Citation please.

    Liposhperic vitamin C (LET) can provide IV benefits with oral usage.

    Which would completely bypass cellular membrane transport mechanisms, thus being pointless in your assertion regarding out competing, yet again.

    Incorrect. That means that its not meassured, not that its 0. If it was 0, we would see triangles on X-ordinate after 20th day. Basic math.

    I wasn’t referring to after the 20th day. I was referring to the two triangles, one at 10 and another at 20 days. It would not be on the x-ordinate line (i.e. the “days” line), since the “zero” mark is defined as being above that. Look to the very first data points, where the red circles for ketone bodies are at zero. And then note that is on the same plane at the triangles for insulin. One of us knows how to read a graph. And it certainly isn’t you.

    You then link me to a google search that has nothing to do with that graph, specifically, which top hits an article from 1969. Which in the abstract states “Blood glucose and insulin concentrations fell acutely..” so yet again I fail to see what relevance that has to the discussion, except to further corroborate what I have been saying.

    Anyway, we have plausible mechasnim and biology here. It should be tested, not ignored.

    I have just demonstrated why it is not particularly plausible. But more than that, it isn’t being ignored. It just isn’t given the import and decisiveness you and Geoff would like to give it by serious scientists.

    Its not like current cancer protocols provided with EPIC results, far from that

    You’re right. Going from a 20% to more than 90% survival rate for childhood leukemia in only a couple of decades using chemotherapy isn’t epic at all. Lets just scrap the whole thing and let those 70% die because majiknetor thiks vitC and ketosis will do a better job.

    its evident that current medicine about it is in dead end

    You really are off your rocker.

    My personal beleif (which is just that, beleif), is that cancer is consequence of bad immune system due to nutritional deficiences which were always there to control ‘misbehaving’ cells. Cells were probably always like that, however, system is weakend enough in our urban style of life using toxic industrial foods that it allows deliquents to survive and destroy the system

    Your beliefs have no bearing on reality, so are utterly pointless to bring into a scientific discussion.

    Its well known that cancer is disease of civilisation

    Insofar as civilization has been allowing people to live long enough to get cancer, yes. I would agree with that statement. But not your toxins gambit attempt.

    Thx for the discussion. It was enlightening.

    Clearly not.

  54. nybgrus says:

    made a typo:

    Says the person who just asserted that somehow humans use the non-functional GULO gene which is, when operational, used to synthesize vitC as a gluconeogenic pathway that is not only used but preferred by RBCs. Yes, I am clearly that one that needs to educate myself more.

    should read:

    Says the person who just asserted that somehow humans use the non-functional GULO gene which is, when operational, used to synthesize vitC and not as a gluconeogenic pathway that is not only used but preferred by RBCs. Yes, I am clearly that one that needs to educate myself more.

  55. majkinetor says:

    “You insult me with some ad hominem”
    I didn’t insult you. I told you to learn to use google. You told me to learn about gluconegensis. I listened, you didn’t. Furthermore, you seem easily pissed of and can’t tolerate at all little bit joking here and there. Your post is pretty aggresive as I didn’t imagine you know nothing about Vitamin C transport. If I can’t tell you where are you wrong, and you can tell entire world in this blog where are they wrong, that makes you hypocrite.

    Now, to the topic.

    “AA (amino acids)”
    AA – Ascorbic acid.

    “Svct2 imports reduced ascorbate from the plasma into very active tissues like the brain”

    Ascorbate is transported into the brain and neurons via the sodium-dependent vitamin C transporter 2 (SVCT2), which causes accumulation of ascorbate within cells against a concentration gradient. Dehydroascorbic acid, the oxidized form of ascorbate, is transported via glucose transporters of the GLUT family.
    http://www.sciencedirect.com/science/article/pii/S0891584909000021

    “Says the person who just asserted that somehow humans use the non-functional GULO gene”
    LOL ? I said, “Furthermore RBCs have stomatin switch that shifts preference from glucose to C which is thought to be adaptation to losing GULO gene function.”

    “First off, RBCs don’t prefer glucose – they can only use glucose”
    They prefer it in specific times. GLUT transport both glucose and DHA but for different reasons.
    Erythrocyte Glut1 Triggers Dehydroascorbic Acid Uptake in Mammals Unable to Synthesize Vitamin C

    “We identified stomatin, an integral erythrocyte membrane protein, as regulating the switch from glucose to DHA transport. Notably though, we found that erythrocyte Glut1 and associated DHA uptake are unique traits of humans and the few other mammals that have lost the ability to synthesize AA from glucose. Accordingly, we show that mice, a species capable of synthesizing AA, express Glut4 but not Glut1 in mature erythrocytes. Thus, erythrocyte-specific coexpression of Glut1 with stomatin constitutes a compensatory mechanism in mammals that are unable to synthesize vitamin C.”

    “So once again, no RBC’s have no way to utilize vitC for energy ergo cannot prefer it over glucose.”

    When did I say RBS will utilise C for energy ? I said it will prefer it over glucose in times of stress to deliver it where it is needed and to protect themselves. I am not aware that erythrocytes express SVCT1/2 so its probable that GLUT receptors are the only source.

    “Citation please? In starvation states GLUT4 is downregulated – and pointedly so. This has no bearing on the conversation.”

    During fasting or ketogenic diet, insulin levels are lowered. Lower insulin levels upregulate GLUT transporters. Search for such effect in TDM1.

    “Since your google-fu is so strong, why don’t you find an article that demonstrates that you can outcompete glucose in that manner in vivo?”
    Do I need to do all the hard work for you ? My google-fu is strong remember :)
    Its basically in all biochemistry books. But here is one:

    “Ascorbic Acid and the Immune System”
    The inhibitory effect by glucose of the actions of ascorbic acid could well explain the lack of beneficial effect of ascorbic administration in many studies reported in the literature because few, if any, such studies controlled for dietary carbohydrates.

    “Inhibition of Ascorbic Acid Transport in Human Neutrophils by Glucose” (Levin et all.)
    We report here that both ascorbic acid transport activities in human neutrophils are reversibly inhibited by glucose, but by different mechanisms. The high affinity transport activity was inhibited noncompetitively, while the low affinity transport activity was inhibited competitively. In both cases there was marked decrease in the uptake and accumulation of Vitamin C.

    After those, check out this in-vivo study: “Role of sugars in human neutrophilic phagocytosis”
    but like I said, this is really not debatable. Its basic chemistry, just like with sugar and cancer – while I agree with you that you can’t starve it to death via reduction of dietary glucose you at least don’t have to bath it in energy.

    “Which would completely bypass cellular membrane transport mechanisms, thus being pointless in your assertion regarding out competing, yet again.”
    Not at all, because cells release C back to plasma once they swallow liposomes. See the brain pathway again.

    “So yet again I fail to see what relevance that has to the discussion, except to further corroborate what I have been saying.”
    You said body STOPS making insulin. I think its revelant for discussion and shows your understaing of physiology.

    “Lets just scrap the whole thing and let those 70% die because majiknetor thiks vitC and ketosis will do a better job.”
    Yeah, me, and several Nobel Prise winners. Who knows how many % will live with more productive research. This man lived. .

    “Your beliefs have no bearing on reality, so are utterly pointless to bring into a scientific discussion.”
    Oh cmon, can’t we have some fun too ? This is a blog FFS. If you want hard-core scientific discussion go hang on some other place.

  56. majkinetor says:

    Also, GLUT is main transporter to brain, not SVCT, like I thought: I rechecked it:

    Under physiological conditions, no expression of SVCT2 in brain capillary endothelial cells was detected in a study by Qiao et al. [35]

    Our study presented here demonstrates expression of SVCT2 and transport of ascorbic acid in brain capillary endothelial cells only after stroke, not under physiological conditions.

    From “Sodium-Dependent Vitamin C Transporter 2 (SVCT2) Expression and Activity in Brain Capillary Endothelial Cells after Transient Ischemia in Mice”

    In other words, DHA is probably the main transport to the brain. Once in brain, DHA is recycled to C. This is why when you do sugar surges, brain suffers and other cells which is the reason why ketogenic diet in combination with C is good strategy.

  57. nybgrus says:

    Oh cmon, can’t we have some fun too ? This is a blog FFS. If you want hard-core scientific discussion go hang on some other place.

    Science Based Medicine

    And if you can’t even type in such a way as to be comprehensible, I have no interest in furthering this conversation. It is completely off-topic anyways – as I said, no bearing on attempting to starve cancer cells of glucose nor chemotherapy.

    You fling typo-strewn screeds my way, anecdotes, can’t read graphs, and nit-pick details which have no bearing on the discussion. This is patently tedious and uninteresting.

    This is why when you do sugar surges, brain suffers and other cells which is the reason why ketogenic diet in combination with C is good strategy.

    And after all this you haven’t even come close to demonstrating that statement to be true or even particularly likely. All you’ve done is cherry pick vitC transport mechanisms and well… that’s about it.

  58. majkinetor says:

    “It is completely off-topic anyways – as I said, no bearing on attempting to starve cancer cells of glucose nor chemotherapy.”

    Your deduction is seriously flawed. It has everything to do with the topic.

    If the same transporter is used for both glucose and Vitamin C and if cancer overexpresses GLUT transporters as main mechanism for survival it is critical to discussion. It has nothing to do with chemotherapy, tho, in that, you are correct.

    Have a nice day.

  59. majkinetor says:

    “It has nothing to do with chemotherapy, tho, in that, you are correct.”

    Actually, on second thought, even this is incorrect:

    From Vitamin C Pharmacokinetics: Implications for Oral and Intravenous Use

    The vitamin C free radical species, ascorbyl radical, is detectable in animals only when they receive intravenous vitamin C equivalent to a 10-g dose in humans (19). We propose that detectable ascorbyl radical forms only when human plasma concentrations are greater than 1000 µmol/L and that either the radical itself or its unpaired electron induces oxidative damage that can be repaired by normal but not cancer cells. Understanding mechanisms of cytotoxicity may further the investigational use of vitamin C in patients with cancer, used alone or with other agents that potentiate such actions (20). Although minimal data are available, intravenous vitamin C is expected to have little toxicity compared with conventional chemotherapeutic agents (3). In this context and in light of our new pharmacokinetic data, a role for intravenous vitamin C in cancer treatment should be reevaluated.

  60. nybgrus says:

    keep grabbing at straws.

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