February 4, 2014

Preventing Chronic Disease

Is there a way to exploit the metabolic quirk of cancer?

Can we starve the disease?

Read Time 9 minutes

One night, as I alluded to in this post, Tim and I were having dinner and the topic of cancer came up.  Personally and professionally I have a great interest in cancer, so when Tim asked if I could write something about cancer that was: (i) interesting to a broad audience, (ii) not technically over the top, (iii) not my typical 5,000 word dissertation, (iv) yet nuanced enough for his readers, I agreed to give it a shot, in about 1,000 words.  (The content of this blog went up on Tim’s blog last week, but I’ve reproduced it here, less Tim’s commentary.)

Semantics and basics

Before jumping into this topic I want to be sure all readers — regardless of background — have a pretty good understanding of the ‘basics’ about cancer and metabolism.  In an effort to do this efficiently, I’ll list concepts here, such that folks can skip them if they want to, or refer back as necessary. This way, I don’t need to disrupt the ‘story’ with constant definitions. (Yes, I realize this is sort of cheating on my 1,000 word promise.)

Cancer – a collection of cells in our bodies that grow at roughly normal speeds, but that do not respond appropriately to cell signaling. In other words, while a collection of ‘normal’ cells will grow and stop growing in response to appropriate messages from hormones and signals, cancer cells have lost this property.  Contrary to popular misconception, cancers cells do not grow especially fast relative to non-cancer cells.  The problem is they don’t ‘know’ when to stop growing.

Metabolism – the process of converting the stored energy in food (chemical energy contained mostly within the bonds of carbon and hydrogen atoms) into usable energy for the body to carry out essential and non-essential work (e.g., ion transport, muscle contraction).

ATP – adenosine triphosphate, the ‘currency’ of energy used by the body.  As its name suggests, this molecule has three (tri) phosphates.  Energy is liberated for use when the body converts ATP to ADP (adenosine diphosphate), by cutting off one of the phosphate ions in exchange for energy.

Glucose – a very simple sugar which many carbohydrates ultimately get broken down into via digestion; glucose is a ring of 6-carbon molecules and has the potential to deliver a lot, or a little, ATP, depending on how it is metabolized.

Fatty acid – the breakdown product of fats (either those stored in the body or those ingested directly) which can be of various lengths (number of joined carbon atoms) and structures (doubled bonds between the carbon atoms or single bonds).

Aerobic metabolism – the process of extracting ATP from glucose or fatty acids when the demand for ATP is not too great, which permits the process to take place with sufficient oxygen in the cell.  This process is highly efficient and generates a lot of ATP (about 36 units, for example, from one molecule of glucose) and easy to manage waste products (oxygen and carbon dioxide).

The process of turning glucose and fatty acid into lots of ATP using oxygen is called ‘oxidative phosphorylation.’

Anaerobic metabolism – the process of extracting ATP from glucose (but not fatty acids) when the demand for ATP is so great that the body cannot deliver oxygen to cells quickly enough to accommodate the more efficient aerobic pathway. The good news is that we can do this (otherwise a brief sprint, or very difficult exertion would be impossible).  The bad news is this process generates much less ATP per carbon molecule (about 4 units of ATP per molecule of glucose), and it generates lactate, which is accompanied by hydrogen ions.  (Contrary to popular belief, it’s the latter that causes the burning in your muscles when you ask your body to do something very demanding, not the former).

Mitochondria – the part of the cell where aerobic metabolism takes place.  Think of a cell as a town and the mitochondria as the factory that converts the stored energy into usable energy.  If food is natural gas, and usable energy is electricity, the mitochondria are the power plants. But remember, mitochondria can only work when they have enough oxygen to process glucose or fatty acids. If they don’t, the folks outside of the factory have to make due with suboptimally broken down glucose and suboptimal byproducts.

DNA – deoxyribonucleic acid, to be exact, is the so-called “building block” of life. DNA is a collection of 4 subunits (called nucleotides) that, when strung together, create a code.  Think of nucleotides like letters of the alphabet. The letters can be rearranged to form words, and words can be strung together to make sentences.

Gene – if nucleotides are the letters of the alphabet, and DNA is the words and sentences, genes are the books – a collection of words strung together to tell a story.  Genes tell our body what to build and how to build it, among other things.  In recent years, scientists have come to identify all human genes, though we still have very little idea what most genes ‘code’ for.  It’s sort of like saying we’ve read all of War and Peace, but we don’t yet understand most of it.

FDG-PET – a type of ‘functional’ radiographic study, often called a ‘pet scan’ for short, used to detect cancer in patients with a suspected tumor burden (this test can’t effectively detect small amounts of cancer and only works for ‘established’ cancers). F18 is substituted for -OH on glucose molecules, making something called 2-fluoro-2-deoxy-D-glucose (FDG), an analog of glucose. This molecule is detectable by PET scanners (because of the F18) and shows which parts of the body are most preferentially using glucose.

Phosphoinositide 3-kinase – commonly called PI3K (pronounced “pee-eye-three-kay”), is an enzyme (technically, a family of enzymes) involved in cell growth and proliferation.  Not surprisingly, these enzymes play an important role in cancer growth and survival, and cancer cells often have mutations in the gene encoding PI3K, which render PI3K even more active. PI3Ks are very important in insulin signaling, which may in part explain their role in cancer growth, as you’ll see below.

The story (in about 1,000 words, as promised)

In 1924 a scientist named Otto Warburg happened upon a counterintuitive finding. Cancer cells, even in the presence of sufficient oxygen, underwent a type of metabolism cells reserved for rapid energy demand – anaerobic metabolism.  In fact, even when cancer cells were given additional oxygen, they still almost uniformly defaulted into using only glucose to make ATP via the anaerobic pathway. This is counterintuitive because this way of making ATP is typically a last resort for cells, not a default, due to the very poor yield of ATP.

This observation begs a logical question? Do cancer cells do this because it’s all they can do? Or do they deliberately ‘choose’ to do this?  I’m not sure the answer is entirely clear or even required to answer the macro question I’ve posed in this post. However, being curious people we like answers, right?

The first place to look is at the mitochondria of the cancer cells.  Though not uniformly the case, most cancers do indeed appear to have defects in their mitochondria that prevent them from carrying out oxidative phosphorylation.

Explanation 1

Cancer cells, like any cells undergoing constant proliferation (recall: cancer cells don’t stop proliferating when told to do so), may be optimizing for something other than energy generation.  They may be optimizing for abundant access to cellular building blocks necessary to support near-endless growth.  In this scenario, a cancer would prefer to rapidly shuttle glucose through itself. In the process, it generates the energy it needs, but more importantly, it gains access to lots of carbon, hydrogen, and oxygen atoms (from the breakdown of glucose).  The atoms serve as the necessary input to the rate-limiting step of their survival — growth.  The selection of cancer cells is based on this ability to preferentially grow by accessing as much cellular substrate as possible.

Explanation 2

Cells become cancerous because they undergo some form of genetic insult.  This insult – damage to their DNA – has been shown to result in the turning off of some genes (those that suppress tumor growth) and/or the activation of other genes (those that promote cell growth unresponsive to normal cell-signaling).  Among other things, this damage to their DNA also damages their mitochondria, rendering cancer cells unable to carry out oxidative phosphorylation.  So, to survive they must undergo anaerobic metabolism to make ATP.

Whichever of these is more accurate, the end result appears the same – cancer cells almost exclusively utilize glucose to make ATP without the use of their mitochondria.  A detailed discussion of which explanation is better is beyond the scope of my word allotment, and it’s not really the point I want to make.  The point is, cancer cells have a metabolic quirk.  Regardless of how much oxygen and fatty acid they have access to, they preferentially use glucose to make ATP, and they do it without their mitochondria and oxygen.

So, can this be exploited to treat or even prevent cancer?

One way this quirk has been exploited for many years is in medical imaging.  FDG-PET scans are a useful tool for non-invasively detecting cancer in people.  By exploiting the obligate glucose consumption of cancer cells, the FDG-PET scan is a powerful way to locate cancer (see figure).

You can probably tell where I’m leading you.  What happens if we reduce the amount of glucose in the body? Could such an intervention ‘starve’ cancer cells?  An insight into this came relatively recently from an unlikely place – the study of patients with type 2 diabetes.

In the past few years, three retrospective studies of patients taking a drug called metformin have shown that diabetic patients who take metformin, even when adjusted for other factors such as body weight and other medications, appear to get less cancer. And when they do get cancer, they appear to survive longer. Why? The answer may lie in what metformin does.  Metformin does many things, to be clear, but chief among them is activating an enzyme called AMP kinase, which is important in suppressing the production of glucose in the liver (the liver manufactures glucose from protein and glycerol and releases it to the rest of the body).  This drug is used in patients with diabetes to reduce glucose levels and thereby reduce insulin requirement.

So, the patients taking metformin may have better cancer outcomes because their glucose levels were lower, or because such patients needed less insulin. Insulin and insulin-like growth factor (IGF-1) also appear to play an integral role in cancer growth as recently demonstrated by the observation that people with defective IGF-1 receptors appear immune to cancer. Or, it may be that activation of AMP kinase in cancer cells harms them in some other way.  We don’t actually know why, but we do know that where there is smoke there is often fire. And the ‘smoke’ in this case is that a relatively innocuous drug that alters glucose levels in the body appears to interfere with cancer.

This may also explain why most animal models show that caloric restriction improves cancer outcomes.  Though historically, this observation has been interpreted through the lens of less ‘food’ for cancer. A more likely explanation is that caloric restriction is often synonymous with glucose reduction, and it may be the glucose restriction per se that is keeping the cancer at bay.

Fortunately this paradigm shift in oncology – exploiting the metabolic abnormality of cancer cells – is gaining traction, and doing so with many leaders in the field.

Over a dozen clinical trials are underway right now investigating this strategy in the cancers that appear most sensitive to this metabolic effect – breast, endometrial, cervical, prostate, pancreatic, colon, and others.  Some of these trials are simply trying to reproduce the metformin effect in a prospective, blinded fashion.  Other trials are looking at sophisticated ways to target cancer by exploiting this metabolic abnormality, such as targeting PI3K directly.

To date, no studies in humans are evaluating the therapeutic efficacy of glucose and/or insulin reduction via diet, though I suspect that will change in the coming year or two, pending outcomes of the metformin trials.

Last point (beyond my 1,000 word allotment)

Check out this blast from the past! Gary Taubes, who is currently working hard on his next book, came across the article the other day from 1887.


I’ve been absurdly blessed to study this topic at the feet of legends, and to be crystal clear, not one thought represented here is original work emanating from my brain.  I’m simply trying to reconstruct the story and make it more accessible to a broader audience.  Though I trained in oncology, my research at NIH/NCI focused on the role of the immune system in combating cancer. My education in the metabolism of cancer has been formed by the writings of those below, and from frequent discussions with a subset of them who have been more than generous with their time, especially Lewis Cantley (who led the team that discovered PI3K) and Dominic D’Agostino.

  • Otto Warburg
  • Lewis Cantley
  • Dominic D’Agostino
  • Craig Thompson
  • Thomas Seyfried
  • Eugene Fine
  • Richard Feinman (not to be confused with Richard Feynman)
  • Rainer Klement
  • Reuben Shaw
  • Matthew Vander Heiden
  • Valter Longo

Further reading

I do plan to continue exploring this topic, but for those of you who want to know more right now and/or for those of you with an appetite for depth, I recommend the following articles, some technical, some not, but all worth the time to read. This is the short list:

  1. Relatively non-technical review article on the Warburg Effect written by Vander Heiden, Thompson, and Cantley
  2. Science piece written about cancer (for non-technical audience) by Gary Taubes
  3. Non-technical talk by Craig Thompson
  4. Detailed review article by Tom Seyfried
  5. Review article on the role of carb restriction in the treatment and prevention of cancer
  6. Talk given by author of above paper for those who prefer video
  7. Moderately technical review article by Shaw and Cantley
  8. Clinical paper on the role of metformin in breast cancer by Ana Gonzalez-Angulo
  9. Mouse study by Dom D’Agostino’s group examining role of ketogenic diet and hyperbaric oxygen on a very aggressive tumor model
  10. Mechanistic study by Feinman and Fine assessing means by which acetoacetate (a ketone body) suppresses tumor growth in human cancer cell lines

Figure of FDG-PET imaging showing no evidence of recurrent tumor after standard care treatment including a water-only fast and a ketogenic diet by Zuccoli et al., 2009 is licensed under CC by 2.0

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  1. Regarding your statement: “To date, no studies in humans are evaluating the therapeutic efficacy of glucose and/or insulin reduction via diet….” There have been a couple small (and at least one ongoing) studies of ketogenic diet on glioblastoma. Simply search on “ketogenic glioblastoma.”

    • I don’t know what an “efficacy study” is, but this one from the Barrow Neurological Institute looks like one to me. Here is the purpose of the study:

      “This study aims to see if reducing blood sugar and increasing ketones (a metabolic product that comes from using fats for energy) can increase survival and enhance the the effects of standard radiation and chemotherapy treatments used to treat glioblastoma multiforme (GBM). These changes occur from use of a ketogenic diet. This research has 2 goals:

      1. Show that patients can tolerate the diet and maintain low blood glucose and high blood ketone levels.
      2. Show if this diet enhances the effectiveness of standard treatment by prolonging survival of patients with a GBM.”


  2. Nice writeup!

    “To date, no studies in humans are evaluating the therapeutic efficacy of glucose and/or insulin reduction via diet, though I suspect that will change in the coming year or two, pending outcomes of the metformin trials.”

    While a one-arm Phase 1 trial, “Effects of a ketogenic diet on the quality of life in 16 patients with advanced cancer: A pilot trial” did monitor and report glucose, % ketosis, triglycerides, cholesterol, and disease progression. See Table 5 and Figure 5.

  3. Great post Peter!

    I find this topic very interesting. There’s no doubt that cancer seems to travel with the so-called “diseases of civilization” such as heart disease, diabetes, and obesity. It wouldn’t be at all surprising to me if the underlying cause of cancer is the same as the rest of these diseases. Wouldn’t it be something if Ketogenic diets turned out to be the primary cancer intervention? Thanks for posting. BTW, I have been eagerly awaiting any news regarding Gary Taubes next book since I enjoyed both “Why We Get Fat” and “Good Calories Bad Calories” so much. Do you have any idea what the topic might be?

    • Ha! I should dig up the earlier versions of this before I chopped it down to 1,000. I would actually like to do a talk on this subject to cover it in greater detail. You can definitely get your itch scratched by reading the 10 “further readings” at the bottom. At least to hold you over.

  4. This was a great read! I read a lot of similar stuff in Taubes work. I posted it to my local low carb group ( https://www.facebook.com/groups/699448060101662/ ), feel free to leave a comment :). I’m going to be sure to check out all the articles. I really appreciate your scientific detail on these subjects. I’m very meticulous and so are you and I appreciate it. I too would like the 4000 word blog. Also, maybe you could share some more excerpts from Taubes new book eh?

  5. Explanation 3: Oxidative (or other) damage to mitochondria (membrane and/or mtDNA) activate anaerobic pathways and destabilize the genome (see Seyfried). Possibly an ancient adaptive response left over from our single-celled ancestors?

    • Fair point. This is really a 2B, though. Either, they do this because they need the throughput (1) or the do this because they have no choice due to mitochondrial damage (2); “2A — genetic cause” and “2B — oxidative cause”

  6. Hi Peter, Great work as usual. You really are doing a public service here. As I was reading your post I thought you’d like this recent article (if you haven’t seen it already) on the decline in lactate in the tumor microenvironment in patients on a ketogenic diet. It connects cancer metabolism to cancer immunology. Sounds like your kind of thing. And others here would be interested as well. It’s just one more mechanism by which the KD might have an anticancer effect. http://www.jimmunol.org/content/191/3/1486.full.pdf

    • Oops. Meant to include the money quote: “Depletion of glucose levels using a ketogenic diet to lower lactate production by glycolytic tumors resulted in smaller tumors, decreased MDSC frequency, and improved antitumor immune response. These studies provide evidence for an immunosuppressive role of tumor-derived lactate in inhibiting innate immune response against developing tumors via regulation of MDSC and NK cell activity.”

  7. Peter, even though this is not in direct relation to what is mentioned above, do you think that anaerobic metabolism can only be done via the breakdown of glucose outside mitochondria?
    If so, does this means that when you’re ketoadapted you can’t actually improve strength training under ketosis?

    I dont know what to attribute this to, but I did increase my gym lifting performances once I got ketoadapted (after a few weeks of ketosis). It would be interesting to know your opinion because you know there’s a great debate in the exercise community.

    • No, remember anaerobic metabolism is a place on a spectrum, between aerobic and CK. The question is “How fast is the body asking for ATP?” In strength training you will typically hit 2 of these 3 systems, but you’re still using BHB for fuel, it’s just insufficient to meet all of the demands. I have now witnessed enough athletic performance in ketosis to say without hesitation that ketosis does not imply a reduction in athletic performance and activities that demand strength and speed. Perhaps for some people under some conditions, but certainly not universally, and not if a person is adapted. To fully get into my thoughts on this, however, requires a full post, which I can’t do at the moment.

    • If you ever get time, or maybe a quick “yes” or “no” answer, I would like to hear your thoughts about strength gains on a ketogenic diet. Now that everything is “solid” in ketosis I find myself at a plateau at the gym in regards to strength increases (squats, deadlifts, etc) and was starting to wonder if an insulin spike might be necessary to trigger additional muscle growth (e.g. “carb nite” or cyclical ketogenic diet).

      Have you seen “arbitrary” strength gains on athletes on a ketogenic diet ? My only other theory is that too much running/aerobic activity/catabolic time is interfering with the anabolic side of the coin. If I can figure out a way to gain strength while staying ketogenic (without resorting to carbs) I would be one happy camper.

      • Addressed in other comments, but I don’t recall which post(s). Short answer: probably more related to training and muscle fiber recruitment than ketosis per se.

  8. Hi Peter,

    another great article, thanks for writing it.

    I was just curious how you thought Dr. Nicholas Gonzalez work fit in with your article, as I seem to recall that his work involves HCLF for some cancers and LCHF for others IIRC?


    • > I guess we’ll see.

      And relatively soon, I should think.

      Meanwhile, some key data might already be “out there”, waiting to be harvested.

      If NK has a role in cancer therapy, it could also be expected to be prophylactic.

      A subset of the population have already chosen to be low carb, if not keto, and have been so for a decade or more. If there is some cancer prevention value therein, it might be possible to quantify it. A statistical population may exist, but is anyone studying it?

      The problems, of course, include:

      Healthy people often don’t go to doctors at all, and when they do, MDs usually have zero curiosity about why they aren’t sick, never suspect diet, wouldn’t know what questions to ask if they did, and probably have no means of reporting data in any useful form.

      Epidemiologists may not be studying healthy people either, also probably don’t inquire about diet, again wouldn’t know what questions to ask if they did, and have no template for reporting.

      Oncologists are in no position to report anything, because they never see people who don’t get cancer.

  9. Thanks for another great article Peter!
    Do you know anything about DCA (Dichloroacetic acid) and Cancer? the early studies (U of Alberta, 2007, 2010) appear promising and further anecdotal testimonials are also interesting. The claim is that DCA somehow activates the cancer cell’s mitochondria to utilize Oxygen again rather then ferment Sugar, thus creating the “natural” Apoptosis of a defected cell.
    It sounds “to good to be true” sort of thing, so I wander what’s your take on it.

    • I’m not aware of any human clinical data on DCA, but some of the in vitro stuff looked promising, as you note. I guess, much like this, we’ll need to wait and see how it fully pans out in humans. The good news is one can’t act on DCA now. One can, if they choose, act on this metabolic insight.

    • He also remarked that these studies are “just biochemistry,” as though biochemistry, biology, and physiology were non-overlapping fields. This is someone with an excellent reputation, highly respected in his field, so it just goes to show the tendency for each specialty to be “driving down the highway looking at the road through a drinking straw.”*

      *From one of Malcolm Gladwell’s books.

  10. Hi Peter,

    Way back in the early 70’s nine obese men in an VA hospital in SoCal were fasted for two months (yikes!) and then administered an insulin infusion to the point that blood glucose levels were as low as 0.5 mmoles/liter (9 mg/100 ml) yet they failed to exhibit hypoglycemic reactions. It would be interesting to see if that low of a blood glucose would starve cancer cells. This would have to be done in an acute care setting, of course, ideally an ICU.

    Their levels of ketones were remarkable in and of themselves in terms of whether or not we can run almost completely on ketones. I guess this shows that we can, although muscle wasting would probably produce some glucose through gluconeogenesis. Still a FBS of 9 doesn’t lie.




    • Hi Paul,

      I was going to post about the study you reference but luckily you beat me to it!

      Even during complete therapuetic fast, blood sugar is obviously maintained. I belong to Dr. Richard Feinman’s (“the other”) blog in which he points out that cancer cells are great at “pirating” sugar even in low sugar environments. (Do they have an over expression of GLUT transporters on their cell walls?)

      So a complete fast may not be enough to starve the cancer of it’s life giving glucose. But a keto-adapted person can be infused with insulin and achieve EXTREMELY low levels of blood sugar. Maybe that would do the trick.

      It would be great to see this therapy attempted – would a Dr. be risking their license if they tried it?


  11. Peter, thank you very much! I really wanted some expert insight because it didnt seem to make sense. You know all the mumbo jumbo in the industry that you need carbs to perform well in strength training. I will dig more into this because it’s a really interesting topic. I know you love it as well!

    Thanks again Doc!

  12. And coincidentally (timed for World Cancer Day, today), WHO has a report this week on the “alarming” increase in cancer world-wide.

    Being wedded to the somatic theory of cancer, they are in a panic about what to do about it. “Global battle against cancer won’t be won with treatment alone” indeed, since most Standard of Care treatment provides appallingly little return on the huge expenses involved.

    WHO proposes “taxes, advertising restrictions, and other regulations” to restrict consumption of cancer correlates, including tobacco, alcohol and, curiously, sugar-sweetened beverages.

    They don’t seem to be interested in why sugar correlates, of course. Might it be something about the pervasive HFCS used, or perhaps there’s a problem with too much glucose and/or fructose generally, or both. Ordinary citizens are going to figure this out decades before WHO does.

    “Adequate legislation can encourage healthier behaviour, …”
    Rubbish. In the case of tobacco and alcohol, it will just reward organized crime, who will bootleg around the taxes. People who smoke or consume excess booze know the score. If they aren’t deterred by the well-known health and longevity consequences, taxes, and even outright prohibitions aren’t much further disincentive.

    And as with that nanny state initiative in NYC, restricting sugar pop will have near zero effect on the real problem: the full time high glycemic metabolism that most of the world is on. I suspect there’s a direct correlation between the rise in cancer and a shift in macronutrient balance in world diets (plus contributions from the makeup of the carbs and fats consumed).

  13. As an oncology dietitian, I work with patients everyday who have cancer cachexia. Is is well-established that some cancers as they become more advanced, specifically oral, esophageal, gastric, pancreatic, and some lung cancers, result in derangements in metabolism that result in cachexia. Patients with cachexia are also often anorexic at this stage of the disease and eat very little. Despite this, the cancer progresses.

    What’s not making sense to me about this idea of attempting to “starve” cancer through caloric restriction is that cancer cells will demand energy substrate whether it’s endogenous or exogenous. In other words, if cancer patients restrict carbohydrates, the cancer cells will obtain glucose by breaking down body proteins resulting in more rapid decline and malnutrition. In fact, in cancer cachexia, endogenous protein and fat breakdown at higher than normal rates. It may be slowed to a degree by withholding exogenous energy substrate, but even under starvation conditions cancer cells continue to grow by demanding energy substrate from healthy cells.

    Many of my (non-cachectic) patients ask me about the ability to “starve” their cancers by following a low-carb diet. But I use the analogy of pregnancy. We know that a fetus will get its energy and nutrients it requires at the expense of the mother’s body, if necessary, to continue to grow and develop. The fetus will fail to survive only if the mother’s nutrient stores become so depleted that her life, too, is at risk.

    While I think this all very, very fascinating, it seems more plausible to exploit this idea through the development of pharmacological treatments rather than through specific dietary restrictions. I always argue that we cannot tell our food which cells to feed and which to starve. If you attempt to starve the cancer cells through dietary restriction, you will also starve the healthy cells that give the body a fighting chance to sustain itself – not to mention the cancer patient’s quality of life during the time they have left to live it. So until we can find a way to orchestrate this, I question the ability of very low carb diets as a means to slow cancer growth to the point of any meaningful clinical outcome.

    • You make a lot of great points, and ultimately, I think the best treatment for cancer will first and foremost be avoidance. I believe diet plays a role here, at least as far as what we can control. Second, that is, once cancer is present, “success” will probably be a combination of things — diet, drugs, non-pharma interventions (e.g., hyperbaric oxygen), but all will need to be tailored to metabolic (vs. genetic) markers specific to the tumor itself, not just the histology.

    • Is it possible that the cachexia is a result of the fact that cancer is a constant drain on the body’s stores of glucose? By inefficiently utilizing glucose for its energy needs, the cancer puts such a drain on blood glucose that the patient feels as though they are on a low carb diet (or that they are constantly doing high intensity intervals…carb burning exercise). If a tumor used 20 kcal/hr of glucose (the equivalent of only 2 kcal/hr aerobic), that would be nearly 500 kcal per day or over 0.25 pounds of glucose per day. This is on top of normal basal metabolic needs.

      Ironically, following this logic, the patient with cachexia would be best served by going on a very high carb diet. Clearly this will not address the underlying problem, but it may well improve appetite and allow for stabilization of weight loss. Have such experiments been tried?

    • One thing is missing in the big picture. Yes, tumor cells will try everything to suck the glucose, also those out of gluconeogenesis. However, the cells, even the tumor cells need “door opener” to get the glucose inside the cells and that is insulin. When somebody does ketogenic diet, the insulin is usually at very low level so the energy supply to the tumor cells will be limited and on the long run the chance should be there that the tumor cells get starved.

    • (This is directed at XO2062)

      You are mistaken; unfortunately – well, as far as cancer treatment is concerned, at least – cells are, in fact, not dependent on insulin as far as their glucose uptake is concerned – that is nothing more than a widely propagated myth ; see for example http://weightology.net/weightologyweekly/?page_id=571 – , so there goes that line of reasoning.

    • I do not pretend to fully understand the arguments of biochemists, astrologers or the other learned people who each explain the causes and cures for cancer in such highly technical terms.

      However this I know, in September 2014 I was diagnosed with metastatic melanoma. The surgeon advised me the best that could be done for me was reduces the suffering by surgically removing tumors as they surfaced.

      I was led to adopt a hi fat lo carb diet at the same time as I developed this deadly cancer. Some four months later I had a PET scan and guess what? There is no further sign of the dreaded disease. To boot, my blood pressure has dropped back to 120/69 and the fat round my waist has gone having lost some 8kgs. My energy levels are those I enjoyed five maybe more years ago.

      My fear is that those who stand on the edge of the pool, telling us how to swim, often fail to appreciate which of the objects of their research are the cause and which are the effect. Would I be in error if I suggested this could represent a fundamental flaw in the subsequent conclusions

      If you are a fellow cancer victim please don’t sit on the edge of the pool discussing the pros and cons of swimming. Jump into the water by adopting a strict way of life like “Banting” and enjoy the results. Please gentlemen and ladies we need to focus on correcting all the contributing causes and then trust that the effects will disappear.

      PS Regarding the issue of caloric restriction and it’s effect on cachexia, I highlight the fact that I get my calories from fat, and suffer no malnutrition or cachexia as a result. I am well nourished.

  14. Thanks for another great piece Peter.

    Would you please elaborate on this : “PI3Ks are very important in insulin signaling”

    In diabetics how effective/ineffective is it to inject insulin as compared to metphormin to control glucose levels?

  15. I’ve been waiting for this post and it was really informative and on a good technical level for me to understand. Thanks!!
    I’ve been eating a lchf diet since I started reading up on this about a year and a half ago when my dad was fighting cancer in the esophagus. What’s your take on other reasons for cancer to develop, like radiation, chemicals etc? My mom was a flight attendant for many years and she died of breast cancer as did many of her colleges. Coincinence or perhaps caused by the radiation on the aircrafts? My parents were both lean, healthy and active but sure they ate carbs like all “normal” people do.
    What about children’s cancer? Can that too have to do with diet or what causes that? How about leukemia where you don’t have a tumour?
    I want cancer to be a metabolic disease 100% cus then I feel I can affect my own destiny so to speak, but I just don’t get these questions into the equation even though I am very exited about this research and hope it will lead to great stuff in cancer care. Sorry about my english (I’m Swedish).

    • Ok, let me try something shorter.
      A college of mine has leukemia (not sure which kind) and he has a major sweet tooth, eating mars-bars and cupcakes for breakfast, drinking at least two cokes a day.
      Do you believe the same principles for cancer cell metabolism goes for leukemia cancer cells? If so, do you know where I can read about this with a specific focus on leukemia so I can try and convince him he should think about his sugar intake? Thank you!

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