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Sugar May Feed Cancer, But Does Protein Build It?

In February, 2009, over seven years ago, I posted: Sugar Feeds Cancer. Reading that post now, I have to wonder if I failed to make a critical distinction between building and feeding.

So the classic alternative view, simply stated—let’s call it Warburgian‘—is that cancer cells lack the ability to fuel from ketones (fat metabolism), require glucose (sugar), and even typically respirate differently (fermentation)…so starve them by means of various approaches to very low-carbohydrate dietary intake—restricting your metabolism into making essential glucose rather than feeding it glucose, thereby ensuring it gets just enough, not too much. Makes obvious sense, even by means of my gross simplification.

But is this just aspirin for a headache, discounting other variables and assuming it’s even effective?  I seem to recall that at least in some mouse models, it has been shown to be effective.

Putting on my critical distinction hat, what builds growing humans and what fuels them? Well, if you take human mammalian milk, it’s a pretty “balanced diet” of protein, carbohydrate (lactose…sugar), and fat. Low-fat-diet advocates will acknowledge that the relatively important amount of human-chick-aminal fat—that outweighs the other macros—is important for fat-head development. High-fat-diet advocates will say it falsifies the notion that animal fat is bad for you, per se. What if they’re both right, there is wide overlap (you can be healthy with an emphasis on either); but also, both discount the role of protein?

You can’t build a human on exclusively fat or carbohydrate, or any combination of the two, excluding protein. This is no new revelation but since nobody talks about protein except muscle heads, perhaps it’s an essential that requires some emphatic call for detente in the war over fat vs. carbohydrate. What if protein turned out to be the most important variable in dietary concerns and cancer is a telltale, or canary, or analog, or whatever?

To put it most simply: human bodies (made up of cells) are built by protein. All three macronutrients—protein, carbohydrate, and fat—can fuel them but in hierarchical order, carbohydrate is king (and alcohol is king of kings). Some would say fat comes next, but I have come to wonder that what if, in the absence of healthy carbohydrate as the body’s easiest food source, if it doesn’t cause undue chronic stress (rather than healthful and autophagic acute stress, such as in fasting). This is becoming my chief quibble with forever low-carbohydrate diets as a lifestyle. Ray Peat folks have been saying this for years. When you stop and listen, it’s not that sugar is a great nutritious food, but that it lowers chronic stress. Calculated tradeoff, and, not letting the mediocre be the enemy of the good: which is a less stressful, happy, healthy life.

We have new research and it’s very interesting the timing in which it dropped, since just over the last few days, I have seen references to this NYT article dozens of times: AN OLD IDEA, REVIVED: STARVE CANCER TO DEATH. I must admit that I didn’t read it before now. See, I never stake a position and hold it. I stake a position and then see how old and rusty it gets over time, lying in wait. From my first post on this, I always understood there was something to it; but eventually, understood that if it was everything to it, we’d know it by now (No, I am not a cancer conspiracy fan. Neither am I an idiot.).

Indeed: Scientists surprised to find that amino acids, not sugar, supply most building blocks for tumor cells. It’s an article covering a study published about a month ago in Cell: Amino Acids Rather than Glucose Account for the Majority of Cell Mass in Proliferating Mammalian Cells (Aaron M. Hosios, Vivian C. Hecht, Laura V. Danai, Marc O. Johnson, Jeffrey C. Rathmell, Matthew L. Steinhauser, Scott R. Manalis, and Matthew G. Vander Heiden). Thanks to Dr. Mike Eades for sending me the full text, plus a couple of supplementary articles.

Cancer cells are notorious for their ability to divide uncontrollably and generate hordes of new tumor cells. Most of the fuel consumed by these rapidly proliferating cells is glucose, a type of sugar.

Scientists had believed that most of the cell mass that makes up new cells, including cancer cells, comes from that glucose. However, MIT biologists have now found, to their surprise, that the largest source for new cell material is amino acids, which cells consume in much smaller quantities.

The findings offer a new way to look at cancer cell metabolism, a field of research that scientists hope will yield new drugs that cut off cancer cells’ ability to grow and divide.

“If you want to successfully target cancer metabolism, you need to understand something about how different pathways are being used to actually make mass,” says Matthew Vander Heiden, the Eisen and Chang Career Development Associate Professor of Biology and a member of MIT’s Koch Institute for Integrative Cancer Research.

Get it? What makes them grow and proliferate is not necessarily what constitutes their preferred fuel for routine operation—any more than that’s true for a human infant, or probably any other baby mammal; and since we’re talking baby tumorous growths, that’s probably a reasonable way of thinking about it generally, in order to derive a general understanding—and I’m the best there is for trying to do that rather than impress you with my metabolic pathway knowledge (I have never once written ATP—adenosine triphosphate—on this blog in over 4,500 posts…nor do I wax on about beta oxidation).

…To determine where cells, including those in tumors, were getting the building blocks they needed, the researchers grew several different types of cancer cells and normal cells in culture dishes. They fed the cells different nutrients labeled with variant forms of carbon and nitrogen, allowing them to track where the original molecules ended up. They also weighed the cells before and after they divided, enabling them to calculate the percentage of cell mass contributed by each of the available nutrients.

Although cells consume glucose and the amino acid glutamine at very high rates, the researchers found that those two molecules contribute little to the mass of new cells—glucose accounts for 10 to 15 percent of the carbon found in the cells, while glutamine contributes about 10 percent of the carbon. Instead, the largest contributors to cell mass were amino acids, which make up proteins. As a group, amino acids (excluding glutamine) contribute the majority of the carbon atoms found in new cells and 20 to 40 percent of the total mass.

Although initially surprising, the findings make sense, Vander Heiden says, because cells are made mostly of protein.

“There’s some economy in utilizing the simpler, more direct route to build what you’re made out of,” he says. “If you want to build a house out of bricks, it’s easier if you have a pile of bricks around and use those bricks than to start with mud and make new bricks.”

Folks, I don’t know why it is, but this kinda shit is just my favorite to blog about…perhaps because I think it’s a great opportunity to generalize in a way that’s truly educational. At any rate, I don’t know how one could possibly come away without feeling they learned something, that something made even more sense, or an ah-ha moment.

So where does that leave me with respect to LC diets? Well, offhand, still therapeutic but if one is honest, perhaps this gives clues into why they’re notably therapeutic and in particular, like pharmaceutical level when it comes to no-shit pure ketogenic for epilepsy and interestingly, brain cancer (though the latter is less established).

So I’m not going to reign down with my quibbles over the years regarding folks overextending ketogenic pharmacology—as specifically proven or very promising therapies—to general lifestyle ketogenic prophylactology. I’ve gotten to where, when I hear Americans generally implicate carbohydrate without distinction, as Gary Taubes did just now, once again, I have one word, to serve as both falsification and dismissal: Asians.

You see, if you take a drug that cures your cancer or other ailment, it does not follow that not taking the drug as a lifestyle is what caused your cancer or ailment. But it seems to me that some elements of that thinking are prevalent in many dietary circles and low-carb is no exception.

That said, we now have greater insight into effective drug therapy vis-a-vis a ketogenic diet. We now know from various avenues including the epilepsy interventions that protein level is important. It may be for a different reason. For brain stuff, your goal is to produce lots of ketones. But now we seemingly have another, different reason to consider ketogenic for cancer, without getting wrapped up in what caused it (Asians!). Once you have cancer, you can go at it two ways. Starve it by restricting glucose down to minimum and also, keep building blocks (protein) to a minimum. This describes a fully, objective ketogenic diet.

That said, it appears from the research that low protein might outweigh low glucose by factorial magnitude for cancer (4-5 times, I’m getting the gist?) and this would be a distinction from it’s role for brain stuff like epilepsy, where ketone production is job one, and I think glucose limitation exceeds protein restriction in that application.

Well, so there you have my take.

Richard Nikoley

I'm Richard Nikoley. Free The Animal began in 2003 and as of 2021, contains 5,000 posts. I blog what I wish...from health, diet, and food to travel and lifestyle; to politics, social antagonism, expat-living location and time independent—while you sleep—income. I celebrate the audacity and hubris to live by your own exclusive authority and take your own chances. Read More

44 Comments

  1. kayumochi on May 16, 2016 at 16:25

    Is it Rosedale who recommends eating only three ounces of protein a day?

  2. Matt on May 16, 2016 at 16:26

    To follow their bricklaying metaphor, glucose predominantly takes the role of the bricklayer, while amino acids are the bricks. Through a ketogenic diet, one can hold their blood glucose level at a very low level, so that bricks don’t get laid (heh!). My question is if the same is even possible with amino acids? Can you starve a tumor of its structural components with the analogous low-protein diet? Seems unlikely, but I really don’t know.

  3. GTR on May 16, 2016 at 17:51

    The anabolic tumor growth part of cancer might not be the worst one as growing tumors can just be cut off. It looks like catabolic processes can make cancer more mobile, more metastasing.

    http://medicalxpress.com/news/2015-06-treatment-pi3k-inhibitors-cancers-aggressive.html

    “Now, new research from scientists at The Wistar Institute shows that treatment with PI3K inhibitors alone may actually make a patient’s cancer even worse by promoting more aggressive tumor cell behavior and increasing the cancer’s potential of spreading to other organs.[…] The study showed that treatment with a PI3K inhibitor causes the mitochondria to migrate to the peripheral cytoskeleton of the tumor cells. While the mitochondria in untreated cells cluster around the cell’s nucleus, exposure of tumor cells to PI3K therapy causes the mitochondria to move to specialized regions of the cell’s membrane implicated in cell motility – meaning that the cell is able to move spontaneously – and invasion. In this “strategic” position, tumor mitochondria are ideally positioned to provide a concentrated source of energy to support an increase in cell migration and invasion.”

    PI3K is a major anabolic mechanism
    http://www.bodybuilding.com/fun/par26.htm

    Autophagy, which is a catabolic process seems necessary for cancers to move. Cells that loose this property are fixed in a localized tumor.
    “Disrupting autophagy, a cellular housekeeping process, limits cancer spread”
    http://www.eurekalert.org/pub_releases/2016-05/uocm-sci050916.php

    Autphagy in fibroblast cells neighbouring cancer cells also feeds cancer (Reverse Warburg Effect). So starving yourselv via not eating might be counterproductive as cancer can consume the neighbouring tissue, while like a quarter of deaths from cancer comes from muscle wasting. That muscle wasting may soon be eliminated by pharmaceuticals.

    https://cosmosmagazine.com/life-sciences/how-stop-cancer-patients-wasting-away
    “The team moved quickly, making antibodies that block Fn14. A mouse with a normal, Fn14-producing tumour will start to lose weight and sicken within eight days. But when mice with Fn14-expressing tumours were injected with the antibody, the weight loss never materialised.”

    If fasting works for some cases it may be because long fasting leads to the rebuild of immune system, which then helps fight cancers.

    http://www.medicalnewstoday.com/articles/277860.php

    It doesn’t mean that there are no catabolic processes that destroy cancer. For example blocking the ability of creating new mitochondria by antibiotics like doxycyclin or azithromycin helps decrease cancer spread.

    ” It is well known that antibiotics, commonly used to treat bacterial infections, as a side effect mitochondrial biogenesis is inhibited. So he treated eight different tumor types with known concentrations of 4 antibiotics (azithromycin, doxycycline, tigecycline, chloramphenicol and pyrvinium pamoate), showing that there was a significant inhibition of cancer stem cell growth, measured through 3D spheroid formation. The positive effect of doxycycline in the treatment of cancer had already been tested. Since 2002, there are published several reports showing the efficacy of the treatment with this antibiotic in bone metastasis, human oral squamous cell carcinoma, and some others. Last year, a paper was published showing the effect of azithromycin combined with conventional chemotherapy in lung cancer patients, which increased 1-year survival rate from 45% to 75% of patients. “

    • Richard Nikoley on May 16, 2016 at 18:26

      Excellent input, GTR, and just goes to show what a complex bitch cancer is.



  4. Resurgent on May 16, 2016 at 20:03

    I am not a scientist – But I am thinking that Blood Glucose levels can be controlled through a diet intervention, but how does one inhibit protein.. Even with zero protein in the diet, the body has a huge reserve of protein for cancer cells to feed from.

    • Nenad Kojić on May 16, 2016 at 22:59

      With which diet intervention do you make glucose disappear from the blood? The levels of glucose in blood are actually pretty constant independent of the dietary intake. Isn’t that the whole point of the “carbz are not essential”? And then restricted diets even cause higher blood glucose level through the “magic” physiological insulin resistance.



  5. Gemma on May 16, 2016 at 22:25

    I hope you did not mean to suggest that ketogenic diet is a general recipe how to cure cancer. It is not. There is no evidence.
    And if you meant that at least it is slowed down, then my question is for how long.
    As GTR says above, real fasting might be more therapeutic.

    If you read the article, you would find this:

    “Cancer is an incredibly persistent foe. Blocking one metabolic pathway has been shown to slow down and even stop tumor growth in some cases, but tumors tend to find another way. “You block glucose, they use glutamine,” Dang says, in reference to another primary fuel used by cancers. “You block glucose and glutamine, they might be able to use fatty acids. We don’t know yet.”

    • Michael on May 17, 2016 at 00:34


    • Richard Nikoley on May 17, 2016 at 07:07

      Not suggesting that at all. What I’m saying is that IF a TRUE keto diet were effective, looks like it would be more attributable to the protein restriction.



    • GTR on May 17, 2016 at 15:39

      @Gemma – not only cancers are flexible, but also our anti-cancer mechanism are not static but adaptive, rather than static. Eg. anti-cancer P53 gene works in different ways depending on the context.

      http://www.cell.com/cell-metabolism/fulltext/S1550-4131%2813%2900289-1

      ” The outcome of the p53-mediated stress response depends on cell type and context as well as the extent, duration, and origin of the stress.”
      “In its role as a “guardian of the cell,” p53 can eliminate the deleterious effects of oxidative insult either by limiting ROS damage in cells that can be salvaged or by using ROS to eliminate cells damaged beyond repair. ”

      Same with immune system – cancer rates skyrocket at the ages, where the immune system decreases its learning capability, that is becomes less intelligent, because of the aging of thymus where the learning takes place. Usually at the age of 60 or so. There are some concepts of therapies to restore an old thymus to a fully functional state. Some of them involve using growth hormone to achieve this.

      I don’t know if external anti-cancer means have to be context-dependant, adaptive, and intellingent too, to address the flexibility and adaptivness of cancer cells. If there’s such a need then simple static means like fixed diets, or a single-mechanism drug won’t work.



    • Gemma on May 18, 2016 at 08:07

      GTR

      “I don’t know if external anti-cancer means have to be context-dependant, adaptive, and intellingent too, to address the flexibility and adaptivness of cancer cells. If there’s such a need then simple static means like fixed diets, or a single-mechanism drug won’t work.”

      Spot on.

      If, in Tim’s words, cancer is “a living, breathing system trying to free it’s inner animal”, how could you even hope to tame it by eating more and more fat?

      You have to be smarter than that.



  6. Daniel F on May 17, 2016 at 04:52

    Going back to the issue raised in Richard’s now classic “Theory of Everything” post from last year, guess what else cancer requires to grow? Iron.

    Iron is most important for growing children, and it turns out it is crucial for all growth, including cancerous growth.

    Dennis Mangan expounded on this issue in the following post (drawing the connection between IP6’s anti-cancer properties and the fact that it is an iron chelator.)

    http://roguehealthandfitness.com/anti-cancer-neuroprotective-ip6/

    Richard: when will you do a podcast with Dennis Mangan? 🙂

  7. Thhq on May 17, 2016 at 08:11

    Random thought.

    The first one is on diet-as-therapy. Therapy is for sick people. My sister went through a year of chemo for cancer. Throwing diet at cancer is not effective therapy. It might be in there but it’s way down the list.

    The second is diet-as-pharmacology. Cordain is eloquant on this subject. Yet when I read about the Salish, who lived on a close to perfect Paleo Diet, there was no protection from fever and smallpox which decimated their population. Their diet kept them alive from day to day but no better than any other diet. They needed quinine. They needed effective therapy not imaginary Paleo homeopathy.

  8. tw on May 17, 2016 at 08:23

    I’ve thought about this overnight to make sure I understood your argument. I remember seeing this study before and it occurred to me that the only way this “discovery” would be a surprise would be if you believed in the genetic theory or hypothesis of cancer only.

    If cancer cells more often than not are normal cells that have been converted through a change in coding (death function malfunction), all the amino acids present in the original cell would be present in the cancer cell as well. So this should not be a surprise at all.

    What is complex as you say is the various nutrient pathways. Glucose, glutamine, lactic acid, and in some cases (or maybe more) fats.

    In a PET scan you are fasted and the glucose molecule bonded to an isotope is given an hour to circulate, arriving at its intended target which is usually a cancer cell or Tumor. I say usually because other areas can show a bit of uptake as well. They do not use other products for this, and perhaps testing would be an interesting option here.

    In energy production it would seem that fat utilization is secondary to glucose or carbohydrate if present of which the byproducts are carbon dioxide and lactic acid (unless I’m mistaken). So regular use of carbohydrate produces a secondary source for tumor growth.

    A ketogenic diet, at least the one proposed by Phinney and Volek is lowish protein, which as he points out in cereal killers 2 also acts as a “glucose source” when glucose is low. This gets back to your posts on eating habits of Eskimos.

    You will also note as a side bar the Veterens study, cut short demonstrating a substantial increase in cancer due to vegetable oil intervention, obviously neither a protein or a sugar.

    …….and the most prominent infection fighting white cells that will be bombed to near oblivion during (some) treatment (neutrophils) require glucose to do their job further complicates the subject. I read this in Jaminets book and decided on moderate carb for my treatment for this reason. (And could have been mistaken).

    I do not believe that once disease is developed, that no treatment is an option in most cases, and further, that a non chemical approach (i.e. Purely nutritional) is viable in most cases. However, utilizing nutrition and training strategies, a patient can compete with cancer cells for nutrients while these cells are being crushed by intervention treatment.

    The question is whether the body can compete for protein, glucose and other nutrients if scarce through activating its natural break down and repair cycles which are admittedly taxed under treatment conditions. Fitness, real fitness may actually be valuable for this reason.

    So to sum up, the “surprising” conclusions of the study you highlight would likely seem surprising if your school of thought originated from the genetic origins of cancer. From a metabolic standpoint a cell, that was normal and converted would not be surprisingly made up of amino acids like the other cells around it.

    As for nutrients, no grain, no sugar, no seed oils is probably the most important list of exclusions for a patient approaching treatment. What the other compositions should be is unknown. However my belief is that looking at ultra endurance sport, we might get some insight into how bodies can perform in adverse high duress conditions and derive some real benefits for patients approaching and going through treatment.

    Currently several athletes are using lower carbohydrate and ketogenic diets for remarkable efficiency, low inflammation, and faster recoveries for huge ultra events. Is this good long term? Don’t know. But the short term benefits are increasingly clear.

    • Hap on May 17, 2016 at 11:44

      The fasting before a PET FDG scan is primarily to reduce or eliminate the uptake of the tracer in heart muscle and to a lesser degree, other glucose avid organs. the brain, however, is “hot” as hell. It’s interesting that in just an overnight fast, the heart can convert from primary glucose utilization to FFA’s…. This ,of course , led to fluorine and Carbon labeling of all sorts of potential substrates for energy production and anabolic functions. These are routinely used in PET research and some clinical PET. The problem is that these PET agents, other than FDG, tend to require the operation of a medical cyclotron on site with substantial support infrastructure, including a radiochemistry program as non fluorinated compounds have fairly short half lives (C 11 about 10 minutes). There is a lot of new clinical research using F18 labeled glutamate as an adjunct to FDG in cancer diagnosis and treatment evaluation. Other common pet agents are labeled methionine, tryrosine, and choline….as well as many FFA’s. Imaging of molecular processes to be introduced into human research is proceeding at a slow pace because A) it is the most highly regulated industry in pharma and B) is expensive and infrastructure intensive.



    • Tim Steele on May 17, 2016 at 12:32

      Hap – Guess what also shows up on the glucose fueled PET scans…Brown fat. They have to keep the room warm, if too cool, brown fat kicks in and starts using glucose at an alrming rate, in fact, brown fat was discovered in a cold PET scan room, they thought the poor dude was covered in cancer, lol.

      Must be a lesson here somewhere.



    • tw on May 17, 2016 at 14:37

      Hap,

      Where I am the PET is considered an experimental diagnostic tool for many but not all cancers. I am not aware of the use of other agents in the diagnosis process, at least they didn’t mention it when I was asking questions on both occasions. Interesting notes on the fasting period.

      I considered fasting as a possible solution but due to the fact that it was a)unfamiliar and b) I wasn’t convinced that I would be able to retain my weight while training through treatment I decided to use a treatment day strategy: bacon and eggs, nuts during treatment, fried eggs for lunch and dinner and an everything else strategy: without grain, sugar, vegetable oils. I did circuit training and the rowing ergometer and skied on occasion for the duration. Less at the end than beginning.

      My weight going in: 222. My weight after 4 months of treatment (and of feeling like I had the shit beat out of me) 222.

      I did not take any of the recommended shots prior to treatment, not on purpose, but because I filed the info away before reading it due to the overwhelming info. Having said that I suffered no fevers, or adverse immune system events in spite of low whites. I was probably just lucky but maybe all that cholesterol I have did some good.

      Complex topic.



  9. Tim Steele on May 17, 2016 at 09:24

    The whole “sugar feeds cancer so eat less sugar” has never, ever made sense to me. The cancer is not feeding off sugar in the belly, it feeds of glucose in the bloodstream. The human body attempts to regulate blood glucose within a very narrow band, even when you eat NOTHING for weeks. Cancer will have a source of glucose even if you eat a 100% ketogenic diet for 30 years.

    If that’s not enough, cancer is not just a lump of crap that lazily slogs around, it’s a living, breathing system trying to free it’s inner animal. Researchers are stymied at every turn, Block one pathway to cancer growth, and another pops up to take its place, as described just today, here: http://medicalxpress.com/news/2016-05-blocking-cancer-driver-unexpectedly-reveals.html
    “While investigating a potential therapeutic target for the ERK1 and 2 pathway, a widely expressed signaling molecule known to drive cancer growth in one third of patients with colorectal cancer, University of California San Diego School of Medicine researchers found that an alternative pathway immediately emerges when ERK1/2 is halted, thus allowing tumor cell proliferation to continue.”

    • GTR on May 18, 2016 at 06:23

      Cancers are graded according to the level of differentiation – the less differentiated (more primitive) are a bad prognosis, the well-differentiated ones are a better prognosis.

      http://www.cancer.gov/about-cancer/diagnosis-staging/prognosis/tumor-grade-fact-sheet

      In this sense the architecture of cancers is primitive, looks ancient. But the basic blocks, bricks that this cancer uses are refinded by evolution, up to the modern times. Eg. cancer uses anabolic growth, and the anabolic growth in modern organisms is a result of their intensive evolution: the organisms having efficient anabolic growth surviving, those with bad growth fell worse, perhaps even went extinct. So cancer uses current, modern versions of pathways, that won the evolutionary race. If cancer was like a full atavism – primitive architecture, and rough, unoptimized, ancient versions of biological pathways – it would likely fare much worse than using primitive architecture and modern, optimized basic building blocks and work mechanisms.

      What is improtant is that this primitive, low-differentiated, growth-oriented and flexible architecture is superior in many aspects to differentiated one. Especially when it comes to the survival skills, which are increased by the architecture itself. Low differentiation means few difficult-to-replace specialsts but rather many alike-cells, one being able to replace another, growth-orientation means constant apperance of new cells to replace cells lost due to various factor, including being attacked, flexibility – like this ability to change from fixed to mobile cell and back means the survival problems can be dealt with moving around.

      The full, differentiated architecture is fragile. It includes some very specialized organs, not easily replaceable by other organs, that are critical to the survival. Eg. death of a a 300g heart kills and entire 80kg organism.

      They are right that there’s also a conflict with the evolutionary history: for billions of years cells genes learned how not to die, how to survive in bad conditions, while the differentiated architecture is heavily reliant of cell suicide (for the good of the organism) as a way to deal with the issues – which evolved only for few hundred million year.

      Looks like multiple contradictory programs in genes. With the primitive one being “stronger”, while differentiated one being preferred by the management – put perhaps only up to a certain age, that is as far as they are useful for evolution? Evolution might be only partially helpful here, as there are tradeoffs. For example rats or mice tend to have:
      1) High transposons activity, causes frequent mutations
      http://www.anti-agingfirewalls.com/2015/11/14/transposable-dna-elements-part-2-the-self-copy-machines-in-your-genes/
      ” So, largely because of active TEs, mice are more open to evolution than we are and they get a lot more cancers.”
      “Compared to humans, mice have a 100-fold higher rate of mutations caused by retrotransposon insertions (10% vs 0.1-3%).”
      2) Low protection from mtDNA – nuclear DNA incompatibilty

      3) High growth rates, and fast reproduction.
      All these simultaneously speed up their evolution and allow them to conquer the world, but also makes them more prone to getting cancers. So the chose evolutionary path preserves the tendency for having cancer. In fact an artificial genetic modification – extra anti-cancer genes – significantly increased anti-cancer protection. So the cancer protection was possible just not worth it for the evolution to pursue.

      So by finding the origin of cancer vunerability a look at evolutionary strategy of a species is important, including tradeoffs helping cancer, which this atavism theory tends to lack. Perhaps the thing is allowed by evolution to exist after certain age (after reproductin) plus for minority of pre-reproductive individuals.

      This would substantially strengthen the hypothesis that the architecture of living thing is broken. And falsify the “humans are not broken” slogan.



    • GTR on May 17, 2016 at 18:00

      The alternative pathway doesn’t emerge, it’s already there. One of the view of genes is that they are not a custom-designed set of features for a specific species, but they contain like a library of mechanisms acquired during billions of years of evolution. A giant bag of tricks, that also include things useful for less diversified or even single celled life. Control genes, or some epigenetic mechanisms are supposed to choose only the appropriate genes from the library, at the appropriate times, but what if they fail?

      And natural selection cannot cut many of the most dangerous of mechanisms off, because they are critical for some functions. For example this whole expotential replication of cells mechanism that everyone of us has in our genes, in every cell is basically like a bomb waiting to explode, when the control mechanism break. But without the expotential growth there would be no reproduction or tissue repair.
      And control mechanism can be turned off because they are in the genes, and there needs to be a general way to turn off genes for an organism to work… As well as change genes for the evolution to work. Bad, fragile architecture overall. As a comparison: in nuclear power plants it’s necessary for a safety mechanism to be a separate mechanism from a normal-state control mechanism.

      In this sense cancers are like reconfiguration of control – using the same library of mechanisms in a different way. Including upregulatig some mechanisms multiple times, downregulating or turning off another, or even finding out some old trick from eons ago in the library and utilizing them. Some cancers have new genes, like the ones caused by viruses, which include some viral genes; some genes can also be acquired from the bacteria
      https://directorsblog.nih.gov/2016/02/18/creative-minds-bacteria-gene-swaps-and-human-cancer/
      But these genes are still a minority, majority of mechanisms come from the library of human genetics, that is from human genetic history.

      Cancer is like a successful configuration of using these mechanisms from the genetic library, that “wins” over other configurations. It involves things like (this is not a full list):

      1) Giving up on cell suicide (apoptosis). To win – don’t kill yourself? Normal cells kill themselves for such trivial reasons like breaking off extracellurar matrix. Basic rule of the cell – if things are wrong – commit suicide. Elephant cells, that have more copies of anti-cancer P53 gene commit suicide at twice the rate of human cells during stress.
      2) Giving up on the high level of diversification. Diversification is efficient but fragile: a higher diversified organism relies on few critical organs, eg. can be killed by a stab in the heart, or a cut in an aorta. Lower diversification means more redundancy, less dependance on single points of failure and thus more resilence.
      Gaining the ability to get back in the development path: normal cell go from stem cell to a fully diversified cell and never back, cancer cells can go from the diversified to more primary mode.
      3) Multiplying intensively. That’s an obvious way to win over normal cells that limit their reproduction at some level. But it has consequences, side effects – it needs upregulating stuff necessary for multiplication, which is used by anti-caner drugs as a target.
      4) Moving around an organism to find new opportunities to colonize. Including ability to do a transition to a mobile form from the stationary form.
      5) Protecting from problems: eg. upregulated telomerase and perhaps also hyaluronic acid synthesis makes cancer cells younger (these produce anti-aging substances), additional antioxidants protect from self-induced stress.
      6) Speeding up the speed evolution by turning on transposons. Are transposons evil from the point of view of the good of the individual (rather than the evolution of species)?

      These general features look like a description of some kind of more primitive form of life living inside a host organism. There were some cancers that even evolved into something like a separate parasitic species:
      https://en.wikipedia.org/wiki/Canine_transmissible_venereal_tumor



    • Tim Steele on May 17, 2016 at 18:38

      GTR – A couple years ago, fed up with lack of progress from cancer researchers, the NIH gathered a couple brilliant astrophysicists and said, “Cure cancer!”

      Their view of cancer was unlike any other. They proposed an “atavistic” model. Cancer to them was an ancient life form reappearing from time-to-time as cancer.

      http://www.scientificamerican.com/article/did-cancer-evolve-to-protect-us/

      “Together they have come up with an “atavistic” model positing cancer is the reexpression of an ancient “preprogrammed” trait that has been lying dormant. In a new paper, which appeared in BioEssays in September, they argue that because cancer appears in many animals and plants, as well as humans, then it must have evolved hundreds of millions of years ago when we shared a common single-celled ancestor. At that time, cells benefited from immortality, or the ability to proliferate unchecked, as cancer does. When complex multicellular organisms developed, however, “immortality was outsourced to the eggs and sperm,” Davies says, and somatic cells (those not involved in reproduction) no longer needed this function.”



  10. Hap on May 17, 2016 at 10:35

    The ketogenic diet probably does not help in the cancer battle. What we seem to know , with some scientific precision, is that a dietary restriction protocol (ie fasting), absolutely does have a salutary effect. All you need to do is review the work of Dr Luongo at USC….and many others.

    Fasting holds back on every major macronutrient so only thing you can do is measure some biomarkers that you have determined are involved in the effect (ie IGF-1 etc) and look at the genes switched on or off….and what happens to the immune system etc. So I am “down” with fasting although I am not sure anyone can say what is the best way to move forward. It’s a little suspicious , although not a deal breaker , that Dr Luongo claims that there is a proprietary “fast mimicking” diet he has developed and licensed through the University which is claimed to produce the desired effects, measured by outcomes and biomarker changes. So far I am not able to decode the diet but somebody with more time on their hands could probably figure it out easily enough. From what I have read……it’s roughly 40 % carbohydrates, 44% fat, and the rest protein…by total calories consumed. This is clearly NOT A KETOGENIC diet, at least as far as I know about them. Dr Luongos recommended fasting diets, one that will switch all organ systems from glucose to ketones is minimum 4 days, with some leeway for less than 200 cal/day. By “recommended”…he does not recommend any severe fasting diet, even 4 days, and defers to medical supervision.

    Like I said….the licensed, patented, fast mimicking diet…is a small monkey wrench in the works. There are multicenter clinical trials underway to evaluate fasting, fasting mimicking diet, and chemotherapy.

    Interesting information on Dr Warburg above. Not sure how he survived the war in Germany as he was Jewish….and apparently and very stubbornly would not leave, despite what he knew was happening.

    • Tim Steele on May 17, 2016 at 12:35

      Can you say, Potato Hack?”

      There’s also the theory that everyone, at any given time, is riddled with cancer. It’s a normal occurance. But also, normally the cancer is quickly dealt with through apoptosis or other mechanisms the healthy immune system has evolved to rid itself of runaway cells. This makes the only “cure” an active and functional immune system which destroys cancer before it gets a foothold.



  11. Aaron on May 17, 2016 at 10:57

    I remember reading an article on http://www.strongfirst.com called “The Cost of Adaptation: What Do You Choose? There is a quote from that article that mentioned an interesting hypothesis. “When supply is tight and demand is high, competition for the resources is fierce. Years ago, a Russian named Martinyuk even proposed a cancer treatment based on this fact. He suggested putting patients on an ultra-low protein diet and an intense bodybuilding regimen at the same time. As his theory went, the body would search for places to cannibalize proteins for the muscles and the tumor would be one of the places it would go first. To the best of my knowledge, no studies of the sort have ever been conducted, but I hope they will be. If you know an oncology researcher, pass this idea along.” http://www.strongfirst.com/the-cost-of-adaptation/

    • kayumochi on May 17, 2016 at 11:03

      A lot of interesting Soviet medical research came to light in the 1980’s. Maybe the Soviet researchers, under that system, were free to pursue projects that Western Pharma wouldn’t bother with. Dunno. But all that research seems to have been largely ignored in the years since.



    • Hap on May 17, 2016 at 13:42

      Tim
      I am a fan of potato hack and read your book. Not getting a lot of spousal support.. As regards the immune system I’m not sure that it supports or protects the immune system. However, fasting does. The science is pointing strongly to protective effects during chemotherapy of previously fasted patients by upholding leukocyte counts and other biomarkers of a reasonably healthy immune system. Chemo usually wipes that out without fasting.

      Yes…I did not mention brown fat. As with any other physical feature , some are more well endowed than others (like DT’s big hands)…and brown fat which is quite glucose avid is bioactive and implicated in thermogenesis…hence it is a target of weight loss drug development. You can wipe it out of PET scans with beta blockers and/or benzodiazepines. Since it is my business I recently read that fasting along with IV heparin is very effective in inhibiting glucose uptake in myocardium for PET. I’ve yet to see a good explanation how that works.

      PS….I ate one small cold russet for lunch the other day and got a pretty good glucose spike and hour or solater. that is all I ate all day except for some morning coffee.



  12. Hap on May 17, 2016 at 11:16

    People here are “free” to pursue any kind of research they wish. It’s the funding that matters. Government and pharma are 800 lb gorillas in this but there are private foundations, individuals, and others who offer opportunities. Several recent articles about billionaires who are throwing money around, especially at ageing research. they do like University based superstars, typically.

    • kayumochi on May 17, 2016 at 11:29

      I think you know what I mean Hap. Your subtextual political commentary is unnecessary. Soviet scientists were doing all kinds of things their counterparts in the West were not. What today’s billionaires are currently funding has no bearing on what went on during the Cold War.



  13. Hap on May 17, 2016 at 17:43

    The reason you don’t see many PET drugs in clinical practice…..is a bit complex. It took almost 40 years to get F18 FDG approved for use by FDA and a little more time for Medicare. Approvals are only for very specific purposes, but often used “off label” because oncologists and neurologists need the information and it is the prerogative of physicians to do this. It is also the prerogative of the insuranceand medicare companies to deny reimbursement. After all this time there are only five drugs approved for clinical use…FDG, three versions of amyloid imaging agent (Amyvid), and C11 Choline for recurrent prostate cancer(and this only in a couple of approved large cancer centers, Mayo , MD Anderson, MSK etc). Everything else, and there are quite a few drugs in various phases of investigation . I work with agents that track the deposits of Tau proteins in various dementias. these are likely to be approved someday. Lots of research in traumatic brain syndromes…..as well as dementias and other degenerative disorders, some for diagnosis, but others as markers for drug therapy development.

    the medical system is already a strain on the pockets of people because the technology is expensive. For the PET drugs alone you need a 5 million dollar medical cyclotron unit producing isotopes and a multimillion dollar radiochemistry lab making various labelled drugs. And an army of administrators, lawyers to be in compliance with the mountain of regulations.

    • thhq1 on May 18, 2016 at 05:51

      Many imaginary beneficial treatments like this have to be provided free of charge to those who can’t afford them under the federal mandates. No wonder the major health providers around here are asking for 30% rate increases for next year. Only a few small players seeking subscribers are asking for less.

      http://www.oregonlive.com/business/index.ssf/2016/05/oregon_health_insurers_seek_do.html

      There’s no cost/benefit analysis in politics.



    • Thhq on May 18, 2016 at 07:02

      I’m personally PO’d about all this generosity because I receive no subsidy. But in a couple years I will start getting Medicare. And then I’ll be part of the problem.

      Those that should be deservedly PO’d are the kids. While the feds fund most of the free medical care with borrowing, the states make up the difference. Since they can’t borrow enough, they mine their budgets. What was going for education now goes to Medicaid. The money stays with the old and the kids inherit IOU’s.

      http://www.acenet.edu/the-presidency/columns-and-features/Pages/state-funding-a-race-to-the-bottom.aspx



  14. Hap on May 17, 2016 at 17:48

    As for being “riddled with cancer”…..all you need to do is look under the hood and all is putrefaction and death. Why something and not nothing?

    • Hap on May 18, 2016 at 11:55

      thhq

      I cannot blame you for being PO’ed about government largesse . Of course it’s a fallacy that medicine becomes cheaper when it is subsidized, same as the fallacy of insurance =access to medical care. I get no subsidy or employer contributions…..one of those poor shmucks who pays all the freight and tries to absorb the massive premium increases. Apparently, the executive branch did not care that congress passed a bill prohibiting the use of funds to make insurance companies whole, and just ignored the constitution by using monies anyway. It still is not enough. Constitution is no big deal anyway. Just an old document , hand written , parchment paper, limited government, maximum individual freedom. We have geniuses now that know a lot better….

      We cannot avoid some form of radical medical rationing, everybody knows it, but this will be government run, expensive, and as covert as possible, with the blessing of media lapdogs. No where to go….no where to hide.

      The bigger the government…the smaller the citizen. They already control the air, the water, and the bathroom.

      I think I am mostly attracted to this blog and the blogger because I get succor from thinking I can at least learn or find ideas that are in my interest to “deploy” that don’t require me to rely on some government program, especially as regards my health. BTW….Medicare for me in 1.5 years…WOOHOO!! Problem is that funding for medicare is only good until 2030 and SS until 2034…if you can believe any of it.



    • thhq on May 18, 2016 at 12:55

      @hap

      No use me being sentimental about it. All politicians are prone to pander for votes. One gives you the ADA, the next one gives you Medicare Part B, and we haven’t even started in on Democrats. Every politician that tries to cut spending and balance the budget gets run out of office. WE let them get away with it.

      I lived in Chicagoland during the days of Blago, Daley Jr and the freshman senator. One fall I heard a helpful story on the radio about helpin’ the kids that explains how things work.

      You decide to hold a neighborhood Halloween party. But you don’t have any money for treats. So you go around soliciting for candy, telling everyone you’re helpin’ the kids with a big party. Halloween comes and you and your friends sort out the big candy bars from the sticky homemade caramel apples and popcorn balls. The good stuff goes in a bowl in front of the TV for your party, and you and your friends enjoy it. The crap goes in a plastic pumpkin on the porch, with a sign that says “Take One”. That’s for helpin’ the kids.



    • Richard Nikoley on May 18, 2016 at 13:42

      “We cannot avoid some form of radical medical rationing, everybody knows it, but this will be government run, expensive, and as covert as possible, with the blessing of media lapdogs. No where to go….no where to hide. ”

      Who is “we” and who is “everybody” and what exactly do you think _I_ “know?”

      😉



  15. Hap on May 17, 2016 at 20:42

    What the heck….a USC promotional video for Dr Longo and his research as well as his early phase clinical trials in fasting for cancer patients.

    https://pressroom.usc.edu/valter-d-longo/

    The theory goes like this….as it was put in laymans’ terms. Fasting provides an extreme environment and acute stress on cells and organ systems. Certain genetic mechanisms come into play that protects normal cells by shifting a number of molecular processes into the protective mode. That gene expression can be documented fairly simply. Cancer cells, since they have genetic mutations that confer the advantage of high rates of growth under normal conditions lose the ability to adapt and change in response to the challenge of fasting….no food of any kind. Within 48 hrs of fasting these issues are observed in gene expression of cancer cells. the secondary advantage is that chemotherapies designed to kill the tumor cells become even more effective but less effective on normal tissues. This approach has some very appealing properties….it does not cost anything and is completely systemic, potentially affecting tumor deposits everywhere and including circulating tumor cells. There may be other advantages reported , including the autophagy angle and the revved up stem cell response angle…for repair.

    I am old enough to have suffered through the effects of the investment adage, if it sounds too good to be true then…. However, in this case we are not really talking novel in the primary sense. The next step which starts sounding like snake oil is that since fasting is not for everybody and is not always so pleasant, then there must be some “shortcut”….which in this case is the patented “fasting mimicking diet”. Hmmmm….. Hey , I hope it works. Possibly metformin is a gateway drug to the future of chemoprevention.

    One anecdote….I have had two young friends who had different cancers and were put on medically supervised LC diets….. It did not do shit. I am not certain the end wasn’t hastened. WE’ll never know. One of them got to smoke a lot of dope and the other stuck to the carb thing to his last breath. I think I would have gobbled down a cheesecake or two.

    • Richard Nikoley on May 18, 2016 at 08:02

      Hap, I think I blogged first about this like 7 years ago, when still in the mouse stage. As I recall, in some models, fasting before chemo took it from 1-1 war of attrition to a 20-1 kill ratio advantage for normal cells.

      Yep, that would be my approach. 72 hour water-only fast, then chemo. And note that a fast is the original “ketogenic” diet. And resricts both carbohydrate and protein absolutely. Part of why I find all of this highly interesting.

      …I wonder how closely Longo’s diet macros resemble those of human milk…



    • tw on May 18, 2016 at 08:03

      Hap,

      A great video however the various qualifiers at the end and a careful lack of specific findings regarding the particular cocktails and cancers where fasting was tested makes this challenging; but interesting. I considered fasting for many of the reasons he describes which D’Agostino and Seyfried have been exploring.

      Reflecting on Jason Fungs book: The Obesity Code, a recent release (and outstanding book imho) the advantages of fasting are clear for resetting hormone resistance and moving the body to a fat adapted state, not unlike some aspects of a LCHF or ketogenic diet. The primary difference however is pretty much no insulin secretion during fasting (allowing for access to fat stores) and the up regulation of HGH in a fasted state. (If I remember correctly)

      I have been wondering if the problems Warburg was looking at was really an insulin issue, or some other building hormone. I noticed my blood sugar prior to PET 1 was 4.9 fasted with no sugar for 3 weeks and no bread for 6 months. PET 2 was 5.9. The difference was treatment, and another drug for ltbi, stress. Not dietary.

      On reflection, I don’t think I could have managed the hunger driven by Dexamethosone (for nausea control in treatment and considered a valuable yet unknown part of treatment) in a fasted state. The hunger is the same one you get as a bread eater, that insatiable feeling. It literally makes you feel sick, but it’s just extreme hunger pangs easily quelled with a few nuts. Imagine eating sugar and bread, getting dexamethosone and trying to fast? Possible but extremely difficult.

      Fasting is used to accelerate fat adaptation in athletes. Cereal Killers 2 reflects on this. Perhaps the missing ingredient in a dietary strategy is adding a physical exercise component to drive adaptive mechanisms in the body and accelerate fat metabolism. Post chemotherapy (ABVD) I felt like had been “turned off”. Less than 48 hours later I was doing a 20 minute weight circuit session and felt like the switch had been turned back on. Is this the difference? Maybe. Maybe not.

      Is EPOC (exercise post oxygen consumption) a way to further destabilize anaerobic cancer cells as the compete with the organism for nutrients?

      A researcher in Denmark has demonstrated (in mice) the the release of natural killer cells is generated by intense exercise. Not any exercise but intense only. Is this a missing part of the current equation?



  16. GTR on May 18, 2016 at 13:49

    Some evidence that long term protein restriction has some negative effects, indirectly – because it has the potential to lower albumin in the blood.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3019132/

    “Of the 29 studies reviewed on cancers of the gastrointestinal tract, all except three found higher serum albumin levels to be associated with better survival in multivariate analysis. Of the 10 studies reviewed on lung cancer, all excepting one found higher serum albumin levels to be associated with better survival. In 6 studies reviewed on female cancers and multiple cancers each, lower levels of serum albumin were associated with poor survival. Finally, in all 8 studies reviewed on patients with other cancer sites, lower levels of serum albumin were associated with poor survival.”

    Albumin levels are typically growing with protein intake.

    Now is it only statistics (especially – cancer causing albumin to go low), or is there some mechanism of albumin action against cancer, or both? There seem to be some mechanisms for anti-cancer action of this substane, at higher blood concentrations.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3975446

    “Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle
    The presence of albumin in serum reduces the phosphorylation of Rb proteins and enhances the expression of p21 and p57, following an increase in the G0/G1 cell population, and suppresses cell proliferation. These results suggest that albumin itself suppresses the proliferation of hepatocellular carcinoma.”

  17. thhq on May 18, 2016 at 09:34

    Here are three things known to feed and build cancer

    Being fat (compare Colorado (150 per 100K) vs Mississipi (275 per 100K) on cancer vs % obese rates, and those are the ends of a significant correlation for all states)

    Being old (UK exponential rise in cancer rates with age, and worldwide high longevity countries have the highest cancer mortality rates)

    Smoking (UK huge drop in men’s lung cancer over decades of falling smoking rates)

    Sorry, I’m not able to post the links, but they’re easy enough to google up.

    Diet can only fix obesity. That would support fasting as an effective therapy insofar as it eliminates obesity. It might be somewhat helpful as short-term therapy too. But a simple view would say that it’s much more effective for prevention than as an effective cure. It’s a matter of playing best odds before it happens, and if it does using best available medical technology.

    • Marc on May 19, 2016 at 04:01

      “using best available medical technology.”
      Tough to find these days here in the U.S. for cancer, diabetes, cv, etc.

      Thank you Richard, you keep allowing me to investigate and learn….extremely grateful.

      Make no mistake, as it relates to cancer specifically, there are many countries now deploying new protocols with great success rates. Not so much here in the U.S.A, caveat emptor.



    • Hap on May 19, 2016 at 10:51

      Also relatively easy to google up…..in the UK men are far more likely to die of prostate cancer than in America. Rates range from x2 to x6. The standout metric is the much higher PSA screening rates in the US. NHS policy is such that it won’t pay for this. It is an example of “rationing” for which Richard pointed out when he asked who are “they” and how does “he know”.(common sense is a denial of reimbursement letter from your insurance company) Now some might ask what is the real cost of this screening in terms of overtreatment etc? Sure…you gotta look at that.

      My real point is that we need to learn more about how to evaluate PSA screening results and how to act accordingly, not to make government policy that it is useless or to recognize it for the rationing that it is. Furthermore, we need to know more about what PSA means and what we as individuals can do in terms of lifestyle modification (very possibly dietary) to affect this early warning system of prostate cancer. The USPTF tried the same thing with mammography….saying they would not support (ie pay for) screening mammography. Since it caused such a backlash from organized women’s groups, they backed off…..quickly. Point taken….don’t piss off the women.



  18. tw on May 18, 2016 at 15:34
  19. Dave on May 21, 2016 at 12:50

    Thank you to all that post for this interesting discussion. I have a dog in the fight as I have cancer. I tried the keto diet for a while. It seemed to help, but wasn’t a cure. Maybe I didn’t do it long enough. I would try it again if it got to the point where I had nothing to lose. I read (I think it was Patrick Arnold, but not 100% sure) ketones kill cancer cells. They suggested taking ketone salts to help fight cancer and that the keto diet might not be necessary. Also fasting revs up AMPK which can help in the fight of cancer.

    Another amino acid that some say you want to avoid if you have cancer is methionine. If you are ramping down protein (meat, eggs, dairy), you can be reducing mOTR and the arachidonic acid cascade to 5-LOX and 5-HETE. This seems like it would be a positive thing if you are trying to prevent or fight cancer.

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