October 8, 2013

Preventing Chronic Disease

The War on Cancer

How are we faring in the War on Cancer?

Read Time 9 minutes

A couple of weeks ago Tim Ferriss and I were having dinner and the topic of cancer came up. As some of you may know my background is in oncology, specifically in exploring immune-based therapies for cancer by exploiting the properties of regulator T-cells.  But that was a long time ago.  Like many of you, I expect, I’ve also been personally impacted by cancer having lost a friend to glioblastoma multiforme (GBM). I often describe GBM to people as one of the cancers that gives cancer a bad name.  When I went to medical school I planned on becoming a pediatric oncologist, and though I ultimately chose to pursue surgical oncology, my interest in helping people with cancer never wavered.

Over dinner that night, Tim asked me if I could write – in about 1,000 words! – a post on cancer that would be interesting and digestible to a broad audience.  “1,000 words?!,” I asked. “How about 30,000 words?,” I responded only half kidding. After explaining why I couldn’t possibly write such an abridged version, Tim talked me into it. And so, I plan to accept the challenge and hope to provide readers with such a post (it will be on Tim’s blog when I do so), hopefully in the next month or two.

For an introduction, however, I’d like take a step back and place this topic in a broader context. I don’t need to say much about cancer that you don’t already know.  You probably know that about one in three Americans will develop cancer in their lifetime, and you probably know that about half of them will succumb to the disease.  What you may not know, however, is that we have made virtually no progress in extending survival for patients with metastatic solid organ tumors since the “War on Cancer” was declared over 40 years ago.  In other words, when a solid organ tumor (e.g., breast, colon, pancreatic) spreads to distant sites, the likelihood of surviving today is about what it was 40 years ago with rare exceptions. We may extend survival by a few months, but not long-term (i.e., overall) survival.

We screen better today for sure, but subtracting lead-time bias, it’s not clear this extends overall survival.  We’ve had success in treating and even curing hematologic cancers (e.g., some forms of leukemia and lymphoma).  Certainly testicular cancer patients (especially seminomatous) are better off today and those with GI stromal tumors (GIST), too.  Surgical control of cancer is much better today and some local treatments (e.g., specific radiation), too.  But for the most part, when a patient has metastatic cancer today, the likelihood of living 10 more years is virtually unchanged from 40 years ago.

About a year ago, I was asked to give a talk about metabolic disease to a group of physicians. But before I spoke, a very astute and soft-spoken oncologist, Dr. Gary Abrass, gave the following introduction as a way to frame the context of my talk.  After all, I’m sure many in the audience were wondering what could a discussion of insulin resistance have to do with cancer. I have thought often of his words that night in the many months since he so eloquently and informally introduced me.

I asked Dr. Abrass if I could have a copy of his talk and share it with you, to which he kindly agreed. Below is, nearly verbatim, the talk he delivered that night.  (Dr. Abrass did give me the liberty of tweaking the text a bit, for emphasis and clarity.)

How have we fared in the War on Cancer?

On December 23, 1971, President Nixon declared war on cancer by signing the National Cancer Act. I was going to title this, “40 years in 4 minutes,” but I think this will take me a bit longer. At the time I was a third year medical student.  Two years before, Neil Armstrong had inflated our national pride by setting foot on the moon, and there seemed no scientific goal unachievable. Activist Mary Lasker published a full-page advertisement in The New York Times: “Mr. Nixon: You Can Cure Cancer.” And she went on to quote Dr. Sidney Farber, Past President of the American Cancer Society and whose name now sits atop the Harvard Cancer Center, “We are so close to a cure for cancer. We lack only the will and the kind of money and comprehensive planning that went into putting a man on the moon.”  Since then, the federal government has spent well over $105 billion on the effort.

Forty years later, Dr. Farber’s prophecy remains unfulfilled.  In 2012 cancer killed an estimated 577,190 people in the United States.  The death rate, adjusted for the size and age of the population, has decreased by only 5 percent since 1950.  And most of this decline is due to mammography screening in breast cancer and cessation of smoking, resulting in less lung cancer in men.

We have however developed a greater understanding of the biological and molecular basis of cancer.  When I was a medical student, this graphic summarized what we knew about the growth cycle of the cancer cell.

By Zephyris at en.wikipediaderivative work: Beaoderivative work: Histidine (Cell_Cycle_2.svg) [CC-BY-SA-3.0 or GFDL], from Wikimedia Commons
There was an S-phase in which DNA was synthesized, a mitotic phase when the cell divided and a G1 and G2, which to my mind stood for “gaps” in our knowledge.  We added a few dozen chemotherapy drugs on this wheel, and treatment basically amounted to carpet-bombing. And for some diseases — particularly leukemias, lymphomas, and testicular cancers — it was quite effective.

The next graphic demonstrates what we have learned, a truly overwhelming accomplishment, a dizzying array of interconnecting signaling “pathways,” and spawned a whole new field, “translational medicine.”

Roadnottaken at the English language Wikipedia [GFDL or CC-BY-SA-3.0], via Wikimedia Commons
Receptors have been identified on the surface of cells, which function as locks to be opened by various circulating substances (i.e., hormones) initiating a series of downstream events. Mutations in this cascade of on/off switches can promote tumor growth.

With the completion of the Human Genome Project, new sequencing technologies have also opened up the prospect of personal genome sequencing as an important diagnostic tool. A major step toward that goal was the completion of the sequencing of the full genome, first on James D. Watson, one of the co-discoverers of the structure of DNA.  In fact, Steve Jobs had personal genome sequencing.  The price is down to $1,000 and Mayo Clinic Proceedings recently had an article raising the concern of direct to consumer advertising for genomic sequencing. We are now able to sequence gene by gene, pathway by pathway, the genetic code of some cancers.  New “smart” drugs have been developed that target various mutations in these pathways. And currently there are over 800 “targeted agents” in clinical development.  These drugs have been described by some investigators as “The Holy Grail,” but the clinical results suggest more of a commemorative cup for a “Happy Meal.”

While there is nothing unique about this paper, it is a good example of a typical negative trial targeting the IGF-1 receptor with a monoclonal antibody.  The lack of response does not make us question the role of the IGF pathway as a prime driver of malignancy, but rather demonstrates the ability of the cancer to resist therapy.  It seems there is so much redundancy in the system that the cancer finds alternate pathways. The cancer cell continues to defend itself, to bob-and-weave like the arcade game “Whack-a-Mole.”

So the investigators combined the IGF-1 monoclonal antibody with various other therapies: standard platinum based chemotherapy regimens, the “small molecule” tyrosine kinase inhibitor gefitinib (Iressa) targeting another common pathway (EGFR), and also the mTOR inhibitor temsirolimus (Torisel) which targets the IGF-1 pathway a bit further along.  In any case, the point is, it still didn’t work. But why?

Investigators have mapped the genome of a typical lung cancer patient and found over 50,000 mutations. That’s a lot of targets! Granted they are not all ‘driver’ mutations, some are ‘passenger’ mutations. The patient whose genome was mapped was a 51-year-old man who’d reported smoking 25 cigarettes a day for 15 years. At 50,000 mutations, it works out to one mutation for every 2.7 cigarettes.

Last year the New England Journal of Medicine published a study by Gerlinger and colleagues. These investigators looked at intra-tumor heterogeneity. They performed a molecular dissection. They found diversity within the tumor itself.  Each cancer is not cancer but, indeed, it is CANCERS. In other words “all cancers are rare cancers.”  Let me repeat this point.  Each tumor is a collection of heterogeneous – not homogenous – mutated cells. This article has engendered some discussion and some controversy. Many say that the results of the study bring the idea of personalized medicine to a halt, or at least dramatically slow it down.  Are there exceptions? Yes, but they are rare.  One example of an exception to this revelation is chronic myelogenous leukemia (CML), a cancer with a known single driver mutation.

In September 2011, biologist Dr. Alasdair MacKenzie of the University of Aberdeen, speaking at the British Science Festival in Bradford, explained that researchers trying to fully understand how our DNA causes disease might not be looking in all the right parts of the genome. The past decade of genetic studies has revealed that our 3.2-billion-long-DNA-letter code is more complex than anyone could have thought.  More than 98% of the human genome does not encode protein sequences. It’s been referred to as “Junk DNA” and thought not to have a function, but maybe more correctly is that we do not know the function.  He refers to this as the “dark matter” of the genome. And it’s thought that some of these “alternate pathways”, in which our resourceful cancer cell seeks refuge, may reside here. If this was not complicated enough, the new field of Epigenetics has grown exponentially resulting in a widening of the battlefield.

These are factors that can affect the expression of genes without causing mutations, turning switches on and off.  In terms of cancer, much of this research has concentrated on what are called “Nononcogenic stress targets.”  We can stress an organism in many ways: heat, poison, starvation, suffocation or more scientifically thermal, chemical, metabolic and oxidative stress.  Organisms have an ingenious way of responding to such stress.  In the 1960s an assistant in FM Ritossa’s lab accidentally boosted the incubation temperature of Drosophila (fruit flies), and when later examining the chromosomes, Ritossa found a “puffing pattern” that indicated the elevated gene transcription of an unknown protein.

This was later described as the “Heat Shock Response” and the proteins were termed the “Heat Shock Proteins.” This same HSP increases survival under a great many pathophysiological conditions. The HSP70s are an important part of the cell’s machinery for protein folding and help to protect cells from stress. While it enhances the organism’s survival and longevity under most circumstances, HSF1 has the opposite effect in supporting the lethal phenomenon of cancer. These proteins enhance the growth of cancer cells and protect tumors from treatments. This remarkable protein affords a protective response to other proteins in the cell, acting as a “chaperone” preventing them from mis-folding or “denaturing,” like when a boiled egg white turns opaque. These heat shock proteins are expressed at high levels in many tumor types: breast, endometrial, lung, prostate, even brain tumors. HSP overexpression signals a poor prognosis in terms of survival and response to therapy. HSP’s are now on the radar as a key target in the ongoing battle. This protein folding stress response is a hot topic in current cancer research.  I have been communicating with Dr. Debu Tripathy who is currently studying epigenetic changes and protein folding stress responses associated with obesity. This protein folding stress response affords the cancer cell a survival advantage, and we share this protective mechanism with a fly, such a distant relative in our family tree, that one can only conclude that the cancer cell has hijacked this maneuver, this protective drive for immortality from the legacy of 100’s of millions of years of evolution…such a resourceful and formidable opponent.

In any case, when the Human Genome Project was near completion, President Clinton hosted a White House ceremony and announced that, “it will revolutionize the diagnosis, prevention and treatment of most, if not all, human diseases, and that humankind is on the verge of gaining immense new power to heal.”

The hubris of it all.  It’s reminiscent of the quote of Sidney Farber.  Hopefully this is not tempting fate.  Theologians tell us the only unforgivable sin is pride. The increasing complexity of the science is affording us quite a dose of humility.  British Physicist Brian Cox said that “being at the junction of the known and the unknown is a beautiful place to be for a scientist,” but it seems the more we know, the more we don’t know.  Not unlike Winston Churchill’s characterization of Russia as “a riddle wrapped in a mystery inside an enigma.”  Not unlike modern theoretical physics, one questions whether we are capable of understanding the complexity of the science.  Hopefully it’s not like trying to teach my dog quantum theory. We are so smart, but it seems that the cancer cell is smarter. It bobs and weaves, slips our punches, and when we back it into a corner, it defends itself in remarkable ways borne of millions of years of evolutionary acumen much of it hidden in the dark matter of our genome.

Maybe we should call a truce in the War on Cancer and concentrate on prevention. Besides smoking, the most preventable cause of cancer seems to be obesity.  It is generally thought that obesity may account for about a third of many cancer types, particularly breast, colon, uterus, kidney and esophagus.  Obesity is a risk factor for type II diabetes and these patients are not only more likely to get cancer, but to have poor outcomes. Other speakers will explore the relationship of obesity and cancer, the epidemiology and the science, and see if this lends support to any practical prevention measures.

Gary Abrass, M.D.
April 19, 2012

Afterword

Just as the best way to get in shape is not to ever get out of shape, the best treatment for cancer is almost assuredly not to get cancer. And that’s clearly the theme of the introduction Dr. Abrass gave me.  But I’m sure many of you are asking a more important question — what happens if I or someone I care about has cancer? If you can be patient with me, I do plan to address this, to the best of my understanding, in the coming months.

 

Disclaimer: This blog is for general informational purposes only and does not constitute the practice of medicine, nursing or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this blog or materials linked from this blog is at the user's own risk. The content of this blog is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard, or delay in obtaining, medical advice for any medical condition they may have, and should seek the assistance of their health care professionals for any such conditions.

220 Comments

  1. Reading all the fascinating comments on this blog I would like to add an article I recently published in the Washington Post newspaper. MY ADVISE TO ALL OF YOU IS: do NOT GIVE UP ON YOUR RESEARCH AND FIND THE OUT OF THE BOX THINKERS, AS I DID FINDING the virus infusion therapy at Duke university which has so far controlled my GLIOBLASTOMA FOR OVER 2.5 years
    Regards Fritz Andersen, MDQ

    http://www.washingtonpost.com/national/health-science/surgery-radiation-and-chemo-didnt-stop-the-tumor-but-an-experimental-treatment-did/2013/09/23/1b8e8f92-0f4f-11e3-85b6-d27422650fd5_story.html

    • About T. Ferriss…..

      Dr P., Alexandra M, Curtis, Jeff, et al-

      I don’t know the guy, I don’t if Tim Ferriss & TImothy Ferris are the same guy. I don’t know the details of this brain supplement product or business. But it appears they might be the same person. http://en.wikipedia.org/wiki/Timothy_Ferriss

      That said, before I was introduced to his 4 Hour Body book I was dabbling in carb restriction ala Dr Mark Hyman (PBS infomercial fame) . Again, people can poo poo this guy too. BUT using Hyman’s techniques, then Ferriss’, then Primal Bluprint & finally PaleoDiet, I went from 200 to 190 (I’m 6′) … with ease & very little exercise. A year has gone since I started and there is no sign that the fat will return.

      I’m an older mechanical engineer who is used to unconventional solutions…. I constantly question conventional solutions, show me the results / data). I always look for “better”. I reflect on my processes.

      Before I was given a copy of 4 Hour Body, I was poking my finger MANY times per day to determine my own blood sugar response to all manner of foods & meals. Once I saw that Ferriss’ extensive data set mirrored mine, I gave my finger a rest. 🙂

      People can bash Mr. Ferriss but I have had great success with his techniques. His techniques are similar to Hyman, Sisson & Paleo, they all occupy the “overlapping space” of carb restriction. They differ somewhat in their detailed recommendations but they all work (for me). Maybe carb restriction is really more of an “energy matching” philosophy? That coupled with eating real food, not the over processed fare producted by food corps.

      I’m not sure what the perfectly correct model is…that’s for Dr. P & his associates to discover. I’m happy with the current results of my N=1 experiment. I fitter & stronger than I have been in 15 years and it’s relatively easy.

      The conventional wisdom of the last 60 years (lowfat, whole grains) did not not prevent my father or father-in-law from suffering death by cancer or heart disease. One was fat, the other “skinny fat”.

      I’ll take my chances with carb restriction.

      And now to address Jeff’s comments….
      >>He has a public persona and his business is literally selling himself, his worldview, and his techniques.<<>>..does this from the perspective of a sociopath and unapologeticly promotes the schemer mentality.<<<

      that's pretty generalized & unsupported comment…. show me the data / links?

      And btw…."Promotes the Schemer Mentality"… is that your original thought or did you lift it from
      http://dontstepinthepoop.com/get-rich-sociopath ?

  2. Maybe the whole paradigm needs to shift.

    We share tumor growth on sugar over consumption with fruit flies. For creatures so far removed evolutionarily from each other to share the same “problem” says there’s some advantage to it.

    That says to me that maybe cancer is like sickle-cell disease — it normally provides an advantage, but sometimes it over-expresses and causes problems.

    Chronic sugar poisoning kills pretty quickly in the wild, but most cancers take months or years.

    Cancer cells use 200 times as much sugar as normal cells, so a little tumor may eat enough sugar to keep one alive until the sugar runs out. The common loss of appetite associated with cancer would help starve the tumors and limit the amount of sugar that has to be dealt with.

    If cancer is an evolutionarily-conserved protective mechanism against excess carbohydrate consumption then trying to short-circuit it without fixing the dietary problem is going to be very hard.

  3. Thanks for yet another great post :). After being slightly overweight for my whole life, I completely changed my diet this summer to low carb. I’m currently on very strict low carb and fluttering in and out of ketosis (I’m in ketosis during the week and fall out of it in the weekends due to wine drinking. Student life, eh?) I absolutely loving being in a ketogenic state! I used to be constantly thinking about food and couldn’t go more than 4 hours between meals. As I used to say: I lived to eat. Now I can skip one or even two meals without anywhere near the discomfort I used to have, my mood and energy levels are a lot more stable and I feel great! However, I’m not losing weight as fast I expected. I try to stay in ketosis, I eat when I’m hungry and eat till I’m full. After years of calorie counting, I find it hard to resist not to count, so I’m wondering: what happens to excess calories (from fat) when you eat low carb? Since the fat won’t elevate insulin levels, would any excess would just “pass through” the system?

    A couple of days ago I came across this article (http://www.bodyrecomposition.com/fat-loss/insulin-levels-and-fat-loss-qa.html) stating:

    “Contrary to popular belief (espoused by people still reading literature from the 1970?s), insulin is neither the only nor single most important hormone involved in fat storage. Rather, a little compound called acylation stimulation protein (ASP) has been described as “the most potent stimulator of fat storage in the fat cell”. And ASP levels can go up without an increase in insulin (although insulin plays a role).”

    The article is poorly written and lacks references, but still piqued my interest. I tried to read up on ASP myself, but what I found was a bit too technical for a layman like me. What are your thought on insulin vs ASP? Do you think you could do a post on the other hormones apart from insulin that affects lipolysis one day? Have you got any tips that might speed up my weight loss?

    Thanks again for sharing your knowledge and for writing this blog!

    • Marie, I’ve commented on ASP before. I have not seen any evidence suggesting ASP plays a greater role in the role of fat balance than insulin. You may find the fat flux post interesting.

  4. Hi Peter,

    I have previously told you about an episode on Australia’s science show Catalyst called ‘Toxic Sugar’ (in which Taubes/Lustig amongst others were interviewed). The same show has just (very controversially) aired part 1 of a similar show about cholesterol and saturated fat (Taubes interviewed again).

    Heart of the Matter part 1 – Dietary Villains: http://www.abc.net.au/catalyst/stories/3876219.htm

    Part 2 of the series airing in 2 days talks about statins. Which has caused more controversy:

    Professor urges ABC to pull Catalyst episode on cholesterol drugs, says it could result in deaths:
    http://www.abc.net.au/news/2013-10-28/professor-says-abc-catalyst-episode-could-result-in-deaths/5050866

    If anyone is interested the ‘Toxic Sugar’ episode can be found here: http://www.abc.net.au/catalyst/stories/3821440.htm

    Thanks,
    Amanda

    • Amanda, thanks for sharing the links for the Catalyst series. These are great for sending to my friends who are not easily persuaded that “it has all been a big fat lie”.

    • You are welcome John. I’ll also post up links to part 2 if it airs as promised tomorrow.

      I’m not sure if you are Australian or not, but one of the reasons it is getting so much attention here is because the ABC is the government/taxpayer funded national broadcaster. So people seem to think they should only report on what the ‘establishment’ believes.

  5. Hey Peter,

    Since fat suppresses HSL, is this effect large enough to warrant being cautious about eating “too much fat” or “too many calories from fat” ?

  6. Bob K.

    Re. Ferriss

    That website you link, your’re exactly right, and there is no shortage of other spot-on Ferriss critique in various blogs and one-star amazon reviews.

    Peter, please don’t misunderstand, I believe your blog is one of the best and most valuable on the internet; I can think of few more worthwhile non-profits than NuSci. But, re. Ferriss, there is nothing “stunning” about calling a spade a spade.

    • Jeff October 29, 2013
      Re. Ferriss

      I was looking for you to produce real proof… just because someone is bashed or vilified on a website doesn’t make it true. I’m sure for every negative comment or characterization there are many more positives.
      I’m more focused on results…. not personality or character attacks.

      My “experience” with Tim Ferriss?
      My limited data set matches his. His techniques worked for me.
      He appears to be a self-promoter …. omg, unheard of behavior! oh, I guess not. 🙂

      Not my style but I cannot argue with the outcome.

      You appeared to parrot (plagiarize?) an insulting description …
      I was hoping for something more substantive….show me real data.

  7. Great blog here Peter, I’m glad to have discovered you after seeing your talk over on Ferriss’ blog. I’ve trawled through your FAQ and exercise/ketosis posts and have begun piecing together a plan to lose the last few kg of fat I have around my midsection.

    Thus far I’ve gleaned that removing grains, dairy and carb-laden foods is what get’s me 80% of the beneficial fat loss via ketosis. I also want to know how exercise, or whatever else, can play a role to get that remaining 20%. When you get a chance, please consider doing a prescriptive post for the more athletically inclined bunch that want an effective and efficient route to fat loss — perhaps, as the answer to the question: If you could go back in time to your chubby twenty-something athlete self, what would you have him do, from dawn to dusk, to lose the most bodyfat as quickly as possible?

  8. Dear Peter

    I have read a whole lot on your site and I think it is great. I am from Iceland and I came across your lecture about your nutritional journey on youtube. Since then I decided to try out this ketosis for myself.
    I have been doing it for two weeks now.

    I wanted to ask you about your opinion on carb-loading. Many people here in Iceland are on a low carb diet, but many others are following a low carb 20-30 grams for 6 days a week but then have one day where the load up on simple carbs to make the fat burning hormones spike and by that increase the fat burning and to not lose muscle.

    I exercise a lot and have been thinking about doing this but it seems so contradictory with the purpose of being on a ketogenic diet.

    I have seen many doctors recommend low carb/ketogenic diet but I have not seen any research about this carb loading day once in a week.

    If you have the time, can you tell me your view on this matter?

    Kind regards and keep up the good work 🙂

    Bryndís Steinunn

  9. Dr Attia – What is your opinion about William Li’s Ted talk “Can we eat to starve cancer?” and the role of angiogenesis in cancer growth?

    • I have not seen this talk yet, but am pretty familiar with the anti-angiogenesis work. If you want to read a good book about it, I’d recommend “Dr. Folkman’s War.” Despite the promise of this idea it has, despite literally billions of dollars in research and development through to FDA approval, not lived up to the promise we had in the late 90’s.

  10. Hi Peter,

    I am new to your website and blog. Thank you for all the great information, personal and profession, you provide to readers.

    I have been low carb/high fat for about a month now. At my heaviest, I was 250lbs and my height is 70 inches. I have lost about 20 lbs in the first three weeks with virtually no exercise. What is a reasonable amount of weight I should expect to lose month to month, given that I continue to lower my carbohydrate and protein, and increase fat?

    Thanks,
    Russ

    • Range of sustainable weight loss in most literature seems to be about 1 pound of fat per week, but can be higher (or lower). Initial weight loss is often accompanied by water loss.

    • Russ-
      Welcome to low carb eating!
      I’m about your size. A little over a year ago, I started at 220 and in ~ 7 months I got down to ~190.
      I’ve been more or less 190 since Jan 2013.
      I was a total newbie when I started but I’ve read a LOT. I used various low carb techniques in sequence & parallel.
      Mark Hyman – Blood Sugar Solution,
      Tim Ferriss – 4 Hour Body,
      Mark Sisson – Primal Blueprint,
      Paleo DIet

      My weight weight loss averaged about 1 pound a week BUT some weeks I lost nearly 3 pounds… sometimes I plateaued for a week or so. I did minimal exercise; walking & some minor self weight work.

      I also lost about 3 inches on my waist. Funny thing? My BMI at 25.8 still tags me as “overweight” despite the fact that most people who know me think I’m too thin! Personally I think the BMI model pretty much sucks, since two people of the same height & same weight have the same BMI. No consideration that one person might be ripped & the other a couch potato. The BMI model does not consider ‘body shape’ or body fat %.

      Here’s website that has an interesting calculator and also discusses waist to height ratio.
      http://home.fuse.net/clymer/bmi/
      By adding ones waist measurement to the mix, they at least attempt to consider ‘fat’ vs ‘muscle’. In the writing there is a link to a USAF thesis that examines the usefulness of waist to height ratio as a fitness predictor.

      As you lose weight consider recording your waist measurement. As you “recomp”, lose fat & gain muscle, the tape might be more useful than the scale.

  11. Need help in the BM department, any suggestions for fiber supplements that will not kick me out of ketosis. The lowest I can find is sugar free Metamucil at 6 carbs which is big number when trying to stay under 20 – 25 per day. any magical, low carb super fibers out there?

    Love your approach, very inspiring.

    • Peter – I’ve had the same problems when going lower carb. I recommend raw potato starch. Most of the starch is “resistant starch” and indigestible by humans – it goes to the large intestine where it is digested by our microbiome. Do a search for “potato starch ketosis” – you should find some articles where people have personally experimented and verified that potato starch does not kick them out of ketosis.

      DO NOT COOK the starch.

  12. Peter, I have to ask this. You noted in the thread that you are familiar with Thomas Seyfried’s work on cancer. One thing about his research is that he defines specific metabolic targets to effectively fight cancer: glucose 55-65 and ketones >5, combined with calorie restriction on a ketogenic diet (~20 kcal/kg ideal body wt). I also remember reading the experiment by George Cahill in your ketosis post where subjects were injected with insulin until glucose was <20 and their high levels of ketones kept them from experiencing severe hypoglycemic symptoms. Do you think glucose could be safely lowered even more than in Seyfried's work (even if not as low as 20), and do you think it would increase its effectiveness in fighting cancer?

    • Doug, good memory! Yes, Cahill showed repeatedly that humans could remain asymptomatic with glucose at 1 mM (less than 20 mg/dL) if BHB was north of about 5 mM. I can also speak to this from personal experience. However, to get that low requires insulin injections. Even in starvation — complete starvation — glucose rarely goes below about 3 to 3.5 mM. That said, I don’t think injecting insulin is an effective anti-cancer strategy, which is probably where Seyfried gets his range.

  13. Hey Peter, great article. Now on the topic of cancer, have you heard the theory of that some forms of cancer may be caused by a Vitamin Deficiency. There has been this age old theory that the actual root cause to many forms of cancer have been a result of a Vitamin (Vitamin B17/ leatrile) that has been processed out of our diets and never fortified back in, thus creating these cancer cells. Of course, it has stirred up a lot of controversy over the years with the most prominent of pharmaceutical companies and the FDA calling it “quackery” and “poisonous”. Of course, I am not necessarily buying into these statements but I am curious to hear your thoughts on this. Of course like most doctors, I am sure you have probably never even heard of this Vitamin or these cancer claims, as they have been suppressed from the public with conscious effort.

    Here is a link to a book on Amazon called “A World without Cancer” that discusses the preceding paragraph in finer detail with scientific proof. If you click on this link you will find an overwhelming amount of positive reviews of people citing how “life saving” it was. I myself, have bought this book, and can admit that it is definitely enlightening and brings about the discreet corruption of the Cancer industry. It’s honestly unbelievable. There is also a phenomenal documentary about it on Youtube as well as doctors and cancer survivors making videos of this idea.
    http://www.amazon.com/World-Without-Cancer-Story-Vitamin/dp/0912986190/ref=sr_1_2?s=books&ie=UTF8&qid=1383262617&sr=1-2&keywords=a+world+without+cancer

    Of course this vitamin is illegal in the US, but here is a Hospital in Mexico called the Oasis of Hope that uses laetrile as one of their main treatments. Just look at the unbelievable survival rates: http://www.oasisofhope.com/patient-survival-statistics.php

    And here is a description of the treatments they used to achieve these results:
    http://www.oasisofhope.com/laetrile-therapy.php#amygdalin

    What do you think of this?

    • Alison, hard for me to believe. Certainly one of the most famous examples is Pauling’s insistence that vit C deficiency caused cancer. Given his status, this was given much credibility for a while until it seemed there was no evidence to support it. I don’t doubt what you say about the cancer “industry” but I have not seen compelling evidence of the vitamin hypothesis.

  14. OT, but I figured the people on this blog would be most likely to know the answer to this:

    I’d like to monitor my ketone levels regularly, and it sounds like the product most recommended for that is the Precision Xtra. But on Amazon the strips cost $5.69 each, which gets really expensive if you’re using 1-2 per day. Has anyone found a cheaper alternative?

  15. Hemp is a very valuable plant, serving a number of mankind’s needs. It make superior rope, superior cloth as in canvas, and would be in production today if not for its famous quality of making one relaxed and forgetful. To keep the worker base alert and motivated to meet corporate goals, cannabis has been banned or regulated by most of human society. It is not just rope and cloth production that suffers. The very qualities that allow hemp to make one relaxed and forgetful have a positive effect on numerous diseases.

    Cannabis smokers get red eyes because circulation is improved. Nancy will relay that her swollen ankles and feet were cured by hemp seed, which is sky high in Omega-3 and Omega-6 oils. Her doctor is astonished that she does not need the elastic stockings that he prescribed for her when she flashes her trim ankles at him. How does hemp oil, which unlike hemp seed does contain THC, cure cancer and ease MS and glaucoma? Many diseases are caused by the body itself, a reaction to stress or depression. Ease that, and the body’s normal functions return.

    Cancer is a result of a failing immune system, most often due to a sense of helplessness, an inability to escape. This accounts for spontaneous remissions, where the cancer, even at the point of death, just turns around and shrinks out of sight. The person has decided to live. A stoned or even slightly stoned cancer patient forgets why he was depressed. He instead notices the birds singing, the smile and wink from a stranger passing by, and the short term memory loss cannabis is famous for allows him to see that life is worth living.

    MS is an auto-immune disease, where the body attacks and destroys its own cells. It is caused by a hyper-vigilant immune system, a reaction to stress. Relaxed by cannabis, and with a short term memory unable to even recall what the worries were, the MS patient finds their immune system reverting to normal. It is not just relaxation from muscle spams, it is in fact moving in the direction of a cure. This is the case for disease after disease, where the body has created the problem. The trend is thus for cannabis to become legal, else at least provided to sufferers.

    In the Aftertime, this plant will become a mainstay in survival communities, as well it ought. It is as prevalent as weeds, its alternate name, despite being illegal throughout much of the world. Unlike alcohol, which consumes sugar or corn or rye for its production, and thus takes food from starving mouths, cannabis is not a food crop. It asks nothing more than to be allowed to grow, and does not require special treatment in order to do so. Like many of the plants that mankind has found particular useful as medicine, cannabis was seeded here on Earth. Planted, for mankind’s benefit.

    (Zetatalk)

  16. ZetaTalk: Genetic Engineering
    written Oct 15, 2005
    ________________________________________
    Where is man going awry in his tinkering? First, as a base, man should realize that genetic engineering has already been done, by nature, during evolution. Some of the things man struggles with, some of his diseases, are in fact protections from other problems, genetically selected to be passed forward only because they were of benefit in prior ages. The ability to pack food around one’s middle in the form of fat, a buffer against starvation. This was of course balanced in the past by times of food shortage, the fat dropped. Man was not intended to be perpetually pudgy. High cholesterol or high blood pressure is an advantage when one has to fight a tiger or bear with naught but a knife or stone, or run like hell to escape. This was of course balanced in the past by a period of tranquility, unlike what modern man faces in his daily battles with tension in the work place, the figurative tiger never dispelled. Even diabetes, developing later in life by the chubby and inactive, has a genetically selected advantage. The ancestors of those who did not develop diabetes during times of plenty, when early man had naught to do but sit in the berry fields or by streams overflowing with fish, were easy prey for predators, as they gained weight endlessly, huge toads that could not waddle away. Diabetes, type II, resists an intake of sugar by the cells and forces the body to lose weight, at a horrific rate, then lifts when the human is again slim.

  17. This is not necessarily relevant to the above post, but as a avid 5k runner and nutrition/fitness enthusiast I highly enjoyed your post “How a low carb diet affected my athletic performance”. It was very cool to see your results as far as aerobic efficiency and have since been very motivated to eat as close to a ketogenic diet as possible the last year. As you know, VO2 max is a big factor in performance (especially in the 5k) and I am very interested to know if you have answered this question you posed yourself in that post regarding your drop in VO2 max:
    “is there a way to reap the benefits of keto-adaptation of on the aerobic side, without any of the anaerobic cap costs?”
    If so, i’d love to hear more. If you have not yet, I look forward to the day you post on this topic. Thank you for all of the wisdom you’ve passed on. I know by body appreciates it.

  18. Hey Peter,

    Is it possible to defend whole grain pasta, all-bran cereal and porridge as being as good as fatty meats, vegetables, dairy, etc? I’m excluding any added sauces, milk, etc. for now. I used to enjoy moderate portions of pasta with Parmesan cheese and no sauce (I don’t like the sauce), but now I don’t eat it. The GI and insulin index of pasta (both white and brown) are both quite low, particularly if it is thicker and cooked al dente (due to gluten?). The satiety index of white pasta is actually very low compared to brown pasta, suggesting a higher “insulemic” load, and it’s why I made the distinction. This is as opposed to both white and brown rice, white bread, and other refined grain products, which all have high “insulemic” loads.

    Here is the data Im using, I put it into excel. Definitely have a look at it. It’s from Holt et al. and from my understanding it’s really one of the few studies done on insulin response to food? http://s8.postimg.org/a3xlkwgb9/insulin.png

    • By one of the few studies I mean specifically with regards to insulin & satiety indices.

    • Do you really think that pasta needs to be defended? There are very few foods that are going to be have ill effects on every person who eats it. If it works for you, go for it. I’d say start with what you KNOW works for you, and then try adding different things like pasta. I’d guess that some human populations are better suited to grains at this point in time than others.

      One thing to search for on this site is where Peter talks about his wife – she can consume carbs with very few ill effects in comparison to Peter who tends to get more not thin when he eats the carbohydrates.

  19. Just wanted to drop a note to thank you for your blog. I, like you, was around 160 in high school, but during college (Queen’s, incidentally), ballooned to 190. I then proceeded to gain more fat in law school, despite regular exercise and plenty of complex carbs.

    I’ve been attempting to lose weight and have been diligently reading LCHF literature. You blog is perhaps the most data-driven and intellectually satisfying of all the sites I’ve frequented.

    Thank you!

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