Of Mice and Morons

I’ve received a number of questions about this recent paperthe official title being “Pathway to diabetes through attenuation of pancreatic beta cell glycosylation and glucose transport” but the popular media title usually running something like: “High fat diet causes diabetes.”

The only thing I’ve seen popularized more in the media, only to be subsequently proven wrong, would be a headline something to the effect: “End times are Neigh”. Granted, with the latter someone may well get that right and we will only see one example, but in the case of the former…well, this shit just won’t go away.

Today we will look at a number of concepts in this post to help folks wade through this mess in a more effective way. Right upfront let’s consider what goes into the “high fat” diet they are feeding the mice. From the paper:

Mice were provided either a standard diet (16.4% protein, 73._% carbohydrates and 10.5% fat with 4.07 kcal g−1; D12329, Research Diets) or a high-fat diet (16.4% protein, 25.5% carbohydrates and 58.0% fat with 5.56 kcal g−1; D12331, Research Diets).

In science we like to keep variables consistent, otherwise it’s not science, it’s voodoo. Now, we have some inherent problems when altering macronutrient ratios as we have three macros and if you tweak one, you generally tweak them all. What hormonal consequences might this have? More importantly, how much did the animals actually eat? We don’t know, the study design was not in a metabolic cage format so we don’t know if we have the confounder of a significant difference in total calorie intake between the two groups. Several other papers I reference later do provide information collected in a metabolic cage format, so it can and should be done. What we do see is an interesting bias on the part of the study authors. This from the introduction to the paper (which is repeated a dozen or so times throughout the paper):


A high-fat or Western-style diet leading to obesity is evidently a predisposing factor in disease susceptibility and onset5

5. Parillo, M. & Ricardi, G. Diet composition and the risk of type 2 diabetes: epidemiological and clinical evidence. Br. J. Nutr. 92, 7–19 (2004).

So, what is it? High fat diet, or a Westernized diet? We have examples of high fat cultures shifting away from traditional food sources and developing diabetes (Inuit) and we have low fat cultures transitioning to higher fat intake and developing diseases of civilization (Kitavans). I can also think of a few NON DIET situations that induce insulin resistance (we’ll talk about those later) but let’s take a look at what was actually fed to the mice. Please click on the links below and peruse the composition of the lab diets fed to the mice.

Low-Fat D12329, Research Diets 

High-Fat D12331, Research Diets

In both situations we have:

Casein-which has some known insulinogenic/proinflammatory properties.

Maltodextrin-likely corn derived and not much happening with regards to micronutrients.

Corn oil-Heavy in linoleic acid, which is known to promote liver pathology and insulin resistance, skinny on n-3’s other than alpha linolenic acid…not our best option for n-3’s, be we mice or men.

Coconut oil-Saturated fat, predominately in the form of lauric acid. Likely the best part of the chow.

As you will see later, the standard mouse chow (even high carb) is so unhealthy it’s oftentimes tough to keep the mice alive through a study.

Now, the high fat diet is designed to PROMOTE metabolic derangement and type 2 diabetes. It was designed for this purpose and it is well known that a high fat diet will induce type 2 diabetes in mice.

Oh, but wait! A high fat diet only induces type 2 diabetes in mice when substantial carbohydrate is present. A ketogenic diet does no such thing. In fact, a ketogenic diet in mice has demonstrated a number of benefits related to type 2 diabetes complications, neuro degeneration and other conditions.

It’s worth mentioning that when you read the methods section of that paper the researchers had to sacrifice the hi-carb diet (AIN-93M) mice early as the animals were dying from…the high carb diet! Or, was it the carbs? Perhaps it was the sugar, linoleic acid, casein…you know, all that shit the mice never evolved to eat…

Now we DO see impaired systemic insulin sensitivity in ketosis…is this a bad thing?


It is completely normal as limited glucose is spared for the brain during ketosis.

So, the hypothesis is clearly: “a HIGH FAT diet causes type 2 diabetes” yet when we dial the fat UP, type 2 diabetes…goes away. Fail, on many levels.

Here is what these folks have done:

1-Fed a diet known to cause insulin resistance to their mice (without tracking how much food either the control or HF mice ate. Sloppy science and sloppy reviewers…this was not even discussed in the limitations section).

2-Induced type 2 diabetes in said mice, and then performed various gene expression studies which indicate impaired glucose sensing in the pancreas (you can bet the same thing is occurring in the brain and liver, yet no mention of these alternate mechanisms is provided)

3-Looked at correlative genes in humans suffering from type 2 diabetes and found similar impairment.

4-Hung the cause of the insulin resistance on a high fat diet despite the fact a ketogenic diet (a REALLY high fat diet) does no such thing.

And somehow these folks get published!!

Now, I can induce insulin resistance via a number of non-dietary means, including sleep deprivation, sepsis and injury. Not surprisingly, when we look at some mechanisms the very same FOX2A gene the folks were looking at in the original paper that spawned this post is affected by sepsis. In this case it is hepatocytes (liver cells) and in the original paper the investigators were looking at pancreatic cells, but as insulin resistance tends to progress in a systemic fashion, and since we know the liver is a key player in this glucose regulations story…I’ll bet it’s the same story in both tissues.

That this paper was published, that these folks even ASKED the questions that they did and proceeded to attempt to answer them in the way they have is frankly shocking. It is also why the AHS11 was so damn important because we have a medical and research community that is just fracking lost. None are operating within an Evolutionary framework and this is the resultant tripe produced. At this point I’d go so far to say that it borders on malpractice or behavior necessitating litigation when researchers so epically drop the ball and the media subsequently grabs this stuff and runs with it.

That’s my finger wagging to the researchers and media, now I’m going to do a little finger wagging at some of y’all. One of the messages I received went like this:

“Robb, did you read this paper? What’s your opinion on it? I ate a high carb, grain based diet for years and was sick. Since I went paleo I’ve lost 65 lbs and what I suspect to be an autoimmune condition has gone away…but is there anything that this paper says that should concern me?”

I’m all for questioning our dearly held beliefs, and burning the house down when necessary, but I have a fair amount of faith in our personal experience. In the case of our eating and lifestyle habits it looks like something along this paleo/primal lifeway will make us Look, Feel & Perform better. Our biomarkers of health & disease go in a favorable direction.

DONE. Now it’s time to LIVE.

On the macro level we do not need much more than that and until the larger research community finally grasps the evolutionary biology perspective they will have limited offerings that are not outright dangerous to our health and wellbeing. This paper is a prime example.

Y’all do not need gurus, you need to tinker and go with your own experience. And do like Mark Sisson suggested and go play.

“The Lost Art of Play” by Mark Sisson from Ancestry on Vimeo.

Categories: Anti inflammatory diet, Autoimmunity, General, Healthcare, Paleo Diet Basics, Paleo in the News


Robb Wolf’s 30 Day Paleo Transformation

Have you heard about the Paleo diet and were curious about how to get started? Or maybe you’ve been trying Paleo for a while but have questions or aren’t sure what the right exercise program is for you? Or maybe you just want a 30-day meal plan and shopping list to make things easier? Then Robb Wolf’s 30 Day Paleo Transformation is for you.


  1. says

    Perhaps the approach of testing your diet against how you look/feel/perform gets a little difficult if you don’t understand the underlying mechanisms well enough to be confident in the duration of the look/feel/perform part.

    In other words, in a very short time frame I can say I feel fantastic after two cups of coffee and some yohimbe. Hell, I perform fantastic as well. But if I keep that up day after day, I will quit feeling fantastic. So the perform/feel part passes at first, then it starts to decline.

    Now obviously, I’m prodding the hell out of my adrenals, and thus it has to be short-term and intermittent. But that’s only obvious because I know what it’s doing.

    If you don’t understand the underlying mechanisms, perhaps its easy to look at diet the same way on a longer time frame. Kind of “I’ve felt great for 5 years, in the best shape of my life, stronger, faster, etc., on this paleo diet, but will it come crumbling down in another year or so?”

    Obviously, a good diet isn’t a transient effect like my stimulant scenario, but for the person who just adopted the diet without the awareness of WHY it’s making them look/feel/perform better doesn’t get those distinctions.

    So, I bet you will ALWAYS get questions like those. And maybe you even want it that way. If understanding isn’t a requirement to get someone to eat in a way that benefits them, you’ll have more people willing to try it.

    Besides, it’s fun to hear you and a few others disassemble a study or report. Don’t shy away from that guru title. 😉

    • says

      Great insights. I am realizing that I am PAINFULLY uncomfortable with “guru-hood”. I saw it go terribly with the CrossFit leadership…to such a degree that I am reminded of Idi Amin. So I want people to think for themselves, trust in themselves…NOT IN ME.

      It literally pains me when I see someone who has made success like I describe in the post ready to throw everything away because of a poorly constructed study. But I guess your point is that not everyone has the background to tear a paper like this apart…I’m literally coming to this as I write, so hopefully it makes sense…I think I feel the weight of responsibility for people succeeding and when I see a potential backpedal like this I take it personally. I see it as a failure on my part to better convey the information, but I’m damned if I know how to do more of it or do it better. I guess it’s “chop wood, carry water”, do our best, don’t get caught up on the outcome?

      Thanks Bill…You helped me a bunch just now, much appreciated.

      • says

        Awesome to hear. One of the characteristics you have is a willingness to look at what you’ve done previously and decide that you have a different take on things. There are other self-proclaimed gurus who will never contradict their former stances.

        I really like having listened to you and Mat Lalonde and hearing you both say that you want to revise previous recommendations. I still laugh at Lalonde’s low-carb + CrossFit reexamination.

        Those types of things are honest, and an indication you’re trying to figure it all out, versus claiming you know it all.

        Keep up the great work.

  2. says

    Hey Robb,

    I hope people reading this really take this line to heart…

    “I have a fair amount of faith in our personal experience.”

    People in general are so quick to ignore their own intuitive knowledge of what is going in their bodies and adopt something because it was in a study or some dude with “Dr.” in front of their names said it.

    I think every study produced should have pics of the these researchers in their underwear, because at the end of the day there is a big difference between talking about something you claim to be true and then taking that info and living it.

    More often than not, most of these people don’t live it.

    OK I’m off to see a personal trainer who is 40lbs overweight who is going to tell me how to get into shape. (I’m kidding…just trying to prove a point)


      • Mary says

        You write really well Robb. Have you approached any mainstream magazines? I bet there are some people in this movement who have an “in” at some magazine or another. Go for it!

        • says

          Thanks Mary. I honestly get more reach from the blog than I’d likely get at most magazines…and if my writing sux I have only myself to blame, not an editor! Very kind of you, I will give it some thought.

          • Mary says

            There is a connection here with your response to Bill re “guru-hood” and your disillusionment when people become confused by the mainstream media’s contant shouting of the OPPOSITE message from the rooftops.

            You have plugged a couple of upcoming books written by other people (Paleo Comfort Foods and Primal Connections), saying that you want them to become mainstream. I personally think that is the right approach! Having a lot of blog readers/podcast listeners is fantastic–and it’s wonderful for us to have access to all of this high-quality content–but in many cases you are preaching to the converted. I think edging this message toward the mainstream is really important.

            Your physician education initiative is right on the money, but, at the risk of being a real pain in the ass, I still strongly encourage you to use your position in the movement as a way to get something published in a mainstream news source.

            I mentioned in the comment below that years of severe undiagnosed gluten intolerance (in my son) may end up costing the Quebec government a hunk of cash. Americans are in a frenzy over health care costs, n’est-ce pas? So that would be a good hook: continued reliance on dietary guidelines that have been debunked by good science is putting a huge financial drain on the system (and taxes could go up as a result–that will get everyone’s attention!). Add some smart slamming of big agro-business (and nobody does smart slamming better then you, Robb) and that would sell some magazines. You would just need to find a magazine bold enough to cash in!

            Again, sorry for being a pain in the ass, but the fact that the mainstream healthcare community is so “frackin’ lost” drives me crazy!

  3. Jake says

    Hey Rob,
    Just to help bolster the message in this post…The oil used in the two different feed formulas was soybean oil and not corn oil. Is soybean oil just as high in linoleic acid as corn oil? And does the fact that the coconut oil is hydrogenated reduce the positive aspect of it being in the feed?

  4. Pattie Pardini-Barrett says

    Dr Weil had a post in his recent newsletter that said red meat causes TypeII Diabetes. It was a study of processed meats however. I was upset to see the headline because it miss leads people.

  5. kevin says

    I read a research article that red meat causes type 2 diabetes. What they failed to mention was what these research subjects were eating with the red meat. Some of the participants were downing sugar and high carb foods known to lead to diabetes! We all need to take a closer look at all research because in a few cases the researchers will alter results to make their hypothesis correct. As a holistic nutritionist I am confident eating a high fat diet will not lead to diabetes.

    • says

      And this is how it inevitably goes. Study claims “meat does X”. Study is a retrospective, epi study with NO proposed mechanism. media picks it up, people freak out… subsequent investigation of the paper shows that “pizza” is counted as “meat” in the epi study.

  6. says

    As usual, solid work. I love how easy it is to shake peoples belief. that 65 lbs of weight loss and remission of auto-immune diseases are not proof enough and a poorly written paper can cause doubt.

  7. says

    Last 5 paragraphs say it all. Some live to be paleo, some are paleo to live. There are too many nice people on the internet, and just in general, so tell it like it is. Live long, and prosper.

  8. Stabby says

    Ah yes, the “high-fat mouse-murder” diet. Which can be extrapolated to the high-fat diet for humans advocated by paleo authors, because, well, they’re both “high-fat”, sigh. All I ever respond to these is that when you distort tissue HUFA ratio so badly you are bound to severely impair the liver’s ability to regulate glucose levels. Stephan Guyenet taught me this http://wholehealthsource.blogspot.com/2009/05/eicosanoids-fatty-liver-and-insulin.html

    • scott says

      I don’t think any extrapolation is required: “We observed that this pathogenic process was active in human islet cells obtained from donors with type 2 diabetes;…”

      I don’t fully understand the negative reaction to this paper (partly because I haven’t read it). It seems to support a low carb (high fat) or low fat (high carb) approach if you’re trying to avoid type 2 diabetes. Isn’t the finding significant?

        • Shannon says

          I meant the part where you said the high-carb diet mice had to be “sacrificed” because they were in such poor health. So the “good” diet killed the mice. You said it was in the methods part of the study, which is a real shame. If it were in the “meat” of the study, there’s at least a chance journalists would pick up on it.

  9. Mary says

    Love the way you took this down. I also loved your finger wagging at the researchers/media, and I think it’s great that you went so far as to mention malpractice/behaviour necessitating litigation.

    You didn’t mention doctors, but they also have a lot to answer for. As a case in point, 4 months ago I put my four-year old autistic son on a Paleo diet based mainly on my own experience with the approach, which I learned through your book and podcast. He has made astounding progress, and testing done through an alternative nutritionist has now confirmed that he is severely gluten intolerant. His developmental pediatrician–who has been seeing him since he was two–recommended the diet (even though it was “unproven”), saying that many parents get positive results. BUT, she did not recommend it until he was four, when I starting asking her for non-mainstream testing (which she refused).

    My own guilt for not acting sooner is very strong, but at the same time I can’t get over the fact that NO healthcare professional made any mention whatsoever of dietary intervention (until he was four) or knew to check for gluten intolerance. He was diagnosed early at two and was developmentally delayed from one year, and has therefore come into contact with a slew of specialized providers. If only one of them had been able to clue me in, can you imagine the difference that would have made for him? Missing out on FOUR YEARS of normal development due (at least in part) to severe gluten intolerance is a really big deal. It’s a life-changer for him (and our family), and will also probably end up costing the Quebec government tens of thousands of dollars.

    From everything I am hearing from the various podcasts and blogs in this ancestral health movement, the case against gluten-containing grains is pretty damn robust, so why isn’t it on anybody else’s radar???? If the evidence is as clear (and the potential consequences as grave and wide-ranging) as people are claiming, then the mainstream healhcare establishment has a clear responsibility to take off their blinders. If they don’t, then that sure seems like malpractice/behaviour necessitating litigation to me.

    Sorry to go on the rampage with this comment, but I just wanted to express that “going so far” as to mention malpractice/behaviour necessitating litigation is not actually going all that far. I think it’s something that should be talked about more, and maybe we need to somehow start talking louder!

    • says

      I’d love to have a write-up on your experience.

      Our medical community is at once in the dark on most of this and perhaps mor insidious, they are hamstrung by standard of care. If someone presents with high blood cholesterol, standard of care dictates the prescription of a statin, not dietary intervention. To a degree we have done this to ourselves with our litigious society.

      But back to the “in the dark” piece. We have folks like Brian Dunning who did a piece on gluten that was little more than a survey of wikkipedia on the topic. He has no understanding of molecualr biology nor the proposed etiology of these conditions. HE is unaware that in 2–4 the term “intestinal permeability” had fewer than 200 search returns on pubmed and was considered the highest levels of quackery. The same search return now produces better than 9,000 returns (http://www.ncbi.nlm.nih.gov/pubmed?term=intestinal%20permeability) and is the subject of some of the most intense immunology research, including work from Alessio Fasano at the University of Maryland. It is no longer the realm of quackery, but it is not the “consensus” therefor it goes largely unnoticed or is easily dismissed.

      • Mary says

        Of course, doctors follow guidelines in part to cover their asses, and no-one can blame them for that, but where is the out for the organizations setting the guidelines? The US is much more litigious than Canada–and I agree that is part of the problem–but when robust scientific findings are being not-noticed/dismissed (consensus, blah, blah) the consequences for people can be devastating, not to mention the massive financial drain on healthcare systems. Your finger wagging at researchers and the media (and us folks ;-)) is well deserved, but honestly–and this is only my personal, hotheaded opinion–the medical associations (and USDA) deserve a lot more than figure wagging. Their failure to serve society–given the consequences–is staggering.

      • Mary says

        With regard to the write-up, I will do that. I want to do everything I can to encourage other parents of autistic kids to try dietary intervention as early as possible. It might take a while though, as I have just accepted a demanding job in translation (which I hate), partly in order to pay for the interventions/guidance needed to fix my son’s gut (which insurance of course will not cover :-().

        • Lainey says

          Mary, aligned with the dietary interventions that deal with gluten intolerance, I have been reading more and more research supporting gut dysbiosis being a factor in autism…SIBO due to chronic overpopulation of toxin producing bacteria (usually endotoxins with a neural effect) , yet another reason a paleo diet may provide improvements for some children with autism..,I can send through some references if interested.

  10. says

    It seems to me they made sure the study read in a way that ensured the continue to get lots of funding from the powers that be. Until there is a level playing field I’m afraid this is all we are going to see. All the more reason we need people like those at the AHS that can break it down and show it for what it is. Isn’t Denise Minger coming out with a book that will help us simple folk learn to dissect theses studies ourselves?

    • Mary says

      Yes, her book is being published by Marc Sisson (he mentioned this on the next to last podcast, I think). Can’t wait for that one!

  11. scott says

    The article cost $32. I didn’t shell out the cash, but the abstract looked interesting. What did you think of the beta cell dis-function part of the paper? My take away from the abstract was that anyone burning ketones should avoid high blood glucose spikes & limit the big carbs to post workout. Also, cycling between ketogenic dieting & non-keto is not advised….agree?

  12. Mary says

    Robb, one thing I forgot to mention is that your title–Of Mice and Morons–is totally priceless. I’m so hoping to see it again in your next book!

  13. Amy B. says

    Studies like this remind me of the innumerable studies trying to disprove the efficacy of lowcarb diets, wherein invariably they compare a diet of 65% carbohydrate to one of 45% carbohydrate and then conclude that “low carb is no more effective than low fat.”

    Robb, never second guess yourself when it comes to this stuff. You’re one of the few people who have the guts (and the scientific background) to really call these folks to task. The research community ought to be ashamed. These types of studies are the inevitable result when researchers enter into experiments with their intended conclusions biasing things from the get-go. “We already *KNOW* saturated fat and cholesterol are bad for you, so starting from *there,* we designed this study to show x, y, and z…” It’s truly horrendous science.

    As for the USDA/ADA, etc, I’ve heard a couple of times that the people there recognize that they’ve gotten things dead wrong (pun intended), but they’ve been so loud for so long that it’s almost impossible to backpedal now. You’ve said it yourself on the podcast: the legal aftermath of those organizations admitting their advice has literally killed people would make big tobacco look like a game of Candy Land.

    My suspicion is that they *will* backpedal, but it’ll be done so gradually that most people won’t even notice. It won’t be until our great-grandchildren’s generation that people will look back on “heart healthy” margarine with the same disdain as we think of smoking on airplanes. (And let’s not forget that the AMA used to *endorse* cigarettes! They do not exactly have a golden track record.)

  14. Shannon says

    If not guru, how about expert? Non-science folks like myself need someone to break this stuff down for us. We are bombarded with messages all the time telling us we’re eating in a way we’re likely to pay for later. (Oh, the irony!) Well meaning friends and family who don’t know better tell me all the time that what I’m doing is stupid/unhealthy/unsustainable. Being able to cite studies like this go a long way towards helping them understand and maybe change their habits. My mom was speechless when I told her the part about what the high carb diet did to the mice! No way I’d have the time/understanding to sift through that study on my own and pull out such great talking points. Keep it up–it helps those of us who are not in a supportive paleo community discuss our choices with people who think we’re doing something wrong even though they’ve seen the physical changes.

  15. says

    Many, many scientific journals are pretty much terrible. One can expect a load of horribly written studies with bad methods, and it can be rather fun to pick them apart. There’s an old saying – 90% of the journals are wrong, 10% of the textbooks are wrong. HOWEVER, in every field there are a few excellent journals that one can generally expect good, thoughtful papers from – for examole the Lancet, New England Journal, JAMA, Science, and… Nature! This paper was published in Nature medicine! I pulled it myself. I am shocked and appalled NM published it, with its weaknesses, poor methods, and obvious bias. shameful.

  16. Jim says


    You say “At this point I’d go so far to say that it borders on malpractice or behavior necessitating litigation when researchers so epically drop the ball and the media subsequently grabs this stuff and runs with it.”

    Very interesting. Litigation is an ugly option – and the personal injury attorneys are not a revered bunch. But litigation can be a great way to build awareness, get issues in the media and apply pressure to “the system.”

    Aren’t there some Paleo Personal Injury attorneys or litigators that might take this on – either vs. USDA and USG or against the boneheaded authors of this particular report?

    C’mon fellows.

  17. Brad says

    Is this the same report being referenced on Fox News this morning with Dr. Isadore Rosenfeld supposedly linking the consumption of red meat with the development of Type II diabetes?

  18. says

    Robb, thanks for giving me the latest piece of the rebuttal puzzle, the study on rodents and the keto diet. I get challenged all the time by fellow diabetics who are swayed by the scare tactics thrown at them. This helps put the rodent studies in their proper place.

    I have had to come to the conclusion that all who need a better change in their health have to wake up to that realization before they truly are open to help. What is your experience in dealing with people who are on the fence? Do you give them your time or do you wait till they are “willing to crawl over broken glass” to get healed? On a personal note, If not Guru then Gurude? An in your face Oracle? Give em hell, 54th.

  19. says

    Hi Robb,

    If you or any of your readers are interested in the full text article that was published, I’ve shared it on my blog in the post I did on this.

    It’s the media and not the scientists that deserve the derision here. It boils down to their use of a high fat diet in mice to induce diabetes and comparing beta cell functions with those of islets donated by diabetic humans. My main complaint about the article itself is that it is a difficult read, not for the content as much as how it is presented.

    FWIW, when I read “high-fat or Western-style” in papers like this, I think the authors are referring to the “high-fat, Western-style diet”. As to the rodent chow, I’ve discussed at least one study where normal rats (not genetically predisposed) fed a lard-based KD gained more fat mass and had impaired glucose tolerance: http://carbsanity.blogspot.com/2011/03/ketogenic-diet-increases-fat-mass-and.html
    I can’t find it at the moment, but I’ve also blogged on at least one study that showed an LCHF diet hastened the onset of diabetes in one genetic animal model (I want to say the Zucker rat).

  20. Sabine says

    Thank you, Robb.
    I read quite a few blogs, and people get confused over and over again by these fake science papers by these tin-foil-hat scientists with the candy wrapper degrees, with ties to……
    Thank you for setting things straight, at least for this ?study? .
    A lot of time and money is being wasted, and a lot of people are being hurt by these ignoramuses.

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