But Is It Even Paleo?

But Is It Even Paleo?

A recent study in the Journal Nutrition and Diabetes has raised some interesting questions about the effects of a high-fat diet on glucose regulation in New Zealand obese mice 1. While only a single study, it has set off a media storm questioning the efficacy of a Paleo-style diet.

Which is interesting because what may be most important about the study is not the questions it raises, but the fundamental and all too pervasive misunderstanding it demonstrates about the Paleo Diet.

The study explores the effects of a very high-fat/low-carbohydrate diet on diabetes prone mice. But as I explained in an article I wrote last spring, there is a danger in talking about the Paleo Diet purely in terms of macronutrient ratios. Hunter gatherers didn’t know what a carbohydrate or fat was. Instead, they ate particular foods while avoiding others. This is one of the most important and progressive aspects of the Paleo diet. It is about what whole foods we should eat (lean natural meats, vegetables, fruits, and nuts) and which we should avoid (grains, legumes and dairy.) All based on how we evolved.

Within the context of these healthy foods, there is a wide range of possible healthy ratios.2

Yet, many in the nutrition community remain locked to trying to determine the “optimal” nutrient ratio while lumping all fats and all carbohydrates together. That is the fundamental mistake of this recent study led by Dr Andrikopoulos and his team in Australia. In their attempt to criticize the Paleo Diet based on these ratios they nearly gloss over the fact that their diet is based on non-Paleo foods like cocoa butter and casein. Foods that, as I’ll explain momentarily, have been proven to have a direct impact on glucose regulation. As a result, the study provides no clarity on the Paleo Diet whatsoever.

But as Dr Cordain says, the devil is in the details. So let’s look more closely at the low-carbohydrate/high-fat diet fed to the mice in the study. The diet broke down as follows:

13% protein
6% carbohydrate
81% fat

  • Carbohydrates came purely from sucrose (simple sugar)
  • The fats were 55% saturated fat, 37% monounsaturated fat, and 8% polyunsaturated fat

While the nutrients ratios can vary in a Paleo diet, an early paper analyzing a sample Paleo Diet had very different ratios3.

38% protein
23% carbohydrate
39% fat

  • The carbohydrates in this sample menu were primarily complex carbohydrates
  • Of the 39% fat in the diet, 7% was saturated, 17.2% was monounsaturated and 10.4% was polyunsaturated

Consequently, even from a macronutrient ratio perspective, the diet fed to the mice did not resemble a Paleo diet.

But the question remains if the ratio in Andrikopoulos’ study could be consumed based on Paleo-friendly foods. We may not know because the study did not attempt to use Paleo foods. In a separate supplement, Andrikopoulos detailed the high-fat/low-carbohydrate diet fed to the mice. The table below shows the breakdown of the diet:

Primary g/kg – %
Cocoa Butter 400 – 40.0%
Casein 200 – 20.0%
Sucrose 106 – 10.6%
Canola oil 100 – 10.0%
Clarified butter fat (Ghee) 100 – 10.0%
Cellulose 50 – 5.0%
Calcium carbonate 13.1 – 1.31%
AIN93G vitamins 10 – 1.0%
Potassium dihydrogen phosphate 6.9 – 0.69%
DL-Methionine 3 – 0.3%
Sodium chloride 0.26%
Potassium citrate 0.25%
Choline chloride (75%) 0.25%
Potassium sulfate 0.16%
AIN93G trace minerals 0.14%


So, in a study that’s being used to criticize the Paleo diet in the media, virtually none of the foods consumed are part of a Paleo Diet. In fact, the “healthier” control diet is in some ways closer to the Paleo Diet with foods like fish meal, only 2% of carbohydrates coming from simple sugars, and a much lower saturated fat content.

More importantly, 60% of the mouse diet (by weight) came from cocoa butter and casein. Yet Andrikopoulos and his team failed to reference many studies exploring the effects of these specific foods on diabetes and glucose regulation.

Among these, a 1991 study tested the effects of saturated vs polyunsaturated vs monounsaturated fats on insulin sensitivity in rats4. The saturated fats which came from cocoa butter hurt peripheral glucose utilization. And even though this earlier study showed better glucose control with polyunsaturated fats, the control diet in Andrikopoulos’ study had a much higher ratio of polyunsaturated fats than the high-fat diet.

Likewise, a study in Diabetologia looked at the effects of casein in two rodent models and found “milk caseins are unlikely to be exclusive promoters of type I diabetes, but could enhance the outcome of diabetes”5. But it is important to point out that this study explored type I diabetes.

A more recent 2006 study in Nutrition Research explored the effects of casein on the insulin/glucose response in normal rats. After an overnight fast, a glucose challenge was found to raise both insulin and glucose levels in the casein-fed rats6. Interestingly, the primary finding of the Andrikopoulos study (which is the basis for the media’s criticism of the Paleo Diet) was virtually identical. A glucose challenge raised the insulin and glucose levels of mice fed the high-fat diet.  The results from both studies are shown in the figures below (figure 4 from the recent Andrikopoulos study and figure 3 from the 2006 study on rats):

Screen Shot 2016-02-23 at 9.35.19 AM

Screen Shot 2016-02-23 at 9.35.29 AM

Andrikopoulos’ group attributed these results to increased insulin resistance. The 2006 study drew a different conclusion: “these findings are consistent with the insulinotropic action of amino acids and with the role of some of them as gluconeogenic precursors.” Again it’s interesting that Andrikopoulos did not reference this study despite having virtually identical results with the same food item.

So can we attribute Andrikopoulos‘ results to casein? No, but that’s the point. Correlation is not cause and Andrikopoulos provides no evidence to prove his results are due to the high-fat/low-carbohydrate ratio of the diet, to casein in the diet, or any of a number of other variables not even addressed. To then go to the media and claim it is evidence of the negative health effects of a Paleo Diet is simply irresponsible.

While Andrikopoulos’ study may raise questions about potential dangers of a very particular high-fat diet, it represents itself an even greater danger. That of drawing any conclusions about an overall diet strategy based on a macro-nutrient ratio while ignoring the type of foods themselves. Until Andrikopoulos can address these very glaring holes and test a diet based on evolutionary foods, I don’t personally plan on changing my Paleo-based diet anytime soon.


Read our Further Responses to this Study:

Loren Cordain, Ph.D. Response
Mark J. Smith, Ph,D, Response


[1] Lamont BJ, Waters MF, Andrikopoulos S. A low-carbohydrate high-fat diet increases weight gain and does not improve glucose tolerance, insulin secretion or [beta]-cell mass in NZO mice. Nutrition & diabetes. 2016;6:e194.

[2] Cordain L, Miller JB, Eaton SB, Mann N, Holt SH, Speth JD. Plant-animal subsistence ratios and macronutrient energy estimations in worldwide hunter-gatherer diets. Am J Clin Nutr. 2000;71(3):682-692.

[3] Cordain L. The nutritional characteristics of a contemporary diet based upon Paleolithic food groups. Journal of the American Nutraceutical Association. 2002;5(5):15-24.


[5] Beales PE, Elliott RB, Flohe S, et al. A multi-centre, blinded international trial of the effect of A(1) and A(2) beta-casein variants on diabetes incidence in two rodent models of spontaneous Type I diabetes. Diabetologia. 2002;45(9):1240-1246.

[6] Cancelas J, Prieto PG, Villanueva-Penacarrillo ML, Malaisse WJ, Valverde I. Casein-rich diet reduces intestinal glucagon-like peptide 1 and may prevent hypoglycemia by increasing plasma glucose in rats. Nutrition research. 2006;26(6):297-302.

About Trevor Connor, M.S.

Trevor Connor, M.S.Trevor Connor was Dr. Loren Cordain’s last graduate student at Colorado State University. His research with Dr. Cordain focused on the effects of a Paleo style diet on autoimmune conditions. Their pilot study included close to 60 volunteers with diverse conditions ranging from Crohn’s Disease, to Multiple Sclerosis to Hashimoto’s Thyroiditis. The results were very promising, including all eight Crohn’s subjects going into remission on the Paleo Diet.

Trevor started working with Dr. Cordain in 2010, soon after retiring as a Professional Cyclist. At 38, he felt it was time to hang up the bike. Trevor had studied traditional sports nutrition for over a decade and was admittedly very reluctant to accept the Paleo Diet. But after experimenting with the diet himself, Trevor was able to return to the Pro Peloton at 40, getting Top Five’s in several races and establishing himself as the top ranked 40+ rider in the country for several years running.

Trevor now writes the Coaching Section of the international cycling magazine Velo, has his own coaching business, and recently managed the semi-Professional cycling team Team Rio Grande who’s alumni include Teejay Van Gaarderen, a top five finisher at the Tour de France and multiple national champions.

Trevor is currently working on publishing several studies and reviews on the effects of wheat on the digestive immune system. Recently, he moved back to Canada so his wife could pursue her dream of making the 2016 Olympics in pole vaulting (as a Paleo Dieter and ranked top 10 in the country in her mid-30’s.)

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“6” Comments

  1. You’ve explained why the casien is a deal-breaker for this being meaningful very clearly here.
    I don’t think peripheral glucose disposal is of much importance in diabetes;

    See http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2963523/

    “What about glucose disappearance? Was hyperglycemia due to lower rates in the diabetic subjects? As is evident from this slide, the answer is no. As is evident from the upper panel of Fig. 4, if anything the rates of glucose disappearance were higher in the diabetic subjects than in the nondiabetic subjects both before and after glucose ingestion…forearm glucose uptake did not differ in the diabetic and nondiabetic subjects.”

    The study was supposed to answer a question that is actually of great importance in diabetes research
    – the blood sugars of people with diabetes usually improve and can become completely normal on the LCHF diet – this is something that has been known for a century or more
    – if you challenge someone who is doing well on the LCHF diet with an oral glucose tolerance test (a sudden large carbohydrate load) their insulin response is often poor
    – is this a physiological adaptation to the diet, or does it indicate a risk of beta cell deterioration (as is usually seen after a few years when recommended high-starch diets are fed to people with type 2 diabetes)?

    The problem with the study, with regard to this question, is
    1) that the NZO mice chosen had a genetic defect, one that has never occurred in humans, which makes them fat-intolerant.
    2) the NZO LCHFD rats gained weight significantly, whereas most overweight humans lose weight on the LCHFD (or the Paleo diet) and it is very rare to gain a significant amount of fat mass.
    Weight is an important determinant of insulin resistance and glycemic control.
    3) there was no difference in the 4 parameters of beta-cell morphology in the LCHFD NZO mice despite their weight gain and insulin resistance.
    4) the diets were in no way designed to test the Paleo premise, which is that specific Neolithic and refined and processed modern foods have deleterious effects on the human organism, including with regard to weight and glycemic control.

    Thus the study was inconclusive on its own terms, and could shed little light on the effect of a LCHFD in humans, and press releases equating its results to the probable effect of a LCHF or a Paleo diet (2 different things) were wholly unjustified.
    These remarks and the wide publicity they received amount to unjustified interference in diabetes treatment methods that are working well.

    • As long as research will be sticked to macronutrients ratio, things will never move on. Food is much more important. Yams have a different effect of refined sugar or flour. In almost every study fake compounds have been used, because of the great misunderstanding of biology due to the need of an oversimplification of reality. But when you have billions of variables working together and you only rely on 3 i.e nacronutrients, and you NEVER go beyond them you are definetly lost.

  2. Isn’t the even bigger issue whether mice and humans are comparable in these kinds of studies? While animal models are tremendously important for studying many, or even most, phenomena it seems to me that the area of proper nutrition is not one of them. Even humans and chimpanzees, who are more gentically similar than humans and mice, naturally tend to eat very different diets. Whether the experiment described above is “paleo” from our perspective, it most certainly isn’t the point of view of the mouse.

    • I think that one of the misunderstandings for what the paleo community has been criticized, is due to the hazardous comparison of DNA. While It’s true that we share most of the DNA with chimps, the differences seem to be on epigenetic switches like the ones found in the “junk” DNA, and such differences drive the digestive and methabolic features. Thus, it should be established where are the similarities and the differences between species regarding what you want to study. If you look at the digestive features and organs proportion, we seem to have more to do with a mice than with a chimp, though it is our closest relative sharing more than 98% of the DNA. Said that, it may be possible that there are differences that may lead to wrong conclusions. Studies on humans, when possible to be performed, smartly designed without conflict of interest, are obviously the most reliable ones.

    • Great conversation everyone! I’m glad to see so many people pushing back against this study. Yes, comparing diets of mice and humans is an issue. Frankly, even within humans, our optimal diets vary depending on whether our ancestors originated from the equatorial region or northern latitudes.

      However that would be more of a concern to me if the study had actually tested a Paleo Diet on the mice. It didn’t.

  3. Either this biased research is driven by ignorance and misunderstanding or we should see who is the real funder of the research. It seems to me scientific misconduct since it’s really hard for me to imagine such ignorance from a researcher. Yet, in my opinion, this is another hint that food is much more important that macronutrients.

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