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I smell a rat, well actually prediabetic New Zealand Obese (NZO) mice.

By Mark J. Smith, Ph.D., Chief Science Officer
February 23, 2016
I smell a rat, well actually prediabetic New Zealand Obese (NZO) mice. image

In this month’s journal Nutrition & Diabetes, a paper titled “A low-carbohydrate high-fat diet increases weight gain and does not improve glucose tolerance, insulin secretion or β-cell mass in NZO mice” hit the headlines around the globe because of the University of Melbourne’s (home of the paper’s authors) publicity of the paper via an online article by Jane Gardner in Pursuit.

Of course the click-bait title of this article, “Paleo diets = weight gain”, is a little different from that of the journal paper in question. In fact, if you download the PDF version of the study and then search for the word Paleo or Paleolithic within Adobe Acrobat, you’ll discover something rather interesting. The word Paleo (or Paleolithic) isn’t used once in the actual paper!

I smell a rat, well actually prediabetic New Zealand Obese (NZO) mice. image

And, if you actually read the paper, you should expect that the word Paleo would not be used anywhere because absolutely nothing about the research pertains to Paleolithic nutrition for humans or; for that matter, Paleolithic nutrition for mice. Although, the fact that the control diet represents a better version of ancestral eating for mice, the study actually provides support for the premise that all species should follow a diet that closely resembles the diet consumed throughout the species’ evolution, including humans.

Okay, so, then, Jane Gardner must just have some bias against the Paleo diet and has simply referenced a study that she’s interpreted as “Paleo” because she’s heard the term “low-carbohydrate high-fat diet” (LCHFD) used alongside the Paleo diet on occasion, right? Unfortunately, after reading the first few typical anti-Paleo rhetoric lines of calling the Paleo diet a fad diet without scientific backing (the research is not difficult to find), it does not take you long to discover the article is based upon an interview with submitting author Associate Professor Sof Andrikopoulos. Andrikopoulos “was interested to learn whether the Paleo diet could benefit patients with diabetes or pre-diabetes”. If that was his main interest, he probably would have been better off simply reading some research1,2,3,4,5,6,7 conducted on humans using an actual diet attempting to emulate Paleolithic foods rather than conduct this ill-conceived study.

So flawed is the paper, that leading researcher in LCHFD, Professor Richard Feinman (Professor Bio) has written a letter to the editor of the journal calling for its retraction (Link Here)*.

Referring to the diet group, Dr. Andrikopoulos was further quoted as saying he “had been expecting some weight loss, but instead was completely surprised by the extent of the weight gains.” This seems disingenuous given that unlike humans that need dietary carbohydrates to be high, mice have been shown to gain weight on high-fat (low-carbohydrate) diets.8 And “the high fat-fed mouse is a widely investigated model of obesity, insulin-resistance and susceptibility to diabetes.”9

It is very clear that Andrikopoulos wants you to believe that this research is about the effects of a Paleo diet. He is even quoted as saying “the hypothesis was that the Paleo diet group would gain less weight and we would see improvements in glycemic control”. And in case you might be thinking he was misquoted in his use of “the Paleo diet”, Pursuit has been kind enough to provide a video of Associate Professor Andrikopoulos actually stating it for us. But why would Dr. Andrikopoulos, use “The Paleo diet group” when his paper doesn’t even use the word Paleo? Of course the paper would not have even been published if he had used the term Paleo diet for the diet group as the peer review process would pretty quickly eliminate it for the obvious non-Paleo criteria. Choosing to falsely use the term in an article is clearly a deliberate attempt to mislead the public – there is simply no other plausible explanation. A further misleading statement in the article by Associate Professor Andrikopoulos is “we are told to eat zero carbs and lots of fat on the Paleo diet.” No, that is not the message.

But why would a scientific researcher make purposefully misleading statements you might ask? Well, it’s no secret that the successful growth of the Paleo diet down-under has not been received well by the establishment and there has been a concerted effort to attack the diet itself for quite some time now. In particular, “celebrity” chef, Pete Evans, who has helped popularize the diet and, in doing so, helped thousands of individuals regain their health.

You might further ask, but why wouldn’t the establishment embrace a diet that is clearly helping thousands of people? Okay, I’m not going to insult your intelligence, I think you can figure that one out for yourself if, of course, you don’t already know the answer.

Finally, to his statement “If you put someone with a sedentary lifestyle on a high-fat, low-carb diet, I bet you that person will gain weight.”, be careful with that. I know a few people who would probably take that bet. The question is, Associate Professor Andrikopoulos, how much are you prepared to wager?

* For those without Facebook access, here is Professor Feinman’s letter to the editor of Nutrition & Diabetes.

Dear Professor Atkinson,

I am writing in regard to the paper by Lamont B, et al. Nutrition & Diabetes 2016, 6:1-7 which recommended against the use of low-carbohydrate high-fat diet (LCHFD). The recommendation follows from presumed risk based on experiments with 9 mice from a strain bred for susceptibility to metabolic abnormalities. The study ignored the dozens of studies, listed in their own references, comprising hundreds of human subjects, that contradicted the mice data. In addition, Dr. Andrikopoulos, the submitting author, participated in a wide-spread media program that was not scientifically accurate, included ad hominem attacks on all workers in the field and was outside of normal scientific protocol.

For these reasons, this paper should be retracted. The data should be subject to new peer review, sensibly including people with experience with LCHFD in humans.

There are numerous papers demonstrating the value of dietary carbohydrate restriction. Our review ([1], reference (5) in Lamont, et al.) includes 77 references and documents the evidence that nothing is better than LCHFD for obesity, diabetes and metabolic syndrome. We do not think that this is the final word and we are open to criticism. However, a study of 9 mice for eight weeks does not raise questions about this extensive body of knowledge.

Such a miniscule study would not be considered of major import even if it were exceptional but Lamont, et al. is not. The results are, in fact, ambiguous:

  1. The LCHFD had better improvement than control on TAG and HDL (“good cholesterol”) and there were no significant differences in total cholesterol or LDL. The ratio of HDL/TAG is considered one of the best indicators of CVD risk: the LCHFD conferred decreased risk.

2, The result that a reduction in dietary carbohydrate worsened glycemic control, if reproducible, would be a landmark phenomenon demonstrating that conditions could be found where an NZO mouse showed metabolic behavior completely the opposite of what is seen in humans. That increasing dietary carbohydrate will decrease blood glucose in humans is absurd and has been contradicted by thousands of recorded measurements.

  1. Similarly, the result (Figure 1) that the low-carbohydrate mice gained more weight even though they consumed fewer calories makes no sense at all. In fact, in the numerous diet studies in humans, the low-carb arm almost always loses more weight and critics claim that that is only because they took in fewer calories.

The paper and associated media reports exemplify the contentious nature of this field. Low carbohydrate diets have been the subject of unrestrained criticism and bias by the medical establishment for forty years. Even with this background, however, Lamont, et al. has crossed some line of irrational opposition to a therapy that has met every challenge for safety and efficacy and is widely used if not totally accepted. Dr. Andrikopoulos’s reported comments to the Mail, for example [2], that “In people with pre-diabetes or diabetes, the low-carb, high-fat (LCHF) diet could be particularly risky…. there is no scientific evidence that these diets work.” are completely out of line.

In the end, it is people struggling with obesity and diabetes who are the real victims of this breakdown in scientific practice. There is a serious ethical issue in that Andrikopoulos’s paper and his reported public statements are intended to deny a treatment to people with obesity, diabetes and metabolic syndrome, a treatment that, in fact, is established as effective and safe and is even included in the “individualization” recommended by health agencies. It is impossible to tell how much harm has been done but retraction of the paper will be a start to correction.

Richard David Feinman

  1. Feinman RD, Pogozelski WK, Astrup A, Bernstein RK, Fine EJ, Westman EC, Accurso A, Frassetto L, Gower BA, McFarlane SI et al: Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base. Nutrition 2015, 31(1):1-13.
    2. Hodgkins A: The Paleo diet is 'dangerous and increases weight gain', diabetes expert claims. In: Mail Online. 2016, last accessed, February 20, 2016.

Read our Further Responses to this Study:

Loren Cordain, Ph.D. Response
Trevor Connor, M.S. Response


[1] O’Dea K: Marked improvement in carbohydrate and lipid metabolism in diabetic Australian aborigines after temporary reversion to traditional lifestyle. Diabetes 1984, 33(6):596-603. (//[2] Jönsson T, Granfeldt Y, Ahrén B, Branell UC, Pålsson G, Hansson A, Söderström M, Lindeberg S. Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study. Cardiovasc Diabetol. 2009;8:35. (//

[3] Jönsson T, Granfeldt Y, Lindeberg S, Hallberg AC. Subjective satiety and other experiences of a Paleolithic diet compared to a diabetes diet in patients with type 2 diabetes. Nutr J. 2013 Jul 29;12:105. doi: 10.1186/1475-2891-12-105. (//

[4] Frassetto LA, Shi L, Schloetter M, Sebastian A, Remer T. Established dietary estimates of net acid production do not predict measured net acid excretion in patients with Type 2 diabetes on Paleolithic-Hunter-Gatherer-type diets. Eur J Clin Nutr. 2013 Sep;67(9):899-903. (//

[5] Tóth C, Clemens Z. Type 1 diabetes mellitus successfully managed with the Paleolithic ketogenic diet. Int J Case Pep Images. 2014 5(10):699-703. (//

[6] Tóth C, Clemens Z. Successful treatment of a patient with obesity, type 2 diabetes and hypertension with the paleolithic ketogenic diet. Int J Case Rep Images 2015;6(3):161–167. (//

[7] Masharani U, Sherchan P, Schloetter M, Stratford S, Xiao A, Sebastian A, Nolte Kennedy M, Frassetto L. Metabolic and physiologic effects from consuming a hunter-gatherer (Paleolithic)-type diet in type 2 diabetes. Eur J Clin Nutr. 2015 Apr 1. doi: 10.1038/ejcn.2015.39. (//

[8] Feinman RD, Pogozelski WK, Astrup A, et al. Dietary carbohydrate restriction as the first approach in diabetes management: Critical review and evidence base. Nutrition. 2015;31(1):1-13. (//

[9] Borghhjid S, Feinman RD. Response of C57BI/6 mice to a carbohydrate-free diet. Nutr. Metab. 2012; 9: 69. (//

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