Rodent keto studies

Next time someone says VLC/keto is harmful or at least not helpful for fat loss because of a new rodent study, they’ll probably be wrong.


Rodent studies on ketogenic diets or exogenous ketones are valuable and interesting in a variety of #contexts, although I’d argue that regulation of fat mass isn’t really one of ’em.

For starters, rodents aren’t particularly ketogenic – it’s rare to see ketones >1 after an overnight fast even in long-term ketoadapted mice.  Also, many rodents gain weight until they die, whereas humans plateau and stay relatively weight-stable for their entire lives (at least historically, and I’m not talking about yo-yo dieting).

Skeletal muscle, on the other hand, seems more similarly regulated: keto isn’t muscle-sparing in either specie… most people, perhaps unwittingly, increase protein intake on keto, and THIS spares muscle (N.B. this is simply to spare muscle, whereas in non-keto dieters, it’s not uncommon to see increased muscle in the #context of high protein).  That’s because carbs are more anabolic than fat.  QED.

There’s just a fundamental difference in the way fat mass and appetite is regulated between the species.  There are many similarities, which is why these studies are still valuable, but fat mass isn’t one of ‘em.



For example, in 8 recent keto rodent studies, 4 showed weight loss, 1 showed weight gain, 1 showed no effect and 2 showed mixed effects.



With no further ado, the studies:

Kennedy et al., 2007

Keto mice ate more but weighed less than controls; they had lower insulin, similar fat mass (higher body fat %), and less lean mass:


Kennedy body weight


Kennedy body composition



Badman et al., 2009

Wild-type keto mice: weighed less & ate more (NS), and no change in core body temperature (but presumably increased overall energy expenditure).  Note: body composition wasn’t assessed, but given all the other studies reviewed, it could’ve easily been less lean mass.

Genetically obese (ob/ob) keto mice: weighed more (NS), ate less, and had increased core body temperature!


Badman energy balance



Jornayvaz et al., 2010

Keto mice had a lower body weight, more fat mass, less lean mass, higher energy expenditure, and lower food intake relative to controls:


Jornayvaz energy balance



Kinzig et al., 2010

Keto rats had no difference in body weight or food intake:

[sorry, no good figures in this paper]



Garbow et al., 2011

Keto mice ate more but weighed less, had similar fat and slightly less muscle mass:


Garbow energy balance



Borghjid and Feinman, 2012

Keto mice ate the same amount of food but weighed WAY more:


Borghjid body weight



Bielohuby et al., 2013

LC-HF1 = higher protein, less ketogenic (they likened this to Atkins)
LC-HF2 = lower protein, more ketogenic

Food intake was controlled.

Both keto groups weighed less, had more fat mass, and less lean mass than controls… the high protein group fared slightly better with regard to body composition (as expected, because #protein):


Bielohuby body composition



Ellenbroek et al., 2014

Keto mice lost a little at first (artefact), but rapidly caught up to controls (despite remarkably high ketonez for mice):


Ellenbroek body weight


These studies are very nuanced: animals started at different ages, different duration and types/levels of fat & protein, etc.   All of these factors potentially played into the differential outcomes… maybe.  The full texts are free online, check ’em out!

In sum, I still think rodent studies are very valuable, just not so much in this #context: ketogenic diets and the regulation of appetite and fat mass.  “Muscle-sparing” is generally a product of higher protein (in both humans and rodents).



calories proper


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  • George

    More here from the early days –

    It seems that, prior to the breeding of disease model rats and mice, ketogenic diets (7:1) had no different effect on weight and growth from other diets. Of course, there were no DEXA scans in those days.

    • yep — we’ve used 5:1 and found no change in food intake or body comp, and most (but not all) of the expected metabolic effects, eg, profound IGT & low HbA1c

      Nerd alert: I still think it’s an exciting area of research! currently involved in some studies on glucagon & muscle/liver metabolism, cognitive stuff, and of course various circadian effects

      also looking into models other than C57 mice & SD rats

  • rs711

    how do you think the (x7, is it?) faster rodent metabolism plays into the different effects on 1) lean 2) fat mass than seen in humans? I know it’s a bit of general question, but still curious about it…

    • no major differences in the regulation of lean mass and changes in fat mass are all over the board… so no consistent effect of the “faster rodent metabolism” is really feasible

      • rs711

        ok thanks!

  • Phil Thompson

    “We conclude that B-OHB decreases leucine oxidation and promotes protein synthesis in human beings.” Nair et al. infused ketones and tracer study of amino acids.

  • TechnoTriticale

    That’s a lot of papers to dive into, with no assurance of necessarily discovering precisely what the KD chows were (Harlan?). The chows are often a confounding mess – perhaps not being as LC as supposed, and/or being loaded with non-native modern fake fats like canola or other potentially inflammatory forms of ?6.

    Aside on canola (mutant rapeseed, often GMO as well): do wild rodents even eat rapeseed if they have any other choice? (legit question – I don’t know)

    • You’re killing me!

      these studies reflect a variety of different keto diets; the thing in common is “ketosis”

      most of the time, the fats are lard-based

      Lab rodents happily eat canola! They’ll eat just about anything.