Mice on an Ad Lib Keto Diet

Here is a nice paper from 2009 on mice fed an ad libitum ketogenic diet (Kennedy AR, Pissios P, Otu H, Roberson R, Xue B, Asakura K, Furukawa N, Marino FE, Liu FF, Kahn BB, Libermann TA, Maratos-Flier E. A high-fat, ketogenic diet induces a unique metabolic state in mice. Am J Physiol Endocrinol Metab. 2007 Jun;292(6):E1724-39. Epub 2007 Feb 13).

The study looked at:

C57BL/6 mice animals were fed one of four diets:

1) KD;

2) a commonly used obesogenic high-fat, high-sucrose diet (HF);

3) 66% caloric restriction (CR); and

4) control chow (C).

Calories were the same but weight was lower on the ketogenic diet.

Mice on KD ate the same calories as mice on C and HF, but weight dropped and stabilized at 85% initial weight, similar to CR.

In fact, they moved mice from the High Fat High Carb diet to the Ketogenic diet and had the following:

Animals made obese on HF and transitioned to KD lost all excess body weight, improved glucose tolerance, and increased energy expenditure. 

Even more along my own area of interest:

KD fed mice had a unique metabolic and physiological profile, exhibiting increased energy expenditure and very low respiratory quotient

The macronutrient composition of the diets was interesting:

Macro	Chow	HF	KD
Fat	16.7%	45%	95.00%
Protein	26.80%	24%	0%
Carbs	56.40%	35%	5%

Note this was not a high protein KD. I.e., The dietary advantage wasn’t protein. The percentage of calories from protein was the lowest on the KD – by far. This is a much higher level of fat than most people will tolerate and the protein level is pretty low.

Most telling was the body composition changes (Table 5).

DEXA	Chow	KD	HF
Fat	4.54	5.16	13.27
Lean	28.98	23.85	30.59
Mass	33.52	29.01	43.86
%BF	13.5%	17.8%	30.3%

The Chow fed mice were a bit over 10% heavier but at a lower % of Body Fat (13.5%) vs the Ketogenic fed mice. This can be attributed to the much lower protein consumption of the KD.

A contrasting study (Protein Leverage Hypothesis Counterpoint) showed an inflection point around 70% for fat where additional fat did not result in additional weight. In my opinion (study needed) – substituting protein for some of the fat should not be an issue.

The study concluded:

the effects that diet composition can have on metabolism and found that diets high in fat and low in carbohydrate do in fact lead to weight loss by increasing energy expenditure. 

Remarkably, animals eating ketogenic diet lost a small amount of weight and achieved the same weight and body composition as animals that were calorie restricted to 66% of usual daily intake.

In a related paper (Bielohuby M1, Menhofer D, Kirchner H, Stoehr BJ, Müller TD, Stock P, Hempel M, Stemmer K, Pfluger PT, Kienzle E, Christ B, Tschöp MH, Bidlingmaier M. Induction of ketosis in rats fed low-carbohydrate, high-fat diets depends on the relative abundance of dietary fat and protein. Am J Physiol Endocrinol Metab. 2011 Jan;300(1):E65-76) noted the same issue with KD :

One problem with ketogenic LC-HF diets is that it is difficult to attribute observed effects (e.g., loss of body weight) to either the presence of ketone bodies or to the normally very low protein content of these diets.

The ideal ketogenic diet for research purposes would be a LC-HF diet that is ketogenic but ensures the sufficient supply of protein at the same time. However, until now, it is not clear whether the absence of dietary carbohydrates per se or the absence of carbohydrates in combination with a specific abundance of the two other macronutrients, fat and protein, is required to induce ketosis.