The Study

Douris et al. (2015) aimed to explore the short-term and the long-term effects of a ketogenic diet (KD) using mice model. It is interesting to note that, despite many previous studies of the short-term effects of a KD, it was the first study of the long-term effects of this particular type of diet in mice.


In the present study, they separated a group of 8-week old mice in two subgroups, one feeding on a normal diet and one feeding on a KD. The effects of the KD in comparison with the normal diet were then studied after 8 weeks to assess the short-term effects and after 66-80 weeks to assess the long-term effects.


KD-fed mice initially lost weight and started to gain back mass again, but at a lesser rate than the mice fed with a normal diet. Consequently, KD-fed mice remained leaner and lighter than their normal-fed counterparts throughout the duration of the study. KD-fed mice also spent more calories daily than mice fed with a normal diet. These findings suggest that KD-fed mice are less prone to obesity than normal-fed mice. Furthermore, KD-fed mice had better glucose levels and insulin responses than normal-fed ones, meaning that they were better at managing their glucose level and less susceptible to diseases such as type 2 diabetes.

Some minor negative effects were observed in KD-fed mice including higher levels of certain lipids in their liver, such as cholesterol and triglycerides, leading to a condition called fatty liver. Furthermore, molecules associated with inflammation were also more present in KD-fed mice. These effects were observed in the short-term group and were stable in time, meaning that they did not aggravate in the long-term group. Moreover, the authors suggest that the positive effects of the KD compensated for these negative effects.

All these effects revealed deep changes in the energy metabolism of KD-fed mice in comparison with normal-fed mice. These changes were mainly triggered by changes in the expression of different genes in KD-fed mice. For instance, the expression of genes involved in the metabolism of fatty acids was increased in KD-fed mice while the expression of genes involved in the production of different lipids was decreased. This is explained by the high fatty acid content of the KD that shifted the normal metabolism relying mainly on carbohydrates to produce energy for the body to another type of metabolism producing energy mainly from lipids. The KD-fed mice adapted their metabolism to produce energy from a high fat, low carbohydrates diet. Furthermore, the metabolism of amino acids, the component of proteins, was altered in KD-fed mice in order to slow down their degradation. As KD contains less amino acids than the normal diet, this is probably a necessary adaptation in order to preserve a sufficient level of essential amino acids to generate new proteins in the body.


Finally, it is interesting to note that KD-fed mice had approximately the same life expectancy than the normal-fed ones, meaning that KD has no incidence on the mortality and the morbidity in mice. Furthermore, this study did not find any harmful long-term adverse effects on health in the KD-fed group. On the contrary, the the authors were of the view that a KD seemed to bring many beneficial effects for the general health of the mice.

Study Editor

Marie-Christine Brotherton holds a Ph.D. in Cellular and Molecular Biology with specific expertise in Parasitology, Proteomics, Drug Resistance and Genomics. She also holds a MBA with a major in Corporate Social and Environmental Responsibility. She has strong experience with the scientific publication process, including author guidelines requirements, as well as with the medical and social/environmental fields. She can be reached by email at


Douris, N., Melman, T., Pecherer, J. M., Pissios, P., Flier, J. S., Cantley, L. C., … & Maratos-Flier, E. (2015). Adaptive changes in amino acid metabolism permit normal longevity in mice consuming a low-carbohydrate ketogenic diet.Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease1852(10), 2056-2065.