The Study

Greco et al. (2015) studied the molecular mechanisms beyond the protective effects of ketogenic diet (KD) after a traumatic brain injury using adolescent rats. The majority of the damage caused by traumatic brain injury do not arise because of the traumatic event itself, but rather because of all the subsequent cellular and molecular changes occurring in the brain afterwards that are susceptible and lead to neuronal dysfunction and ultimately cell death. These processes are mediated by oxidative and nitrosative stress coming from a dysfunction of mitochondria, the energy-producing components of the cell. The main hypothesis is that KD can offer a protective effect against oxidative and nitrosative stress by providing ketones, known to have anti-inflammatory and antioxidant capabilities in the brain, instead of glucose as the main energy source.


Thirty-six adolescent rats of 35 days of age were used in this study. They received either a sham surgery or a controlled cortical impact representing a traumatic brain injury and were then assigned immediately to either a normal rat diet (59.8% carbohydrates, 6.2% fat, 18.6% protein and 4.5% fiber) or a KD (0.8% carbohydrates, 78.8% fat, 8.4% protein and 5% fiber).


Results obtained at 6 hours suggest that, early after the brain injury, it is most likely that ketones in high concentration in the brain have the ability to scavenge molecules responsible for the oxidative and nitrosative stress. As such, a significant decrease in oxidative and nitrosative stress were observed in post-traumatic brain injury KD-fed rats compared with rats fed with normal food. This is correlated by the findings that KD-fed rats had an increased expression of proteins with antioxidant properties both in the cytosol and the mitochondria. A subsequent preservation of the mitochondrial functions was also observed in KD-fed rats, as the alternative ketone fuel instead of glucose was used to produce energy. It is interesting to note that these results were observed in 35-day old adolescent rats, but not in the age-related controls of 70-day old adult rats. Those differences may be explained by the significant age-dependent decrease of enzymes responsible for ketone metabolism, as well as the age-dependent decrease in the number of transporters responsible for the effective entry of ketones in the brain.


In the context of juvenile traumatic brain injury, the scavenging by ketone of molecules responsible for oxidative damages and the subsequent preservation of mitochondrial functions mediated by the KD had significant protective effects against oxidative and nitrosative brain damages. These neuroprotective properties were most likely mediated by the abilities of ketones to induce multiple protective antioxidant pathways in the brain following an injury. However, the protective potential of KD in the case of traumatic brain injury was not observed in adult rats and might be limited to younger individuals.

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


Greco, T., Glenn, T. C., Hovda, D. A., & Prins, M. L. (2015). Ketogenic diet decreases oxidative stress and improves mitochondrial respiratory complex activity. Journal of Cerebral Blood Flow & Metabolism, 0271678X15610584.