A ketogenic diet (KD) appears to be a promising therapeutic strategy for treating symptoms of mild traumatic brain injury (mTBI), early research suggests.
Results from a mouse study showed the high-fat, low-carbohydrate diet, which induces fat metabolism and ketone production, was associated with a reduction in TBI-induced cognitive impairment, neuronal loss, and neuroinflammation.
"Our results suggest that KD may be a vital treatment modality," Meirav Har-Even Kerzhner, a registered dietitian PhD student, Sackler Faculty of Medicine, Tel Aviv University, Israel, and colleagues write.
The investigators report they plan to conduct a similar study in humans with TBI.
The findings were published online December 7 in Scientific Reports.
No Proven Treatment
Military injuries, road accidents, falls, assaults, and sports injuries are the most common causes of TBIs.
It's estimated that about 2.8 million people in the United States receive medical care each year for a TBI, primarily as a result of road accidents, falls, assault, and sports injuries. Mild TBIs account for 80% to 95% of these cases. They are difficult to diagnose because routine tests, including imaging, fail to show changes in brain structure.
Patients with TBI can experience behavioral, emotional, and cognitive impairments that could include memory and concentration deficits, poor executive function, depression, and anxiety. The brain trauma is also a risk factor for diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). There is currently no proven effective treatment for TBI.
The ketogenic diet induces ketosis, a metabolic state in which the body uses ketone bodies as energy instead of glucose, and results in a state of fasting.
The diet has been used for years in patients with resistant epilepsy, but recent studies have explored its benefit in other neurologic disorders, including Parkinson's and Alzheimer's disease.
Previous research suggests a ketogenic diet may induce anti-inflammatory effects, improve the brain's ischemic tolerance, and reduce activated microglial expression. There are also indications the diet is neuroprotective, possibly through the alteration of SIRT1 expression.
SIRT1 is involved in developing the hippocampus and in various physiologic processes, such as oxidative stress response, genetic silencing, genome stability, and cell life extension, the investigators note.
"SIRT1 is a very important protein in the whole body but especially in the brain because it plays a really important role in cellular aging," Har-Even Kerzhner told Medscape Medical News.
Researchers used four groups of adult male mice for the experiments. In two groups with mTBI, some mice were fed the keto diet and others a standard diet. Two sham control groups with no injury were fed either a keto diet or a standard diet.
The ketogenic diet consisted of 90.5% fat, 9.2% protein, and 0.3% carbohydrate, while the standard diet consisted of 10.1% protein, 77.4% carbohydrate, and 12.5% fat. All mice were followed for up to 30 days.
To simulate an mTBI, mice were struck on the right temporal side of the head between the ear and corner of the eye.
"This model was chosen because it simulates traumatic head injuries such as road accidents or falls, as it imposes a diffuse and non-specific injury," write the investigators.
Compared with control mice without injury, those with TBI had decreases in visual and spatial memory and high levels of astrocytes and other markers of brain neuroinflammation.
Researchers also conducted a number of cognitive and cellular tests to measure effects of the keto diet. They found diet ameliorated the cognitive deficits in spatial and visual memory, as well as cellular changes in neurons and glial cells induced by the injury.
To better understand the molecular effects of diet and TBI, the investigators also evaluated SIRT1 levels in two brain regions that play a crucial role in memory formation: the cortex and hippocampus.
TBI reduced levels of SIRT1 in the cortex and hippocampus 30 days post injury, which was ameliorated by the keto diet. This, note the researchers, suggests a potential mechanism contributing to cognitive impairment and the improvement in cognitive symptoms when given this type of diet.
The researchers are now planning a clinical study in human patients with TBI. As the diet is extremely restrictive, the study will include consultations with registered dietitians, said Har-Even Kerzhner.
The plan is to assess cognitive outcomes with standard tests such as the Mini Mental State Exam and Montreal Cognitive Assessment, as well brain activity with EEG examinations at 1 month and maybe 3 months after diet initiation, she added.
The study was funded by the Ari and Regine Aprijaskis Fund, the Dr Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases, and the Sylvan Adams Sports Institute. The investigators have reported no relevant financial relationships.
Sci Rep. Published online December 7, 2021. Full article
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