How Can a Ketogenic Diet Improve Motor Function?

Abstract

A ketogenic diet (KD) is a normocaloric diet composed by high fat (80–90%), low carbohydrate, and low protein consumption that induces fasting-like effects. KD increases ketone body (KBs) production and its concentration in the blood, providing the brain an alternative energy supply that enhances oxidative mitochondrial metabolism. In addition to its profound impact on neuro-metabolism and bioenergetics, the neuroprotective effect of specific polyunsaturated fatty acids and KBs involves pleiotropic mechanisms, such as the modulation of neuronal membrane excitability, inflammation, or reactive oxygen species production. KD is a therapy that has been used for almost a century to treat medically intractable epilepsy and has been increasingly explored in a number of neurological diseases. Motor function has also been shown to be improved by KD and/or medium-chain triglyceride diets in rodent models of Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and spinal cord injury. These studies have proposed that KD may induce a modification in synaptic morphology and function, involving ionic channels, glutamatergic transmission, or synaptic vesicular cycling machinery. However, little is understood about the molecular mechanisms underlying the impact of KD on motor function and the perspectives of its use to acquire the neuromuscular effects. The aim of this review is to explore the conditions through which KD might improve motor function. First, we will describe the main consequences of KD exposure in tissues involved in motor function. Second, we will report and discuss the relevance of KD in pre-clinical and clinical trials in the major diseases presenting motor dysfunction.

Dietary Intake of Parkinson's Disease Patients

“…Some studies suggest a protective effect of intake of different vitamins and antioxidants in PD, but further investigation is warranted (8). A ketogenic diet has also been proposed as treatment of motor dysfunction in neurologic disease, but lack of clinical data and risk of adverse events currently prevents the therapeutic use (9).…”

Evaluation of a ketogenic diet for improvement of neurological recovery in individuals with acute spinal cord injury: a pilot, randomized safety and feasibility trial

“…A wide variety of evidence [4][5][6][7][8][9][10] suggests that the ketogenic diet (KD) may have beneficial disease-modifying effects in a broad range of neurological disorders characterized by hyperexcitability and death of neurons. The diet is composed of 80-90% fat, with carbohydrate and protein constituting the remainder of the nutrient intake.…”

“…These fats are converted to the ketone bodies, β-hydroxybutyrate (BHB), acetoacetate, and acetone, which serve as an alternative energy source to glucose. Although the exact mechanism by which the diet provides neuroprotection is not fully understood, its effects on cellular energetics likely play a key role [10][11][12][13]. KDs increase circulating levels of ketone bodies, a more efficient fuel for the brain, resulting in enhanced capacity for energy production and an improved ability of neurons to resist negative metabolic challenges [14,15].…”

Ketogenic Diet-mediated Steroid Metabolism Reprogramming Improves the Immune Microenvironment and Myelin Growth of Spinal Cord Injury Rats Through Gene Analysis and Co-expression Network Analysis

“…The ketogenic diet has been widely used in the treatment of a variety of neurological and metabolicrelated diseases, especially epilepsy [22][23]. In recent years, some studies, including previous studies performed by our team, have shown that the ketogenic diet has a protective effect after spinal cord injury by increasing the spontaneous movement and ne manipulation of SCI animal models [17,[24][25]. However, the mechanism of treatment is still unclear.…”