The Ketogenic Diet - What It Means For Neurological Disorders
The ketogenic diet follows a high-fat, moderate-protein, low-carbohydrate eating pattern that differs from most healthy eating guidelines.
Fruits, vegetables, whole grains, milk, and yogurt are just a few of the nutrient-dense foods that contain carbohydrates.
While the mechanisms underlying the ketogenic diet's anticonvulsant effects are unknown, there is mounting experimental evidence for its broad neuroprotective properties, as well as data indicating that it can be used to treat a variety of neurological disorders.
This fascinating clinical observation is the basis for the hypothesis that the ketogenic diet may have anti-epileptogenic properties.
The keto diet has been one of the most widely used treatments for epilepsy for hundreds of years. Various studies have recently examined the keto diet as a potential treatment for obesity and diabetes. There is very little research on the keto diet's benefits for these health conditions. Studies on the keto diet's effectiveness were conducted on small groups of people. In addition, the majority of Alzheimer's disease research is done on laboratory animals. To determine the safety of this eating pattern, more research is needed. Additionally, research on the keto diet's long-term health effects is required.
The speed with which different people produce ketones is influenced by their BMI and metabolic rates. This means that while everyone on the keto diet loses weight at the same rate, some people lose weight more slowly than others. The keto diet can be frustrating for this group of people, and it may detract from their desire to make healthy dietary changes. Furthermore, many people are unable to maintain the keto diet and revert to their previous eating habits, causing them to gain weight.
A keto diet for beginners
Over the last decade, researchers have discovered a number of mechanisms by which the ketogenic diet may provide neuroprotective activity.
Two hallmark features of ketogenic diet treatment are an increase in ketone body production by the liver and a reduction in blood glucose levels. The oxidation of fatty acids is the primary source of ketones.
Polyunsaturated fatty acids (PUFAs) such as arachidonic acid, docosahexaenoic acid, and eicosapentaenoic acid may regulate neuronal membrane excitability by blocking voltage-gated sodium and calcium channels, reducing inflammation by activating peroxisome proliferator-activated receptors (PPARs), or inducing the expression of mitochondrial uncoupling proteins that reduce reactive oxygen species (ROS) production.
The second major biochemical feature of the ketogenic diet is the reduction in glycolytic flux. Calorie restriction has been shown in a variety of animals, including primates, to reduce seizures and extend lifespan.
Finally, other mechanisms are likely to be involved in the neuroprotective effects of the ketogenic diet. Many of these mechanisms are thought to be linked to the ketogenic diet's anticonvulsant effects, but some, if not all, may also play a role in cellular homeostasis and the prevention of neuronal injury or dysfunction.
The Warburg effect is a well-known biochemical phenomenon in which cells with the highest metabolic rates are particularly sensitive to a lack of metabolic energy to fuel their activity. Depriving rapidly dividing, highly metabolic cancer cells of their normal fuel source, such as glucose, could theoretically be clinically beneficial. Despite this well-documented cellular finding, the ketogenic diet has only recently been considered as a clinical treatment for cancer.
Several studies published in the last decade have found that animals on a ketogenic diet with experimentally created brain tumors have significantly lower tumor growth rates, and these remarkable effects appear to be due to calorie restriction rather than ketogenic diet-induced ketosis as the primary mechanism.
Although no clinical trials of the ketogenic diet in patients with stroke have been conducted to date, several animal studies of hypoxia-ischemia support the diet's potential benefits. The ketogenic diet is used in the majority of these models, which results in less structural and functional damage following a stroke.
Given the growing body of evidence that the ketogenic diet improves mitochondrial function and biogenesis, it's only natural to wonder if patients with mitochondrial cytopathies could benefit from the ketogenic diet and/or ketone bodies like BHB.
At the same time, inherent mitochondrial dysfunction may predispose individuals to negative toxicities from high fatty acid loads, which may overwhelm β-oxidation within the mitochondrial matrix.
Many lines of evidence point to the rationale of therapeutically targeting mitochondrial bioenergetics for other disease states, as evidenced by the experimental data described above.
Unfortunately, both civilian and military populations are experiencing an increase in brain injury. A penetrating or blunt/blast injury to the brain can have serious cognitive and motor consequences.
Furthermore, the emergence of hyperexcitable neuronal circuits months to years after brain trauma increases the morbidity of affected individuals and points to the emergence of hyperexcitable neuronal circuits over time. As a result, given the clinical problem of post-traumatic epileptogenesis and the fact that the ketogenic diet can reduce seizure activity, the idea has emerged that dietary therapy could help with brain injury and possibly long-term consequences like epilepsy.
Although the ketogenic diet is thought to have mood-stabilizing properties, no clinical studies have been done as of this writing. The ketogenic diet's potential role in depression has been investigated in rats using a forced choice model of depression, which showed that it had a beneficial effect similar to that of conventional antidepressants.
Migraine is a type of paroxysmal neurological disorder that shares a lot of clinical phenotypic similarities with epilepsy. Despite the fact that the intrinsic mechanisms underlying seizures and migraine attacks are fundamentally different, there are theoretical reasons to consider the ketogenic diet for chronic migraine. Both disorders are characterized by paroxysmal excitability changes in the brain, and the pharmacological agents used to treat them share a lot of similarities.
Although it may seem unlikely that a migraine sufferer would follow such a complicated dietary regimen as the ketogenic diet, given the lack of better options, this option is worth considering, especially for those who have been medically refractory.
The ketogenic diet was first used for migraine treatment in 1928, just a few years after it was first used for epilepsy. Although the validity of this clinical study is questionable and some patients admit to poor compliance, nine of the 28 patients reported "some improvement."
Amyotrophic lateral sclerosis (ALS) is a disease that causes degeneration of the spinal cord's cortex and anterior horn. As a result, despite maintaining a high level of cognitive function, voluntary motor activity deteriorates over time, leaving the affected person profoundly weak. The fundamental pathophysiological mechanisms underlying this relentless disorder are unknown, but energy-producing systems are likely to play a role, and mitochondrial dysfunction is likely to contribute to disease pathogenesis, as is the case with other neurodegenerative disorders.
In this regard, a mouse model of ALS created by knocking out the gene encoding the copper/zinc superoxide dismutase SOD1-G93A, which results in progressive muscle weakness and death due to respiratory failure, suggests that the ketogenic diet could be a promising adjunctive treatment for this devastating disease.
The ketogenic diet improved the histological and functional outcomes of these mutant mice when compared to non-ketogenic diet fed animals. The ketogenic diet did not extend survival time in comparison to control mice fed a non-ketogenic diet. Mitochondria from these mutant mice produced more ATP, counteracting complex I inhibition of the electron transport chain.
Certainly, hyperglycemia has been repeatedly shown to be deleterious to the injured brain. During these times, an exogenous supply of ketones may force the brain to shift its reliance from glucose to ketones, thus taking advantage of improved transport and cellular metabolism.
The newest science suggests that a ketogenic diet — heavy on fat and very light on carbohydrates — could improve thinking in people with Alzheimer's disease, and that it may even help reduce the risk of the deadly brain disorder in the first place.
A ketogenic diet also increases the number of mitochondria, so called “energy factories” in brain cells. A recent study found enhanced expression of genes encoding for mitochondrial enzymes and energy metabolism in the hippocampus, a part of the brain important for learning and memory.
The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as β-hydroxybutyrate (βHB) and acetoacetate (AcAc), as occurs with fasting, prolonged starvation or chronic feeding of a high fat/low carbohydrate diet (ketogenic diet).
Despite a lack of clinical evidence, the ketogenic diet is increasingly being used to treat a variety of neurological disorders. These preliminary studies are based on the hypothesis that metabolic changes can have neuroprotective effects.
The ketogenic diet is a very restrictive way of eating. Due to the complexity of epilepsy treatment, research supports this eating pattern when managed in conjunction with a healthcare team. The verdict is still out on the keto diet as a tool for weight loss and other health benefits.