Is the Ketogenic diet only for weight loss?
Diets are not always created or used for the main purpose of weight loss. Diets also may be used to mitigate chronic disease. Studies support that nutrition therapy, specifically the Ketogenic diet (KD), may be considered as a course of treatment for neurological disorders.
Ketogenic diet and neurological disorders
There is evidence supporting the efficacy of the Ketogenic diet for the treatment of neurological disorders, such as epilepsy and Alzheimer’s disease. Cerebral blood flow (CBF) and the blood-brain barrier (BBB) play a major role in the determination of cognitive capability and impact neurovascular integrity. Studies have shown that neurovascular integrity may be regulated by the gut microbiome.
A focus on promoting a healthy gut microbiome and in turn, preserving neurovascular integrity may be achieved through the implementation of the KD. Studies have shown that the KD increased the relative supply of microbiota assumed to protect neurovascular integrity; subsequently, the KD reduced the microbiota related to inflammation.
A counter to the support of the efficacy of the KD in aiding in the treatment of neurological disorders is that the KD decreased the diversity of the microbial. Reduced microbial diversity is associated with disease progression. A study conducted by Ma et al. found while the microbial diversity may have decreased, the quantity of beneficial microbiota increased.
Ketogenic diet in treating Epilepsy
Glucose, fatty acids, and ketone bodies are some of the major fuel sources for the body.
Glucose is the primary fuel source for the brain. Glucose, fatty acids and ketone bodies are the primary fuel sources for muscles. Traditionally, glucose is positioned as the primary fuel source for most body functions. While that is not incorrect, there have been studies supporting the theory of ketones functioning as a primary fuel source as well.
The majority of glucose utilization in humans can be replaced with ketone body and fatty acid utilization. The body’s glucose needs may also be produced from other substance inputs, such as fat. This finding challenges the traditional belief that glucose should be considered as a primary fuel source for the body. It also supports the consideration of another fuel source, such as ketone bodies, as an alternative.
The discovery of the KD’s positive effects in the treatment of epilepsy have resulted in further studies exploring how this approach mitigates the symptoms associated with the disorder. Gamma-amino butyric acid (GABA) is an amino acid acting as a neurotransmitter in the central nervous system. GABA inhibits nerve transmission in the brain resulting in calming nervous activity. GABA is dependent on the maintenance of low level intracellular concentration, which is driven by the neuron specific potassium chloride cotransporter-2 (KCC2). Studies have shown the response of KCC2 is suppressed in epileptic patients. A decrease of KCC2 expression levels and a decrease in GABA inhibiting effects is present in patients diagnosed with epilepsy.
Support of the utilization of the KD in treating epilepsy generates from a focus on the prevention of neuronal overexcitation. Neuronal overexcitation is achieved through:
- Changes in brain pH.
- Direct inhibition of ion channels.
- Shifts in amino acid metabolism to favor the conversion of the stimulatory glutamate to the neurotransmitter GABA (as a result of the inhibiting properties of GABA).
Ketone bodies produced by the KD provoke a response on GABA polarization by supplementing, bypassing or modulating the effects of down-regulated KCC2.
So, what does this mean?
Since KCC2 is found to be suppressed in epileptic patients and KCC2 maintains the low level intracellular concentration in the neurotransmitter, GABA (which calms nervous activity), the presence of ketone bodies can help the negative effects from the suppression of KCC2. This may help epileptic patients control or temper seizure activity associated with the disorder of epilepsy.
Mitochondrial disorders are common genetic disorders of energy metabolism that weaken tissues with high-energy requirements, such as the brain, and tend to manifest themselves as seizures. This infers that seizures may be induced by a decrease in nutrient supply or the reduction of a specific substrate metabolism. This is of importance since studies have shown that the ketone body metabolizing pathways aid in reducing some of the mitochondrial respiratory chain complications associated with mitochondrial disorders. Mitochondrial biogenesis is the “formation of new mitochondria.” This is an important process as it reduces reactive oxygen species (ROS) damage and results in the increased response of host antioxidant defenses. Ketone bodies have shown to impede the mitochondrial production of ROS, as well as, provide protection in promoting the antioxidant effect. These results also support the consideration of nutrition therapy through the implementation of the KD in the management of epilepsy.
Ketogenic diet in treating Alzheimer’s disease
Alzheimer’s disease (AD) is the primary cause of dementia and affects about 24 million people worldwide. The prevalence of the disorder is expected to double every 20 years.
The progression of AD is related to the toxic amyloid beta plaque and tangles in the brain resulting in the deterioration of cells. While much research on AD has been focused on controlling and understanding this factor of the disorder, the cause of the underlying plaque and tangles has shown to be related to neurometabolic issues. As a result, there has been a focus in identifying other methods in treating the underlying associated symptoms through dietary interventions such as the KD.
One of the earliest signs of AD is impaired glucose metabolism on the brain. The adult brain consumes 20–30% of the body’s energy requirements mainly through glucose. The ketone bodies produced as a bi-product of the high fat intake associated with the KD can be used as a supplementary energy source for the brain, which increases mitochondrial efficiency and cognitive function. Similar to glucose, ketones are more than fuel for cells, they also support a glutamatergic function. A difference between glucose and ketones is ketones generate adenosine triphosphate (ATP) uniquely via oxidative phosphorylation; whereas, glucose is metabolized by aerobic glycolysis producing lactate, which then generates ATP. As a result, if the brain is provided with more ketones, it may aid in the deficit in glucose uptake and metabolism which would then delay brain energy exhaustion and possibly minimize the risk of AD. The ability for ketone bodies to cross the blood-brain barrier (BBB) supports the hypothesis that ketones are an alternative energy source to glucose for the brain.
Another important factor to consider in implementing a dietary intervention such as the KD in the treatment and possible prevention of AD is the reduced glucose utilization that occurs in AD. While glucose utilization declines, ketone body utilization does not. This further supports the beneficial impacts of relying on ketones as a primary energy source to glucose through the KD for patients diagnosed with AD.
As referenced previously, studies have also shown that higher levels of ketone bodies are associated with lowered levels of amyloid beta plaque, which is a primary symptom associated with AD.
In fact, the metabolic pathway of one of the ketone bodies, BHB, has shown to reverse amyloid beta toxicity and repair the damage caused by it. There has also been research relating the role of the ApoE gene and intake of carbohydrates and how that is attributed to the development of AD. It has been proposed that diets higher in carbohydrate intake (lower in fat intake) result in excessive blood glucose levels and these higher levels damage important proteins, such as the ApoE protein. ApoE proteins are prone to glycation which then turns the proteins into advanced glycation end-products (AGEs). AGEs are found in large amounts in the cerebrospinal fluid and brains of patients diagnosed with AD. This evidence supports the consideration to implement the KD for patients diagnosed with AD.
Implementation of the Ketogenic diet as a method of treating neurological disorders is a legitimate consideration as an alternative to medicinal means. The research in the efficacy of the KD in treating neurological disorders, specifically epilepsy and Alzheimer’s disease, is still developing; however, there is strong evidence to support the consideration of nutritional therapy such as the KD in the treatment of these disorders. While there are still outstanding concerns regarding the KD’s biochemical impact and its effects on the brain and its role in ketoacidosis, the KD offers many beneficial results in the treatment of epilepsy and AD.
- Ma D, et al. Ketogenic diet enhances neurovascular function with altered gut microbiome in young healthy mice. Scientific Reports. 2018;8(6670):1–11. doi:10.1038/s41598–018–25190–5.
- Clanton RM, Wu G, Akabani G, Aramayo R. Control of seizures by ketogenic diet-induced modulation of metabolic pathways. Amino Acids. 2016;49(1):1–20. doi:10.1007/s00726–016–2336–7.
- Chen L, et al. KCC2 downregulation facilitates epileptic seizures. Scientific Reports. 2017:7(156):1–13. doi:10.1038/s41598–017–00196–7.
- Broom GM, Shaw IC, Rucklidge JJ. The ketogenic diet as a potential treatment and prevention strategy for Alzheimer’s disease. Nutrition. 2019;60:118–121. doi:10.1016/j.nut.2018.10.003.
- Cunnane SC, Courchesne‐Loyer A, St‐Pierre V, et al. Can ketones compensate for deteriorating brain glucose uptake during aging? implications for the risk and treatment of Alzheimer’s disease. Annals of the New York Academy of Sciences. 2016;1367(1):12–20. doi:10.1111/nyas.12999.
- Pinto A, Bonucci A, Maggi E, Corsi M, Businaro R. Anti-Oxidant and Anti-Inflammatory Activity of Ketogenic Diet: New Perspectives for Neuroprotection in Alzheimer’s Disease. Antioxidants. 2018; 7(5):63. doi:10.3390/antiox7050063.
- Taylor M, Sullivan D, Mahnken J, Burns J, Swerdlow R. Feasibility and efficacy data from a ketogenic diet intervention in Alzheimer’s disease. Alzheimer’s & Dementia. 2018;28–36:1–9. doi:10.1016/j.trci.2017.11.002.