Affecting over 50 million people worldwide, Alzheimer’s disease (AD) is the one of the most significant contributors to dementia.1 This multifactorial disease state is comprised of a progressive decline in memory, impaired self-care, and personality changes. Based on the current research, the ketogenic diet may be a suitable nutritional therapy to help mitigate the early stages of AD and possibly stave off its progression. According to Rusek et al., there may be several aspects of the ketogenic nutritional profile that may support its use as suitable dietary intervention for AD. The pathology of AD involves the progressive deposition of amyloid B-peptides and phosphorylated tau proteins leading the neurotoxicity. Patients with AD may present with metabolic changes that occur intracellularly leading to the propagation of these amyloid-B fragments. As a result, there may be reduced glucose uptake, inefficient glycolysis, and downregulation of glucose transporter (GLUT1). It has been observed that a dietary regimen high in carbohydrates may be associated with a reduced insulin resistance and may further increase the risk of developing AD. In addition, altered glucose metabolism may lead to an increase of advanced glycation end products (AGEs).1 These end products have been also associated with AD pathology. It is believed though that the ketogenic diet (KD) may circumvent and possibly attenuate the metabolic disruption involved.
When patients transition to a ketogenic diet, they are supposed to follow a macronutrient ratio of 4 g of fat to 1 g of carbohydrates.1 They may consume no more than 10% of their daily intake in the form of carbohydrates. This transition in macronutrient utilization may be drastic, but nonetheless beneficial for this specific population. Like glucose, both fatty acids (FA) and ketone bodies (Acetone and B-hydroxybutyrate) can pass through the blood brain barrier. They can provide energy to the brain and essentially bypass glycolytic pathways. Scientists have found that ketones may be more efficient at providing an energy source compared to glucose. By bypassing glycolytic pathways, they can directly enter the citric acid cycle and provide immediate adenosine triphosphate (ATP) or energy for the cell. These beneficial downstream metabolic changes in the cell lead to increase mitochondrial biogenesis and function. The resulting ketosis also leads to a lower concentration of serum glucose resulting in protection from neuronal loss. It is also believed that the ketogenic diet increases the expression of the uncoupling proteins (UCP) involved in the electron transport chain during oxidative respiration.1 UCP has been found to reduce the expression of reactive oxygen species (ROS) and thereby, may decrease potential oxidative stress in the brain as well. By providing an alternative energy source in the form of ketones, a portion of metabolic function in the brain might be restored and benefit a patient diagnosed with AD in a multitude of ways.
References
- Rusek M, Pluta R, Ulamek-Koziol M, Czuczwar SJ. Ketogenic Diet in Alzheimer’s Disease. International Journal of Molecular Medicines. 2019;20(3892). doi:10.3390/ijms20163892