Investigating the Therapeutic Potential of the Ketogenic Diet in Modulating Neurodegenerative Pathophysiology: An Interdisciplinary Approach

Abstract

The ketogenic diet (KD) is a dietary intervention comprising a high-fat, low-carbohydrate, and moderate-protein intake designed to induce a metabolic state known as ketosis, whereby ketone bodies are produced as an alternative source of energy. Initially established as a treatment for intractable epilepsy, the KD has subsequently gained significant attention for its potential to manage neurodegenerative diseases, including Alzheimer's, Parkinson's, and Huntington's disease. Ketone bodies, such as beta-hydroxybutyrate (BHB), have been demonstrated to possess neuroprotective properties. The increasing prevalence of neurodegenerative diseases, such as Alzheimer's, Parkinson's, and Huntington's disease, poses a significant public health challenge worldwide. With neurological disorders being the second-leading cause of death globally, the need for effective therapeutic interventions has never been more urgent. Recent evidence suggests that dietary interventions, particularly the ketogenic diet, offer promising potential in mitigating the progression of these diseases by influencing metabolic processes and providing neuroprotective benefits. The ketogenic diet, characterized by high-fat and low-carbohydrate intake, induces ketosis, leading to the production of ketone bodies like beta-hydroxybutyrate, which enhance mitochondrial efficiency, reduce oxidative stress, and modulate inflammatory pathways-mechanisms critical in neurodegenerative pathophysiology. This review explores the role of the ketogenic diet in managing neurological conditions, examining its mechanisms of action, historical context, and therapeutic efficacy. The paper also discusses emerging evidence linking the ketogenic diet to improved cognitive function, reduced motor symptoms, and enhanced mitochondrial activity in patients with neurodegenerative disorders. Additionally, the review highlights the need for further research to refine the therapeutic applications of the ketogenic diet, investigate its impact on various neurodegenerative diseases, and better understand its potential long-term effects. This study underscores the importance of nutrition as a vital aspect of the treatment strategy for neurological diseases, advocating for continued exploration of dietary interventions to improve brain health and function.

Keywords: Alzheimer’s disease; Parkinson’s disease; beta-hydroxybutyrate; cognitive function; ketogenic diet; mitochondrial function; neurodegenerative diseases; neuroprotection.

Figure 1

The proposed method by which the ketogenic diet may maintain brain health and enhance cognitive function.

Figure 2

A reduction in carbohydrate intake can result in an elevation of the ketone bodies (KBs) produced by the liver. The liver is unable to utilize ketone bodies (KBs) due to the absence of the mitochondrial enzyme succinyl-CoA:3-ketoacid (alkaloid). The enzyme acetoacetate transferase (SCOT) facilitates the conversion of acetoacetate to acetoacetyl-CoA. Following this, succinyl-CoA:3-CoA transferase (SCOT) and methylacetoacetyl-CoA thiolase (MAT) facilitate the conversion of succinyl-CoA into acetyl-CoA, which allows for the entry of KBs into the citric acid cycle.

Figure 3

The biology of Alzheimer’s disease includes the basic biological processes and mechanisms that contribute to the disease’s appearance and advancement. The various factors that contribute to Alzheimer’s disease progression are shown in Figure 1. Amyloid plaques and hyperphosphorylated tau are the main factors that play a role. The development of senile plaques is facilitated by extracellular amyloid formation. The cytoskeleton and signal transmission in neural cells are disrupted by hyperphosphorylated tau, which also causes microtubules to break down. Neuroinflammation, oxidative stress, acetylcholine weakness, mitochondrial dysfunction, and autophagy failure all greatly contribute to the progression of the condition.

Figure 4

This new figure illustrates the key molecular pathways involved in Parkinson’s disease and how the ketogenic diet may influence them.

Figure 5

We have included a figure that highlights the neuroprotective effects of the ketogenic diet on Huntington’s disease pathology, focusing on mitochondrial dysfunction and neuroinflammation.