Ketogenic Diet in Alzheimer’s Disease

Abstract

At present, the prevalence of Alzheimer’s disease, a devastating neurodegenerative disorder, is increasing. Although the mechanism of the underlying pathology is not fully uncovered, in the last years, there has been significant progress in its understanding. This includes: Progressive deposition of amyloid β-peptides in amyloid plaques and hyperphosphorylated tau protein in intracellular as neurofibrillary tangles; neuronal loss; and impaired glucose metabolism. Due to a lack of effective prevention and treatment strategy, emerging evidence suggests that dietary and metabolic interventions could potentially target these issues. The ketogenic diet is a very high-fat, low-carbohydrate diet, which has a fasting-like effect bringing the body into a state of ketosis. The presence of ketone bodies has a neuroprotective impact on aging brain cells. Moreover, their production may enhance mitochondrial function, reduce the expression of inflammatory and apoptotic mediators. Thus, it has gained interest as a potential therapy for neurodegenerative disorders like Alzheimer’s disease. This review aims to examine the role of the ketogenic diet in Alzheimer’s disease progression and to outline specific aspects of the nutritional profile providing a rationale for the implementation of dietary interventions as a therapeutic strategy for Alzheimer’s disease.

Influence of the Mediterranean and Ketogenic Diets on Cognitive Status and Decline: A Narrative Review

“…In recent years, several hypotheses have been proposed to explain the neuroprotective role of KBs [23]. Some studies have shown that during a long period of starvation, KBs may provide up to 70% of cerebral energy requirements, representing a more efficient energy source than glucose due to the fact that KBs can enter directly into the Krebs cycle to produce ATP, while glucose needs to be first metabolized through glycolysis [118].…”

“…Data from recent studies show that reducing the intake of trans-fat and saturated fats, (e.g., red and processed meats); decreasing the consumption of dairy products; and increasing intake of fruits, vegetables, legumes, and whole grains could be associated with the improvement of cognitive function and prevention of AD [19,20]. Moreover, it has been suggested that different eating patterns, including Mediterranean diet (MedDi), Ketogenic Diet (KD), caloric restriction, Dietary Approaches to Stop Hypertension (DASH), and Mediterranean-DASH diet Intervention for Neurological Delay (MIND), could possibly reduce the pathophysiological hallmarks of AD [19,[21][22][23].…”

“…Among others, in the last decade, the MedDi and KD have been the two most studied eating patterns for their possible beneficial effect on cognitive functions. Both of them have, in fact, demonstrated to be effective in reducing or delaying cognitive impairment in older people by acting through different pathophysiological mechanisms [22][23][24]. Table 1 synthetizes the most important features of these two dietary patterns.…”

The Role of Dietary Antioxidants in the Pathogenesis of Neurodegenerative Diseases and Their Impact on Cerebral Oxidoreductive Balance

“…Single studies with human participants have demonstrated a reduction of neurodegenerative symptoms after application of ketogenic diet [198,199]. The presence of ketone bodies has potent mitochondrial effects modulating the expression of enzymes involved in mitochondrial metabolism and increasing mitochondrial biogenesis in key brain regions such as the hippocampus.…”

“…The presence of ketone bodies has potent mitochondrial effects modulating the expression of enzymes involved in mitochondrial metabolism and increasing mitochondrial biogenesis in key brain regions such as the hippocampus. Under the influence of ketone bodies, the concentration of ROS in the organisms decreases, while the biosynthesis of GSH and SOD2 increases [198,200].…”