Does Neuroinflammation Underlie the Cognitive Changes Observed With Dietary Interventions?

Abstract

Dietary interventions, such as calorie restriction and ketogenic diet, have been extensively studied in ageing research, including in cognitive decline. Epidemiological studies indicate beneficial effects of certain dietary regimes on mental health, including mood disorders and dementia. However, randomised-controlled trials (the gold-standard of evidence-based medicine) on calorie restriction diets and the ketogenic diet have yet to show clinically convincing effects in neuropsychiatric disorders. This review will examine the quality of studies and evidence base for the ketogenic and calorie restriction diets in common neuropsychiatric conditions, collating findings from preclinical experiments, case reports or small clinical studies, and randomised controlled clinical trials. The major cellular mechanisms that mediate the effects of these dietary interventions on brain health include neuroinflammation, neuroprotection, and neuromodulation. We will discuss the studies that have investigated the roles of these pathways and their interactions. Popularity of the ketogenic and calorie restriction diets has grown both in the public domain and in psychiatry research, allowing for informed review of the efficacy, the limitations, and the side effects of these diets in specific patient populations. In this review we will summarise the clinical evidence for these diets in neuropsychiatry and make suggestions to improve clinical translation of future research studies.

Metabolic correction of neurodegenerative pathologies: the role of macronutrients and timing

“…It is worth mentioning a popular dietary regimen, caloric restriction, which reduces food intake without incurring malnutrition. In fact, both the KD and caloric restriction diets are thought to act primarily through the same mechanisms as both diets result in an overall reduction in caloric intake and an increased level of circulating ketone bodies [93,105,106]. Indeed, the caloric restriction regimen represents a specific case of intermittent fasting, which is discussed below.…”

β-Hydroxybutyrate Regulates Activated Microglia to Alleviate Neurodegenerative Processes in Neurological Diseases: A Scoping Review

“…Additionally, it has been demonstrated that the ketogenic diet (KD) has comparable health advantages [ 23 , 24 , 25 , 26 ]. This low-sugar, moderate-protein, high-fat diet was recently discovered to significantly increase the life expectancy of aged mice while maintaining their physiological functions in comparison to controls [ 23 ].…”

“…This low-sugar, moderate-protein, high-fat diet was recently discovered to significantly increase the life expectancy of aged mice while maintaining their physiological functions in comparison to controls [ 23 ]. As it mimicked caloric restriction, it presented similar health outcomes in terms of disease improvement through increased ketone body production [ 24 , 27 ]. These molecular breakdown products of ketones are typically known as substitutes for fuel under glucose-deprived conditions [ 28 ].…”