Effects of the ketogenic diet on cognition: a systematic review

Abstract

ABSTRACT Introduction: Ketogenic diet (KD) therapy has been used as a dietary intervention in drug-resistant epilepsy for several years. Research currently suggests that KD therapy may carry neuroprotective and cognition enhancing effects for individuals with non-epileptic conditions as well as for healthy individuals. Therefore, KD may have potential as a non-invasive, nutritional treatment approach for difficult to manage conditions such as neurodegenerative illnesses or mood disorders. The aim of this review is to summarize the available evidence on ketogenic interventions and the resulting cognitive outcomes. Materials and Methods: The paper was based on PRISMA 2020 guidelines. The search was conducted in June 2021 on the following databases: CENTRAL, PubMed, EMBASE, PsycInfo, Web of Science. The search yielded 2014 studies, of which 49 were included. Results: There were 22 animal studies assessing murine models and 27 studies on humans. The primary indications in these studies were epileptic conditions, neurodegenerative disorders, cognitive impairment, and healthy populations. Discussion: Administration of KD seems to confer cognitive-enhancing effects in areas such as working memory, reference memory and attention. Studies found that KD treatment in animals has the potential to alleviate age-related cognitive decline. Over 80% of the 27 human studies reported a favourable effect of intervention, and none reported a detrimental effect of KD. While these findings suggest that KD may improve the functioning of certain cognitive domains, definitive conclusions were limited by studies with small sample sizes, the absence of controls and randomization, and the lack of objective measures of cognition.