The Effects of Intermittent Fasting on Brain and Cognitive Function

Abstract

The importance of diet and the gut-brain axis for brain health and cognitive function is increasingly acknowledged. Dietary interventions are tested for their potential to prevent and/or treat brain disorders. Intermittent fasting (IF), the abstinence or strong limitation of calories for 12 to 48 h, alternated with periods of regular food intake, has shown promising results on neurobiological health in animal models. In this review article, we discuss the potential benefits of IF on cognitive function and the possible effects on the prevention and progress of brain-related disorders in animals and humans. We do so by summarizing the effects of IF which through metabolic, cellular, and circadian mechanisms lead to anatomical and functional changes in the brain. Our review shows that there is no clear evidence of a positive short-term effect of IF on cognition in healthy subjects. Clinical studies show benefits of IF for epilepsy, Alzheimer's disease, and multiple sclerosis on disease symptoms and progress. Findings from animal studies show mechanisms by which Parkinson's disease, ischemic stroke, autism spectrum disorder, and mood and anxiety disorders could benefit from IF. Future research should disentangle whether positive effects of IF hold true regardless of age or the presence of obesity. Moreover, variations in fasting patterns, total caloric intake, and intake of specific nutrients may be relevant components of IF success. Longitudinal studies and randomized clinical trials (RCTs) will provide a window into the long-term effects of IF on the development and progress of brain-related diseases.

Keywords: brain-related diseases; cognition; intermittent fasting; prevention and progress.

Figure 1

Different forms of intermittent fasting.

Figure 2

Biochemical pathways involved in the metabolic switch. During intermittent fasting, glucose levels drop and through the process of lipolysis, fats (triacylglycerols and diacylglycerols) are metabolized to free fatty acids (FFAs). These lipids are then transported to the liver where they through the process of β-oxidation and the intermediate stages acetyl CoA and HMG-CoA are transformed into the ketones: acetoacetate (AcAc) and β-hydroxybutyrate (BHB). BHB and AcAc are transported from the blood into the brain and then into neurons. In addition to ketones metabolized in the liver, astrocytes are also capable of ketogenesis, which may provide an important local source of BHB for neurons. The reduction in availability of glucose and elevation of ketones lowers the AMP: ATP ratio in neurons, which activates the kinases AMPK and CaKMII and, in turn, through the activation of CREB and PGC1α stimulates autophagy. In addition, lower levels of glucose during fasting decrease the activity of the mTOR pathway, leading to autophagy. BHB can also upregulate the expression of brain-derived neurotrophic factor (BDNF) and may thereby promote mitochondrial biogenesis, synaptic plasticity, and cellular stress resistance. IF leads to lower levels of circulating insulin in the blood, which enhances neuroplasticity and protection against metabolic and oxidative stress through the insulin/IGF signaling pathway. Retrieved from [18] with small modifications.