Energy Restriction Enhances Adult Hippocampal Neurogenesis-Associated Memory after Four Weeks in an Adult Human Population with Central Obesity; a Randomized Controlled Trial

Abstract

Adult neurogenesis, the generation of new neurons throughout life, occurs in the subventricular zone of the dentate gyrus in the human hippocampal formation. It has been shown in rodents that adult hippocampal neurogenesis is needed for pattern separation, the ability to differentially encode small changes derived from similar inputs, and recognition memory, as well as the ability to recognize previously encountered stimuli. Improved hippocampus-dependent cognition and cellular readouts of adult hippocampal neurogenesis have been reported in daily energy restricted and intermittent fasting adult mice. Evidence that nutrition can significantly affect brain structure and function is increasing substantially. This randomized intervention study investigated the effects of intermittent and continuous energy restriction on human hippocampal neurogenesis-related cognition, which has not been reported previously. Pattern separation and recognition memory were measured in 43 individuals with central obesity aged 35–75 years, before and after a four-week dietary intervention using the mnemonic similarity task. Both groups significantly improved pattern separation (P = 0.0005), but only the intermittent energy restriction group had a significant deterioration in recognition memory. There were no significant differences in cognitive improvement between the two diets. This is the first human study to investigate the association between energy restriction with neurogenesis-associated cognitive function. Energy restriction may enhance hippocampus-dependent memory and could benefit those in an ageing population with declining cognition. This study was registered on ClinicalTrials.gov (NCT02679989) on 11 February 2016.

Late-life intermittent fasting decreases aging-related frailty and increases renal hydrogen sulfide production in a sexually dimorphic manner

“…8). These memory improvements were in line with previous DR studies in which DR (1) improves memory in adults [150] and older adults [45], (2) protects against hippocampal-dependent memory deficits and accumulations of hippocampal amyloid β-peptide plaques and neurofibrillary tangles in Alzheimer's disease model of mice [76], and (3) rejuvenates hippocampal transcriptome profiles in middle-aged mice [151]. Additionally, similar to our present findings, Li et al (2013) [73] showed that 11-month long EOD fasting in CD-1 wild-type male mice produced time-dependent memory enhancements.…”

The Effects of Intermittent Fasting on Brain and Cognitive Function

“…Therefore, this could indicate that IF might primarily have positive effects on cognition later in life when insulin sensitivity and glucose metabolism decays. However, Kim and colleagues did not find any differences of improvement in neurogenesis-associated memory after a PF diet between healthy younger subjects (from 35 years old) and healthy older subjects (till 75 years old) [153]. In addition, Brandhorst and colleagues also did not find age differences on reduced risk factors for age-related diseases and stroke vulnerability in healthy subjects after a 3-month FMD compared to a control group [146].…”

“…There are more studies that report indications of a reduced risk for neurological diseases due to IF in healthy people. For instance, lowered APP levels [74], enhanced hippocampal neurogenesis [153] and decreased mTOR pathway activity [21], which are all protective of developing AD [154]. An interesting translational effort was done by Brandhorst et al, 2015, where middle aged mice (20 months) and 38 human adults (age 20 -68 years) followed a FMD protocol.…”

Intermittent fasting enhances long-term memory consolidation, adult hippocampal neurogenesis, and expression of longevity gene Klotho

“…Calorie restriction (CR), typically defined as a 10-40% total reduction in daily calorie intake, and intermittent fasting (IF), typically involving every-other-day feeding, are two established dietary paradigms that extend life-and healthspan across species [1][2][3][4][5]. A recent study demonstrated that adoption of 30% CR or a single meal feeding strategy for 10 months enhanced longevity and health status in mice, regardless of whether their content was high or low in sugar [6].…”