Intermittent Fasting Produces Indeterminate Effects on BDNF Levels in Humans

The circulating level of brain-derived neurotrophic factor (BDNF) is a widely-researched target for intervention. Increased BDNF seems to be wholly beneficial, particularly in its effects on neurogenesis, the production of new neurons and their integration into existing neural networks in the brain. Neurogenesis declines over the course of adult life, and is necessary to the function of memory and maintenance of brain tissue. Circulating BDNF, where levels also decline with age, might be the most convenient of the available mechanisms with which to affect neurogenesis. It can be increased by exercise, butyrate supplementation, and by interventions targeting the gut microbiome. Separately, BDNF also appears to influence muscle aging, reduce inflammatory microglial activation, increase dopamine levels, and slow metabolic aging, among other effects.

If exercise can increase circulating BDNF, what about intermittent fasting and calorie restriction? There is some evidence for this to work. In today's open access paper, researchers review the literature and find the results to be very varied, however. This suggests that either specific protocols are needed, or other factors interact meaningfully with reduced calorie intake, or both. It remains the case that both intermittent fasting and calorie restriction have been demonstrated to be great for long-term health, but it is always interesting to find evidence for a mechanism that may not be improved by these practices.

Effect of Calorie Restriction and Intermittent Fasting Regimens on Brain-Derived Neurotrophic Factor Levels and Cognitive Function in Humans: A Systematic Review

The potential positive interaction between intermittent fasting (IF) and brain-derived neurotrophic factor (BDNF) on cognitive function has been widely discussed. This systematic review tried to assess the efficacy of interventions with different IF regimens on BDNF levels and their association with cognitive functions in humans. Interventions with different forms of IF such as caloric restriction (CR), alternate-day fasting (ADF), time-restricted eating (TRE), and the Ramadan model of intermittent fasting (RIF) were targeted.

A systematic review was conducted for experimental and observational studies on healthy people and patients with diseases published from January 2000 to December 2023. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statements (PRISMA) for writing this review. Sixteen research works conducted on healthy people and patients with metabolic disorders met the inclusion criteria for this systematic review. Five studies showed a significant increase in BDNF after the intervention, while five studies reported a significant decrease in BDNF levels, and the other six studies showed no significant changes in BDNF levels due to IF regimens. Moreover, five studies examined the RIF protocol, of which, three studies showed a significant reduction, while two showed a significant increase in BDNF levels, along with an improvement in cognitive function after RIF.

The current findings suggest that IF has varying effects on BDNF levels and cognitive functions in healthy, overweight/obese individuals and patients with metabolic conditions. However, few human studies have shown that IF increases BDNF levels, with controversial results. In humans, IF has yet to be fully investigated in terms of its long-term effect on BDNF and cognitive functions. Large-scale, well-controlled studies with high-quality data are warranted to elucidate the impact of the IF regimens on BDNF levels and cognitive functions.