The Effect of Four-Week Intermittent Fasting from Dawn to Sunset on Circulating Brain-Derived Neurotrophic Factor Levels in Subjects with Metabolic Syndrome and Healthy Subjects

Abstract Background Brain-derived neurotrophic factor (BDNF) is a key neurotrophin that regulates food intake and energy hemostasis. BDNF also promotes neurogenesis, neuroplasticity, and neuroprotection. There are conflicting reports regarding how intermittent fasting affects circulating BDNF levels. We tested the hypothesis that 4-week intermittent fasting from dawn to sunset (4-week-IF) would decrease circulating BDNF levels in subjects with metabolic syndrome and healthy subjects. Methods We conducted pilot studies in subjects with metabolic syndrome and healthy subjects who fasted from dawn to sunset for more than 14 hours for four consecutive weeks. We measured serum BDNF levels and metabolic parameters before 4-week-IF, at the end of 4th week during 4-week-IF, and one week after 4-week-IF. Results We enrolled 28 subjects, 14 with metabolic syndrome (women/men:6/8) with a mean age of 59 years and 14 healthy subjects (women/men:1/13) with a mean age of 32 years. Overall, BDNF levels decreased at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF (mean paired difference= -98.5 ng/ml, P=0.0006). There was a lower mean paired reduction in BDNF levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF in the subjects with metabolic syndrome than the healthy subjects (mean paired difference= -27.6 ng/ml vs. -169.5 ng/ml, P=0.003). Multivariate linear regression analysis showed a positive correlation between the change in tumor necrosis factor-alpha and BDNF levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF in subjects with metabolic syndrome and healthy subjects. The change in weight and body mass index independently predicted the change in BDNF levels 1 week after 4-week-IF compared with the levels before 4-week-IF in subjects with metabolic syndrome. Conclusion Four-week-IF resulted in a reduction in the BDNF levels at the end of 4th week during 4-week-IF. Higher BDNF levels and a lower reduction in BDNF levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF in subjects with metabolic syndrome than healthy subjects suggest a potential BDNF resistance similar to insulin and leptin resistance in metabolic syndrome. A positive correlation between changes in the BDNF and tumor necrosis factor-alpha levels at the end of 4th week during 4-week-IF compared with the levels before 4-week-IF suggests that BDNF is a biomarker of inflammation and endothelial dysfunction in addition to its neurotrophic and anorexigenic features.