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 h 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). When subjects with metabolic syndrome were compared with healthy subjects, subjects with metabolic syndrome had 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 (BDNF 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 change 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 (P = 0.040) and healthy subjects (P = 0.007). 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 the change in BDNF and change in 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.

Molecular Study of the Protective Effect of a Low-Carbohydrate, High-Fat Diet against Brain Insulin Resistance in an Animal Model of Metabolic Syndrome

“…It promotes neurogenesis, neuroplasticity, and neuroprotection. Furthermore, BDNF is an anorexigenic protein that regulates the body's energy hemostasis [39]. Like in our results, Lee et al [40], Motamedi et al [41], Jamali et al [42], and Abdulsada et al [39] reported that BDNF is downregulated in MetS and is involved in the pathogenesis of neurodegeneration.…”

Alterations in anthropometric, inflammatory and mental health parameters during Ramadan intermittent fasting in a group of healthy people: a prospective cohort study

“…Some studies showed a significant increase of BDNF levels during RIF ( 35 ). Whereas another study showed a decrease of BDNF levels during RIF ( 44 ). These conflicting reports regarding how IF influence BDNF levels might be because of the different time periods of RIF due to geographical differences and seasonal variations.…”

The impact of dawn to sunset fasting on immune system and its clinical significance in COVID-19 pandemic

“…Several studies of dawn to sunset fasting conducted in subjects with obesity, type 2 diabetes mellitus, or metabolic syndrome showed that dawn to sunset fasting improves components of metabolic syndrome [ 17 , 47 , 57 , 98 ]. The improvement in metabolic components was associated with decreased pro-inflammatory cytokines and oxidative stress parameters and upregulation of the genes that play a pivotal role in immune defense [ 48 , 63 , 64 , 102 ]. A study conducted on 14 subjects with metabolic syndrome showed a significant reduction in body weight, body mass index, and waist circumference at the end of the 4th week during 4-week dawn to sunset fasting and one week after 4-week dawn to sunset fasting [ 17 ].…”

“…This study also showed significant improvement in systolic, diastolic, and mean arterial blood pressures at the end of the 4th week during 4-week dawn to sunset fasting and a significant reduction in homeostatic model assessment for insulin resistance one week after 4-week dawn to sunset fasting [ 17 ]. Another study showed that the levels of brain-derived neurotrophic factor (BDNF), a food intake regulator [ 103 ] decreased during 4-week dawn to sunset fasting compared with baseline BDNF levels, and there was a positive correlation between changes in the BDNF and TNF-α levels at the end of the 4th week during 4-week dawn to sunset fasting suggesting that BDNF may have a role in inflammation attenuated by dawn to sunset fasting [ 102 ]. As dawn to sunset fasting leads to improvement in metabolic parameters; this is one physiologic way of decreasing the risk of morbidity and mortality associated with COVID-19 [ [83] , [84] , [85] , [86] ].…”