Fasting for 20h does not affect exercise-induced increases in circulating BDNF in humans.

Abstract

Intermittent fasting and exercise provide neuroprotection from age-related cognitive decline. A link between these two seemingly distinct stressors is their capability to steer the brain away from exclusively glucose metabolism. This cerebral substrate switch has been implicated in upregulating brain-derived neurotrophic factor (BDNF), a protein involved in neuroplasticity, learning and memory, and may underlie some of these neuroprotective effects. We examined the isolated and interactive effects of (1) 20-h fasting, (2) 90-min light exercise, and (3) high-intensity exercise on peripheral venous BDNF in 12 human volunteers. A follow-up study isolated the influence of cerebrovascular shear stress on circulating BDNF. Fasting for 20h decreased glucose and increased ketones (P≤0.0157) but had no effect on BDNF (P≥0.4637). Light cycling at 25% of peak oxygen uptake ( ) increased serum BDNF by 6 ± 8% (independent of being fed or fasted) and was mediated by a 7 ± 6% increase in platelets (P<0.0001). Plasma BDNF was increased from 336 pg l-1 [46,626] to 390 pg l-1 [127,653] by 90-min of light cycling (P=0.0128). Six 40-s intervals at 100% of increased plasma and serum BDNF, as well as the BDNF-per-platelet ratio 4- to 5-fold more than light exercise did (P≤0.0044). Plasma BDNF was correlated with circulating lactate during the high-intensity intervals (r=0.47, P=0.0057), but not during light exercise (P=0.7407). Changes in cerebral shear stress - whether occurring naturally during exercise or induced experimentally with inspired CO2 - did not correspond with changes in BDNF (P≥0.2730). BDNF responses to low-intensity exercise are mediated by increased circulating platelets, and increasing either exercise duration or particularly intensity is required to liberate free BDNF. KEY POINTS: Intermittent fasting and exercise both have potent neuroprotective effects and an acute upregulation of brain-derived neurotrophic factor (BDNF) appears to be a common mechanistic link. Switching the brain's fuel source from glucose to either ketone bodies or lactate, i.e. a cerebral substrate switch, has been shown to promote BDNF production in the rodent brain. Fasting for 20h caused a 9-fold increase in ketone body delivery to the brain but had no effect on any metric of BDNF in peripheral circulation at rest. Prolonged (90min) light cycling exercise increased plasma- and serum-derived BDNF irrespective of being fed or fasted and seemed to be independent of changes in cerebral shear stress. Six minutes of high-intensity cycling intervals increased every metric of circulating BDNF by 4 to 5 times more than prolonged low-intensity cycling; the increase in plasma-derived BDNF was correlated with a 6-fold increase in circulating lactate irrespective of feeding or fasting. Compared to 1 day of fasting with or without prolonged light exercise, high-intensity exercise is a much more efficient means to increase BDNF in circulation.