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

J Physiol. 2023 Jun;601(11):2121-2137. doi: 10.1113/JP283582. Epub 2023 Jan 11.

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 20 h 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 ( V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ ) 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 V ̇ O 2 peak ${\dot V_{{{\rm{O}}_{\rm{2}}}{\rm{peak}}}}$ 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 20 h 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 (90 min) 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.

Keywords: BDNF; brain; exercise; fasting; ketones; lactate; substrate switch.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain-Derived Neurotrophic Factor*
  • Fasting
  • Follow-Up Studies
  • Humans
  • Lactic Acid
  • Neuroprotective Agents*

Substances

  • Brain-Derived Neurotrophic Factor
  • Neuroprotective Agents
  • Lactic Acid