The effects of interval training on peripheral brain derived neurotrophic factor (BDNF) in young adults: a systematic review and meta-analysis

Abstract

The aim of the current meta-analysis was to determine the effects of acute and chronic interval training (IT) on serum and plasma BDNF concentrations in healthy young adults. A literature search was performed using six databases until February 2020. The TESTEX scale was used to assess the quality of studies. Effect sizes (ES) were computed and two-tailed α values < 0.05 and non-overlapping 95% confidence intervals (95% CI) were considered statistically significant. Heterogeneity, inconsistency (I²), and small-study effects using the Luis Furuya-Kanamori (LFK) index were examined. Fifteen studies (n = 277 participants, age = 24 ± 3 years) were included. The overall effects of IT on circulating BDNF concentrations were moderate and significant (ES = 0.62, 95% CI 0.00, 1.24, heterogeneous (p < 0.001), highly inconsistent (I² = 90%), and with major asymmetry (LFK index = 2.76). The acute effect of IT on peripheral BDNF levels was large and significant (ES = 1.10, 95% CI 0.07, 2.14), heterogeneous (p < 0.001), highly inconsistent (I² = 92%), and with major asymmetry (LFK index = 3.34). The chronic effect of IT on circulating BDNF was large and significant (ES = 0.93, 95% CI 0.40, 1.46), heterogeneous (p < 0.001), with moderate inconsistency (I² = 70%), and minor asymmetry (LFK index = 1.21). Acute and chronic IT elicited a moderate increase in serum and plasma BDNF concentrations in a healthy young population.

Figure 1

Flow diagram depicting the search process.

Figure 2

The overall effect of interval training (IT) on peripheral BDNF concentration. The lines indicate 95% confidence intervals (CI), and the square reflects the standardized differences (SMD) for each study. The diamond in the forest plot indicates the overall effect size (ES).

Figure 3

The effect of acute interval training (IT) on circulating BDNF concentration. The lines indicate 95% confidence intervals (CI), and the square reflect the standardized differences (SMD) for each study. The diamond in the forest plot indicates the overall effect size (ES).

Figure 4

The effect of chronic interval training (IT) on circulating BDNF concentration. The lines indicate 95% confidence intervals (CI), and the square reflects the standardized differences (SMD) for each study. The diamond in the forest plot indicates the overall effect size (ES).

Figure 5

Interval training increases circulating BDNF levels in healthy adults (upper right). During this response, the brain (hippocampal region) seems be the main BDNF source; nevertheless, other tissues function as BDNF synthesizers. The mechanism of activation during IT has not elucidated yet (above right). In brain, BDNF synthesis is activated by an increase of calcium (Ca2+) concentrations in the cytosol. Inside neurons, Ca2+ activates calmodulin dependent kinase II (CaMKII), triggering activation of the MAPK/ERK/MSK cascade resulting in an increase in the expression and phosphorylation of cAMP response element-binding protein (CREB). CREB initiates BDNF transcription resulting in increased BDNF synthesis and release (left). Once secreted, the neurotrophin regulates molecular mechanisms associated with neuronal growth, cognition, and neuron survival (above left). Finally, scientific evidence suggests that other circulating molecules such as lactate and estrogen enhance BDNF synthesis in brain (center). The putative mechanism indicate that lactate increases calcium current in the neurons, and estrogens activates nuclear estrogen receptors and membrane estrogen receptors that enhance the BDNF synthesis. Figure made with adobe illustrator cs6. https://www.adobe.com/products/illustrator/free-trial-download.html. Figure conceived and designed for PCGS.