The effect of acute exercise on pre-prandial ghrelin levels in healthy adults: A systematic review and meta-analysis

Background: Ghrelin is a gut hormone with numerous physiological effects, including the regulation of energy balance, insulin sensitivity, vascular health, and body composition. Acylated (AG) and des-acylated (DAG) ghrelin constitute approximately 22 % and 78 % of total plasma ghrelin (TG), respectively. Alterations in the TG concentration and the AG/DAG ratio may be implicated in conditions involving energy imbalances and insulin resistant states (e.g., metabolic syndrome or Type 2 diabetes mellitus). Exercise is a therapeutic option that can potentially optimize ghrelin levels. Understanding the precise intensity and dose of exercise to optimize ghrelin levels may lead to targeted interventions to restore metabolic regulation in obesity and other clinical conditions. Objective: To perform a systematic review and meta-analysis on the effects of acute exercise on pre-prandial levels of TG, AG, and DAG in healthy adults and to determine if sample demographics or exercise doses moderate such effects. Methods: Electronic databases (PubMed, Medline, SPORTDiscus, Web of Science, and Google Scholar) were searched with articles published through August 2020. The following criteria was determined a priori for article inclusion: (i) the study was a randomized controlled trial (RCT),(ii) exercise was an acute bout, (iii) the exercise bout for the intervention group(s)/condition was structured, (iv) the control group/condition received no exercise, (v) participants were adults age 18 or older, (vi) ghrelin was sampled through blood, (vii) there was at least one baseline measure and one post-exercise measure of ghrelin, (viii) there were at least 3 timepoints where ghrelin was measured while participants were fasted to allow for pre-prandial total area-under-the-curve (AUC(total)) calculation, (ix) participants were healthy with no overt disease, (x) interventions were carried out without any environmental manipulations. Standardized mean difference (SMD) with 95 % confidence intervals were calculated using the restricted maximum likelihood estimation Moderator analyses to determine whether the overall pooled effect was influenced by: sex, ghrelin form, method of ghrelin analysis, age, body mass index, body fat percentage, fitness, intensity of exercise bout, duration of exercise bout, energy expenditure, and length of AUC(total) data. Results: The analysis included 24 studies that consisted of 52 trials, n = 504 (age 27.0 (8.8) years, BMI 24.7 (2.7) kg/m(2)) and measured AG (n = 38 trials), DAG (n = 7), and TG (n = 7). The overall model indicated that exercise lowered ghrelin levels compared to control (no exercise); (SMD=-0.44, p < 0.001), and exercise intensity exhibited an inverse relationship with ghrelin levels (regression coefficient (beta)=-0.016, p = 0.04). There was no significant difference by ghrelin form (p = 0.18). Discussion: Acute exercise significantly lowers plasma ghrelin levels, with higher intensity exercise associated with greater ghrelin suppression. The majority of studies applied a moderate intensity exercise bout and measured AG, with limited data on DAG. This exercise dose may be clinically significant in individuals with metabolic dysregulation and energy imbalance as a therapy to optimize AG levels. More work is needed to compare moderate and high intensity exercise and the ghrelin response in clinical populations.