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

This systematic review and meta-analysis investigated the impact of a single session of exercise (referred to as an "acute bout") on the levels of ghrelin, a hormone primarily known for stimulating appetite, in healthy adults.

The **intervention** was any structured acute bout of exercise. This means participants engaged in a single, defined session of physical activity.

The **comparator** was a control condition where participants did not engage in any exercise. This allowed researchers to isolate the effect of the exercise itself.

The **outcome measures** were the levels of ghrelin in the blood, specifically measured before a meal (pre-prandial). The researchers looked at three forms of ghrelin:

**Total Ghrelin (TG):** The overall amount of ghrelin circulating in the blood.

**Acylated Ghrelin (AG):** This is the biologically active form of ghrelin, making up about 22% of total ghrelin. AG is known to stimulate appetite, inhibit insulin release, and promote fat storage.

**Des-acylated Ghrelin (DAG):** This is the more abundant form, making up about 78% of total ghrelin. While its receptor is unknown, DAG has been shown to potentially counteract the effects of AG, promoting a negative energy balance, reducing fat mass, and improving insulin sensitivity.

The study also aimed to determine if factors like the participant's sex, age, body mass index (BMI), body fat percentage, fitness level, or specific characteristics of the exercise (intensity, duration, energy expenditure) influenced the ghrelin response.

The meta-analysis synthesized data from 24 individual studies, which collectively included 52 distinct experimental trials. In total, the analysis involved **504 healthy adult participants**.

The average characteristics of these participants were:

**Age:** 27.0 years, with a standard deviation of 8.8 years (meaning most participants were between 18 and 36 years old).

**Body Mass Index (BMI):** 24.7 kg/m², with a standard deviation of 2.7 kg/m² (indicating participants were, on average, in the healthy weight range, as a BMI between 18.5 and 24.9 is considered healthy).

All included participants were explicitly described as **healthy adults with no overt disease**. This means individuals with conditions like metabolic syndrome, Type 2 diabetes, or other significant health issues were excluded from the primary studies and, consequently, from this meta-analysis. The studies were conducted in various research settings, typically university laboratories or clinical research centers, as is common for controlled exercise and hormone measurement studies.

The primary outcome, ghrelin, was measured through **blood sampling**. Specifically, ghrelin levels were quantified from plasma, which is the liquid component of blood.

To capture the overall ghrelin response over time, the researchers focused on **pre-prandial total area-under-the-curve (AUCtotal)**. This method involves taking multiple blood samples while participants are in a fasted state (before eating) over a specific period after exercise. By plotting these ghrelin concentrations against time and calculating the area under the curve, researchers get a single value that represents the total ghrelin exposure during that fasted period. This is considered a more comprehensive measure than a single time-point reading.

For studies that reported AUC data directly, those values were used. For studies that did not report AUC but provided ghrelin concentrations at various time points in figures, the data points were extracted using **ImageJ software**. These extracted points were then used to manually calculate the AUCtotal using the **linear trapezoidal method**. All ghrelin values were standardized and recorded in **pg/mL (picograms per milliliter)**.

The specific forms of ghrelin measured varied across the included trials:

**Acylated Ghrelin (AG):** Measured in 38 trials.

**Des-acylated Ghrelin (DAG):** Measured in 7 trials.

**Total Ghrelin (TG):** Measured in 7 trials.

Other participant characteristics and exercise parameters were also extracted from the primary studies:

**Body Mass Index (BMI):** Typically measured using standard height and weight measurements.

**Body Fat Percentage (BF%):** Measured using various body composition assessment techniques (e.g., DEXA, bioelectrical impedance, skinfolds).

**Fitness:** Often assessed by peak oxygen uptake (VO2peak), measured during a graded exercise test.

**Exercise Intensity:** Quantified as a percentage of VO2peak (%VO2peak) or other objective measures.

**Exercise Duration:** The total time spent exercising.

**Exercise Energy Expenditure (EE):** The total calories burned during the exercise bout.

The consistency of data extraction was high, with two authors independently extracting data and demonstrating an interclass correlation coefficient of 1.0, indicating perfect agreement. If ghrelin time points or standard deviations were missing, study authors were contacted; if no response, standard deviations were imputed using reported baseline values.

This study was a **systematic review and meta-analysis** of **Randomized Controlled Trials (RCTs)**. This design is considered the highest level of evidence for determining the effectiveness of an intervention.

**How they ran the study:**

1. **Systematic Search:** Two independent authors systematically searched five electronic databases (PubMed, Medline, SPORTDiscus, Web of Science, and Google Scholar) for relevant articles published up to August 2020. They also manually checked reference lists of relevant studies, reviews, and book chapters. The search terms were specific: `((((adult) AND (physical activity OR exercise)) AND ghrelin AND human) NOT (child OR children OR adolescent OR rat OR mouse OR animal)))`. This comprehensive search aimed to identify all pertinent studies and minimize publication bias.

2. **Article Selection (Inclusion Criteria):** The authors applied strict pre-defined criteria for including studies in their analysis. These criteria were crucial for ensuring the quality and comparability of the pooled data:

* The study had to be a **Randomized Controlled Trial (RCT)**. This is a critical design feature, as RCTs are designed to minimize bias by randomly assigning participants to either an intervention (exercise) or a control (no exercise) group.

* The exercise had to be an **acute bout** (a single session).

* The exercise bout for the intervention group(s) had to be **structured**, meaning it followed a defined protocol.

* The control group/condition received **no exercise**.

* Participants were **adults aged 18 or older**.

* Ghrelin was sampled through **blood**.

* There was at least one **baseline measure** and one **post-exercise measure** of ghrelin.

* There were at least **3 timepoints** where ghrelin was measured while participants were **fasted** to allow for pre-pr