Effect of vagus nerve stimulation on metabolism: a systematic review and meta-analysis

Vagus Nerve Stimulation (VNS) has long been a standard surgical procedure for patients with treatment-resistant depression or epilepsy. However, several studies have confirmed a side-effect of VNS treatment as weight loss. Animal model studies (e.g., rats, minipigs) and clinical trials have shown promising outcomes regarding weight and appetite, but further statistical analysis is limited.

We searched PubMed and several databases for rat model studies, minipig model studies, and human trials between 1966 and March 2024. All reported changes in weight, appetite, and energy expenditure were assessed. Meta-analysis was employed to calculate the overall pooled effects across studies with different durations or measurements.

Of the 529 papers identified, 15 studies were eligible for this meta-analysis, including 12 animal trials and 4 human randomized controlled trials (RCTs). VNS showed a significant effect on reducing weight gain in both animal models (rats 95% CI -0.91 to -0.27, I² = 88%, Z = 3.60, P = 0.0003; minipigs 95% CI -209.17 to -36.61, I² = 98%, Z = 2.79, P = 0.005) and human trials (95% CI 1.06 to 2.07, I² = 98%, Z = 6.11, P < 0.00001). VNS also significantly reduced appetite (95% CI -6.47 to -5.82, I² = 95%, Z = 36.91, P < 0.00001) and changed energy expenditure (95% CI -2.83 to -0.81, I² = 80%, Z = 3.53, P = 0.0004) in the rat model. The effect on human energy expenditure could not be estimated.

VNS has demonstrated notable impacts on reducing weight, suppressing appetite, and enhancing energy expenditure in rat and minipig models, indicating a promising therapeutic application in addressing metabolic disorders. Human trials also showed the effectiveness and safety of VNS on metabolism.