Non-erosive reflux disease (NERD) is the most prevalent gastroesophageal reflux disease. Currently, proton pump inhibitors are the most commonly used treatment for NERD. Recently, the demand for herbal medicines with relatively few side effects is increasing and trials confirming the effectiveness and safety of herbal medicines for the treatment of NERD have been conducted. This study aimed to investigate the effectiveness and safety of herbal medicine in the treatment of NERD through published randomized-controlled trials. Ten electronic databases were searched from inception until May 2023. Disease, intervention-related terms, and publication type keywords were combined as search terms. Studies designed as randomized controlled trials, including participants diagnosed with NERD with any type of herbal medicine as a treatment intervention were included. Data extraction and analysis were conducted by 2 independent reviewers. The total clinical efficacy rate was assessed as a primary outcome, while the secondary outcomes were recurrence rate, reflux diagnostic questionnaire score, short-form 36 health survey score, and serum motilin level. The risk of bias in each study and quality of evidence were assessed. Thirty-four randomized controlled trials involving 3759 patients were analyzed. Herbal medicine was significantly more effective in improving total clinical efficacy, recurrence rate, reflux diagnostic questionnaire score, some domains of short-form 36 health survey, and serum motilin levels in patients with NERD than conventional medical therapy. No severe intervention-related adverse effects were observed. Regarding the quality of evidence, most outcomes were revealed to have moderate to low levels of evidence. This systematic review and meta-analysis suggests that herbal medicine can be an effective and safe therapy for NERD; however, there are several limitations regarding the methodological quality of the included studies. Further research with high methodological quality is necessary to improve the quality of evidence.
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