Herbal and Natural Products for NSAID-Induced Small Intestinal Injury: a systematic review and meta-analysis of randomized controlled trials

Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin, are widely used medications that frequently cause small intestinal injury (enteropathy).Conventional proton pump inhibitors do not prevent this injury and may exacerbate it through dysbiosis.Herbal medicines and natural products offer potential therapeutic benefits, but synthesized clinical evidence remains limited.Thus, this study will systematically evaluate the efficacy and safety of herbal medicines and natural products for preventing NSAID-induced small intestinal injury.Methods: MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and the China National Knowledge Infrastructure will be searched to identify articles published since inception, without restrictions on publication date or language.Randomized controlled trials involving adults aged ≥ 18 years receiving NSAIDs will be included.Two reviewers will independently perform study selection, data extraction, and risk-of-bias assessment using the RoB 2 tool.If appropriate, a meta-analysis will be conducted.The primary outcome will be mucosal injury, objectively assessed using video capsule endoscopy or measures of intestinal permeability.Secondary outcomes will include symptoms and adverse events.Results: This study will synthesize the current clinical evidence on natural interventions for NSAID-induced enteropathy.Conclusion: The findings will inform the management of small intestinal injury and guide future research.