Hwang · Antioxidants (Basel, Switzerland) 2026 · systematic review · n=22 studies

Protective Effects of Natural Products, Functional Foods, and Probiotics on NSAID-Induced Small Intestinal Injury: A Systematic Review with Mechanistic Considerations of Oxidative Stress and Microbiome Modulation.

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Level 1 - systematic review of randomized trials

Systematic review of predominantly randomized controlled trials

PubMed 42510634 · doi:10.3390/antiox15070903 · record verified 2026-08-26

What was done

A systematic review was conducted searching PubMed, Embase, CENTRAL, and CNKI through January 2026. The authors included randomized studies evaluating natural products, functional foods, and probiotics for preventing or treating NSAID- or aspirin-induced enteropathy in adults, assessed via capsule endoscopy or intestinal permeability testing. Risk of bias was assessed with RoB 2 and ROBINS-I. Due to substantial clinical and methodological heterogeneity, results were synthesized narratively across 22 included studies (21 randomized controlled trials and one quasi-randomized trial).

What was found

The abstract reports no pooled numerical effect estimates or confidence intervals. Geranylgeranylacetone demonstrated protective effects in 3 of 4 capsule endoscopy studies. Lactoferrin, zinc carnosine, and fish protein hydrolysate reduced indomethacin-induced intestinal hyperpermeability. Probiotics showed outcome-dependent effects, with more consistent benefits on capsule endoscopy mucosal injury than on permeability outcomes. Among randomized trials, 3 had low risk of bias, 15 had some concerns, and 3 had high risk of bias.

Why it matters

Options for managing NSAID-induced enteropathy are limited. This review identifies candidate natural and probiotic agents that may reduce mucosal injury and hyperpermeability, establishing specific targets for future confirmatory research.

Limits

No meta-analysis could be performed due to substantial heterogeneity. The total number of human participants was not reported in the abstract. Most included randomized trials (18 of 21) had risk-of-bias concerns or high risk, resulting in an overall low or very low certainty of evidence.

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