ACTION Trial: Acupuncture vs. Sham in Diarrhea-Predominant Irritable Bowel Syndrome — Multicenter RCT (Gastroenterology 2025)

Diarrhea-predominant irritable bowel syndrome (IBS-D) affects between 5% and 10% of the global population and is one of the most common functional diagnoses in gastroenterology. Available pharmacologic options — antispasmodics, antidiarrheals, and serotonergic agonists such as eluxadoline — provide partial and inconsistent relief, with tolerability limitations during long-term use and response rates frequently below 50% in clinical trials. Patients with IBS-D often report functional impact disproportionate to the medical perception of disease severity, with restriction of social activities, work absenteeism, and impaired quality of life.

The ACTION trial (ACupuncTure in Irritable bOwel syNdrome), published in Gastroenterology (vol. 169, no. 5, pp. 958–969, October 2025), is the largest and most rigorous RCT to date on acupuncture for IBS-D. Multicenter, sham-controlled, and with a demanding composite endpoint, its results position medical acupuncture as a therapeutic alternative with robust evidence from a rigorous study — although consolidation as high-grade evidence will require independent replication — for a condition that conventional gastroenterology still manages unsatisfactorily.

Trial design and primary endpoint

Patients aged 18 to 75 years with a diagnosis of IBS-D by Rome IV criteria were randomized 1:1 to 15 sessions of real or sham acupuncture over six weeks (frequency of 2 to 3 sessions per week), followed by 12 weeks of follow-up without intervention. Of the 584 patients assessed for eligibility, 280 were randomized — 140 to each group — reflecting strict selection criteria.

The sham group used blunt-tip (non-penetrating) needles applied at non-acupuncture points, ensuring effective patient blinding. The composite primary endpoint was defined in a clinically relevant and conservative manner: at least 30% improvement in worst abdominal pain and concurrently a reduction of 50% or more in days with diarrhea at week 6 — a criterion that requires real benefit on both symptomatic axes of IBS-D. Analysis was conducted by intention to treat (ITT).

Main results

At week 6, the composite response rate was 57.9% in the acupuncture group (71 of 123 evaluable patients) versus 41.4% in the sham group (47 of 114 evaluable patients), with a risk ratio of 1.40 and robust statistical significance (p = 0.008). Separation of the response curves was evident from week 3 onward, indicating that clinical benefit emerges early in the treatment course and does not depend on the accumulation of multiple sessions to manifest.

Effects were maintained throughout the 18 weeks of total follow-up, with sustained statistical significance from week 3 in all weekly assessments — except at week 16, when there was a transient narrowing of the difference between groups. Consistent decline began only at week 16, that is, approximately 10 weeks after the end of sessions. No serious adverse events were attributed to acupuncture throughout the study.

Gut–brain axis mechanisms

The efficacy of acupuncture in IBS-D is biologically plausible and supported by multiple lines of mechanistic evidence. In mechanistic reviews, neuroimaging studies and biomarker work have documented that acupuncture modulates the gut–brain axis through several converging pathways: regulation of visceral hypersensitivity via brainstem nuclei (especially the nucleus of the solitary tract), modulation of colonic motility through parasympathetic autonomic pathways, reduction of pro-inflammatory cytokines in the intestinal mucosa (IL-6, TNF-alpha), and normalization of enteric serotonergic signaling — the intestinal 5-HT system, which directly controls colonic secretion and motility.

The fact that effects persist for more than 10 weeks after the end of sessions suggests that the functional changes induced by acupuncture have durability beyond the acute stimulus — consistent with the concept of neuroplasticity induced by repeated peripheral stimulation. Modulation of the gut–brain axis is not a transient effect of each session but a progressive functional reorganization that consolidates over the treatment cycle.