{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T05:16:04Z","timestamp":1783055764442,"version":"3.54.6"},"reference-count":26,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Gallstone disease is a major global health concern with a steadily increasing prevalence, affecting approximately 7% of the global population and imposing substantial health and economic burdens. Globally, gallstone disease accounts for 10\u201315% of all gastrointestinal hospital admissions, with annual direct medical costs exceeding $6 billion in the United States and \u00a520 billion in China, primarily driven by cholecystectomy and post-surgical complications. According to clinical observations, oral administration of olive oil may facilitate the expulsion of small gallstones; however, high-quality evidence supporting this dietary therapy remains limited. In our preliminary study, a 6-day regimen of orally administered functional fatty acids effectively promoted the elimination of small gallstones.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to evaluate the efficacy and safety of oral functional fatty acid supplementation for facilitating the expulsion of small gallbladder stones, and to assess its potential as a noninvasive therapeutic option. The primary endpoint is the complete expulsion rate of small gallbladder stones at day 3 post-intervention, confirmed by two independent blinded ultrasound technologists. The complete expulsion rate at day 6 post-intervention is designated as a key secondary endpoint.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This prospective, single-center, double-blind, randomized controlled trial will enroll 100 adult patients with ultrasonographically confirmed small gallstones (maximum diameter &amp;lt;2\u202fmm) and no prior treatment history. Participants will be randomly assigned at a 1:1 ratio to either the intervention group (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f50), which will receive 50\u202fmL of functional fatty acids daily on an empty stomach for 6 consecutive days, or the control group (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f50), which will receive placebo for the first 3\u202fdays followed by the same dose of functional fatty acids for the subsequent 3\u202fdays. Abdominal ultrasound examinations will be performed on days 3 and 6 post-intervention to assess gallstone expulsion. Adverse events, including nausea, vomiting, abdominal pain, diarrhea, and signs of biliary obstruction, will be closely monitored throughout the study period.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>If proven effective, this intervention could provide a noninvasive alternative to surgery for patients with small gallstones, inform clinical practice, and help reduce the healthcare burden associated with gallstone disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>ClinicalTrials.gov<\/jats:ext-link>\n                      , identifier: NCT06699030\n                    <\/jats:p>\n                  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