Effect of Lower Doses of Colonic Nutrient Supplementation on Appetite Hormones and Food Intake in Obese Adults

Previous research by the investigators demonstrated that targeting specific dietary nutrients to the lower gut (colon) activates nutrient-sensing receptors (GPR84 and GPR120/FFAR4) on enteroendocrine L-cells, triggering release of appetite-suppressing hormones including PYY and GLP-1 into the bloodstream. In a proof-of-concept study (NCT04292236), colon-targeted delivery of DIM, lauric acid, and Perilla oil at a high dose reduced food intake in obese volunteers. Subsequent laboratory work demonstrated that DIM and Perilla oil alone were sufficient to trigger hormone release, allowing removal of lauric acid to produce a simpler two-component formulation. A subsequent clinical study (QMERC23.061) confirmed that this two-component formulation at a medium dose was equally effective. The current study aims to establish the minimum effective dose of this formulation by comparing a medium dose (250 mg DIM + 1050 mg Perilla oil) with a low dose (125 mg DIM + 525 mg Perilla oil), both delivered via GuardCap™ colon-targeted capsules (Evonik Industries, Germany) in a randomised, double-blind, parallel-arm design. A total of 16 participants with obesity completed the study (9 female, 7 male; mean age 46 years; mean BMI 33.8 kg/m²), with 10 participants allocated per arm. On the single study visit day, participants fasted from 20:00 h the previous evening. Capsules were administered at 08:00 and again at 12:00, with standardised gender-adjusted meals provided (total 2539 kcal for males and 2180 kcal for females across breakfast and lunch combined). Blood samples were collected every 30 minutes across 17 time points to measure circulating levels of PYY, GLP-1, active ghrelin, GIP, and 5-HT. Hunger and appetite perception were assessed using visual analogue scales (VAS) at each time point. Hormone AUC and total caloric intake were compared between dose groups using Student's t-test, and VAS scores were analysed using two-way ANOVA with Sidak's multiple comparisons test.