Rodent studies show that oligofructose promotes weight loss, stimulates satiety hormone secretion, reduces energy intake, and improves lipid profiles. Our objective was to examine the effects of oligofructose supplementation on body weight and satiety hormone concentrations in overweight and obese adults. This study was a randomized, double-blind, placebo-controlled trial. Forty-eight otherwise healthy adults with a body mass index (in kg/m2) > 25 were randomly assigned to receive 21 g oligofructose/d or a placebo (maltodextrin) for 12 wk. Body composition (by dual-energy X-ray absorptiometry); meal tolerance tests, including satiety hormone response; food intake; and subjective appetite ratings were determined. There was a reduction in body weight of 1.03 +/- 0.43 kg with oligofructose supplementation, whereas the control group experienced an increase in body weight of 0.45 +/- 0.31 kg over 12 wk (P = 0.01). A lower area under the curve (AUC) for ghrelin (P = 0.004) and a higher AUC for peptide YY (PYY) with oligofructose (P = 0.03) coincided with a reduction in self-reported caloric intake (P < or = 0.05). Glucose decreased in the oligofructose group and increased in the control group between initial and final tests (P < or = 0.05). Insulin concentrations mirrored this pattern (P < or = 0.05). Oligofructose supplementation did not affect plasma active glucagon-like peptide 1 secretion. According to a visual analog scale designed to assess side effects, oligofructose was well tolerated. Independent of other lifestyle changes, oligofructose supplementation has the potential to promote weight loss and improve glucose regulation in overweight adults. Suppressed ghrelin and enhanced PYY may contribute in part to the reduction in energy intake. The trial was registered at clinicaltrials.gov as NCT00522353.