A Randomized Clinical Trial of a Standardized Pumpkin-Seed-Derived Peptide Extract: Body Composition Outcomes and Exploratory Analysis by Baseline Adiposity in Overweight Adults

This 12-week, randomized, double-blind, placebo-controlled trial enrolled 50 overweight adults who received either a standardized pumpkin-seed-derived preparation (IRK-19^®, 600 mg/day) or placebo. The clinical preparation contained 66.2% crude protein; components with apparent molecular weights ≤6.29 kDa accounted for 23.6% of the total SEC-UV chromatographic area, and the combined HPLC-measured content of six selected peptide markers was 2.79% (w/w). Among the 48 participants with evaluable DXA data at Week 12, between-group comparisons of body weight, BMI, and adiposity-related outcomes did not reach statistical significance in the overall study population. In a post hoc exploratory subgroup defined by baseline total fat mass ≥28.4 kg (the study-specific 75th percentile; n = 13), adjusted between-group differences (IRK-19^® minus placebo) at Week 12 were −2.30 kg for body weight (95% CI, −4.08 to −0.51; p = 0.018), −0.75 kg/m² for BMI (95% CI, −1.48 to −0.02; p = 0.045), and −1.60 kg for total fat mass (95% CI, −3.23 to 0.04; p = 0.055). Treatment-by-baseline-fat-mass interactions did not reach statistical significance for body weight, BMI, or total fat mass (p = 0.065, 0.106, and 0.057, respectively). These post hoc subgroup findings warrant further investigation but were not adjusted for multiple comparisons. Prospectively designed trials with prespecified adiposity strata are needed to determine whether baseline fat mass is associated with differential treatment response. Individual metabolic laboratory abnormalities also warrant further assessment in future prospective trials.