Effect of Oral Collagen and Bromelain Supplementation on Pressure Ulcer Healing in Intensive Care Unit Patients: A Randomized Controlled Trial

Abstract

Background: Pressure ulcers are a major complication among intensive care unit (ICU) patients and are associated with increased morbidity and mortality. Nutritional interventions aimed at promoting wound healing remain underexplored in this population. Objectives: This study aimed to evaluate the efficacy of combined oral collagen hydrolysate and bromelain supplementation in promoting the healing of pressure ulcers in ICU patients. Methods: This randomized, triple-blind, placebo-controlled trial was conducted at Labbafinejad Hospital, Tehran, Iran, from October 2024 to December 2025. Sixty ICU patients with stage II-IV pressure ulcers were randomly assigned 1:1 to receive either oral collagen hydrolysate (Heallagen, 26 g twice daily; total, 52 g/day) plus bromelain (Anaheal, 500 GDU twice daily; total, 1000 GDU/day) or matching placebos for 21 days. The primary outcome was the change in wound depth from baseline to day 21. Secondary outcomes included wound surface area. Outcomes were assessed on days 1, 6, 11, 16, and 21 using a repeated-measures analysis. Covariate adjustment for baseline hemoglobin and albumin was performed post hoc because baseline imbalances were observed. Results: All 60 randomized patients (30 per group) completed the study. Baseline characteristics were similar between groups, except for higher hemoglobin (12.0 ± 1.9 vs 10.5 ± 1.8 g/dL; P = 0.002) and albumin (3.1 ± 0.5 vs 2.7 ± 0.5 g/dL; P = 0.001) in the intervention group. Wound depth was significantly lower in the intervention group from day 11 onward (day 21: 1.8 ± 1.6 vs 4.3 ± 3.8 mm; P = 0.001). Repeated-measures analysis confirmed a significant treatment effect on wound depth (P < 0.001). No significant between-group difference was observed in wound surface area (P = 0.874). Conclusions: Oral collagen hydrolysate combined with bromelain significantly reduced wound depth, but not wound surface area, in ICU patients with pressure ulcers. These findings support the potential role of this combination as an adjunctive nutritional intervention; however, larger, multicenter trials with prespecified adjusted analyses are needed to confirm efficacy. Trial Registration: Iranian Registry of Clinical Trials (IRCT20190215042716N7), registered prospectively on 2024 - 10 - 17 before enrollment of the first participant.