Investigation of oral bromelain supplementation on the healing of skin flap reconstruction after Mohs micrographic surgery (MMS) for non-melanoma skin cancers (NMSCs).

2026-05-14
BMC surgery 26(1)
- Ehsanollah Rahimi-Movaghar
- Amir Ehtemami
- Melina Ghaneiyan
- Tahmineh Tahouri
- Sahand Hedayati Omami
- Hila Fahimi

PubMed: 42135693
DOI: 10.1186/s12893-026-03820-4

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 60
Population: 60 patients with non-melanoma skin cancer undergoing Mohs micrographic surgery and flap reconstruction
Methods: Single-center, parallel-group, single-blinded RCT, 60 patients randomized to bromelain 1500 mg/day for 15 days postoperatively or control
Blinding: Single-blind
Duration: 15 days
Funding: Unclear

Introduction

Non-melanoma skin cancers (NMSCs) are the most common malignancies and Mohs micrographic surgery (MMS) with flap reconstruction is the treatment of choice. This study aims to investigate the effect of bromelain on the healing of skin flaps following MMS for NMSCs.

Methods

In a single-center, parallel-group, single-blinded randomized clinical trial, 60 patients with NMSC who underwent MMS and flap reconstruction were assigned (1:1) to either an intervention group receiving bromelain (1500 mg/day, Rataheal™) for 15 days postoperatively or a control group receiving standard care alone. The primary outcome was time to suture removal; the early wound healing score (EWHS) was recorded supportively. Secondary outcomes included pain, inflammation, keloid/scar formation, cosmetic satisfaction, and traction quality.

Results

Baseline characteristics (age: 69.2 ± 13.5 years; 71.7% male; flap size: 116.1 ± 7.0 mm²) were analyzed. Bromelain significantly shortened time to suture removal compared with controls (2.6 days, 95% CI: 0.74-4.11; p = 0.006). The EWHS was also significantly improved at the day 7 (7.2 vs. 5, p < 0.001) and day 14 (8.56 vs. 7.3, p = 0.014) of follow up. Other outcomes, including inflammation, pain, and cosmetic satisfaction, showed non-significant trends favoring bromelain. No major complications were reported.

Conclusion

Bromelain supplementation is associated with earlier postoperative wound healing of skin flaps following MMS for NMSC, leading to 2.6 days earlier suture removal plus improvement in the EWHS without adverse effects. Our findings support the potential of bromelain as a safe and effective adjunct therapy for reconstructive skin cancer surgery.

Trial registration

Iranian Registry of Clinical Trials (IRCT20240903062943N1|| https://irct.behdasht.gov.ir/trial/79056 ), 2024.10.28, enrollment started after registration.

Research Insights

Bromelain→Improved Cosmetic Satisfaction
Other outcomes, including inflammation, pain, and cosmetic satisfaction, showed non-significant trends favoring bromelain.
Effect
Neutral
Effect size
Small
Dose
1500 mg/day
Bromelain→Improved Wound Healing Score
The EWHS was also significantly improved at the day 7 (7.2 vs. 5, p < 0.001) and day 14 (8.56 vs. 7.3, p = 0.014) of follow up.
Effect
Beneficial
Effect size
Moderate
Dose
1500 mg/day
Bromelain→Reduced Inflammation
Other outcomes, including inflammation, pain, and cosmetic satisfaction, showed non-significant trends favoring bromelain.
Effect
Neutral
Effect size
Small
Dose
1500 mg/day
Bromelain→Reduced Pain
Other outcomes, including inflammation, pain, and cosmetic satisfaction, showed non-significant trends favoring bromelain.
Effect
Neutral
Effect size
Small
Dose
1500 mg/day
Bromelain→Reduced Time to Suture Removal
Bromelain significantly shortened time to suture removal compared with controls (2.6 days, 95% CI: 0.74-4.11; p = 0.006).
Effect
Beneficial
Effect size
Small
Dose
1500 mg/day

Adverse Events Reported

Bromelain→Overall tolerability
No major complications were reported.
Finding
Reported