Bromelain

European trial (PMID: 24074719)

Design and size: multicenter, open-label, randomized trial in patients aged 4 to 55 with deep partial-thickness and full-thickness burns over 5 to 30 percent of body surface, comparing a 4-hour NexoBrid application with standard care (surgical or non-surgical debridement); the FDA label reports 182 patients enrolled and 156 randomized (PMID: 24074719; NexoBrid FDA label). Findings: NexoBrid cut the time from injury to complete debridement (2.2 versus 8.7 days), the share of patients needing surgery (24.5 versus 70.0 percent), the burn area excised (13.1 versus 56.7 percent) and the need for skin grafts (17.9 versus 34.1 percent), with similar scar quality, quality of life and adverse event rates (PMID: 24074719). In randomized patients, median time to at least 95 percent wound closure was 33 days with NexoBrid and 24 days with standard care (NexoBrid FDA label).

DETECT, adults (PMID: 37715999)

Design and size: phase 3 trial in adults with deep burns over 3 to 30 percent of body surface, randomized 3 to 3 to 1 to NexoBrid (75), standard care (75) or the gel without enzymes (25) (PMID: 37715999). Primary endpoint met: complete eschar removal occurred in 93 percent with NexoBrid and 4 percent with the plain gel (P<0.001) (PMID: 37715999). Surgical excision was needed in 4 percent with NexoBrid and 72 percent with standard care, median time to eschar removal was 1.0 versus 3.8 days, blood loss during eschar removal was 14 versus 814 mL, and scar scores at 12 and 24 months were noninferior (PMID: 37715999). Median time to at least 95 percent wound closure was 31 days with NexoBrid and 36 days with standard care (NexoBrid FDA label).

CIDS, children (PMID: 40117996)

Design and size: open-label randomized trial at 36 burn centers in Europe, the United States, Israel and India in 145 children aged 0 to 18 with deep burns over 1 to 30 percent of body surface (72 NexoBrid, 73 standard care) (PMID: 40117996). All three primary endpoints met: median time to complete eschar removal was 1 versus 6 days, the mean share of wound area surgically excised was 1.5 versus 48.1 percent, and 12-month scar scores were noninferior (3.8 versus 4.9); adverse events were similar, with no deaths (PMID: 40117996).

Expanded access and pooled analyses

In a single-arm US program at 23 burn centers from 2019 to 2024, 239 patients (215 adults, 24 children) received NexoBrid; eschar was removed within 4 hours in 95 percent of adults and all children, and 4 percent of adults needed surgical excision (PMID: 42153543). A 2025 meta-analysis of 7 studies (484 participants) found shorter time to eschar removal (by 7.6 days), less surgical excision (risk ratio 0.17) and fewer skin grafts (risk ratio 0.40), with no difference in time to wound closure or scar scores (PMID: 39259807). A 2026 meta-analysis of randomized trials found less surgical excision (risk ratio 0.11) and named open-label design as the main source of possible bias (PMID: 42520422).

Other topical research

In proof-of-concept studies by the same group, a topical bromelain-enriched enzyme concentrate was applied to basal cell carcinomas: all 6 lesions in the first study appeared eradicated, and in later studies of 16 patients, tissue examination confirmed eradication in 7, with incomplete eradication in 9 whose dressings were compromised (PMID: 39518762).

Oral bromelain

Wisdom tooth surgery

Three 2019 meta-analyses of small trials disagree on details. One, of 6 placebo-controlled trials, found less facial swelling at 2 to 3 days and at 7 days and less pain at 7 days, but no effect on early pain or jaw opening (PMID: 30986376). A second, of 6 trials, found less pain at 24 hours and 7 days and better quality of life, but no effect on swelling or jaw opening (PMID: 30573710). A third, of 5 trials with 252 patients, found less pain at 48 to 72 hours but no effect on swelling or jaw opening (PMID: 30224314). In a dose-finding crossover trial of 75 patients, higher doses were no better than the standard dose, and pooled bromelain treatment showed a trend in favor of bromelain over placebo (PMID: 27601419). One of the seven authors of that trial worked for a German drug company (PMID: 27601419). In an 84-patient trial, bromelain alone did not reduce swelling significantly compared with no drug, while bromelain combined with the steroid dexamethasone gave the best results (PMID: 27755433).

Knee osteoarthritis

• Placebo-controlled: in a randomized, double-blind trial of 47 patients with moderate to severe knee osteoarthritis, 12 weeks of bromelain at 800 mg a day did not improve the primary outcome, the total WOMAC score, compared with placebo (P=0.27); 31 patients completed the trial (PMID: 17121765).
• Against diclofenac: in a single-blind pilot trial of 40 patients, bromelain at 500 mg a day and diclofenac gave similar results at 4 weeks (PMID: 27470088).
• Uncontrolled: in an open postal study of 77 adults with mild knee pain, symptom scores fell by 41 and 59 percent from baseline with 200 and 400 mg a day (PMID: 12587686).

Combination enzyme products

Several trials tested tablets that combine bromelain with trypsin and the flavonoid rutoside, so their results cannot be assigned to bromelain alone. Such a combination was non-inferior to diclofenac over 6 weeks in 103 patients with knee osteoarthritis (PMID: 15278753) and similar to diclofenac over 3 weeks in 50 patients (PMID: 11584936). In a 2025 placebo-controlled crossover trial of 45 patients, the combination improved the pain and symptom subscales of a knee score but not the overall score, and raised the anti-inflammatory signal interleukin-10 (PMID: 40803821). Three of that trial's ten authors were employees of a nutrition company (PMID: 40803821).

Sinusitis

In a German multicenter cohort study of 116 children under 11 with acute sinusitis, symptoms lasted a mean 6.66 days with bromelain alone, 7.95 days with standard treatment and 9.06 days with both; the study was not randomized (PMID: 15796206). An open-label pilot study of 12 patients with chronic sinusitis reported improved symptom scores with no adverse events (PMID: 24273953).

Other surgery and inflammation

In a 46-patient placebo-controlled trial after rhinoplasty, bromelain reduced bruising around the eyes and bleeding in the white of the eye at day 7 but did not change swelling (PMID: 39904804). A 2023 systematic review of 7 randomized trials of oral bromelain, alone or combined with other oral compounds, found that the effects on blood markers of inflammation were inconsistent (PMID: 37202035).

Oral bromelain

In a 12-week knee osteoarthritis trial, adverse events were generally mild (PMID: 17121765). In a German study of 116 children with sinusitis, one 10-year-old with a known pineapple allergy had a mild, self-limiting allergic reaction (PMID: 15796206). Across 7 randomized trials of bromelain alone or combined with other oral compounds in a 2023 systematic review, 11 participants reported side effects, mainly gastrointestinal, and 2 stopped treatment (PMID: 37202035). In a crossover trial after wisdom tooth removal, adverse events were not more frequent with bromelain than with placebo (PMID: 27601419).

Allergy from work exposure

Bromelain powder is an occupational allergen. A pharmaceutical worker who handled bromelain developed asthma and rhinitis and reacted both to an inhaled challenge with 0.03 mg of bromelain and to eating 190 g of pineapple, and 5 of 6 workers sensitized to papain also reacted to bromelain, which showed cross-reaction between the two plant proteases (PMID: 498486). Four workers in a blood grouping laboratory developed occupational allergy to bromelain, and the authors concluded that bromelain is a strong sensitizer, that sensitization usually occurs by inhalation rather than ingestion, and that skin testing with it can cause whole-body reactions (PMID: 3233722). In a pharmaceutical factory, 7 of 10 workers sensitized to enzymes had positive skin prick tests to bromelain (PMID: 9298178). The sugar chain attached to bromelain (MUXF) is used in allergy testing to detect antibodies against cross-reactive plant carbohydrates (PMID: 21557753).