Bromelain supplementation and inflammatory markers: A systematic review of clinical trials

Abstract

Background and aims: The inflammatory process is a response mechanism to any stressor agent. Emerging novel therapeutic options derived mainly from natural products such as bromelain have been used to reduce the significant side effects of available anti-inflammatory drugs. Bromelain is an enzyme complex derived from Ananas comosus, known for its anti-inflammatory potential and good tolerance. Therefore, the aim was to assess whether bromelain supplementation exerts anti-inflammatory effects in adults.

Methods: The systematic review was registered in PROSPERO (n° CRD42020221395), and the search was performed in MEDLINE, Scopus, Web of Science, and Cochrane Library. The terms used in the search were: "bromelains", "bromelain", "randomized clinical trial", and "clinical trial". Eligibility criteria were: randomized clinical trials with participants aged 18 years or over, of both sexes, who received supplementation with bromelain alone or in combination with other oral compounds, with an evaluation of inflammatory parameters as primary and secondary outcomes, published in English, Portuguese or Spanish.

Results: 1375 studies were retrieved, of which 269 were duplicates. Seven (7) randomized controlled trials were eligible for the systematic review. In most studies, supplementation with bromelain, isolated or in combined therapy, reduced inflammatory parameters. Regarding the reduction of inflammatory parameters among studies with associated bromelain, two presented reduction of inflammatory parameters, while in the evaluation of bromelain treated alone, two studies also showed reduction. In relation to doses supplemented, the studies with associated bromelain ranged from 99.9 to 1200 mg/day and the supplementation time ranged from 3 to 16 weeks. Moreover, the inflammatory parameters evaluated were: IL-12, PGE-2, COX-2, IL-6, IL-8, TNF-α, IL-1β, IL-10, CRP, NFγ B1, PPAR-α, TNF, TRAF, MCP-1 and adiponectin. In studies with isolated bromelain supplementation, it ranged from 200 to 1050 mg/day for 1 week to 16 weeks. Markers associated with inflammation varied between studies, including IL-2, IL-5, IL-6, IL-8, IL-10, IL-13, IFNγ and MCP-1, PGE-2, CRP and fibrinogen. Eleven (11) participants experienced side effects, and two discontinued treatment in the studies. The reported adverse effects were mainly gastrointestinal but well tolerated.

Conclusion: The general effect of bromelain supplementation on inflammation is inconsistent because of population heterogeneity, doses used, treatment duration, and parameters evaluated. The observed effects are punctual and isolated, and further standardization is needed to establish doses, supplementation time, and which type of inflammatory condition is indicated.

Keywords: Bioactive compounds; Bromelains; Cysteine endopeptidases; Enzyme therapy; Inflammation.