Risk Assessment of Bromelain in Foods and Food Supplements

Bromelain, a proteolytic enzyme complex from Ananas comosus (pineapple), is used in foods, food supplements, and medicinal products, yet its oral safety remains insufficiently characterized. Pharmacological, toxicological, clinical, and regulatory evidence was reviewed in a weight-of-evidence approach complemented by a market survey of bromelain supplements in Germany and an exploratory dose–response analysis. Acute oral lethality was very low (LD50 > 10,000 mg/kg bw). A more sensitive endpoint, transient heart-rate increase after single oral doses in humans, yielded an exploratory acute reference value (0.7 mg/kg bw); surveyed single dosage units exceeded it 2- to 15-fold. Exploratory benchmark-dose modeling of the heart-rate data placed the threshold for pharmacological action at approximately 400 mg per single dose. Given statistically significant clinical effects from about 100 mg/day, all surveyed products fell within the reported pharmacologically active dose range. For chronic intake, no adequate oral repeated-dose study was available, so a provisional, screening-level health-based guidance value of 0.18 mg/kg bw/day was derived from a 28-day human no observed adverse effect level of 53.4 mg/kg bw/day and an uncertainty factor of 300; recommended intakes exceeded it about 8- to 78-fold. These exceedances indicate insufficient data to establish the safety of supplement doses, especially for long-term use, not demonstrated harm. Adequate repeated-dose data are needed, and products at pharmacologically active doses require case-by-case regulatory evaluation.