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, and exposure was estimated from bromelain supplements marketed in Germany. Acute oral lethality was very low (LD₅₀ >10,000 mg/kg bw), with large margins of exposure. A more sensitive endpoint, a transient heart-rate increase after single oral doses in humans, yielded an exploratory acute reference value (0.7 mg/kg bw) that the surveyed single doses exceeded 2- to 15-fold. Benchmark-dose (BMD) modeling of the same heart-rate data placed the threshold for pharmacological action at approximately 390 mg per single dose; with statistically significant clinical effects from about 100 mg/day, all surveyed products were in the pharmacologically active range. For chronic intake, no adequate oral repeated-dose study was available. A preliminary health-based guidance value (HBGV) of 0.18 mg/kg bw/day was therefore derived from a 28-day human no-observed-adverse-effect level (NOAEL) of 53.4 mg/kg bw/day and a composite uncertainty factor of 300; recommended intakes exceeded it about 8- to 78-fold. Both exceedances indicate uncertainty rather than demonstrated risk; pending adequate long-term data, a precautionary approach appears warranted, and products at pharmacologically active doses may qualify as function-based medicinal products.