A Review of the Safety Evidence on Recombinant Human Lactoferrin for Use as a Food Ingredient

Published studies on the glycosylation, absorption, distribution, metabolism, excretion, and safety outcomes of orally ingested recombinant human lactoferrin (rhLF) were reviewed in the context of unanswered safety questions, including alloimmunization, allergenicity, and immunotoxicity potential during repeated exposure. Results from animal and human studies showed that rhLF was well tolerated and safe: animal data showed no significant toxicity-related outcomes, with no-observed-adverse-effect levels at the highest tested doses, while no animal studies directly assessed immunogenicity/immunotoxicity from a safety perspective. Human studies, reported primarily as adverse events, showed no or fewer rhLF-related adverse events compared to control and no evidence of toxicity, dose-limiting toxicities, or changes in iron status, though no human studies evaluated rhLF's immunomodulatory potential as a safety measure. Following this review, a roadmap outlining preclinical and clinical studies with relevant safety endpoints was developed to address the unanswered safety questions.