A Randomized, Double-Blind, Controlled Trial to Assess the Effects of Lactoferrin at Two Doses vs. Active Control on Immunological and Safety Parameters in Healthy Adults

Abstract

ABSTRACTBackgroundRecombinant human lactoferrin (rhLF) is of commercial interest for support of the immune system and iron homeostasis but is not currently available as a food ingredient.ObjectiveThe objective was to evaluate the immunogenicity/alloimmunization potential of Helaina rhLF (effera™) fromK. phaffiiover a 28-day period compared to bovine LF (bLF). It was hypothesized that rhLF would have an equal or lower immunogenic potential compared to bLF, which is permitted for use in conventional foods and infant formula in the EU and US.MethodsStudy 1 was a randomized, double-blind, parallel arm, controlled trial where 66 healthy adults were randomly allocated to 1 of 3 groups: high-dose rhLF (3.4 g/d), low-dose rhLF (0.34 g/d), or bLF (3.4 g/d) (clinicaltrials.gov:NCT06012669). Participants completed a 28-day (Day 28) supplementation period followed by a 28-day washout period (Day 56) and an additional 28-day follow-up period (Day 84). Study 2 was a 12-week observational study with no intervention that enrolled 24 healthy adults. In both studies, fasting blood was obtained on Days 0, 28, 56, and 84 for analysis of anti-bLF and anti-hLF antibody levels as the primary endpoint as well as other secondary safety endpoints including complete blood count, iron biomarkers, and metabolic panel.ResultsIn Study 1, the change from baseline to Day 56 in serum anti-bLF antibodies in the bLF group (least squares geometric mean and 95% confidence interval for the post/pre ratio: 3.01; 2.08, 4.35) was greater than the changes in serum anti-hLF antibodies in the low-dose rhLF (1.07; 0.77, 1.49; P<0.001) and high-dose rhLF (1.02; 0.62, 1.70; P<0.001) groups. In Study 2, the post/pre ratio at Day 56 in serum anti-hLF and anti-bLF antibodies were 1.00 (0.93, 1.08) and 1.01 (0.94, 1.09), respectively, confirming no change in anti-hLF antibodies in Study 1 or Study 2. Changes in all safety outcomes in Study 1 were similar between groups and within normal ranges.ConclusionThese results support the safety and tolerability of efferaTMas a food ingredient at an intake level up to 3.4 g/d in healthy adults.