(OR23-02-24) A Randomized, Double-Blind, Controlled Trial to Assess the Effects of Lactoferrin at Two Doses vs. Active Control on Markers of Immune Safety in Healthy Adults

Objectives: Recombinant human lactoferrin (rhLF) is of commercial interest for support of the immune system and iron homeostasis but is currently not permitted as a food ingredient due to outstanding safety questions on immunogenicity/alloimmunization. In this clinical study, the immunogenicity potential of Helaina rhLF (Effera™) from K. phaffii was assessed over a 28-day period compared to bLF, which is permitted for use in conventional foods and infant formula in the EU and US, among others. Serum anti-LF antibodies and other safety outcomes were evaluated in healthy adults over an 84-day period

Methods: In this randomized, double-blind, parallel-arm, controlled trial, 66 adults were allocated to high-dose rhLF (3.4 g/d, n = 22), low-dose rhLF (0.34 g/d, n = 21), or bLF (3.4 g/d, n = 23). Participants completed a 28-day beverage supplementation period, followed by a 4-week (Day 56) and 8-week (Day 84) follow-up. Blood was collected every 4 weeks for analysis of anti-LF antibodies, iron homeostasis, and other safety outcomes. An observational study in healthy adults was conducted in parallel to assess variability of anti-LF antibodies over time.

Results: The median percent change in serum anti-bLF antibodies from baseline to Day 56 in the bLF group [152%; interquartile range limits (IQRL): 41%, 546%] was greater than the changes in serum anti-hLF antibodies in the low-dose rhLF (6%; 0%, 11%) and high-dose rhLF (-3%; -12%, 3%) groups (P < 0.001 for both), and higher than normal anti-bLF variation. Importantly, the rhLF groups had similar changes to the observational study, indicating no induction of anti-hLF antibodies. Changes in all other safety outcomes were similar between groups and within normal ranges.

Conclusions: Consumption of rhLF for 28 days did not produce an increase in median anti-hLF antibodies whereas bLF produced a marked increase in anti-bLF antibodies. This is the first time alloimmunization potential has been assessed in a clinical setting for any rhLF and the results show that supplementation of rhLF at two doses had low alloimmunization potential with no evidence of breakdown of tolerance over the 84-day study period. Other safety measures were not altered in any of the treatment groups. These results support safety and tolerability of Effera™ as a food ingredient at an intake level up to 3.4 g/d in healthy adults.

Funding Sources: Funded by Helaina, Inc