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.

Recombinant human lactoferrin (rhLF) is of commercial interest for immune support as a food ingredient. The objective was to evaluate the immunogenicity/alloimmunization potential of Helaina rhLF (effera™) from K. phaffii over a 28-day period compared to bovine LF (bLF). Study 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). Participants completed a 28-day supplementation period with follow-up visits on Days 28, 56, and 84. Study 2 was a 12-week observational study with no intervention that enrolled 24 healthy adults. In both studies, serum was obtained for analysis of anti-LF antibody levels as the primary endpoint. In Study 1, 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. The rhLF groups had similar changes to the observational study, indicating no change in anti-hLF antibodies and no evidence of alloimmunization following ingestion. Changes in safety outcomes were similar between groups and within normal ranges. These results show that under the conditions of the protocol, no increased anti-hLF antibodies or adverse events were identified following ingestion of effera™ as a food ingredient at an intake level up to 3.4 g/d in healthy adults (clinicaltrials.gov: NCT06012669).