Immune modulating effects of oral lactoferrin in healthy, older adults: a randomised controlled trial

Immunoceuticals are natural products used to enhance immunity (1) . Lactoferrin (Lf) is an immunoceutical supplement which has been shown to have immunomodulatory properties (2) . The immuno-protective functions of Lf are of interest in older adults, as immune function declines with increasing age (3) . This study examined the effects of oral Lf supplements on ex vivo immune cell responses to respiratory virus infection, circulating immune cell subsets, and systemic inflammation. Healthy adults (≥ 50 years old, n = 103) were randomised to High dose (600 mg/d) or Low dose (200 mg/d) Lf or placebo, in a 4-week, parallel, double-blinded trial. Ex vivo cytokine release of interferon (IFN)-α2, IFN-γ, interleukin (IL)-6 and tumour necrosis factor (TNF)-α) in isolated peripheral blood mononuclear cells (PBMCs) infected with rhinovirus A-16 (RV-16) and influenza A virus (H1N1), circulating immune cell subsets, and plasma IL-6, C-reactive protein (CRP) and TNF-α were assessed and analysed by multivariate regression models. Analysis included 102 participants at baseline, and 96 participants at follow up. High dose Lf decreased RV-16-induced IL-6 (p = 0.001 vs placebo), and increased RV-16-induced IFN-α2 (p = 0.041, vs low dose) in PBMCs. H1N1-induced IL-6 decreased following Low dose Lf and placebo (p = 0.009, p = 0.021 vs baseline), while High dose Lf increased H1N1-induced TNF-α (p = 0.023 vs low dose, p = 0.049 vs placebo) and decreased H1N1-induced IFN-γ (p = 0.032 vs baseline) in PBMCs. High dose Lf increased total T cells (p = 0.031), CD4+ T cells (p = 0.028) and BDCA-1 cells (p = 0.016), and decreased γδ T cells (p = 0.046) compared to placebo, while Low dose Lf reduced circulating neutrophils (p = 0.044), natural killer cells (p = 0.045), activated CD8+ T cells (p = 0.031), and γδ T cells (p = 0.031) compared to placebo. High dose Lf decreased plasma IL-6 and CRP compared to Low dose Lf (p = 0.004, p = 0.026), but not placebo. There was no difference between intervention groups in the number of adverse events. This 4-week trial in healthy, older adults showed both High and Low dose Lf interventions enhanced ex vivo immune cell responses to respiratory virus infection, with decreased pro-inflammatory cytokine and increased anti-viral cytokine release observed. Low dose Lf reduced the frequency of both pro-inflammatory and cytotoxic innate immune cells, while increased T-cell populations following High dose Lf indicate improved cellular adaptive immune responses which provide protection against infection, tumours and chronic disease. Effects on systemic inflammation were only seen following High dose Lf, suggesting higher doses of lactoferrin are required to address this outcome. Oral lactoferrin supplements are generally regarded as safe, and appear to have immunoceutical benefits in healthy, older adults.