Oral lactoferrin reduces systemic inflammation, enhances anti-viral responses and modulates immune cell profiles: a randomised controlled trial in healthy, older adults

This randomised controlled trial examined the effect of a 4-week, high-dose (Lf-High, 600 mg/d) or low-dose (Lf-Low, 200 mg/d) oral lactoferrin (Lf) intervention <i>v</i>. placebo on immune cell responses to respiratory virus, immune cell subsets and systemic inflammation. In healthy older adults (<i>n</i> 103, ≥50 years old), <i>ex vivo</i> cytokine release of interferon (IFN)-α2, IFN-γ, IL-6 and TNF-α from rhinovirus A-16 (RV-16) or influenza A virus (H1N1) stimulated peripheral blood mononuclear cells, circulating immune cell subsets, and plasma IL-6, C-reactive protein (CRP) and TNF-α were assessed. Ninety-seven participants completed the 4-week intervention (Lf-High <i>n</i> 32, Lf-Low <i>n</i> 31, placebo <i>n</i> 34, withdrawals <i>n</i> 6). There was no difference in RV-16 or H1N1-induced IFN-γ release between groups. RV-16-induced IL-6 was lower in Lf-High <i>v</i>. placebo (<i>P</i> = 0·001), and RV-16-induced IFN-α2 was higher in Lf-High <i>v</i>. Lf-Low (<i>P</i> = 0·04). Lf-High increased total T cells (<i>P</i> = 0·03) and CD4⁺ T cells (<i>P</i> = 0·03) <i>v</i>. placebo. Lf-Low reduced neutrophil (<i>P</i> = 0·04), natural killer cell (<i>P</i> = 0·045), activated CD8⁺ T cell (<i>P</i> = 0·03) and γδ T cell (<i>P</i> = 0·03) frequency <i>v</i>. placebo. Plasma IL-6 (<i>P</i> = 0·004) and CRP (<i>P</i> = 0·03) were lower following Lf-High <i>v</i>. Lf-Low, but not placebo. Both high- and low-dose Lf altered <i>ex vivo</i> immune cell responses after 4 weeks. High-dose increased T-cell subsets, promoting adaptive immunity, and reduced systemic inflammation, while low-dose reduced proinflammatory and cytotoxic immune cells. High- and low-dose Lf supplements may have immunoceutical benefits in older adults.