Clinical research review: usefulness of bovine lactoferrin in child health.

Lactoferrin (LF) is abundant in human milk and plays an important role in the health of children. Bovine LF (bLF) has high homology with human LF and has been reported to have multiple biological functions. Several clinical studies have been conducted considering these properties, which reported the usefulness of bLF. This review was aimed to provide an overview of the clinical evidence in children. We searched clinical reports investigating the effects of bLF in children and identified 36 studies on the role of bLF in infections, iron metabolism, body growth, cerebral development, and fecal microbiome. Considering the accumulated evidence, bLF may contribute to the child health, particularly by suppressing or alleviating gastrointestinal and respiratory symptoms, and improving the iron status of children with anemia or those at high risk of anemia. The dose of bLF varies depending on the expected effect and target age, but may not necessarily have to be as high as human LF in human milk. Some of the beneficial effects of bLF have not been fully validated due to limited clinical evidence or being observed in the secondary analysis of some studies. Further clinical evidence would add significant value to the use of bLF in child health.

Lactoferrin and its digestive peptides induce interferon-α production and activate plasmacytoid dendritic cells ex vivo.

Plasmacytoid dendritic cells (pDCs) recognise viral single-stranded RNA (ssRNA) or CpG DNA via Toll-like receptor (TLR)-7 and TLR9, and produce interferon (IFN)-α. Activated pDCs upregulate human leukocyte antigen (HLA)-DR and CD86 expression levels. Ingestion of bovine lactoferrin (LF) activates pDCs, but little is known about its effects. In this study, the effects of LF and its pepsin hydrolysate (LFH) on the production of IFN-α from peripheral blood mononuclear cells (PBMCs) and pDCs were examined. PBMCs were prepared from peripheral blood of healthy adults and incubated with LF, LFH, or lactoferricin (LFcin) in the absence or presence of ssRNA derived from human immunodeficiency virus. The concentration of IFN-α in the supernatant and the expression levels of IFN-α, HLA-DR, and CD86 in pDCs were quantified by enzyme-linked immunosorbent assay and flow cytometry. In the absence of ssRNA, the concentration of IFN-α was negligible and LF had no effect on it. In the presence of ssRNA, IFN-α was detected at a certain level, and LF and LFH significantly increased its concentration. The increase caused by LFH and LFcin were comparable. In addition, LF significantly upregulated the expression levels of IFN-α, HLA-DR, and CD86 in pDCs. LF and its digestive peptides induced IFN-α production and activated pDCs in the presence of ssRNA, suggesting that LF modulates the immune system by promoting pDC activation upon viral recognition.

Wide-ranging migration and destination of early olfactory placode-derived neurons in chick embryos.

Cell migration from the olfactory placode (OP) is a well-known phenomenon wherein various cell types, such as gonadotropin-releasing hormone (GnRH)-producing neurons, migrate toward the telencephalon (TEL) during early embryonic development. However, the spatial relationship between early migratory cells and the forebrain is unclear. We examined the early development of whole-mount chick embryos to observe the three-dimensional spatial relationship among OP-derived migratory neurons, olfactory nerve (ON), and TEL. Migratory neurons that express highly polysialylated neural cell adhesion molecule (PSA-NCAM) emerge from the OP and spread over a relatively wide TEL area at the Hamburger and Hamilton (HH) stage 17. Most migratory neurons form a cellular cord between the olfactory pit and rostral TEL within HH18-20. The earliest axons from the olfactory epithelium (OE) were detected along this neuronal cord using DiI-labeling at HH21. Furthermore, a few PSA-NCAM-positive neurons were dispersed around the cellular cord and over the lateral TEL at HH18. A long cellular cord branch extending to the lateral TEL was transiently observed within HH18-24. These results suggest a novel migratory route of OP-derived neurons during the early developmental stages. Following GFP vector introduction into the OP of HH13-15 embryos, labeled neurons were detected around and within the lateral TEL at HH23 and HH27. At HH36, labeled cells were observed in the rostral-lateral TEL, including the olfactory bulb (OB) region. GFP-labeled and calretinin-positive neurons were detected in the OB, suggesting that early OP-derived neurons enter the forebrain and function as interneurons in the OB.

Effects of Lactoferrin on Sleep Conditions in Children Aged 12-32 Months: A Preliminary, Randomized, Double-Blind, Placebo-Controlled Trial.

PURPOSE: To investigate preliminarily the effect of lactoferrin (LF)-fortified formula on sleep conditions in children. STUDY DESIGN: A preliminary, randomized, double-blind, placebo-controlled trial. METHODS: Healthy children between the ages of 12 and 32 months who attended nursery schools in Japan were divided into two groups and assigned a placebo or LF (48 mg/day)-fortified formula. Children's sleep conditions were investigated before and after the 13-week intervention using the Japanese Sleep Questionnaire for Preschoolers (JSQ-P). RESULTS: Altogether, 109 participants were randomized. Eight participants were eliminated due to lost to follow-up, withdrawal of consent, and ineligibility, with 101 participants (placebo, n = 48; LF, n = 53) included in the full analysis set (FAS) and used for analysis. Wake-up time, bedtime, and nighttime sleep were comparable between the two groups before and after intervention. The change in total JSQ-P T scores tended to improve in the LF group (placebo vs LF: 0.5 ± 6.5 vs -1.9 ± 6.1, p = 0.074), in particular, morning symptoms significantly improved (grumpy in the morning, hard to wake-up, and hard to get out of bed) (placebo vs LF: 0.8 ± 6.2 vs -1.9 ± 6.2, p = 0.028). A better trend was also observed in the LF group regarding restless legs syndrome (RLS)-motor (rubs feet at night and touches feet at night) (placebo vs LF: 2.3 ± 10.7 vs -0.6 ± 13.5, p = 0.083) and insufficient sleep (stays up more than one hour later the day before a holiday and wakes up more than one hour later on a holiday) (placebo vs LF: 0.1 ± 9.8 vs -1.7 ± 8.8, p = 0.095). No adverse drug reactions were found. CONCLUSION: LF intake may improve sleep condition, especially morning symptoms in children above one year of age.

Effects of Lactoferrin-Fortified Formula on Acute Gastrointestinal Symptoms in Children Aged 12-32 Months: A Randomized, Double-Blind, Placebo-Controlled Trial.

Objective: We investigated the effects of lactoferrin (LF)-fortified formula on acute gastrointestinal and respiratory symptoms in children. Design: Randomized, double-blind, placebo-controlled trial. Setting and subjects: Children aged 12-32 months in Japan. Intervention: Intake of placebo or LF (48 mg/day)-fortified formula for 13 weeks. Primary endpoint: Prevalence of acute gastrointestinal and respiratory symptom. Results: One hundred nine participants were randomized. Eight participants were lost to follow-up, withdrew consent, or were deemed inappropriate for the trial, with 101 participants receiving complete analyses (placebo group, n = 48; LF group, n = 53). Outcomes: The prevalence of acute gastrointestinal symptoms was significantly less in the LF group (22/53 [41.5%]) than in the placebo group (30/48 [62.5%], p = 0.046). The total number of days having acute respiratory symptoms was significantly lower in the LF group (9.0) than in the placebo group (15.0, p = 0.030). Harms: The rate of adverse events was similar between the groups. No adverse drug reactions were found. Conclusions: LF intake decreased the prevalence of acute gastrointestinal symptoms in children aged 12-32 months.

Effects of Lactoferrin on Subjective Skin Conditions in Winter: A Preliminary, Randomized, Double-Blinded, Placebo-Controlled Trial.

OBJECTIVE: To investigate the effects of lactoferrin (LF) on subjective skin conditions in winter. DESIGN: A preliminary, randomized, double-blinded, placebo-controlled trial. SETTING AND SUBJECTS: Healthy adults in Japan. INTERVENTIONS: Intake of placebo, 200 mg, or 600 mg of LF for 12 weeks in winter. ENDPOINTS: Changes in the scores of subjective skin conditions. RESULTS: Three hundred and forty-six subjects were randomized. Nine subjects (placebo, n=0; 200 mg, n=5; 600 mg, n=4) withdrew consent, and 7 subjects (placebo, n=4; 200 mg, n=2; 600 mg, n=1) were lost to follow-up, resulting in 330 for a full analysis set. OUTCOMES: Changes in the scores of moisture were greater in the 600 mg group than in the placebo group. Changes in the scores of moisture were greater in the 200 mg and 600 mg groups, and of texture were greater in the 600 mg group than in the placebo group in female subjects. CONCLUSION: Intake of LF may improve moisture or texture of skin in winter.