TABLE 3.
Summary of included trials examining the effect of lactoferrin on respiratory tract infections/illness in adults and children1
| Author, year (country) (ref) | Participants, age, n | Intervention, daily dose | Protocol | Control, daily dose | Duration | Effect of intervention on respiratory tract infections/illness |
|---|---|---|---|---|---|---|
| Adults | ||||||
| Dix, 2018 (Australia) (42) | Healthy males, 18–65 y, n = 12 | Micro-encapsulated bLf capsule, 200 mg/d or 600 mg/d | 1 × 200 mg bLf or 3 × 200 mg bLf capsule/s once daily, after breakfast | bLf capsules, 200 mg/d or 600 mg/d (per intervention protocol) | 4 wk/arm,2-wk w/o | ↔ Viral infections (NFD) |
| Oda, 2020 (Japan) (39) | Healthy adults, 20–65 y, n = 187 | bLf tablet, 200 mg/d or 600mg/d | 6 × 33.3 mg bLf or 6 × 100 mg bLf tablets with water, at bedtime | Placebo tablet (dextrin 250mg) (per intervention protocol) | 12 wk | Summer colds2↔ Incidence↓ Episode duration3,4↔ Episode frequency |
| Pregliasco, 2008 (Italy) (58) | Healthy adults, 36.9 ± 16.7 y (treatment, mean ± SD), 38.5 ± 19.2 y (control, mean ± SD), n = 144 | Synbiotic powder sachet (Lactobacillus plantarum 10 × 109 CFU, L. rhamnosus 10 × 109 CFU, B. lactis 10 × 109 CFU; FOS 3.0 g, with bLf 300 mg/d | 1× sachet (300 mg bLf), dissolved in water once daily | Synbiotic powder sachet (L. plantarum 10 × 109 CFU, L. rhamnosus 10 × 109 CFU, B. lactis 10 × 109 CFU; FOS 3.0 g (per intervention protocol) | 90 d | ↔ Incidence of total or individual respiratory illness (URTI, colds, influenza-like illness)↔ Episode frequency↔ Episode duration↔ Episode severity |
| Takeuchi, 2012 (Japan) (53) | Tube-fed bedridden neurological patients, 50–95 y, n = 61 | Immune-enhancing enteral formula with bLf 1 g/L, ∼1 g/d | As per pre-study enteral feeding schedule, administered by tube (gastrostomy/nasogastric/esophagostomy) | Isocaloric regular enteral formula (per intervention protocol) | 12 wk | ↔ Incidence of RTIs (pneumonia, bronchitis, colds, URTIs) |
| Vitetta, 2013 (Australia) (56) | Healthy adults with ≥3 cold events in 6 mo, ≥18 y, n = 105 | bLf capsule 200 mg with 100 mg Ig-rich fraction, 400 mg/d | 2 × 200 mg bLf capsules daily, NFD | Calcium phosphate (300 mg) capsule, 2× daily | 90 d | Colds5↓ Episode frequency4↔ Cumulative duration↔ Episode severity |
| Children | ||||||
| Chen, 2016 (China) (49) | Healthy, weaned infants, 4–6 mo, n = 213 | Infant formula with iron 4 mg/100 g and bLf 38 mg/100 g, ∼35.8 ± 3.7 mg/d | NR | Infant formula with iron 4 mg/100 g, NFD | 3 mo | ↓ Incidence respiratory illness:4,6↓ Runny nose, cough, and wheezing4↔ Nasal congestionEpisode duration:↓ Respiratory illness4,6↓ Runny nose4↔ Wheezing or cough |
| King, 2007 (USA) (50) | Healthy formula-fed infants, 0–4 wk, n = 52 | Infant formula with iron 3 mg/L and bLf 850 mg/L, ∼833 mg/d | NR | Infant formula with iron 3 mg/L and bLf 102 mg/L, ∼100 mg/d, NR | 12 mo | ↔ URTI7 incidence↔ URTI7 cumulative duration↓ LRTI8 incidence4↔ LRTI8 cumulative duration |
| Li, 2019 (China) (51) | Healthy formula-fed infants, 10–14 d, n = 451 | Staged infant formula with bMFGM,9 60 mg/100 mL bLf, 480–558 mg/d | Exclusive formula feeding until 120 d, stage 1 formula up to 180 d old, stage 2 formula up to 365 d old | Staged infant formula (per intervention protocol) | 12 mo | At 18 months:↓ Respiratory illness10 incidence4↓ URTI incidence4↓ Cough incidence4↓ Respiratory illness10 episode frequency4↓ Number of subjects with >1 URTI episode4 |
| Motoki, 2020 (Japan) (52) | Healthy children, 12–32 mo, n = 101 | Growing-up formula with bLf, 48 mg/d | 1× sachet with 48 mg bLf, once daily, NFD | Growing-up formula (1x sachet) once daily | 13 wk | Respiratory illness11↔ Incidence↓ Cumulative duration4↔ Episode duration↔ Medication use |
| Yen, 2011 (Taiwan) (54) | Healthy children, 2–6 y, n = 172 | Growing-up formula with bLf 35 mg/100mL, 70–85 mg/d | 200–240mL of formula, once daily, morning | Growing-up formula, 200–240 mL, once daily, morning | 15 mo | ↔ Incidence of RTIs (sinusitis, GAS pharyngitis, bronchopneumonia) |
bLf, bovine lactoferrin; bMFGM, bovine milk fat globule membrane; CFU, colony forming units; FOS, fructo-oligosaccharide; GAS, group A streptococcal; GOS, galacto-oligosaccharide; LRTI, lower respiratory tract infection; NFD, not further described; NR, not reported; ref, reference; RTI, respiratory tract infection; URI, upper respiratory illness; URTI, upper respiratory tract infection; w/o, washout; ∼, average intake; ↓, significant decrease, ↑, significant increase, ↔, no change.
Includes a sore throat, cough, nasal secretion, nasal congestion, headache, chills, and fatigue in diary records checked by principal investigator.
Decreased in 600mg bLf compared to placebo only.
Significant difference between groups in change compared with baseline.
Defined as any 2 self-reported cold-associated symptoms, including sore throat, nasal congestion, sinus swelling, sneezing, cough, headache, and fatigue that persisted and lasted 2 d or more.
Respiratory-related illnesses (including at least rhinorrhea, cough, wheezing, or nasal congestion).
Rhinorrhoea, cough, sore throat, or conjunctivitis for 2 consecutive days increased from baseline.
Clinician-confirmed alteration in respiratory status as manifested by chest retractions, tachypnea, rales, wheezing, barky cough or stridor, or an abnormal chest radiograph.
Infant formula with bMFGM and added whey protein lipid concentrate (5 g/L).
Includes URTI and cough.
Includes more than 1 symptom of nasal secretion/congestion, cough/sputum, fever (≥38.0°C) or fatigue.