What is Lactoferrin?

1. Immune System Support & Anti-inflammatory Activity

A comprehensive systematic review and meta-analysis (the highest level of evidence) examined lactoferrin supplementation across 25 clinical studies.[1] Key findings included:

Immune Function 

• Reduced respiratory tract infection (RTI) incidence in infants and children (OR: 0.78; 95% CI: 0.61, 0.98)
• Improved immune function in 75% of adult studies (6 of 8 studies).

Anti-inflammatory Effects 

• Significant reduction in IL-6 levels (MD: -24.9 pg/mL; 95% CI: -41.64, -8.08 pg/mL)
• Decreased systemic inflammatory biomarkers in 61% of studies (8 of 13 studies in adults).

Recent randomised controlled trials support these findings. In a 12-week RCT of healthy adults (n=145), daily lactoferrin supplementation (200 mg/day) significantly reduced total respiratory and systemic symptom scores compared to placebo (respiratory: median 11 vs 32, 66% reduction, p=0.016; systemic: median 5 vs 30, 83% reduction, p=0.045). The protective effects became significant after more than 4 weeks of supplementation, with significant reductions observed during weeks 5-8 and weeks 9-12. Additionally, lactoferrin significantly enhanced plasmacytoid dendritic cell (pDC) activation, increasing expression of CD86 (p=0.032) and HLA-DR (p=0.014), cell surface markers critical for coordinating immune responses to viral and bacterial pathogens (Table 4).[2]  

In a separate summer-based RCT study of 310 healthy adults randomised to receive placebo, 200 mg, or 600 mg of lactoferrin daily for 12 weeks, the duration of total infectious diseases was significantly shorter in both the 200 mg group (median 2.0 days, p=0.045) and 600 mg group (median 2.0 days, p=0.010) compared to placebo (median 3.0 days). The duration of summer colds specifically was shorter in the 600 mg group (median 2.0 days, p=0.036) compared to placebo (median 3.0 days). These effects demonstrated a dose-responsive relationship. In exploratory analyses of subjects with lower baseline neutrophil phagocytic capacity (marker of lower baseline immune function), lactoferrin at 600 mg/day significantly improved this parameter compared to placebo (p=0.049).[3]

Antiviral Mechanisms

Lactoferrin demonstrates broad-spectrum antiviral activity through multiple mechanisms. It inhibits viral entry by binding to cell surface heparan sulfate proteoglycans (HSPGs), which serve as initial attachment sites for numerous viruses including coronaviruses.[4] Beyond blocking viral entry, lactoferrin can bind directly to viral particles to prevent their attachment to target cells and suppress viral replication after cell entry.[4]

Immunomodulatory Properties

Lactoferrin's immunomodulatory properties include the ability to modulate cytokine production and inflammatory responses, as demonstrated by significant reductions in IL-6 levels in clinical studies, while maintaining appropriate immune function.[4,5] In pregnant women with iron deficiency, lactoferrin administration significantly decreased serum IL-6 levels (from 33±10 to 12±10 pg/mL, p<0.0001), demonstrating its anti-inflammatory capacity in clinical populations.[5]

2. Iron Status Support

A 2024 systematic review and meta-analysis by Christofi et al. evaluated the effectiveness of oral bovine lactoferrin compared to iron supplementation in patients with low hemoglobin profiles.[6] The review included 19 randomised clinical trials published between 2006 and 2022, with a total of 2,992 participants. The meta-analysis of seven trials comparing lactoferrin to ferrous sulfate demonstrated a statistically significant increase in hemoglobin levels in the oral bovine lactoferrin group compared to ferrous sulfate (Standard Mean Difference -0.81, 95% CI: -1.21, -0.42, p<0.0001, I²=95.8%). The review concluded that lactoferrin is an effective intervention at doses of 100 to 250 mg/day for patients with low hemoglobin concentration, with significantly (P<0.05) fewer side effects than iron supplementation. 

Lactoferrin has demonstrated superior efficacy to ferrous sulfate in treating iron deficiency and iron deficiency anemia through multiple clinical trials:

• In pregnant women with iron deficiency, lactoferrin oral intake (100 mg/ 2 d) significantly increased hemoglobin levels to 12.7 ± 0.9 g/dL versus 11.5 ± 0.6 g/dL with ferrous sulfate treatment.[7] Similar efficacy was demonstrated in non-pregnant women of childbearing age, where lactoferrin significantly improved all hematological parameters (p<0.0001) after 30, 60, and 90 days of treatment, while ferrous sulfate failed to increase these values.[5] 
• Lactoferrin’s improved efficacy involves restoration of physiological iron homeostasis through modulation of key regulatory factors. In pregnant women, lactoferrin administration significantly decreased serum IL-6 levels (from 33±10 to 12±10 pg/mL, p<0.0001) and increased serum prohepcidin (from 102±27 to 150±32 ng/mL, p=0.0007), while ferrous sulfate increased IL-6 (to 52±13 pg/mL, p=0.0015) and failed to improve prohepcidin levels.[6] This suggests lactoferrin enables iron export from tissues to circulation by decreasing IL-6-mediated ferroportin downregulation, while ferrous sulfate's pro-inflammatory effects hinder iron export, leading to cellular iron sequestration.[5,8]
• Unlike ferrous sulfate supplementation, which caused adverse effects in 95% of patients (including stomach pain, cramps, and constipation), lactoferrin resulted in no adverse effects in any clinical trial participants.[5,7,9]

Clinical Considerations

Dosing: Evidence supports doses of 200-1000 mg daily, depending on clinical indication.

Timing: Administration before meals is recommended for optimal bioavailability.