Introduction

Iron deficiency anemia (IDA) is a major public health problem in infants and young children and may adversely affect growth and neurodevelopment. Oral iron supplementation is the standard treatment; however, conventional ferrous sulfate is often associated with gastrointestinal side effects that may reduce adherence. Liposomal iron has been developed to improve iron absorption and tolerability. 

Aim

To compare the effects of liposomal iron and ferrous sulfate supplementation on hemoglobin (Hb), serum iron (SI), ferritin, total iron-binding capacity (TIBC), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) in infants aged 4 to 6 months with IDA. 

Patient Profile

Exclusively breastfed infants aged 4 to 6 months diagnosed with IDA according to World Health Organization criteria.  

Methods

• Single-blind randomized controlled trial.
• N = 60 infants.
• Intervention group (n = 30): Liposomal iron containing 15 mg elemental iron/mL, administered orally at 1 mL once daily for 6 months.
• Control group (n = 30): Ferrous sulfate containing 25 mg elemental iron/mL, administered orally at 1 mL once daily for 6 months.
• Hematological parameters were assessed at baseline, 2 months, and 6 months. 

Primary Endpoint

• Change in Hb from baseline to 8 weeks (2 months)

Secondary Endpoints

• SI
• Ferritin
• TIBC
• MCV
• MCH
• Transferrin saturation
• Growth parameters
• Adverse events and tolerability outcomes

Results

Hemoglobin Levels and Iron Supplementation

• Both liposomal iron and ferrous sulfate significantly increased Hb levels over the 6-month study period. 
• However, infants receiving liposomal iron experienced greater improvements than those receiving ferrous sulfate. 
• The adjusted mean increase in Hb was significantly higher in the liposomal iron group at: 
  • 2 months: Mean difference (MD) = 0.35 g/dL; P = 0.014. 
  • 6 months: MD = 0.51 g/dL; P < 0.001. 
• These findings indicate that liposomal iron was more effective in correcting anemia despite being administered at a lower elemental iron dose. 

Table 1. Hemoglobin Levels: Liposomal Iron vs Ferrous Sulfate

Time Point	Mean Difference (Liposomal Iron vs Ferrous Sulfate), g/dL	P-value	Interpretation
2 Months	+0.35	0.014	Significantly greater Hb increase with liposomal iron
6 Months	+0.51	<0.001	Significantly greater Hb increase with liposomal iron; the effect increased over time

 

Impact on Other Hematologic Indices

• Both iron formulations improved iron-related hematologic parameters over time. 
• Compared with ferrous sulfate, liposomal iron produced significantly greater improvements in SI and MCH. 
• At 6 months, SI was significantly higher in the liposomal iron group (MD 20.27 μg/dL; P < 0.001). 
• MCH showed greater increases in the liposomal iron group at: 
  • 2 months: MD = 0.93 pg; P = 0.003. 
  • 6 months: MD = 2.43 pg; P < 0.001. 
• TIBC decreased significantly in both groups, with a greater reduction in the liposomal iron group at: 
  • 2 months: MD = −26.6 μg/dL; P < 0.001. 
  • 6 months: MD = −35.16 μg/dL; P < 0.001. 
• Although ferritin and MCV improved over time in both treatment groups, no significant between-group differences were observed. 
• For ferritin, the between-group differences were 3.17 ng/mL at 2 months (P = 1.000) and −9.13 ng/mL at 6 months (P = 0.623). 
• Similarly, MCV did not differ significantly between groups at either follow-up assessment (MD −1.06 fL; P = 1.000 for both time points). 
• Overall, liposomal iron demonstrated superior efficacy in improving Hb, SI, MCH, and TIBC, while exhibiting similar effects on ferritin and MCV compared with ferrous sulfate. 

Table 2. Comparative Efficacy and Tolerability of Liposomal Iron vs Ferrous Sulfate in Infants with IDA

Parameter	Ferrous Sulfate	Liposomal Iron	Significant Difference Between Groups
SI improvement	Improved	Improved	Yes
Ferritin improvement	Improved	Improved	No
TIBC improvement	Improved	Improved	Yes
MCH improvement	Improved	Improved	Yes
MCV improvement	Improved	Improved	No
Hb improvement	Improved	Improved	Yes
Phospholipid bilayer	Absent	Present	Yes
Effect of gastric acidity	Present	None	Yes
Iron oxidation	Yes	No	Yes
Targeted iron delivery	No	Yes	Yes
Iron absorption	Regular	Enhanced	Yes
Absorption via intestinal M cells	No	Yes	Yes
Food effect on absorption	Present	None	Yes
Oxidative damage to intestinal epithelium	Possible	Minimal/Absent	Yes
Gastrointestinal side effects	Present	Minimal/Absent	Yes
Metallic taste	Present	Absent	Yes
Chelation with other metals	Present	Absent	Yes

 

Conclusion

• Both liposomal iron and ferrous sulfate effectively improved iron status and hematological indices in infants with IDA. 
• However, liposomal iron demonstrated superior efficacy in improving Hb, SI, MCH, and TIBC despite a lower elemental iron dose, suggesting that it may be a more effective option for the treatment of pediatric IDA. 

Reference

J Compr Ped. 2026;17(1):e165482.