Liposomal SunActive versus conventional iron for treatment of iron-deficiency anemia in children aged 2–12 years: a prospective randomized controlled trial

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Clin Exp Pediatr. 2025;68(8):608-615

Publication date (electronic) : 2025 July 18

doi : https://doi.org/10.3345/cep.2025.00262

Wael A. Bahbah, MD¹, Yasmin A.H.S. Younis, MD², Hanan Salama Elbelouny, MBBCh³, Asmaa A. Mahmoud, MD^,1

¹Department of Pediatrics, Faculty of Medicine - Menoufia University, Shebin El-Kom, Egypt

²Department of Clinical Pathology, Faculty of Medicine – Menoufia University, Shebin El-Kom, Egypt

³Egyptian Ministry of Health, Cairo, Egypt

Corresponding author: Asmaa Abdel Sameea Mahmoud, MD. Department of Pediatrics, Menoufia University- Shebin El-Kom, Yassin Abdel-Ghafar Street, Shebin El-Kom, Menoufia, Egypt Email: asmaasoliman50@gmail.com, Asmaa_soliman@med.menofia.edu.eg

Received 2025 February 2; Revised 2025 March 1; Accepted 2025 March 14.

Abstract

Introduction

Anemia constitutes a significant global health issue, affecting about 25% of the world's population. Iron deficiency, the leading cause, accounts for 50% of all anemia cases. The prevalence of iron deficiency is higher in developing nations; 9% of children between 12 and 36 months are iron-deficient, with one-third of these children developing anemia [1]. Individuals with anemia experience fatigue, weakness, difficulty focusing, reduced cognitive abilities, and lower work productivity. Since roughly 80% of the iron required by the human body is used for hemoglobin production to generate 200 billion new red blood cells daily, anemia is often associated with iron deficiency [2].

An accurate diagnosis of iron-deficiency anemia (IDA) is crucial for safe treatment, yet it can sometimes be difficult to achieve. Importantly, the absence of anemia does not rule out IDA, as a healthy individual must deplete a significant portion of their iron reserves before hemoglobin (Hb) decreases to levels classified by the World Health Organization as anemia (Hb below 2 standard deviations from the average for the patient's age and sex) [3].

Liposomal iron represents a significant advancement in treating IDA that does not respond to traditional oral iron supplements. Liposomes serve as efficient drug delivery systems capable of targeting various therapeutic agents. Their compatibility with biological systems, ability to biodegrade, and minimal toxicity make them an appropriate choice for drug delivery [4].

Liposomal SunActive iron is an innovative oral iron formulation of ferric pyrophosphate encapsulated in a phospholipid and lecithin membrane, demonstrating excellent gastrointestinal absorption and bioavailability, along with fewer side effects. It utilizes advanced technology that employs liposomes as a transport medium, enabling iron to be absorbed directly in the intestine without interacting with the gastrointestinal mucosa. Ferric pyrophosphate's particle size is reduced through a method called micronization, which enhances iron solubility. Breaking the molecule into smaller particles increases its surface area, which in turn boosts its dissolution rate. Additionally, the micronized iron is surrounded by a lipid bilayer membrane similar to biological membranes via microencapsulation. This procedure ensures that liposomes inhibit the oxidation and degradation of the core's iron components while aiding in precise delivery [5].

The administration of alternative traditional iron supplements is associated with various side effects, such as nausea, vomiting, gas, stomach pain, diarrhea, constipation, indigestion, and dark or sticky stools. These adverse effects have been a major concern with oral iron treatment. Constraints linked to traditional iron salts have led to the development of several oral iron formulations, including carbonyl iron, iron polymaltose complex, ferrous ascorbate, sodium feredetate, and ferrous bisglycinate. Nevertheless, the effectiveness and adverse effects remained similar among these standard iron formulations when administered to patients with iron IDA [6,7].

The purpose of this study was to conduct a thorough comparative evaluation of liposomal SunActive iron and conventional iron supplements (iron polymaltose complex) in addressing IDA in children aged 2 to 12.

Methods

This randomized controlled trial (RCT) was conducted on 192 children diagnosed with IDA who visited the outpatient clinic in the Pediatric Department of Menoufia University Hospitals, a tertiary care facility, from September 2022 to September 2023.

Results

One hundred ninety-two patients completed this 2-arm prospective RCT as detailed: 96 individuals received oral liposomal SunActive iron in group 1, while 96 patients were administered oral conventional iron (iron polymaltose complex) in group 2.

Regarding demographic characteristics of the studied groups, the mean age of group 1 was 4.67±2.62 years, and 4.82±2.98 years in group 2. There were 74 males and 22 females in group 1; while group 2 included 78 males and 18 females.

Regarding anthropometric measurements, there was no significant difference between the 2 groups concerning initial anthropometric values, as illustrated in Table 1. One month after therapy, group 1 showed a significant increase in body weight compared to group 2 (P=0.04). Furthermore, there was a significant increase in body mass index (BMI) in group 1 compared to group 2 (P=0.045), with no notable variation in height between the 2 groups, as in Table 2.

Table 1.

Patients' demographic characteristics and initial anthropometric measurements by study group

Table 2.

One-month posttherapeutic anthropometric measurements by study group

Six months after therapy, group 1 exhibited a significant increase in body weight, weight z score, height, height z score, BMI, and BMI z score compared to group 2 (P=0.045, P<0.001, P=0.043, P=0.042, P=0.014, and P=0.038, respectively), as in Table 3.

Table 3.

Six-month posttherapeutic anthropometric measurements by study group

Regarding laboratory results, there was no significant difference between the 2 groups in terms of initial blood picture parameters and iron profiles, as illustrated in Table 4. A month after therapy, group 1 showed a significant increase in Hb, hematocrit, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) when compared to group 2 (P<0.001, P=0.015, P<0.001, and P=0.006, respectively), whereas red blood cell distribution width (RDW) and platelet count were significantly lower in group 1 than in group 2 (P=0.003 and P=0.038, respectively). Group 1 demonstrated a significant increase in serum iron, serum ferritin, and transferrin saturation, along with a substantial decrease in TIBC when compared to group 2 (P<0.001), as illustrated in Table 5.

Table 4.

Initial complete blood count and iron profiles by study group

Table 5.

One-month posttherapeutic complete blood count and iron profile by study group

Six months after therapy, group 1 showed a significant increase in Hb, hematocrit, MCV, and MCH compared to group 2 (P<0.001), whereas RDW and platelet count significantly decreased in group 1 relative to group 2 (P<0.001 and P=0.015). Group 1 exhibited a notable rise in serum iron, serum ferritin, and transferrin saturation, along with a marked decrease in TIBC compared to group 2 (P<0.001), as illustrated in Table 6.

Table 6.

Six-month complete blood counts and iron profiles by study group

Regarding adverse effects of iron therapy; constipation, black stools, teeth staining and abdominal pain were more prevalent in patients in group 2 than in those in group 1 (P<0.001), as illustrated Table 7.

Table 7.

Side effects of iron therapy by study group

Discussion

Iron is a crucial heavy metal for human nutrition and serves as an essential component of human life. It plays vital roles in oxygen and electron transport, cell division, differentiation, and the control of gene expression [10]. IDA is a commonly encountered health issue seen in routine medical practice. Iron deficiency occurs when the body's requirement for iron cannot be fulfilled due to several physiological factors, such as blood loss and insufficient dietary intake [11].

Over a hundred randomized studies have examined the positive impact of oral iron supplements on hematological factors associated with IDA [12]. There is a lack of targeted clinical trials to assess different iron formulations, dosages, and treatment durations [8].

In this RCT, the response to 2 oral iron formulations was evaluated by studying 192 patients with IDA aged 2 to 12 years. The present study revealed no significant difference between the 2 groups concerning baseline anthropometric measurements. After 6 months of therapy, group 1 showed a notable increase in weight, z scores for weight and height, BMI, and z scores for BMI when compared to group 2. Kiliç et al. [13] conducted a study with 137 children treated with the iron hydroxide-polymaltose complex and 174 children treated with liposomal ferric pyrophosphate; no significant difference was noted between the groups regarding initial anthropometric measurements.

Additionally, they indicated that the group taking liposomal iron supplements showed greater weight and length, expressed as percentiles for weight and height according to age. Tosyalı et al. [14] discovered that the average weight was 9.8 kg in the conventional oral iron therapy group and 9.927 kg in the liposomal iron group.

The current study revealed no notable difference between the 2 groups concerning baseline CBC parameters and iron profile. Tosyalı et al. [14] indicated that there was no significant difference in initial blood count parameters among the study groups. Moreover, Helal et al. [15] discovered no significant difference in initial CBC parameters between group I (which received ferrous bisglycinate supplementation) and group II (which underwent sucrosomial iron therapy).

In this study, 6 months after treatment, group 1 showed a notable increase in Hb, hematocrit, MCV, and MCH compared to group 2, whereas RDW and platelet count were significantly lower in group 1 relative to group 2. In group 1, there was a notable rise in serum iron, serum ferritin, and transferrin saturation, along with a considerable decline in TIBC compared to group 2. Gastrointestinal adverse effects in the form of constipation, black stools, teeth staining and abdominal pain were more prevalent in patients in group 2 than in those in group 1.

Srivastav et al. [16] reported a notable increase in serum iron and serum ferritin following 30 days of liposomal iron therapy. In addition, Ibrahim et al. [17] discovered a statistically significant increase in serum iron, serum ferritin, and serum transferrin following iron therapy for IDA using ferrous sulfate.

Cesarano et al. [18] discovered that oral liposomal iron raised the achievement of transferrin saturation goals from 11.8% at the start to 50.0%, along with elevated Hb levels after a 6-month period.

Helal et al. [15] discovered a notable rise in serum ferritin and iron, as well as a reduction in TIBC in group II, in contrast to group I, during the evaluation period of 8 weeks. Tosyalı et al. [14] found that serum iron and ferritin levels were reduced in the group taking sucrosomial iron compared to those using Fe + 2 and Fe + 3 salts. An initial study suggested that individuals with IDA and inflammatory bowel disease (IBD) receiving liposomal iron experienced a greater rise in Hb levels than those taking ferrous sulfate. An elevation of Hb >2 gm/dL was more common in patients receiving liposomal iron compared to those without iron supplementation. Liposomal iron was effectively tolerated by patients with IDA and IBD [19]. In a comparable study, one-third of the IBD patients administered liposomal iron showed normalization within 12 weeks, with an average Hb rise from 11.1 to 11.8 gm/dL [20]. Oral liposomal iron treatment effectively enhances mild IDA and quality of life, while also reducing fatigue in patients with inactive or mildly active IBD [21]. Oral liposomal SunActive has demonstrated superior effectiveness, with improved Hb recovery and enhanced tolerance, resulting in fewer gastrointestinal adverse effects [22]. Liposomal iron offers improved gastrointestinal absorption and bioavailability compared to conventional ferrous salts. In the former case, amino acids bind to iron to create chemically inert complexes that are absorbed in an unaltered state through specialized active transporters across the mucosal membrane. This active uptake leads to increased bioavailability when contrasted with the limited passive absorption of iron salts. Liposomal iron is absorbed directly by the M cells in the small intestine and, through the lymphatic system, reaches the liver where the iron is released. The bioavailability is higher, and the free iron does not chemically interact with the gastrointestinal membrane [23]. It is 4 times better absorbed compared to conventional iron. Additionally, it is stable against heat, salt, pH, and oxidation [21].

Oral liposomal iron, in contrast to intravenous iron, demonstrated a significant rise in Hb levels and transferrin saturation, normalization of serum ferritin, and a significant reduction in erythropoietin use among individuals with chronic kidney disease [23,24]. In young patients with advanced-stage Hodgkin lymphoma, the addition of oral liposomal iron was well tolerated and kept Hb levels elevated above those needing additional supportive care [25].

Small sample size and the information regrading these formulations in pediatrics remains scarce.

In conclusion, iron formulations are effective in improving anthropometric measurements, complete blood picture parameters and iron profile but liposomal SunActive iron has better effects as being available in oral form, decreasing drug refusal, better compliance with effective impact on children growth.

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