Iron deficiency (ID) is the most common nutritional problem worldwide and prominently arises in individuals with increased physiological requirements for iron, such as infants and young children.
To ensure adequate intakes of iron, dietary interventions can be combined with oral iron supplementation but iron supplements in the form of syrups or drops have an unpleasant taste, may stain the teeth, and cause gastrointestinal disturbances, all of which decrease compliance and thus limit its effectiveness.
In the present double-blind, randomised, placebo-controlled study involving 85 children (aged 9 months to 6 years), researchers sought to evaluate the safety and efficacy of a novel food supplement, >Your< Iron Syrup, across 10 Slovenian pediatric primary care units between December 2017 and June 2020. The study included children with iron deficiency but without anemia requiring medication.
They found mean ferritin levels in the test group improved by 69% (14,5 -> 24,5 μg/l) while the placebo group remained at-risk levels (below 20 μg/l) despite dietary advice.
The test group also showed significantly higher hemoglobin, hematocrit, and erythrocyte levels (biological indicators of iron status).
What's more, the mean compliance was 92% and the number of adverse events was low and not significantly different between the groups.
Only one severe adverse event (abdominal pain) in the test group was evaluated as possibly linked to supplementation.
The report concludes: "Our study results demonstrate that supplementation with Your Iron Syrup is effective in preventing the development of anemia in children with latent sideropenia and even shows a trend towards replenishing the iron stores. However, due to the small size of our sample, a larger study would be needed for a more definitive assessment."
Matevž Ambrožič, marketing and PR Director for PharmaLinea, says this is the first relevant clinical trial on iron supplements for children.
"The results are outstanding - >Your< Iron Syrup was able to raise ferritin levels by 69,7% - from levels at risk of anemia (14,5 μg/l) to healthy levels (24,6 μg/l)," he says. "This means there is finally a clinically proven solution for iron-deficient children to avoid anemia and drugs with harsh side effects."
Study participants were randomly assigned to receive either >Your< Iron Syrup or placebo. Both products were developed, manufactured, and supplied by PharmaLinea Ltd. (Ljubljana, Slovenia).
Products were matched for appearance, smell, taste, and packaging and sets of bottles as well as their respective outer packaging were coded by a unique two-letter-one-number code. >Your< Iron Syrup contained 14 mg of elemental iron in the form of branded micronised, microencapsulated ferric iron (Qfer), 0.7 mg of vitamin B6, and 1.25 µg of vitamin B12 as active ingredients per 5 mL of the product.
Placebo syrup did not contain any iron but was otherwise exactly matched in composition to >Your< Iron Syrup.Children were assessed against inclusion and exclusion criteria and 0.5 mL of capillary blood was sampled for determination of complete blood count (CBC) and plasma ferritin, both being markers of iron status.
Since ferritin concentration can be elevated in case of inflammation, C-reactive protein (CRP) concentration was determined to exclude individuals with high ferritin due to coexistent inflammation.At enrolment visit, children were randomised to either the iron syrup or placebo in a 3:1 ratio.
Each child’s weight was recorded to determine the required amount of syrup (1 mg of elemental iron per kg of body weight). Parents also received counselling on their child’s age-appropriate iron-rich diet and were provided a paper-based study diary to enter any modifications implemented to their child’s diet, any adverse events (AE) and missed doses of syrup.
Enrolment visit was followed by an interim follow-up visit 4 weeks (±3 days) later and a final follow-up visit after a period of 12-weeks (±3 days) of supplementation.
A sample of capillary blood was drawn at interim and final follow-up from each participant to monitor the efficacy of intervention through changes in CBC and plasma ferritin (in conjunction with CRP) parameters.
of the 70 children randomized to >Your< Iron Syrup (YIS) arm, 64 children (91%) completed the study. In the placebo arm, 21 individuals (88%) completed
There was no significant difference in the frequency of children that experienced adverse events (AEs) between the study arms (p = 0.16) and no significant differences in the frequency, type of AE (p = 0.64) and distribution of mild, moderate, and severe AEs (p = 0.07).While 45% of the children in >Your< Iron Syrup arm remained iron deficient (ferritin value below or equal to 20 µg/L) even after the intervention had been completed, this may be explained by the relatively low dose of supplementation used in the study. Hb value may normalize on a small daily dose of iron, but this low dose seldom suffices for metabolic needs or the replenishment of iron stores in the body .Similar studies of iron supplementation in children have reported higher efficacies within a 3-month supplementation period; however, much higher doses of iron (ranging from 2 mg/kg of iron per body weight per day to 6 mg/kg of iron per body weight per day) than the one applied in our study have been used [14,15,16].Of particular importance, these studies were all performed in anemic subjects, whereas our study included children with ID without anemia. It is well established that iron absorption is negatively regulated by the regulatory hormone hepcidin, the level of which tends to be more profoundly reduced in IDA than in ID [17,18], thus possibly differentially affecting the degree of iron absorption in these instances. Significant effects of oral iron supplementation might therefore be evident at earlier time points in IDA as opposed to ID.
Jazbec. J., et al
"Micronized, Microencapsulated Ferric Iron Supplementation in the Form of >Your< Iron Syrup Improves Hemoglobin and Ferritin Levels in Iron-Deficient Children: Double-Blind, Randomized Clinical Study of Efficacy and Safety"