Current World Health Organization (WHO) guidelines for iron supplementation recommend that infants and children living in regions where anaemia is prevalent should take daily elemental iron supplements for three months of the year. Suggested doses are 10-12.5 mg for infants; 30 mg for preschool-age children; and 30-60 mg for school-age children.
“While there is no dispute that iron supplementation is effective at treating iron-deficiency anaemia, we noticed that the meta-analyses, which formed the basis of the WHO's recommendations, did not aim to assess the optimal frequency, dose, and duration of supplementation.
“So, we wondered if looking at the overall body of research could give an indication of whether treatment effects varied according to those factors,” said author Dr Christopher Andersen, of Harvard University’s TH Chan School of Public Health, explaining the background to the study.
The study concluded that intermittent (once or twice a week) and frequent (three to seven times per week) iron supplementation were similarly effective in reducing anaemia. Therefore, in cases where frequent supplementation is not desired or feasible, intermittent supplementation could be considered as an acceptable alternative.
“Our results generally support the WHO recommendations regarding the frequency, duration, and dose of iron supplementation. However, weekly iron supplementation might be considered as an alternative to the recommended daily regimen in some contexts, given evidence of similar efficacy,” wrote the researchers in the journal BMJ Global Health.
These findings challenged a previous meta-analysis of 21 trials which concluded that, compared with daily supplementation, intermittent supplementation had similar effects on haemoglobin levels but was less effective in reducing anaemia.
Frequent vs intermittent iron supplementation
Andersen said that there were good physiological reasons to explain why intermittent supplementation might be as effective as frequent supplementation.
“Mammalian gastrointestinal epithelial cells turn over every two to six days, so intermittent supplementation may not be at a great disadvantage relative to frequent supplementation with respect to the total amount of absorbed iron.
“Furthermore, some evidence points to changes in gastrointestinal epithelial cells following a large bolus of iron that results in reduced transport of iron into portal blood,” he explained.
In addition, the scientists suggested that intermittent regimens might overcome some of the practical obstacles to adherence.
“While [the] WHO recommends daily oral iron supplementation for all children in regions with an anaemia prevalence of 40% or more, the success of such programmes may be threatened by low adherence from adverse gastrointestinal reactions or high caregiver burden to provide daily supplements,” wrote the authors.
The researchers conducted a systemic review and meta-analysis of randomised controlled trials investigating the impacts of oral iron supplementation in children and adolescents. There were 129 trials that met the researchers’ eligibility criteria (participants had to be under 20; supplementation duration had to be 30 days or more; oral iron supplementation had to be randomly assigned and compared with a placebo or control). The researchers compared the impact of interventions by schedule, duration, dose, and co-interventions.
“Our study adds to previous meta-analyses of paediatric iron supplementation by using meta-regression to compare the effect sizes of randomised controlled trials with different schedules, durations, doses, and co-supplementation schemes. As a result, we are able to marshal a much larger body of literature than prior studies which have been restricted to trials specifically to answer questions of effect heterogeneity,” said the researchers.
Their analysis found that frequent and intermittent iron supplementation regimens were equally effective at decreasing anaemia, iron deficiency, and iron-deficiency anaemia. They also found that moderate-high and high-dose supplements were more effective than low-dose supplements at improving haemoglobin, ferritin, and iron deficiency anaemia, but had similar effects to low-dose supplements for overall anaemia.
Strengthening the case for co-supplementation
A further noteworthy finding was that iron supplementation provided similar benefits when administered alone or in combination with zinc or vitamin A, although there was some evidence that iron supplementation alone is more effective at reducing anaemia than when it is co-administered with zinc.
The team said its findings could be used in clinical decision-making and the development of further guidelines on oral iron supplementation for children and adolescents.
Asked how the supplement industry could apply these findings, Andersen said: “Supplements can be marketed according to age in order to ensure that children receive the appropriate dose. Moderate dosages are likely prudent. Package labelling for over-the-counter supplements could indicate ‘once a week’ or ‘twice weekly' when appropriately dosed.”