What is the issue?
Anaemia (low iron levels in the blood) is a health problem worldwide, caused by nutritional (e.g. nutrient deficiencies) or non-nutritional (e.g. diseases or genetic disorders) factors. Its health consequences include fatigue, loss of productivity and adverse pregnancy and child outcomes.
Why is this important?
Iron deficiency (ID) is a common cause of nutritional anaemia, resulting from a lack of iron in the diet or reduced absorption of iron in the body (e.g. components in coffee, tea or cocoa inhibit iron absorption, while beverages and foods high in vitamin C, such as fruits and vegetables, enhance iron absorption). Some types of anaemia are preventable or controllable with iron supplementation (via capsules or drops), fortification (food enriched with sprinkles or powders containing iron) or improvements to diet diversity and quality (e.g. education or counselling).
What evidence did we find?
Infants (6 to 23 months)
Two reviews suggested that iron supplementation increased haemoglobin (Hb) levels, and reduced the risk of anaemia and iron deficiency anaemia (IDA) compared with placebo, no intervention or other interventions. Six reviews suggested that iron fortification of milk or cereals, multiple-micronutrient powder (MMNP), home fortification of complementary foods and supplementary feeding increased Hb levels and reduced the risk of anaemia. In one review apiece, lipid-based nutrient supplementation (LNS) reduced the risk of anaemia, while caterpillar cereal increased Hb levels and reduced IDA prevalence.
Preschool and school-aged children (2 to 10 years)
Two reviews suggested that daily or intermittent (e.g. 1 to 3 times per week) iron supplementation increased Hb levels and reduced the risk of anaemia and ID. For daily versus intermittent iron supplementation, one review found no difference in Hb levels, but an increased risk of anaemia and ID for the intermittent regime. One review apiece found higher Hb levels and reduced risk of anaemia and ID for zinc plus iron supplementation versus zinc alone, multiple-micronutrient (MMN)-fortified beverages, and point-of-use fortification of food with iron-containing micronutrient powder (MNP).
Adolescent children (11 to 18 years)
Three reviews for prevention or treatment suggested that intermittent iron supplementation alone or in combination with other micronutrients, iron supplementation with or without folic acid supplementation, or other micronutrient supplementation increased Hb levels and reduced the risk of anaemia. One review suggested that nutritional supplementation and counselling reduced IDA. In one review for prevention, iron supplementation with or without folic acid appeared to increase Hb levels but have no effect on the incidence of anaemia.
Non-pregnant women of reproductive age (19 to 49 years)
Two reviews suggested that iron therapy (oral, intravenous, intramuscular) increased Hb levels. One review found that intravenous iron increased Hb levels compared with oral iron, and another that daily iron supplementation with or without folic acid or vitamin C increased Hb levels and reduced the risk of anaemia and ID.
Pregnant women of reproductive age (15 to 49 years)
In one review, daily iron supplementation with or without folic acid increased Hb levels in the third trimester or at delivery, and in the postpartum period, and reduced the risk of anaemia, IDA and ID in the third trimester or at delivery. Six reviews suggested that intravenous iron versus oral iron or intramuscular iron increased Hb levels. In one review, vitamin A supplementation alone versus placebo, no intervention or other micronutrient increased Hb levels and reduced the risk of anaemia for the mother. One review found that supplementation with oral bovine lactoferrin versus oral ferrous iron preparations increased Hb levels and reduced gastrointestinal side effects. In one review, compared to iron or folic acid and MMNs, LNS increased the risk of anaemia.
Mixed population (all ages)
Iron supplementation versus placebo or control increased Hb levels in healthy children, adults, and elderly people in four reviews. In two reviews, MMN fortification versus placebo or no treatment increased Hb levels in children, as did iron supplementation, but Hb levels decreased for those receiving dietary interventions. Intravenous iron resulted in higher Hb levels than oral iron in one review. In another, vitamin B12 or folic acid supplementation did not increase Hb levels. Each review suggested that iron fortification of food, iron-fortified soy sauce, double-fortified salt with iron and iodine, and fortified condiments or noodles increased Hb levels and reduced the risk of anaemia. In one review, foods prepared in iron pots showed the potential to increase Hb levels in children.
No review focused on older adult women (50 to 65 years plus) or men (19 to 65 years plus), and anaemia and malaria prevalence were rarely reported.
What does this mean?
Compared to no treatment, daily iron supplementation may increase Hb levels and reduce the risk of anaemia and IDA in infants, preschool and school-aged children and pregnant and non-pregnant women. Iron fortification of foods in infants and use of iron pots with children may have benefits for low-risk populations. Many trials reported the effects of supplementations, but very few reviews focused on fortification or improving diet diversity and quality. Future trials should focus on different types of interventions to increase food variety and dietary quality.
Compared to no treatment, daily iron supplementation may increase Hb levels and reduce the risk of anaemia and IDA in infants, preschool and school-aged children and pregnant and non-pregnant women. Iron fortification of foods in infants and use of iron pots with children may have prophylactic benefits for malaria endemicity low-risk populations. In any age group, only a limited number of reviews assessed interventions to improve dietary diversity and quality. Future trials should assess the effects of these types of interventions, and consider the requirements of different populations.
Anaemia is a prevalent health problem worldwide. Some types are preventable or controllable with iron supplementation (pills or drops), fortification (sprinkles or powders containing iron added to food) or improvements to dietary diversity and quality (e.g. education or counselling).
To summarise the evidence from systematic reviews regarding the benefits or harms of nutrition-specific interventions for preventing and controlling anaemia in anaemic or non-anaemic, apparently healthy populations throughout the life cycle.
In August 2020, we searched MEDLINE, Embase and 10 other databases for systematic reviews of randomised controlled trials (RCTs) in anaemic or non-anaemic, apparently healthy populations. We followed Cochrane methodology, extracting GRADE ratings where provided. The primary outcomes were haemoglobin (Hb) concentration, anaemia, and iron deficiency anaemia (IDA); secondary outcomes were iron deficiency (ID), severe anaemia and adverse effects (e.g. diarrhoea, vomiting).
We included 75 systematic reviews, 33 of which provided GRADE assessments; these varied between high and very low.
Infants (6 to 23 months; 13 reviews)
Iron supplementation increased Hb levels and reduced the risk of anaemia and IDA in two reviews. Iron fortification of milk or cereals, multiple-micronutrient powder (MMNP), home fortification of complementary foods, and supplementary feeding increased Hb levels and reduced the risk of anaemia in six reviews. In one review, lipid-based nutrient supplementation (LNS) reduced the risk of anaemia. In another, caterpillar cereal increased Hb levels and reduced IDA prevalence. Food-based strategies (red meat and fortified cow's milk, beef) showed no evidence of a difference (1 review).
Preschool and school-aged children (2 to 10 years; 8 reviews)
Daily or intermittent iron supplementation increased Hb levels and reduced the risk of anaemia and ID in two reviews. One review found no evidence of difference in Hb levels, but an increased risk of anaemia and ID for the intermittent regime. All suggested that zinc plus iron supplementation versus zinc alone, multiple-micronutrient (MMN)-fortified beverage versus control, and point-of-use fortification of food with iron-containing micronutrient powder (MNP) versus placebo or no intervention may increase Hb levels and reduce the risk of anaemia and ID. Fortified dairy products and cereal food showed no evidence of a difference on the incidence of anaemia (1 review).
Adolescent children (11 to 18 years; 4 reviews)
Compared with no supplementation or placebo, five types of iron supplementation may increase Hb levels and reduce the risk of anaemia (3 reviews). One review on prevention found no evidence of a difference in anaemia incidence on iron supplementation with or without folic acid, but Hb levels increased. Another suggested that nutritional supplementation and counselling reduced IDA. One review comparing MMN fortification with no fortification observed no evidence of a difference in Hb levels.
Non-pregnant women of reproductive age (19 to 49 years; 5 reviews)
Two reviews suggested that iron therapy (oral, intravenous (IV), intramuscular (IM)) increased Hb levels; one showed that iron folic acid supplementation reduced anaemia incidence; and another that daily iron supplementation with or without folic acid or vitamin C increased Hb levels and reduced the risk of anaemia and ID. No review reported interventions related to fortification or dietary diversity and quality.
Pregnant women of reproductive age (15 to 49 years; 23 reviews)
One review apiece suggested that: daily iron supplementation with or without folic acid increased Hb levels in the third trimester or at delivery and in the postpartum period, and reduced the risk of anaemia, IDA and ID in the third trimester or at delivery; intermittent iron supplementation had no effect on Hb levels and IDA, but increased the risk of anaemia at or near term and ID, and reduced the risk of side effects; vitamin A supplementation alone versus placebo, no intervention or other micronutrient might increase maternal Hb levels and reduce the risk of maternal anaemia; MMN with iron and folic acid versus placebo reduced the risk of anaemia; supplementation with oral bovine lactoferrin versus oral ferrous iron preparations increased Hb levels and reduced gastrointestinal side effects; MNP for point-of-use fortification of food versus iron and folic acid supplementation might decrease Hb levels at 32 weeks' gestation and increase the risk of anaemia; and LNS versus iron or folic acid and MMN increased the risk of anaemia.
Mixed population (all ages; 22 reviews)
Iron supplementation versus placebo or control increased Hb levels in healthy children, adults, and elderly people (4 reviews). Hb levels appeared to increase and risk of anaemia and ID decrease in two reviews investigating MMN fortification versus placebo or no treatment, iron fortified flour versus control, double fortified salt versus iodine only fortified salt, and rice fortification with iron alone or in combination with other micronutrients versus unfortified rice or no intervention. Each review suggested that fortified versus non-fortified condiments or noodles, fortified (sodium iron ethylenediaminetetraacetate; NaFeEDTA) versus non-fortified soy sauce, and double-fortified salt versus control salt may increase Hb concentration and reduce the risk of anaemia. One review indicated that Hb levels increased for children who were anaemic or had IDA and received iron supplementation, and decreased for those who received dietary interventions. Another assessed the effects of foods prepared in iron pots, and found higher Hb levels in children with low-risk malaria status in two trials, but no difference when comparing food prepared in non-cast iron pots in a high-risk malaria endemicity mixed population.
There was no evidence of a difference for adverse effects. Anaemia and malaria prevalence were rarely reported. No review focused on women aged 50 to 65 years plus or men (19 to 65 years plus).