Does adding iron to wheat flour reduce anaemia and increase iron levels in the general population?

Why is this question important?

Anaemia is a common condition usually caused by low iron levels in the body. Iron is important because it is the main component of haemoglobin, the protein in red blood cells that carries oxygen around the body. If the body cannot produce enough healthy red blood cells to provide the body with sufficient oxygen, people may suffer from problems such as tiredness and inability to concentrate, children may have learning difficulties, and pregnant women and their babies may be at risk of death or developmental problems. People in low-income countries often have diets that are low in iron, resulting in anaemia or low blood iron levels. Such countries attempt to tackle this problem at the population level by adding iron and other minerals and vitamins (micronutrients) to staple foods, such as wheat flour.

We wanted to know whether adding iron to wheat flour, alone or with additional micronutrients, reduces anaemia and iron deficiency in the general population. We also wanted to know if it causes any unwanted effects, for example diarrhoea, infection or inflammation, constipation, nausea, or death.

How did we identify and assess the evidence?

We searched medical databases for randomised controlled trials (RCTs) that assessed the effects on the general population, aged over two years, of wheat flour with added iron and other micronutrients compared to wheat flour alone or wheat flour with the same added nutrients but no additional iron. RCTs are medical studies where people are chosen at random to receive a treatment (the intervention), or a different treatment or no treatment (the control). RCTs provide the most reliable evidence.

Based on factors such as how studies were conducted and consistency of findings across studies, we categorised the evidence as high, moderate, low or very low certainty. High certainty means we are confident in the evidence, moderate certainty means we are fairly confident, low or very low certainty means that we are unsure or very unsure of the reliability of the evidence.

What did we find?

We found nine relevant RCTs. The study participants were 3166 children, adolescent girls and adult women living in Bangladesh, Brazil, India, Kuwait, the Philippines, Sri Lanka and South Africa. The studies assessed the effects of wheat flour with different forms of iron alone or combined with other micronutrients, compared with wheat flour alone or wheat flour with the same added micronutrients but no iron. Studies lasted from 3 to 24 months and reported anaemia, haemoglobin concentrations, iron deficiency and iron status. Two studies assessed infection and inflammation. None of the included studies assessed diarrhoea, respiratory infections, death, or other unwanted effects. Eight studies clearly reported their source of funding, including three with industry funding.

Key results

Wheat flour with iron may have little or no effect on anaemia and probably makes little or no difference in iron deficiency compared to wheat flour alone. We are uncertain whether wheat flour with iron increases haemoglobin concentrations. Wheat flour with iron probably makes little or no difference to individual risk of infection or inflammation.

Wheat flour with iron plus other micronutrients, may make little or no difference to anaemia, probably makes little or no difference to iron deficiency and may or may not improve haemoglobin concentrations compared to wheat flour alone.

We are very uncertain about the effects of wheat flour with iron plus other micronutrients compared to wheat flour with the same micronutrients but no iron on anaemia and iron deficiency, as the certainty of the evidence was very low. Wheat flour with iron may make little or no difference to haemoglobin concentrations.

What this means

We judged the evidence as very low to moderate certainty, which means we are not certain of the effect of wheat flour with added iron on the reduction of anaemia and iron deficiency on people in countries that add iron to wheat flour. We do not know whether adding iron to wheat flour causes unwanted effects because none of the studies reported unwanted effects.

How up to date is this review?

The review is up to date to September 2019.

Authors' conclusions: 

Eating food items containing wheat flour fortified with iron alone may have little or no effect on anaemia and probably makes little or no difference in iron deficiency. We are uncertain on whether the intervention with wheat flour fortified with iron increases haemoglobin concentrations improve blood haemoglobin concentrations.

Consuming food items prepared from wheat flour fortified with iron, in combination with other micronutrients, has little or no effect on anaemia, makes little or no difference to iron deficiency and may or may not improve haemoglobin concentrations.

In comparison to fortified flour with micronutrients but no iron, wheat flour fortified with iron with other micronutrients, the effects on anaemia and iron deficiency are uncertain as certainty of the evidence has been assessed as very low. The intervention may make little or no difference to the average haemoglobin concentrations in the population.

None of the included trials reported any other adverse side effects. The effects of this intervention on other health outcomes are unclear.

Read the full abstract...
Background: 

Anaemia is a condition where the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body's physiologic needs. Fortification of wheat flour is deemed a useful strategy to reduce anaemia in populations.

Objectives: 

To determine the benefits and harms of wheat flour fortification with iron alone or with other vitamins and minerals on anaemia, iron status and health-related outcomes in populations over two years of age.

Search strategy: 

We searched CENTRAL, MEDLINE, Embase, CINAHL, and other databases up to 4 September 2019.

Selection criteria: 

We included cluster- or individually randomised controlled trials (RCT) carried out among the general population from any country aged two years and above. The interventions were fortification of wheat flour with iron alone or in combination with other micronutrients. Trials comparing any type of food item prepared from flour fortified with iron of any variety of wheat were included.

Data collection and analysis: 

Two review authors independently screened the search results and assessed the eligibility of studies for inclusion, extracted data from included studies and assessed risk of bias. We followed Cochrane methods in this review.

Main results: 

Our search identified 3048 records, after removing duplicates. We included nine trials, involving 3166 participants, carried out in Bangladesh, Brazil, India, Kuwait, Phillipines, Sri Lanka and South Africa. The duration of interventions varied from 3 to 24 months. One study was carried out among adult women and one trial among both children and nonpregnant women. Most of the included trials were assessed as low or unclear risk of bias for key elements of selection, performance or reporting bias.

Three trials used 41 mg to 60 mg iron/kg flour, two trials used less than 40 mg iron/kg and three trials used more than 60 mg iron/kg flour. One trial employed various iron levels based on type of iron used: 80 mg/kg for electrolytic and reduced iron and 40 mg/kg for ferrous fumarate.

All included studies contributed data for the meta-analyses. Seven studies compared wheat flour fortified with iron alone versus unfortified wheat flour, three studies compared wheat flour fortified with iron in combination with other micronutrients versus unfortified wheat flour and two studies compared wheat flour fortified with iron in combination with other micronutrients versus fortified wheat flour with the same micronutrients (but not iron). No studies included a 'no intervention' comparison arm.

None of the included trials reported any other adverse side effects (including constipation, nausea, vomiting, heartburn or diarrhoea).

Wheat flour fortified with iron alone versus unfortified wheat flour (no micronutrients added)

Wheat flour fortification with iron alone may have little or no effect on anaemia (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.61 to 1.07; 5 studies; 2200 participants; low-certainty evidence). It probably makes little or no difference on iron deficiency (RR 0.43, 95% CI 0.17 to 1.07; 3 studies; 633 participants; moderate-certainty evidence) and we are uncertain about whether wheat flour fortified with iron increases haemoglobin concentrations by an average 3.30 (g/L) (95% CI 0.86 to 5.74; 7 studies; 2355 participants; very low-certainty evidence).

No trials reported data on adverse effects in children, except for risk of infection or inflammation at the individual level. The intervention probably makes little or no difference to risk of Infection or inflammation at individual level as measured by C-reactive protein (CRP) (moderate-certainty evidence).

Wheat flour fortified with iron in combination with other micronutrients versus unfortified wheat flour (no micronutrients added)

Wheat flour fortified with iron, in combination with other micronutrients, may or may not decrease anaemia (RR 0.95, 95% CI 0.69 to 1.31; 2 studies; 322 participants; low-certainty evidence). It makes little or no difference to average risk of iron deficiency (RR 0.74, 95% CI 0.54 to 1.00; 3 studies; 387 participants; moderate-certainty evidence) and may or may not increase average haemoglobin concentrations (mean difference (MD) 3.29, 95% CI -0.78 to 7.36; 3 studies; 384 participants; low-certainty evidence).

No trials reported data on adverse effects in children.

Wheat flour fortified with iron in combination with other micronutrients versus fortified wheat flour with same micronutrients (but not iron)

Given the very low certainty of the evidence, the review authors are uncertain about the effects of wheat flour fortified with iron in combination with other micronutrients versus fortified wheat flour with same micronutrients (but not iron) in reducing anaemia (RR 0.24, 95% CI 0.08 to 0.71; 1 study; 127 participants; very low-certainty evidence) and in reducing iron deficiency (RR 0.42, 95% CI 0.18 to 0.97; 1 study; 127 participants; very low-certainty evidence). The intervention may make little or no difference to the average haemoglobin concentration (MD 0.81, 95% CI -1.28 to 2.89; 2 studies; 488 participants; low-certainty evidence).

No trials reported data on the adverse effects in children. Eight out of nine trials reported source of funding with most having multiple sources. Funding source does not appear to have distorted the results in any of the assessed trials.

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