Fortification of rice with vitamins and minerals for addressing micronutrient malnutrition

What is the aim of this review?

The aim of this Cochrane Review was to assess whether rice fortification with one or more vitamins and minerals in the general population aged two years or older improves nutritional status.

Key messages

Fortification of rice with iron alone or in combination with other micronutrients may make little or no difference in the risk of having anaemia but probably reduces the risk of iron deficiency and increases mean haemoglobin concentrations in population aged two years or above. If vitamin A is added, it may reduce the risk of having vitamin A deficiency and when folic acid is added, fortified rice may slightly increase serum folate concentrations.

What was studied in this review?

Micronutrient malnutrition compromises the health and well-being of populations in many low- and middle-income countries. Fortification is the addition of nutrients to foods to improve their nutritional quality. Rice is widely consumed as a staple food and is suitable for adopting as a food vehicle for fortification. This review addresses the benefits and harms of rice fortification with vitamins and minerals on micronutrient status along with health-related outcomes, among participants aged two years and above, in addition to outcomes relevant to deficiencies in iron, vitamin A, zinc and folate.

What are the main results of the review?

We identified 17 studies (involving 10,483 participants) from Bangladesh, Brazil, Burundi, Cambodia, India, Indonesia, Mexico, Philippines, Thailand and USA. Twelve were randomised studies (2238 participants); 10 involved children, and two studies involved non-pregnant non-lactating women. In addition to iron, some studies had vitamin A, zinc or folic acid as fortifying agents, alone or in combination. Five non-randomised studies (8245 participants), were assessed to augment the information on implementation and impact of fortification. The included studies were funded by government, private and non-governmental organisations, along with other academic institutions. The source of funding does not appear to have altered the results.

We are uncertain about whether rice fortification with iron and other micronutrients reduces the risk of having anaemia although this intervention may increase mean haemoglobin concentrations (a biomarker of anaemia). We are uncertain if fortification of rice with iron alone or in combination with other micronutrients as compared to without any fortification, reduces the risk of iron deficiency.

Furthermore, consumption of vitamin A in the fortified rice, may make little difference on haemoglobin and serum retinol concentrations (a biomarker of vitamin A nutrition). We do not know whether fortification of rice has any adverse effects, in the mid- or long-term, as the evidence was very limited. We found that the overall certainty of the evidence ranged from very low to low. Also, all studies used iron to fortify rice, so the effect of isolated nutrients may be hidden. There was no significant publication bias across the studies.

How up-to-date is this review?

The review authors searched for studies that had been published up to 10 December 2018.

Authors' conclusions: 

Fortification of rice with iron alone or in combination with other micronutrients may make little or no difference in the risk of having anaemia or presenting iron deficiency and we are uncertain about an increase in mean haemoglobin concentrations in the general population older than 2 years of age. Fortification of rice with iron and other micronutrients such as vitamin A or folic acid may make little or no difference in the risk of having vitamin A deficiency or on the serum folate concentration. There is limited evidence on any adverse effects of rice fortification.

Read the full abstract...
Background: 

Rice fortification with vitamins and minerals has the potential to increase the nutrition in rice-consuming countries where micronutrient deficiencies exist. Globally, 490 million metric tonnes of rice are consumed annually. It is the dominant staple food crop of around three billion people.

Objectives: 

To determine the benefits and harms of rice fortification with vitamins and minerals (iron, vitamin A, zinc or folic acid) on micronutrient status and health-related outcomes in the general population.

Search strategy: 

We searched CENTRAL, MEDLINE, Embase, CINAHL, and 16 other databases all up to 10 December 2018. We searched ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (ICTRP) on 10 December 2018.

Selection criteria: 

We included randomised and quasi-randomised trials (with either individual or cluster randomisation) and controlled before-and-after studies. Participants were populations older than two years of age (including pregnant women) from any country. The intervention was rice fortified with at least one micronutrient or a combination of several micronutrients (iron, folic acid, zinc, vitamin A or other vitamins and minerals) compared with unfortified rice or no intervention.

Data collection and analysis: 

We used standard methodological procedures expected by Cochrane. Two review authors independently screened studies and extracted data.

Main results: 

We included 17 studies (10,483 participants) and identified two ongoing studies. Twelve included studies were randomised-controlled trials (RCTs), with 2238 participants after adjusting for clustering in two cluster-RCTs, and five were non-randomised studies (NRS) with four controlled before-and-after studies and one cross-sectional study with a control (8245 participants). Four studies were conducted in India, three in Thailand, two in the Philippines, two in Brazil, one each in Bangladesh, Burundi, Cambodia, Indonesia, Mexico and the USA. Two studies involved non-pregnant, non-lactating women and 10 involved pre-school or school-age children.

All 17 studies reported fortification with iron. Of these, six studies fortified rice with iron only; 11 studies had other micronutrients added (iron, zinc and vitamin A, and folic acid). One study had one arm each with vitamin A alone and carotenoid alone. Elemental iron content ranged from 0.2 to 112.8 mg/100 g uncooked rice given for a period varying from two weeks to 48 months.

Thirteen studies did not clearly describe either sequence generation or allocation concealment. Eleven studies had a low attrition rate. There was no indication of selective reporting in the studies. We considered two RCTs at low overall risk of bias and 10 at high overall risk of bias. One RCT was at high or unclear risk of bias for most of the domains. All controlled before-and-after studies had a high risk or unclear risk of bias in most domains. The included studies were funded by Government, private and non‐governmental organisations, along with other academic institutions. The source of funding does not appear to have altered the results. We used the NRS in the qualitative synthesis but we excluded them from the quantitative analysis and review conclusions since they provided mostly contextual information and limited quantitative information.

Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)

Fortification of rice with iron (alone or in combination with other micronutrients) may make little or no difference in the risk of having anaemia (risk ratio (RR) 0.72, 95% confidence interval (CI) 0.54 to 0.97; I2 = 74%; 7 studies, 1634 participants; low-certainty evidence) and may reduce the risk of iron deficiency (RR 0.66, 95% CI 0.51 to 0.84; 8 studies, 1733 participants; low-certainty evidence). Rice fortification may increase mean haemoglobin (mean difference (MD) 1.83, 95% CI 0.66 to 3.00; I2 = 54%; 11 studies, 2163 participants; low-certainty evidence) and it may make little or no difference to vitamin A deficiency (with vitamin A as one of the micronutrients in the fortification arm) (RR 0.68, 95% CI 0.36 to 1.29; I2 = 37%; 4 studies, 927 participants; low-certainty evidence). One study reported that fortification of rice (with folic acid as one of the micronutrients) may improve serum or plasma folate (nmol/L) (MD 4.30, 95% CI 2.00 to 6.60; 215 participants; low-certainty evidence). One study reported that fortification of rice with iron alone or with other micronutrients may slightly increase hookworm infection (RR 1.78, 95% CI 1.18 to 2.70; 785 participants; low-certainty evidence). We are uncertain about the effect of fortified rice on diarrhoea (RR 3.52, 95% CI 0.18 to 67.39; 1 study, 258 participants; very low-certainty evidence).

Rice fortified with vitamin A alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)

One study had one arm providing fortified rice with vitamin A only versus unfortified rice. Fortification of rice with vitamin A (in combination with other micronutrients) may increase mean haemoglobin (MD 10.00, 95% CI 8.79 to 11.21; 1 study, 74 participants; low-certainty evidence). Rice fortified with vitamin A may slightly improve serum retinol concentration (MD 0.17, 95% CI 0.13 to 0.21; 1 study, 74 participants; low-certainty evidence).

No studies contributed data to the comparisons of rice fortification versus no intervention. The studies involving folic acid and zinc also involved iron in the fortification arms and hence we reported them as part of the first comparison.

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