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Meta-Analysis
. 2019 Oct 25;2019(10):CD009902.
doi: 10.1002/14651858.CD009902.pub2.

Fortification of rice with vitamins and minerals for addressing micronutrient malnutrition

Juan Pablo Peña-Rosas  1 , Prasanna Mithra  2 , Bhaskaran Unnikrishnan  2 , Nithin Kumar  2 , Luz Maria De-Regil  3 , N Sreekumaran Nair  4 , Maria N Garcia-Casal  1 , Juan Antonio Solon  5
Affiliations
Meta-Analysis

Fortification of rice with vitamins and minerals for addressing micronutrient malnutrition

Juan Pablo Peña-Rosas et al. Cochrane Database Syst Rev. .

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 methods: 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.

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.

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Conflict of interest statement

Juan Pablo Peña‐Rosas (JPP) co‐ordinates the Evidence and Programme Guidance Unit, Department of Nutrition for Health and Development, which received financial resources from the Bill & Melinda Gates Foundation (2013‐2019); US Centers for Disease Control and Prevention (CDC) (2014‐2019); Nutrition International (2014‐2019) and USAID (2014‐2019). Donors do not fund specific guidelines and do not participate in any decision related to the guideline development process including the composition of policy questions, membership of the guideline groups, the conduct and interpretation of systematic reviews, or the formulation of recommendations.

Prasanna Mithra (PM) received partial financial support from the Department of Nutrition for Health and Development, World Health Organization for this work.

B Unnikrishnan (BUK) received partial financial support from the Department of Nutrition for Health and Development, World Health Organization for this work.

Nithin Kumar (NK) received partial financial support from the Department of Nutrition for Health and Development, World Health Organization for this work.

Luz Maria De‐Regil (LMD) was a full‐time staff member of Nutrition International (formerly Micronutrient Initiative), an international not‐for‐profit organisation that delivers nutrition interventions to children, women of reproductive age and pregnant women. Nutrition International supports the implementation of large‐scale research projects on food fortification. None of them met the inclusion criteria of this review. Nutrition International is a partner of the Food Fortification Initiative and receives funds from the Canadian Department of Foreign Affairs. LMD was an Editor for the Cochrane Developmental, Psychosocial and Learning Problems Group.

Sreekumar Nair (SN) received partial financial support from the Department of Nutrition for Health and Development, World Health Organization for this work.

Maria Nieves Garcia‐Casal (MNG) is a scientist in the Evidence and Programme Guidance Unit, Department of Nutrition for Health and Development, which received financial resources from the Bill & Melinda Gates Foundation (2013‐2019); US Centers for Disease Control and Prevention (CDC) (2014‐2019); Nutrition International (2014‐2019) and USAID (2014‐2019). Donors do not fund specific guidelines and do not participate in any decision related to the guideline development process including the composition of policy questions, membership of the guideline groups, the conduct and interpretation of systematic reviews, or the formulation of recommendations.

Juan Antonio Solon (JAS) is president of the Nutrition Center of the Philippines, a non‐profit organisation working towards nutrition security (www.ncp.org.ph). He received partial financial support for this work. His involvement with the review was at the final stage where he helped with the interpretation of the results.

Figures

1
1
WHO/CDC logic model for micronutrients interventions in public health (with permission from WHO)
2
2
PRISMA study flow diagram
3
3
'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included study Four studies were controlled before‐and‐after studies (Ara 2019; Della Lucia 2016; Gershoff 1977; Nogueira Arcanjo 2013), and one was a controlled cross‐sectional study (Salcedo 1950)
4
4
'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included studies
5
5
Funnel plot of comparison 1. Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added), outcome 1.13, haemoglobin concentration (g/L)
1.1
1.1. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 1 Anaemia (defined as haemoglobin (Hb) below the WHO cut‐off, adjusted for altitude as appropriate).
1.2
1.2. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 2 Anaemia (subgroup: by micronutrient content).
1.3
1.3. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 3 Anaemia (subgroup: by rice fortification method).
1.4
1.4. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 4 Anaemia (subgroup: by cooking method most commonly used in trial setting).
1.5
1.5. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 5 Anaemia (subgroup: by public health significance of anaemia at baseline ).
1.6
1.6. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 6 Anaemia (subgroup: by malaria endemicity).
1.7
1.7. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 7 Iron deficiency (as defined by study authors, based on a biomarker of iron status).
1.8
1.8. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 8 Iron deficiency (subgroup: by micronutrient content).
1.9
1.9. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 9 Iron deficiency (subgroup: by rice fortification method).
1.10
1.10. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 10 Iron deficiency (subgroup: by cooking method most commonly used in trial setting).
1.11
1.11. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 11 Iron deficiency (subgroup: by public health significance of anaemia at baseline ).
1.12
1.12. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 12 Iron deficiency (subgroup: by malaria endemicity).
1.13
1.13. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 13 Haemoglobin concentration (g/L).
1.14
1.14. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 14 Haemoglobin concentration (subgroup: by micronutrient content).
1.15
1.15. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 15 Haemoglobin concentration (subgroup: by rice fortification method).
1.16
1.16. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 16 Haemoglobin concentration (subgroup: by cooking method most commonly used in trial setting).
1.17
1.17. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 17 Haemoglobin concentration (subgroup: by public health significance of anaemia at baseline).
1.18
1.18. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 18 Haemoglobin concentration (subgroup: by malaria endemicity).
1.19
1.19. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 19 Vitamin A deficiency (as defined by study authors, by using a biomarker of vitamin A).
1.20
1.20. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 20 Vitamin A deficiency (subgroup: by micronutrient content).
1.21
1.21. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 21 Vitamin A deficiency (subgroup: by rice fortification method).
1.22
1.22. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 22 Vitamin A deficiency (subgroup: by cooking method most commonly used in trial setting).
1.23
1.23. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 23 Vitamin A deficiency (subgroup: by public health significance of anaemia at baseline ).
1.24
1.24. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 24 Vitamin A deficiency (subgroup: by malaria endemicity).
1.25
1.25. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 25 Serum or plasma folate (nmol/L).
1.26
1.26. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 26 Any adverse effects.
1.27
1.27. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 27 Diarrhoea (as defined by study authors).
1.28
1.28. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 28 Serum or plasma retinol (µmol/L).
1.29
1.29. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 29 Serum or plasma zinc (µmol/L).
1.30
1.30. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 30 Height‐for‐age Z‐score.
1.31
1.31. Analysis
Comparison 1 Rice fortified with iron alone or in combination with other micronutrients versus unfortified rice (no micronutrients added)., Outcome 31 Weight‐for‐height Z‐score.
2.1
2.1. Analysis
Comparison 2 Rice fortified with vitamin A alone or in combination with other micronutrients versus unfortified rice (no micronutrients added), Outcome 1 Haemoglobin concentration (g/L).
2.2
2.2. Analysis
Comparison 2 Rice fortified with vitamin A alone or in combination with other micronutrients versus unfortified rice (no micronutrients added), Outcome 2 Serum or plasma retinol (µmol/L).
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD009902

References

References to studies included in this review

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Hardinsyah 2016 {published data only}
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Hotz 2008 {published data only}
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Hussain 2014 {published data only}
    1. Hussain SZ, Singh B, Rather AH. Efficacy of micronutrient fortified extruded rice in improving the iron and vitamin A status in Indian schoolchildren. International Journal of Agriculture and Food Science Technology 2014;5(3):227‐38.
Losso 2017 {published data only}
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Moretti 2006b {published data only}
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Nogueira Arcanjo 2013 {published data only}
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Parker 2015 (C) {published data only}
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Perignon 2016 (C) {published data only}
    1. Gier B, Campos Ponce M, Perignon M, Fiorentino M, Khov K, Chamnan C, et al. Micronutrient‐fortified rice can increase hookworm infection risk: a cluster randomized trial. PLoS One 2016;11(1):e0145351. - PMC - PubMed
    1. Fiorentino M, Perignon M, Kuong K, Groot R, Parker M, Burja K, et al. Effect of multi‐micronutrient‐fortified rice on cognitive performance depends on premix composition and cognitive function tested: results of an effectiveness study in Cambodian schoolchildren. Public Health Nutrition 2018;21(4):816‐27. [DOI: 10.1017/S1368980017002774] - DOI - PMC - PubMed
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    1. Perignon M, Fiorentino M, Kuong K, Burja K, Parker M, Sisokhom S, et al. Stunting, poor iron status and parasite infection are significant risk factors for lower cognitive performance in Cambodian school‐aged children. PLoS One 2014;9(11):e112605. - PMC - PubMed
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Pinkaew 2013 {published data only}
    1. Pinkaew S, Winichagoon P, Hurrell RF, Wegmuller R. Extruded rice grains fortified with zinc, iron, and vitamin A increase zinc status of Thai school children when incorporated into a school lunch program. Journal of Nutrition 2013;143(3):362‐8. - PubMed
Pinkaew 2014 {published data only}
    1. Pinkaew S, Wegmuller R, Wasantwisut E, Winichagoon P, Hurrell RF, Tanumihardjo SA. Triple‐fortified rice containing vitamin A reduced marginal vitamin A deficiency and increased vitamin A liver stores in school‐aged Thai children. Journal of Nutrition 2014;144(4):519‐24. - PubMed
Radhika 2011 {published data only}
    1. Radhika MS, Nair KM, Kumar RH, Rao MV, Ravinder P, Reddy CG, et al. Micronized ferric pyrophosphate supplied through extruded rice kernels improves body iron stores in children: a double‐blind, randomized, placebo‐controlled midday meal feeding trial in Indian schoolchildren. American Journal of Clinical Nutrition 2011;94(5):1202‐10. - PubMed
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Thankachan 2012 {published data only}
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References to studies excluded from this review

Ando 2012 {published data only}
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Angeles‐Agdeppa 2011 {published data only}
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Arsenault 2010 {published data only}
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Bagni 2009 {published data only}
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Barboza 2011 {published data only}
    1. Barboza Argüello MP, Umaña Solís LM. Impact of the fortification of food with folic acid on neural tube defects in Costa Rica [Impacto de la fortificación de alimentos con ácido fólico en los defectos del tubo neural en Costa Rica]. Revista Panamericana de Salud Publica 2011;30(1):1‐6. - PubMed
Beinner 2010 {published data only}
    1. Beinner MA, Soares AD, Barros AL, Monteiro MA. Sensory evaluation of rice fortified with iron. Ciencia e Tecnologia De Alimentos 2010;30(2):516‐9.
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Castro 2017 {published data only}
    1. Castro LC, Brunoro CN, Pinheiro SH, Fortes LC, Castro FS. Improvement the nutritional status of pre‐school children following intervention with a supplement containing iron, zinc, copper, vitamin A, vitamin C and prebiotic. Ciência & Saúde Coletiva 2017;22(2):359‐68.
Finkelstein 2013 {published data only}
    1. Filkenstein J, Mehta S, Haas JD. Iron fortification interventions: synthesis of results from three trials in Asia. Annals of Nutrition and Metabolism 2013;63(Suppl 1):1‐1960.
Florentino 1998 {published data only}
    1. Florentino RF, Pedro MR. Update on rice fortification in the Philippines. Food and Nutrition Bulletin 1998;19(2):149‐53.
Graham 2007 {published data only}
    1. Graham JM, Haskell MJ, Pandey P, Shrestha RK, Brown KH. Supplementation with iron and riboflavin enhances dark adaptation response to vitamin A ‐‐ fortified rice in iron‐deficient, pregnant, nightblind Nepali women. American Journal of Clinical Nutrition 2007;85(5):1375‐84. - PubMed
    1. Graham JM, Pandey P, Haskell MJ, Shrestha RK, Peerson JM, Brown KH, et al. Riboflavin plus iron supplementation did not enhance improvement of dark adaptation or retinol in night blind pregnant Nepali women receiving vitamin A‐fortified Ultra‐Rice (TM). FASEB Journal 2003;17(5):A1101‐2.
    1. Haskell MJ, Pandey P, Graham JM, Peerson JM, Shresthra RK, Brown KH. Response of plasma retinol and carotenoid concentrations of nightblind, pregnant Nepalese women to daily supplementation with locally available vitamin A‐rich foods or vitamin A‐fortified Ultra‐Rice (TM). FASEB Journal 2002;16(4):A626.
Haskell 2005 {published data only}
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References to ongoing studies

NCT02714075 {published data only}
    1. NCT02714075. Comparison of iron absorption from extruded FePP‐fortified rice containing zinc, citric acid/trisodium citrate and EDTA (MM_Rice). clinicaltrials.gov 2016 (accessed 09 October 2019).
NCT03056625 {published data only}
    1. NCT03056625. Efficacy of vitamin A fortified rice in lactating Thai women (EVAL). clinicaltrials.gov September 2017 (accessed 09 October 2019).

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