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. 2019 May 10;5(5):CD010068.
doi: 10.1002/14651858.CD010068.pub2.

Fortification of staple foods with vitamin A for vitamin A deficiency

Aditi S Hombali  1 , Juan Antonio Solon, Bhumika T Venkatesh, N Sreekumaran Nair, Juan Pablo Peña-Rosas
Affiliations

Fortification of staple foods with vitamin A for vitamin A deficiency

Aditi S Hombali et al. Cochrane Database Syst Rev. .

Abstract

Background: Vitamin A deficiency is a significant public health problem in many low- and middle-income countries, especially affecting young children, women of reproductive age, and pregnant women. Fortification of staple foods with vitamin A has been used to increase vitamin A consumption among these groups.

Objectives: To assess the effects of fortifying staple foods with vitamin A for reducing vitamin A deficiency and improving health-related outcomes in the general population older than two years of age.

Search methods: We searched the following international databases with no language or date restrictions: Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 6) in the Cochrane Library; MEDLINE and MEDLINE In Process OVID; Embase OVID; CINAHL Ebsco; Web of Science (ISI) SCI, SSCI, CPCI-exp and CPCI-SSH; BIOSIS (ISI); POPLINE; Bibliomap; TRoPHI; ASSIA (Proquest); IBECS; SCIELO; Global Index Medicus - AFRO and EMRO; LILACS; PAHO; WHOLIS; WPRO; IMSEAR; IndMED; and Native Health Research Database. We also searched clinicaltrials.gov and the International Clinical Trials Registry Platform to identify ongoing and unpublished studies. The date of the last search was 19 July 2018.

Selection criteria: We included individually or cluster-randomised controlled trials (RCTs) in this review. The intervention included fortification of staple foods (sugar, edible oils, edible fats, maize flour or corn meal, wheat flour, milk and dairy products, and condiments and seasonings) with vitamin A alone or in combination with other vitamins and minerals. We included the general population older than two years of age (including pregnant and lactating women) from any country.

Data collection and analysis: Two authors independently screened and assessed eligibility of studies for inclusion, extracted data from included studies and assessed their risk of bias. We used standard Cochrane methodology to carry out the review.

Main results: We included 10 randomised controlled trials involving 4455 participants. All the studies were conducted in low- and upper-middle income countries where vitamin A deficiency was a public health issue. One of the included trials did not contribute data to the outcomes of interest.Three trials compared provision of staple foods fortified with vitamin A versus unfortified staple food, five trials compared provision of staple foods fortified with vitamin A plus other micronutrients versus unfortified staple foods, and two trials compared provision of staple foods fortified with vitamin A plus other micronutrients versus no intervention. No studies compared staple foods fortified with vitamin A alone versus no intervention.The duration of interventions ranged from three to nine months. We assessed six studies at high risk of bias overall. Government organisations, non-governmental organisations, the private sector, and academic institutions funded the included studies; funding source does not appear to have distorted the results.Staple food fortified with vitamin A versus unfortified staple food We are uncertain whether fortifying staple foods with vitamin A alone makes little or no difference for serum retinol concentration (mean difference (MD) 0.03 μmol/L, 95% CI -0.06 to 0.12; 3 studies, 1829 participants; I² = 90%, very low-certainty evidence). It is uncertain whether vitamin A alone reduces the risk of subclinical vitamin A deficiency (risk ratio (RR) 0.45, 95% CI 0.19 to 1.05; 2 studies; 993 participants; I² = 33%, very low-certainty evidence). The certainty of the evidence was mainly affected by risk of bias, imprecision and inconsistency.It is uncertain whether vitamin A fortification reduces clinical vitamin A deficiency, defined as night blindness (RR 0.11, 95% CI 0.01 to 1.98; 1 study, 581 participants, very low-certainty evidence). The certainty of the evidence was mainly affected by imprecision, inconsistency, and risk of bias.Staple foods fortified with vitamin A versus no intervention No studies provided data for this comparison.Staple foods fortified with vitamin A plus other micronutrients versus same unfortified staple foods Fortifying staple foods with vitamin A plus other micronutrients may not increase the serum retinol concentration (MD 0.08 μmol/L, 95% CI -0.06 to 0.22; 4 studies; 1009 participants; I² = 95%, low-certainty evidence). The certainty of the evidence was mainly affected by serious inconsistency and risk of bias.In comparison to unfortified staple foods, fortification with vitamin A plus other micronutrients probably reduces the risk of subclinical vitamin A deficiency (RR 0.27, 95% CI 0.16 to 0.49; 3 studies; 923 participants; I² = 0%; moderate-certainty evidence). The certainty of the evidence was mainly affected by serious risk of bias.Staple foods fortified with vitamin A plus other micronutrients versus no interventionFortification of staple foods with vitamin A plus other micronutrients may increase serum retinol concentration (MD 0.22 μmol/L, 95% CI 0.15 to 0.30; 2 studies; 318 participants; I² = 0%; low-certainty evidence). When compared to no intervention, it is uncertain whether the intervention reduces the risk of subclinical vitamin A deficiency (RR 0.71, 95% CI 0.52 to 0.98; 2 studies; 318 participants; I² = 0%; very low-certainty evidence) . The certainty of the evidence was affected mainly by serious imprecision and risk of bias.No trials reported on the outcomes of all-cause morbidity, all-cause mortality, adverse effects, food intake, congenital anomalies (for pregnant women), or breast milk concentration (for lactating women).

Authors' conclusions: Fortifying staple foods with vitamin A alone may make little or no difference to serum retinol concentrations or the risk of subclinical vitamin A deficiency. In comparison with provision of unfortified foods, provision of staple foods fortified with vitamin A plus other micronutrients may not increase serum retinol concentration but probably reduces the risk of subclinical vitamin A deficiency.Compared to no intervention, staple foods fortified with vitamin A plus other micronutrients may increase serum retinol concentration, although it is uncertain whether the intervention reduces the risk of subclinical vitamin A deficiency as the certainty of the evidence has been assessed as very low.It was not possible to estimate the effect of staple food fortification on outcomes such as mortality, morbidity, adverse effects, congenital anomalies, or breast milk vitamin A, as no trials included these outcomes.The type of funding source for the studies did not appear to distort the results from the analysis.

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Conflict of interest statement

Aditi S Hombali ‐ none.

Bhumika T Venkatesh ‐ none.

Sreekumar Nair ‐ none.

Juan Antonio Solon works for the Nutrition Center of the Philippines, a non‐governmental organisation working in the field of public health nutrition. The Nutrition Center of the Philippines has several studies in the field of food fortification. Two of these studies are included in the review; one was excluded. Dr Solon is not an author in any of the included studies, and he did not participate in the screening and eligibility of the included studies.

Juan Pablo Peña‐Rosas is a full‐time WHO staff member. The Department of Nutrition for Health and Development, World Health Organization receives financial resources from several external sources including 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.

Figures

1
1
WHO/CDC generic logic model for micronutrient interventions (with permission from WHO)
2
2
PRISMA flow diagram.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
4
4
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
5
5
The effect of clustering on the confidence interval of the mean difference and risk ratio for outcomes serum/plasma retinol and subclinical vitamin A deficiency, for comparison on fortification of staple foods with vitamin A plus other micronutrients versus same unfortified food in Vinod Kumar 2009a (C). The ICC is a measure of the amount of clustering in the data.
6
6
The effect of clustering on the confidence interval of the mean difference and risk ratio for outcomes serum/plasma retinol and subclinical vitamin A deficiency, for comparison on fortification of staple foods with vitamin A plus other micronutrients versus no intervention in Vinod Kumar 2014 (C). The ICC is a measure of the amount of clustering in the data.
1.1
1.1. Analysis
Comparison 1 Staple foods fortified with vitamin A versus same unfortified staple foods, Outcome 1 Serum/plasma retinol (μmol/L) (ALL).
1.2
1.2. Analysis
Comparison 1 Staple foods fortified with vitamin A versus same unfortified staple foods, Outcome 2 Serum/plasma retinol (μmol/L) (by age and physiological condition of population).
1.3
1.3. Analysis
Comparison 1 Staple foods fortified with vitamin A versus same unfortified staple foods, Outcome 3 Serum/plasma retinol (μmol/L) (by food intake).
1.4
1.4. Analysis
Comparison 1 Staple foods fortified with vitamin A versus same unfortified staple foods, Outcome 4 Serum/plasma retinol (μmol/L) (by public health significance).
1.5
1.5. Analysis
Comparison 1 Staple foods fortified with vitamin A versus same unfortified staple foods, Outcome 5 Serum/plasma retinol (μmol/L) (by length of the intervention).
1.6
1.6. Analysis
Comparison 1 Staple foods fortified with vitamin A versus same unfortified staple foods, Outcome 6 Serum/plasma retinol (μmol/L) (by vehicle of the intervention).
1.7
1.7. Analysis
Comparison 1 Staple foods fortified with vitamin A versus same unfortified staple foods, Outcome 7 Subclinical vitamin A deficiency (serum/plasma retinol ≤ 0.70 μmol/L (ALL).
1.8
1.8. Analysis
Comparison 1 Staple foods fortified with vitamin A versus same unfortified staple foods, Outcome 8 Clinical vitamin A deficiency (as defined by night blindness) (ALL).
1.9
1.9. Analysis
Comparison 1 Staple foods fortified with vitamin A versus same unfortified staple foods, Outcome 9 Inadequate Liver vitamin A stores (3,4‐Dehydroretinol‐retinol < 0.06).
3.1
3.1. Analysis
Comparison 3 Staple foods fortified with vitamin A plus other micronutrients versus same unfortified staple foods, Outcome 1 Serum/plasma retinol (μmol/L) (ALL).
3.2
3.2. Analysis
Comparison 3 Staple foods fortified with vitamin A plus other micronutrients versus same unfortified staple foods, Outcome 2 Serum/plasma retinol (μmol/L) (by age and physiological condition population).
3.3
3.3. Analysis
Comparison 3 Staple foods fortified with vitamin A plus other micronutrients versus same unfortified staple foods, Outcome 3 Serum/plasma retinol (μmol/L) (by public health significance).
3.4
3.4. Analysis
Comparison 3 Staple foods fortified with vitamin A plus other micronutrients versus same unfortified staple foods, Outcome 4 Serum/plasma retinol (μmol/L) (by length of the intervention).
3.5
3.5. Analysis
Comparison 3 Staple foods fortified with vitamin A plus other micronutrients versus same unfortified staple foods, Outcome 5 Serum/plasma retinol (μmol/L) (by vehicle of the intervention).
3.6
3.6. Analysis
Comparison 3 Staple foods fortified with vitamin A plus other micronutrients versus same unfortified staple foods, Outcome 6 Serum/plasma retinol (μmol/L) (by study design).
3.7
3.7. Analysis
Comparison 3 Staple foods fortified with vitamin A plus other micronutrients versus same unfortified staple foods, Outcome 7 Subclinical vitamin A deficiency (serum/plasma retinol 0.70 μmol/L or less) (ALL).
4.1
4.1. Analysis
Comparison 4 Staple food fortified with vitamin A plus other micronutrients versus no intervention, Outcome 1 Serum/plasma retinol (μmol/L) (ALL).
4.2
4.2. Analysis
Comparison 4 Staple food fortified with vitamin A plus other micronutrients versus no intervention, Outcome 2 Subclinical vitamin A deficiency (serum/plasma retinol 0.70 μmol/L or less) (ALL).
See this image and copyright information in PMC

Update of

  • doi: 10.1002/14651858.CD010068

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Huo 2012 {published data only}
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Huo 2014 {published data only}
    1. Huo J, Sun J, Huang J, Wang J, Li W, Wang B. School food fortification improves nutrition status of students from poor migrant families. Journal of Food and Nutritional Disorders 2014;3(2):1‐8.
Hyder 2007 {published data only}
    1. Hyder SM, Haseen F, Khan M, Schaetzel T, Jalal CS, Rahman M, et al. A multiple‐micronutrient‐fortified beverage affects hemoglobin, iron, and vitamin A status and growth in adolescent girls in rural Bangladesh. Journal of Nutrition 2007;137(9):2147‐53. - PubMed
Jinabhai 2001 {published data only}
    1. Jinabhai CC, Taylor M, Coutsoudis A, Coovadia HM, Tomkins AM, Sullivan KR. A randomized controlled trial of the effect of antihelminthic treatment and micronutrient fortification on health status and school performance of rural primary school children. Annals of Tropical Paediatrics 2001;21(4):319‐33. - PubMed
Kafwembe 2009 {published data only}
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Kopec 2014 {published data only}
    1. Kopec RE, Cooperstone JL, Schweiggert RM, Young GS, Harrison EH, Francis DM, Clinton SK, Schwartz SJ. Avocado consumption enhances human postprandial provitamin A absorption and conversion from a novel high‐?‐carotene tomato sauce and from carrots. Journal of Nutrition 2014;8(1):1158‐66. - PMC - PubMed
Krause 1998 {published data only}
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Kurihayashi 2015 {published data only}
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Lam 1997 {published data only}
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Lamardo 2004 {published data only}
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Leyvraz 2015 {published data only}
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Lopriore 2004 {published data only}
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Makola 2003 {published data only}
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Malpeli 2013 {published data only}
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Manders 2009 {published data only}
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Mardones 2008 {published data only}
    1. Mardones F, Urrutia MT, Villarroel L, Rioseco A, Castillo O, Rozowski J, et al. Effects of a dairy product fortified with multiple micronutrients and omega‐3 fatty acids on birth weight and gestation duration in pregnant Chilean women. Public Health Nutrition 2008;11(1):30‐40. - PubMed
Mason 2011 {published data only}
    1. Mason JB, Ramirez MA, Fernandez CM, Pedro R, Lloren T, Saldanha L, et al. Effects on vitamin A deficiency in children of periodic high‐dose supplements and of fortified oil promotion in a deficient area of the Philippines. International Journal for Vitamin and Nutrition Research. Internationale Zeitschrift fur Vitamin‐ und Ernahrungsforschung. Journal International de Vitaminologie et de Nutrition 2011;81(5):295‐305. - PubMed
Mejia 1986 {published data only}
    1. Mejia LA, Pineda O. Replacement of peanut oil used for the fortification of sugar with vitamin A for other vegetable oils available in Central America [Sustitucion del aceite de mani usado para la fortificacion de azucar con vitamina "A" por otros aceites vegetales disponibles en Centroamerica]. Archivos Latinoamericanos de Nutricion 1986;36(1):127‐34. - PubMed
Meller 2014 {published data only}
    1. Meller M, Litschig S. Saving lives evidence from a conditional food supplementation program. Journal of Human Resources 2014;49(4):1014‐52.
Mirmiran 2012 {published data only}
    1. Mirmiran P, Golzarand M, Serra‐Majem L, Azizi F. Iron, iodine and vitamin A in the Middle East; A systematic review of deficiency and food fortification. Iranian Journal of Public Health 2012;41(8):8‐19. - PMC - PubMed
Murphy 2007 {published data only}
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Nesamvuni 2005 {published data only}
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Neumann 2013 {published data only}
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Nga 2009 {published data only}
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Nieman 2011 {published data only}
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Ortega 1996 {published data only}
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Osei 2010 {published data only}
    1. Osei AK, Rosenberg IH, Houser RF, Bulusu S, Mathews M, Hamer DH. Community‐level micronutrient fortification of school lunch meals improved vitamin A, folate, and iron status of schoolchildren in Himalayan villages of India. Journal of Nutrition 2010;140(6):1146‐54. - PubMed
Osendarp 2007 {published data only}
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Ouedraogo 2010 {published data only}
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Papathakis 2012 {published data only}
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Penn 1991 {published data only}
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Pineda 1998 {published data only}
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Prasad 2016 {published data only}
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Ribaya 2004 {published data only}
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Rohner 2013 {published data only}
    1. Rohner F, Northrop‐Clewes C, Raso G, Ake‐Tano O, Tschannen A, Jungjohann S, et al. Effect of a fortified oil and flour program in Cote d'Ivoire on micronutrient status of pre‐school children and women. IUNS 20th International Congress of Nutrition Granada (Spain), September 15‐20 2013.
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Rojas 2004 {published data only}
    1. Rojas C, Dominguez C, Ortiz D, Chavez H, Barboza J. Characteristics of energy and nutrients intake and supply with the addition of «papilla» to diet in 6 to 36 months old children who participate in a complementary feeding program [Características del consumo y aporte de energía y nutrientes de una papilla a la dieta de niños de 6 a 36 meses de edad beneficiarios de un programa de complementación alimentaria]. Revista Peruana de Medicina Experimental y Salud Publica 2004;21(3):118‐25.
Romeo 2011 {published data only}
    1. Romeo J, Warnberg J, Garcia‐Marmol E, Rodriguez‐Rodriguez M, Diaz LE, Gomez‐Martinez S, et al. Daily consumption of milk enriched with fish oil, oleic acid, minerals and vitamins reduces cell adhesion molecules in healthy children. Nutrition, Metabolism, and Cardiovascular Diseases: NMCD 2011;21(2):113‐20. - PubMed
Rosado 2010 {published data only}
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Sail 1972 {published data only}
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Sandjaja 2015 {published data only}
    1. Sandjaja, Jus'at I, Jahari AB, Ifrad, Htet MK, Tilden RL, et al. Vitamin A‐fortified cooking oil reduces vitamin A deficiency in infants, young children and women: results from a programme evaluation in Indonesia. Public Health Nutrition 2015;18(14):2511‐22. - PMC - PubMed
Sankhala 2004 {published data only}
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Sarma 2006 {published data only}
    1. Sarma KV, Udaykumar P, Balakrishna N, Vijayaraghavan K, Sivakumar B. Effect of micronutrient supplementation on health and nutritional status of schoolchildren: growth and morbidity. Nutrition 2006;22(1 Suppl):S8‐14. - PubMed
Sazawal 2007 {published data only}
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Sazawal 2013 {published data only}
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Seal 2007 {published data only}
    1. Seal A, Kafwembe E, Kassim IA, Hong M, Wesley A, Wood J, Abdalla F, Briel T. Maize meal fortification is associated with improved vitamin A and iron status in adolescents and reduced childhood anaemia in a food aid‐dependent refugee population. Public Health Nutrition 2007;11(7):720‐8. - PubMed
Semba 2011 {published data only}
    1. Semba RD, Moench‐Pfanner R, Sun K, Pee S, Akhter N, Rah JH, et al. Consumption of micronutrient‐fortified milk and noodles is associated with lower risk of stunting in preschool‐aged children in Indonesia. Food and Nutrition Bulletin 2011;32(4):347‐53. - PubMed
Sheenko 2002 {published data only}
    1. Sheenko IuA, Chuprynina SA, Biriukova ZA, Kovalenko LM, Panteleeva OG. The experience of using sterilized milk enriched with beta‐carotene in the diet of preschool age children in Kursk [Opyt ispol'zovaniia sterilizovannogo moloka, obogashchennogo beta‐karotinom, v pitanii doshkol'nikov Kurska]. Voprosy pitaniia 2002;71(5):13‐5. - PubMed
Silva 2017 {published data only}
    1. Silva LLS, Augusto RA, Tietzmann DC, Sequeira LAS, Hadler MCCM, Muniz PT, et al. The impact of home fortification with multiple micronutrient powder on vitamin A status in young children: A multicenter pragmatic controlled trial in Brazil. Maternal & Child Nutrition 2017;13(4):e12403. - PMC - PubMed
Solon 1979 {published data only}
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Solon 1979a {published data only}
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Stuetz 2012 {published data only}
    1. Stuetz W, Carrara VI, McGready R, Lee SJ, Erhardt JG, Breuer J, et al. Micronutrient status in lactating mothers before and after introduction of fortified flour: cross‐sectional surveys in Maela refugee camp. European Journal of Nutrition 2012;51(4):425‐34. - PMC - PubMed
Stuetz 2016 {published data only}
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Taljaard 2013 {published and unpublished data}
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Tatala 2002 {published data only}
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Thomas 2012 {published data only}
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Toro 1977 {published data only}
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Unger 2017 {published data only}
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Van Stuijvenberg 1997 {published data only}
    1. Stuijvenberg ME, Kruger M, Badenhorst CJ, Mansvelt EP, Laubscher JA. Response to an iron fortification programme in relation to vitamin A status in 6‐12‐year‐old school children. International Journal of Food Sciences and Nutrition 1997;48(1):41‐9. - PubMed
Van Stuijvenberg 1999 {published data only}
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Van Stuijvenberg 2000 {published data only}
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Venkatramanan 2017 {published data only}
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Villanueva 1982 {published data only}
    1. Villanueva LE, Santos FS, Martin JS. The effect of zinc supplementation on serum vitamin A levels of pre‐school children (in the Phillipines). Philippine Journal of Nutrition 1982;34(3):131‐4.
Villanueva 2014 {published data only}
    1. Villanueva L, Ponce S, Alfonso V, Reinhart G. Effect of providing a micronutrient‐fortified corn/soy atole or milk powder on linear growth in young Guatemalan children. FASEB Journal 2014;28(1 Suppl):828.6.
Vinodkumar 2006 {published data only}
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Vinod Kumar 2007 {published data only}
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Vinod Kumar 2009 {published data only}
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Viteri 1995 {published data only}
    1. Viteri FE, Alvarez E, Batres R, Torun B, Pineda O, Mejia LA, et al. Fortification of sugar with iron sodium ethylenediaminotetraacetate (FeNaEDTA) improves iron status in semirural Guatemalan populations. American Journal of Clinical Nutrition 1995;61(5):1153‐63. - PubMed
Widhalm 2011 {published data only}
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Yadav 2013 {published data only}
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Yeudall 2005 {published data only}
    1. Yeudall F, Gibson RS, Cullinan TR, Mtimuni B. Efficacy of a community‐based dietary intervention to enhance micronutrient adequacy of high‐phytate maize‐based diets of rural Malawian children. Public Health Nutrition 2005;8(7):826‐36. - PubMed
Zahrou 2014 {published data only}
    1. Aguenaou H. Efficiency study of iodine fortification of milk on iodine status markers: A longitudinal interventional non randomized, controlled study among school children in Morocco [(trial number PACTR201410000896410)]. Pan African Clinical Trials Registry (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=896) 2014:1‐3.
    1. Benjeddou K, Qandoussi L, Mekkaoui B, Rabi B, Hamdouchi A, Raji F, et al. The effect of multiple micronutrient fortified milk consumption on vitamin D status amongschool‐age children in rural region of Morocco. Applied Physiology, Nutrition, and Metabolism 2018;0(ja):1‐30. - PubMed
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Zhang 2010 {published data only}
    1. Xuan Zhang, Ke Chen, Ping Qu, You Xue Liu, Ting Yu Li. Effect of biscuits fortified with different doses of vitamin A on indices of vitamin A status, haemoglobin and physical growth levels of pre‐school children in Chongqing. Public Health Nutrition 2011;14(4):751. - PubMed
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References to ongoing studies

ACTRN 12616001271493 {published data only}
    1. Arcot J. Effect of nutrition‐improved wheat‐based food on the health of primary school children aged 6‐12 years in Morobe province [Efficacy of multi‐micronutrient fortified wheat‐based food on the nutrition status of primary school children aged 6‐12 years in Lae, Papua New Guinea]. apps.who.int/trialsearch/Trial2.aspx?TrialID=ACTRN12616001271493 (first received 9 September 2016). [ACTRN12616001271493]

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