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     A Brief Narrative of a General Review of the Nutrition and Education Literature


       The study of malnutrition beings in the 1930‟s with the investigation of kwashiorkor

which based on the low protein content in many African foods, was assumed to be a protein

deficiency disorder [1]. The protein deficiency hypothesis extended itself to most areas of

nutritional science for the next few decades until the 1970‟s with the publication of the “The

Great Protein Fiasco” [2]. This debate culminated in a Nature review [3] which argued that the

idea of a global „protein gap‟, derived from the diagnosis of kwashiorkor, is no longer tenable

and instead argued that energy (calorie) deficiency underlies malnutrition. A shorter period of

interest in an „energy gap‟ followed but when total calorie intake is low, intake of other nutrient

is also low.

       Although micronutrients deficiencies were well known in their extreme form (goiter,

cretinism, anemia, blindness, etc.) in the mid 1980‟s milder forms of these deficiencies began to

receive serious attention specifically: iodine, vitamin A and iron [4]. In 1990, UNICEF, the

World Bank and WHO set the goal of eliminating these three micronutrient deficiencies by the

year 2000.

       Essential nutrients are vitamins, minerals and other compounds that the human body

needs for proper functioning yet cannot synthesize. Iron is required in almost all forms of life

and plays a prominent role in human physiology as the key component of the heme group which

plays a critical role in energy generation and oxygen transport (through hemoglobin and the

blood). Additionally, iron plays a role in the brains dopamine system [5-7] and the behaviors it

generates (i.e., reward and motivation). Essential nutrients such as iron must be consumed

through dietary intake.

       Humans acquire dietary iron in two forms: heme iron found in meats, fish and poultry

and nonheme iron found in legumes and other plants. While heme iron is readily absorbed by the

body at a high efficiency, nonheme iron has far lower absorption rates [8]. However other

nutritional factors can influence the level of iron absorption: ascorbic acid (vitamin C) and meat

can increase the absorption of nonheme iron but phytates and polyphenols often present in staple

foods can inhibit iron absorption [9]. Other micronutrients such as Vitamin A can enhance the

effects of iron consumption. The body carefully regulates the level of iron as too much iron can

cause toxicity. In response to bacterial infection, the body can down-regulate its level of iron

(since bacteria require iron from the host), thus in a sense lower iron levels can provide some

protection against bacterial infection. (In some supplementation studies subjects in the treatment

group were more likely to obtain infection since their bodies are now better environments for

bacteria to live in, but a meta analysis shows these results may be an anomaly [10]). However,

chronically low levels of iron can result iron deficiency disorders and even anemia.

       Iron deficiency, the most common micronutrient deficiency in the world, currently affects

up to 2 billion people ~30% of the world‟s populations including both the developed and

developing world. A largely plant based diet, common in developing countries, contains both

low quantities of easily absorbable heme iron and high quantities of inhibitors of iron absorption

common in staple cereals [11]. Lack of dietary iron can lead to disorder sduring periods of high

iron demand. Overall, women have higher iron demands due to menstrual blood loss and

pregnancy. During periods of rapid growth, such as infancy and adolescence, demand for iron

rises. These periods of developmental volatility have increased risk of iron deficiency. During

pregnancy, healthy mothers give a store of iron to their fetus‟s while in utero and supplement it

after birth with breast milk that contains iron [12]. Thus pregnant women with poor iron status

will often have infants with poor iron status. High elevation can also lower body iron levels [13].

Additionally, common parasites such as hookworms and malaria can sequester available iron and

cause deficiency (especially when compounded with already low iron intake) [14, 15]. Severe

iron deficiency is diagnosed as anemia.

       The most accurate way to measure iron deficiency and anemia in a human is through a

bone marrow aspiration. Since this procedure is both impractical and painful, indirect measures

of iron status are used to diagnose iron deficiency disorders. Hemoglobin and ferritin levels are

currently the most efficient indicators of iron deficiency when used together [16]. These

measures cannot effectively distinguish between anemia in otherwise healthy individuals and

anemia caused by chronic illnesses.

       The symptoms of iron deficiency anemia are more subtle than those of other

micronutrient deficiency disorders. A mothers iron status can affect mother-child interaction and

emotions [17]. Iron poor infants suffer from developmental delays such as slower motor and

behavioral development [18, 19]. These early deficits only partially respond to treatment via

supplementation [19, 20]. Anemic children perform worse in school and on attention tests

although these results are partially confounded by the environment of the subjects [19, 21-24].

Iron deficiency decreases work performance and increases fatigue in adults [25-27]. These losses

in worker capital and health have been modeled and may account for significant losses in GDP

per capita [28, 29].


               [note … references are at end of this file … the references for material reviews on
               pages 4 to 6 begin on page 10]

       Three primary strategies exist for treating micronutrient deficiency: food fortification,

nutritional education, and dietary supplementation. Of these options, food fortification is the

most cost efficient and sustainable long term solution for improving the dietary status of

impoverished peoples (Baltussen, Knai, & Sharan, 2004). However in implementing a large

scale fortification paradigm, technical and infrastructural hurdles can occur. Although iodization

of salt has enjoyed large scale success, finding a suitable food and micronutrient vehicle with

adequate shelf-life can be difficult. Fortification of staple foods such as rice has been difficult.

Under-developed infrastructure can inhibit the distribution of the fortified foods to those in need

especially when the poorest populations primarily eat the food they grow. A recent intervention

with NaFeEDTA fortified sodium in Bijie City, Guizhou Province greatly reduced anemia

prevalence. In 3-6 year olds and 7-18 year olds anemia prevalence was reduced from 50-60% of

the population to 10-20% in both males and females (Chen et al., 2005). Whether these fortified

foods can reach rural populations has yet to be determined.

       Educational interventions can promote intake of foods with enhanced nutritional content.

The educational content must align itself culturally with the given audience in order to maximize

compliance. Most educational interventions target the household food provider or the person

responsible for making nutritional choices for the family (often the mother). In order for an

educational intervention to be successful, nutrient rich foods such as animal source food must be

both available and financially accessible. A recent educational intervention in moderately

malnourished children in rural Bangladesh showed that an older nutrition program improved

20% of children yet a newer more intensive culturally relevant program improved the nutritional

status of up to 60% of children. When the intensive education group was also given

supplementary feeding, up to 80% of children improved their nutritional status (Roy et al., 2005;

Roy et al., 2007). Educating pregnant mother in rural Sichuan province resulted in increased

infant weight after one year and better overall nutrition practices (Guldan et al., 2000). However,

compliance was maintained by frequent follow up visits and reports by the mothers. If

implemented correctly educational interventions ideally can prevent malnutrition rather than treat

it (Dewey & Adu-Afarwuah, 2008).

       Dietary supplementation often takes two forms: supplementary feeding in which

participants receive more/better food, and direct supplementation in which specific

micronutrients are given to participants in a refined form. A hybrid approach does supplementary

feeding but with specially fortified foods or animal source products. Although dietary

supplementation can often be expensive, in regions where the anemia rate is high (>40%) almost

the entire population is likely deficient and will thus benefit from supplementation. Direct

supplementation is more cost efficient than direct feeding, but a properly implemented multi-

vitamin requires prior knowledge of the main deficiencies prevalent in a given region (Allen,

2003). Additionally, direct supplements can be taken outside of meal times in order to optimize

the level of absorption (Zimmermann & Hurrell, 2007). Indeed iron supplements eaten with food

can reduce the amount of iron absorbed by 40% (Brise, 1962; Hallberg et al., 1978). High

dosages of iron and other micronutrients can cause unpleasant side effects (such as gastric pain)

lowering long term compliance. Supplementary feeding program may be most efficient where

prevention of micronutrient deficiency is most important while direct supplementation is most

efficient where treatment of deficiency is most important. Of the three intervention possibilities,

supplementation has the most rapid and greatest effect (over 80% reduction in anemia rates).

However, the benefits of supplementation are limited to the targeted populations.

        Worms and other parasites such as malaria can complicate micronutrient treatment. These

parasites can intensify iron deficiencies and enhance the severity of anemia (R. J. Stoltzfus et al.,

1997). Micronutrient interventions are often blunted and less effective when participants have

high parasite load (Rahman, Akramuzzaman, Mitra, Fuchs, & Mahalanabis, 1999; Rebecca J.

Stoltzfus et al., 2004). Thus it is imperative to identify and treat parasites in parallel with

micronutrient deficiencies. Different types of parasites (hookworms, malaria, etc.) may have

differential effect on nutritional status (Ahluwalia, 2002). Additionally in many communities

reacquisition of the parasite can occur after deworming.

        The WHO recommends a direct dietary intervention taken separately from meals for cost

efficient treatment of micronutrient deficiency (Geneva, 2001; Rebecca J. Stoltzfus & L., 1998).

These guides give a clear procedure for diagnosis, treatment and assessment of intervention


                  Literature Review for General Summary
                            (material from pages 1 to 3)

1.    Allen, L.H., Interventions for Micronutrient Deficiency Control in Developing Countries:
      Past, Present and Future. J. Nutr., 2003. 133(11): p. 3875S-3878.
2.    McLaren, D.S., The great protein fiasco. Lancet, 1974. 2(7872): p. 93-96.
3.    Waterlow, J.C. and P.R. Payne, The protein gap. Nature, 1975. 258(5531): p. 113-117.
4.    Bates, C.J., H.J. Powers, and D.I. Thurnham, VITAMINS, IRON, AND PHYSICAL WORK.
      The Lancet, 1989. 334(8658): p. 313-314.
5.    Beard, J., Iron Deficiency Alters Brain Development and Functioning. J. Nutr., 2003.
      133(5): p. 1468S-1472.
6.    Erikson, K.M., B.C. Jones, and J.L. Beard, Iron Deficiency Alters Dopamine Transporter
      Functioning in Rat Striatum. J. Nutr., 2000. 130(11): p. 2831-2837.
7.    Beard, J., Recent Evidence from Human and Animal Studies Regarding Iron Status and
      Infant Development. J. Nutr., 2007. 137(2): p. 524S-530.
8.    Zimmermann, M.B., N. Chaouki, and R.F. Hurrell, Iron deficiency due to consumption of
      a habitual diet low in bioavailable iron: a longitudinal cohort study in Moroccan
      children. Am J Clin Nutr, 2005. 81(1): p. 115-121.
9.    Hurrell, R., How to Ensure Adequate Iron Absorption from Iron-fortified Food. Nutrition
      Reviews, 2002. 60: p. 7-15.
10.   Gera, T. and H.P.S. Sachdev, Effect of iron supplementation on incidence of infectious
      illness in children: systematic review. BMJ, 2002. 325(7373): p. 1142-.
11.   Zimmermann, M.B. and R.F. Hurrell, Nutritional iron deficiency. The Lancet, 2007.
      370(9586): p. 511-520.
12.   Moy, R.J.D., Prevalence, consequences and prevention of childhood nutritional iron
      deficiency: a child public health perspective. Clinical and Laboratory Haematology, 2006.
      28(5): p. 291-298.
13.   Cook, J.D., et al., The influence of high-altitude living on body iron. Blood, 2005. 106(4):
      p. 1441-1446.
14.   Crompton, D.W.T. and M.C. Nesheim, NUTRITIONAL IMPACT OF INTESTINAL
      2002. 22(1): p. 35.
15.   Doherty, C.P., Host-Pathogen Interactions: The Role of Iron. J. Nutr., 2007. 137(5): p.
16.   Mei, Z., et al., Hemoglobin and Ferritin Are Currently the Most Efficient Indicators of
      Population Response to Iron Interventions: an Analysis of Nine Randomized Controlled
      Trials. J. Nutr., 2005. 135(8): p. 1974-1980.
17.   Beard, J.L., et al., Maternal Iron Deficiency Anemia Affects Postpartum Emotions and
      Cognition. J. Nutr., 2005. 135(2): p. 267-272.
18.   Lozoff, B., et al., Preschool-Aged Children with Iron Deficiency Anemia Show Altered
      Affect and Behavior. J. Nutr., 2007. 137(3): p. 683-689.
19.   Grantham-McGregor, S. and C. Ani, A Review of Studies on the Effect of Iron Deficiency
      on Cognitive Development in Children. J. Nutr., 2001. 131(2): p. 649S-668.

20.   Lozoff, B., et al., Poorer Behavioral and Developmental Outcome More Than 10 Years
      After Treatment for Iron Deficiency in Infancy. Pediatrics, 2000. 105(4): p. e51-.
      Lancet, 1985. 325(8421): p. 158-158.
22.   Black, M.M., Micronutrient Deficiencies and Cognitive Functioning. J. Nutr., 2003.
      133(11): p. 3927S-3931.
23.   Halterman, J.S., et al., Iron Deficiency and Cognitive Achievement Among School-Aged
      Children and Adolescents in the United States. Pediatrics, 2001. 107(6): p. 1381-1386.
24.   Pollitt, E., Iron Deficiency and Cognitive Function. Annual Review of Nutrition, 1993.
      13(1): p. 521.
25.   Haas, J.D. and T.I.V. Brownlie, Iron Deficiency and Reduced Work Capacity: A Critical
      Review of the Research to Determine a Causal Relationship. J. Nutr., 2001. 131(2): p.
26.   Horton, S. and C. Levin, Commentary on "Evidence That Iron Deficiency Anemia Causes
      Reduced Work Capacity". J. Nutr., 2001. 131(2): p. 691S-696.
27.   Li, R., et al., Functional consequences of iron supplementation in iron-deficient female
      cotton mill workers in Beijing, China. Am J Clin Nutr, 1994. 59(4): p. 908-913.
28.   Horton, S. and J. Ross, The economics of iron deficiency. Food Policy, 2003. 28(1): p.
29.   Horton, S., The Economics of Food Fortification. J. Nutr., 2006. 136(4): p. 1068-1071.
30.   Laxminarayan, R., et al., Advancement of global health: key messages from the Disease
      Control Priorities Project. The Lancet. 367(9517): p. 1193-1208.
31.   Baltussen, R., C. Knai, and M. Sharan, Iron Fortification and Iron Supplementation are
      Cost-Effective Interventions to Reduce Iron Deficiency in Four Subregions of the World.
      J. Nutr., 2004. 134(10): p. 2678-2684.
32.   Van Thuy, P., et al., The Use of NaFeEDTA-Fortified Fish Sauce Is an Effective Tool for
      Controlling Iron Deficiency in Women of Childbearing Age in Rural Vietnam. J. Nutr.,
      2005. 135(11): p. 2596-2601.
33.   Thuy, P.V., et al., Regular consumption of NaFeEDTA-fortified fish sauce improves iron
      status and reduces the prevalence of anemia in anemic Vietnamese women. Am J Clin
      Nutr, 2003. 78(2): p. 284-290.
34.   Andang'o, P.E.A., et al., Efficacy of iron-fortified whole maize flour on iron status of
      schoolchildren in Kenya: a randomised controlled trial. The Lancet, 2007. 369(9575): p.
35.   Moretti, D., et al., Extruded rice fortified with micronized ground ferric pyrophosphate
      reduces iron deficiency in Indian schoolchildren: a double-blind randomized controlled
      trial. Am J Clin Nutr, 2006. 84(4): p. 822-829.
36.   Haas, J.D., et al., Iron-Biofortified Rice Improves the Iron Stores of Nonanemic Filipino
      Women. J. Nutr., 2005. 135(12): p. 2823-2830.
37.   Idjradinata, P. and E. Pollitt, Reversal of developmental delays in iron-deficient anaemic
      infants treated with iron. The Lancet, 1993. 341(8836): p. 1-4.
38.   Black, M.M., et al., Iron and zinc supplementation promote motor development and
      exploratory behavior among Bangladeshi infants. Am J Clin Nutr, 2004. 80(4): p. 903-

39.   Wasantwisut, E., et al., Iron and Zinc Supplementation Improved Iron and Zinc Status,
      but Not Physical Growth, of Apparently Healthy, Breast-Fed Infants in Rural
      Communities of Northeast Thailand. J. Nutr., 2006. 136(9): p. 2405-2411.
40.   Zhou, S.J., et al., Effect of iron supplementation during pregnancy on the intelligence
      quotient and behavior of children at 4 y of age: long-term follow-up of a randomized
      controlled trial. Am J Clin Nutr, 2006. 83(5): p. 1112-1117.
41.   Wijaya-Erhardt, M., et al., Effect of daily or weekly multiple-micronutrient and iron
      foodlike tablets on body iron stores of Indonesian infants aged 6 12 mo: a double-blind,
      randomized, placebo-controlled trial. Am J Clin Nutr, 2007. 86(6): p. 1680-1686.
42.   Konofal, E., et al., Effects of Iron Supplementation on Attention Deficit Hyperactivity
      Disorder in Children. Pediatric Neurology, 2008. 38(1): p. 20-26.
43.   Murray-Kolb, L.E. and J.L. Beard, Iron treatment normalizes cognitive functioning in
      young women. Am J Clin Nutr, 2007. 85(3): p. 778-787.
44.   Idjradinata, P., W.E. Watkins, and E. Pollitt, Adverse effect of iron supplementation on
      weight gain of iron-replete young children. The Lancet, 1994. 343(8908): p. 1252-1254.
45.   Ahmed, F., et al., Efficacy of twice-weekly multiple micronutrient supplementation for
      improving the hemoglobin and micronutrient status of anemic adolescent schoolgirls in
      Bangladesh. Am J Clin Nutr, 2005. 82(4): p. 829-835.
46.   Sungthong, R., et al., Once-Weekly and 5-Days a Week Iron Supplementation
      Differentially Affect Cognitive Function but Not School Performance in Thai Children. J.
      Nutr., 2004. 134(9): p. 2349-2354.
47.   Sungthong, R., et al., Once Weekly Is Superior to Daily Iron Supplementation on Height
      Gain but Not on Hematological Improvement among Schoolchildren in Thailand. J. Nutr.,
      2002. 132(3): p. 418-422.
48.   Winichagoon, P., et al., A Multimicronutrient-Fortified Seasoning Powder Enhances the
      Hemoglobin, Zinc, and Iodine Status of Primary School Children in North East Thailand:
      A Randomized Controlled Trial of Efficacy. J. Nutr., 2006. 136(6): p. 1617-1623.
49.   Ahmed, F., M.R. Khan, and A.A. Jackson, Concomitant supplemental vitamin A
      enhances the response to weekly supplemental iron and folic acid in anemic teenagers in
      urban Bangladesh. Am J Clin Nutr, 2001. 74(1): p. 108-115.
50.   Ramakrishnan, U., et al., Multimicronutrient Interventions but Not Vitamin A or Iron
      Interventions Alone Improve Child Growth: Results of 3 Meta-Analyses. J. Nutr., 2004.
      134(10): p. 2592-2602.
51.   Stoltzfus, R.J. and D.M. L., Guidelines for the Use of Iron Supplements to Prevent and
      Treat Iron Deficiency Anemia. International Nutritional Anemia Consultative Group,
52.   Guldan, G.S., et al., Culturally Appropriate Nutrition Education Improves Infant Feeding
      and Growth in Rural Sichuan, China. J. Nutr., 2000. 130(5): p. 1204-1211.

                        Literature Review for Interventions

                     (for materials reviewed on pages 4 to 6)
Ahluwalia, N. (2002). Intervention Strategies for Improving Iron Status of Young Children and
        Adolescents in India. Nutrition Reviews, 60, 115-117.
Allen, L. H. (2003). Interventions for Micronutrient Deficiency Control in Developing Countries:
        Past, Present and Future. J. Nutr., 133(11), 3875S-3878.
Baltussen, R., Knai, C., & Sharan, M. (2004). Iron Fortification and Iron Supplementation are
        Cost-Effective Interventions to Reduce Iron Deficiency in Four Subregions of the World.
        J. Nutr., 134(10), 2678-2684.
Brise, H. (1962). Influence of meals on iron absorption in oral iron therapy. Acta Med Scand
        Suppl, 376, 39-45.
Chen, J., Zhao, X., Zhang, X., Yin, S., Piao, J., Huo, J., et al. (2005). Studies on the effectiveness
        of NaFeEDTA-fortified soy sauce in controlling iron deficiency: a population-based
        intervention trial. Food Nutr Bull, 26(2), 177-186; discussion 187-179.
Dewey, K. G., & Adu-Afarwuah, S. (2008). Systematic review of the efficacy and effectiveness
        of complementary feeding interventions in developing countries. Maternal & Child
        Nutrition, 4(s1), 24-85.
Geneva, W. H. O. (2001). Iron deficiency anaemia: assessment, prevention and control: A guide
        for programme managers.
Guldan, G. S., Fan, H.-C., Ma, X., Ni, Z.-Z., Xiang, X., & Tang, M.-Z. (2000). Culturally
        Appropriate Nutrition Education Improves Infant Feeding and Growth in Rural Sichuan,
        China. J. Nutr., 130(5), 1204-1211.
Hallberg, L., Bjorn-Rasmussen, E., Ekenved, G., Garby, L., Rossander, L., Pleehachinda, R., et
        al. (1978). Absorption from iron tablets given with different types of meals. Scand J
        Haematol, 21(3), 215-224.
Rahman, M. M., Akramuzzaman, S. M., Mitra, A. K., Fuchs, G. J., & Mahalanabis, D. (1999).
        Long-Term Supplementation with Iron Does Not Enhance Growth in Malnourished
        Bangladeshi Children. J. Nutr., 129(7), 1319-1322.
Roy, S. K., Fuchs, G. J., Mahmud, Z., Ara, G., Islam, S., Shafique, S., et al. (2005). Intensive
        nutrition education with or without supplementary feeding improves the nutritional status
        of moderately-malnourished children in Bangladesh. J Health Popul Nutr, 23(4), 320-330.
Roy, S. K., Jolly, S. P., Shafique, S., Fuchs, G. J., Mahmud, Z., Chakraborty, B., et al. (2007).
        Prevention of malnutrition among young children in rural Bangladesh by a food-health-
        care educational intervention: a randomized, controlled trial. Food Nutr Bull, 28(4), 375-
Stoltzfus, R. J., Chway, H. M., Montresor, A., Tielsch, J. M., Jape, J. K., Albonico, M., et al.
        (2004). Low Dose Daily Iron Supplementation Improves Iron Status and Appetite but
        Not Anemia, whereas Quarterly Anthelminthic Treatment Improves Growth, Appetite
        and Anemia in Zanzibari Preschool Children. J. Nutr., 134(2), 348-356.
Stoltzfus, R. J., Chwaya, H. M., Tielsch, J. M., Schulze, K. J., Albonico, M., & Savioli, L. (1997).
        Epidemiology of iron deficiency anemia in Zanzibari schoolchildren: the importance of
        hookworms. Am J Clin Nutr, 65(1), 153-159.

Stoltzfus, R. J., & L., D. M. (1998). Guidelines for the Use of Iron Supplements to Prevent and
        Treat Iron Deficiency Anemia. International Nutritional Anemia Consultative Group.
Zimmermann, M. B., & Hurrell, R. F. (2007). Nutritional iron deficiency. The Lancet, 370(9586),


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