MICRONUTRIENTS DEFICIENCIES AND INTERVENTIONS
A Brief Narrative of a General Review of the Nutrition and Education Literature
GENERAL SUMMARY
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
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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
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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].
3
INTERVENTION STRATEGIES FOR THE ELIMINATION OF MICRONUTRIENT
DEFICIENCY
[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
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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 multivitamin 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,
5
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
paradigms.
6
Literature Review for General Summary
(material from pages 1 to 3)
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HELMINTHIASIS DURING THE HUMAN LIFE CYCLE. Annual Review of Nutrition,
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676S-690.
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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.
Horton, S. and J. Ross, The economics of iron deficiency. Food Policy, 2003. 28(1): p.
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Horton, S., The Economics of Food Fortification. J. Nutr., 2006. 136(4): p. 1068-1071.
Laxminarayan, R., et al., Advancement of global health: key messages from the Disease
Control Priorities Project. The Lancet. 367(9517): p. 1193-1208.
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.
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.
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.
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.
1799-1806.
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.
Haas, J.D., et al., Iron-Biofortified Rice Improves the Iron Stores of Nonanemic Filipino
Women. J. Nutr., 2005. 135(12): p. 2823-2830.
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.
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. 903910.
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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.
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.
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.
Konofal, E., et al., Effects of Iron Supplementation on Attention Deficit Hyperactivity
Disorder in Children. Pediatric Neurology, 2008. 38(1): p. 20-26.
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.
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.
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.
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.
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.
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.
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.
Ramakrishnan, U., et al., Multimicronutrient Interventions but Not Vitamin A or Iron
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Treat Iron Deficiency Anemia. International Nutritional Anemia Consultative Group,
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and Growth in Rural Sichuan, China. J. Nutr., 2000. 130(5): p. 1204-1211.
9
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-healthcare educational intervention: a randomized, controlled trial. Food Nutr Bull, 28(4), 375383.
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.
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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),
511-520.
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