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Summary Hidden Hunger: Micronutrient Deficiencies in Low and Middle Income Countries - HNH39806
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Summary literature Hidden HungerRuel-Bergeron – Global Update and Trends of Hidden Hunger, 1995-2011: The Hidden Hunger Index
Abstract:
- Deficiencies in essential vitamins and minerals – hidden hunger – are persuasive and hold negative consequences for
the cognitive and physical development of children
- Globally, hidden hunger improved (- net change in HHI) from 1995-2011
- Africa was the only region to see a deterioration (+ net change in HHI) of hidden hunger
- East Asia and the Pacific performed exceptionally well, while other regions improved only slightly
- Improvements in HHI were mostly due to reductions in zinc and vitamin A deficiencies, while anaemia due to iron
deficiency persisted and even increased
Introduction:
- The burden of macronutrient malnutrition, especially deficiencies in key micronutrients such as iron, vitamin A, iodine
and zinc, is estimated to affect 2 billion people worldwide
- Pregnant women and young children who are undergoing rapid growth and development are the most vulnerable to
micronutrient deficiencies and suffer the greatest adverse effects
- Iron deficiency anaemia is among the most widespread nutritional deficiencies in the world > affecting people of all life
stages, countries, and genders, and holding severe implications for the cognitive and physical development of children
that begins in utero
- In LMI countries, where diets of nutritionally vulnerable groups continue to be inadequate, the co-occurrence of
deficiencies from more than one micronutrient is common
- Hidden Hunger Index (HHI): developed for documenting the distribution and prevalence of three common micronutrient
deficiencies (zinc, iron and vitamin A), thereby providing an advocacy tool to stimulate greater investments and
attention from policy/decisionmakers to eliminate hidden hunger in high-burden countries
Methodology:
- Zinc deficiency estimates are based on the prevalence of stunting among children 0-5 years
- HHI score = [iron deficiency-amenable anaemia (%) + vitamin A deficiency (%) + stunting (%)] / 3
o HHI score is rescaled to range from 0 (best) to 100 (worst)
§ Mild: 0-14.9
§ Moderate: 15.0-24.9
§ Severe: 25-39.9
§ Alarmingly high: 40-100
Results:
- Africa was the only region to experience an overall increase in hidden hunger from 1995 to 2011
- This increase was higher in West and Central Africa as compared to East and Southern Africa
- All other regions made progress in reducing hidden hunger, with East Asia and the Pacific being the top performing
region and the remaining regions achieving only modest reductions
- The contribution of each micronutrient deficiency to the score varies, based on the severity of hidden hunger
o In countries with severe hidden hunger, zinc deficiency and vitamin A deficiency generally contribute a larger
proportion to the HHI score than iron-amenable anaemia
o As countries improve their hidden hunger, however, anaemia due to iron deficiency accounts for a greater
proportion of the HHI than zinc or vitamin A deficiencies
§ This shows that the progress in the reduction of hidden hunger is attributable to reductions in zinc and
vitamin A deficiency rather than in anaemia
Discussion:
- The consequences of sustained and widespread hidden hunger, not only in Africa but also in other regions, are severe,
and represent long-lasting threats to each country’s social and economic development
- Large-scale micronutrient programs can use these findings to better target programs to vulnerable populations in the
highest burden countries, and to specific micronutrients of concern
- In evaluating hidden hinger trends, the level at which each country began does appear to be a strong predictor of
performance over time
- Countries with severe hidden hunger (HHI>25) may be able to achieve more impressive reductions over time than
countries which started with mild hidden hunger (HHI<25)
- Overall, the HHI correlated with other global indicators of hunger and development (HDI and GHI)
o GHI: captures the multidimensional aspects and consequences of hunger and undernutrition
o HDI: reflects the more pervasive and underlying nature of micronutrient deficiencies, the burden and
consequences of which are more difficult to isolate
o HANCI: focuses strongly on the tenants of legal, political and financial commitment
§ Social policies that are equitable and pro-poor, and are matched with financial and human resource
investments in health and education are necessary drivers for change for improving both human
development and reducing hidden hunger
- The five worst performing countries are in SSA, and have undergone some combination of periods of conflict and
vulnerability to food insecurity due to climate-related shocks (drought and floods)
- The remarkable progress by some Asian countries is paralleled by significant economic growth
- Stunting prevalence was used as a proxy for zinc deficiency, which does not reflect the true prevalence of zinc
deficiency, given that multiple factors besides zinc deficiency could impair linear growth
, - However, zinc continues to be the only micronutrient that has been shown to enhance linear growth, albeit with a small
effect on stunting prevalence
Conclusion:
- Deficiencies in essential vitamins and minerals – hidden hunger – are pervasive and continue to be largely hidden
- The impact of hidden hunger holds significant and immediate negative consequences for the cognitive and physical
development of children, as well as longer-lasting effects on productivity and economic potential in later adulthood
Muckenthaler – A Red Carpet for Iron Metabolism
- Iron deficiency is the most common cause of anaemia and represents a global health problem
- Iron deficiency anaemia: low numbers of small (microcytic) and hypoferremic erythrocytes
- Iron is essential for mitochondrial function, DNA synthesis and repairs and many enzymatic reactions required for cell
survival
- Iron deficiency may contribute to cognitive developmental defects in children, poor physical performance and
unfavourable pregnancy outcomes
- Iron overload is also common and equally detrimental; affecting liver, heart and pancreas
Iron metabolism in erythroid cells:
- Erythropoiesis: regulated process that forms red blood cells (RBCs)
- Dietary iron absorption compensates for iron losses (bleeding) or increased needs (pregnancy, childhood, hypxia) and
hepatic iron stores serve as a buffer
- To acquire high amounts of iron, erythroid cells (blood cells) depend on transferrin (Tf) > a glycoprotein with two high-
affinity sides for Fe3+
- In healthy individuals, Tf is about 30% saturated with iron
- Tf binds to the Tf receptor (TFR1, TFRC, CD71) on the surface of developing RBCs > endocytosis of the TfFe3+ complex
> iron release from Tf > Fe3+ reduced to the ferrous form (Fe2+) > transported into the cytosol
- TFR1 complex returns to cell surface and is recycled > crucial for optimal iron uptake
- When the amount of iron exceeds the binding capacity of Tf, non-Tf-bound iron accumulated in the plasma and in
parenchymal cells
- Iron taken up by cells enters the cytosolic pool termed the labile iron pool. The labile iron pool is destined for storage
export or metabolic utilisation
- Iron from the labile iron pool that is not utilised or exported is stored in ferritin chains
- Cells export elemental iron in its ferrous state (Fe2+) via Ferroportin (FPN)
- Ferritin stores iron in a non-toxic form and contributes to intracellular iron bioavailability. Iron retention in ferritin can
inhibit the passage of iron across absorptive enterocytes
- Iron sequestered in ferritin constitutes a store that can be mobilised by ferritin degradation
- Erythroid cells require mechanisms to coordinate the production of heme with iron availability
Iron acquisition for red blood cells:
- Erythrocytes satisfy their iron demands by receptor-mediated endocytosis of iron-bound transferrin, which needs to be
maintained in a physiological range between 16% and 45%
- The daily requirement is met by export from intestinal enterocytes (1-2 mg), iron-recycling macrophages (20-25 mg)
and iron storage tissues and is regulated by the hormone hepcidin
- The supply of and demand of iron are affected by hypoxia, inflammation and infection, and genetic or nutritional iron
deficiency and in response to abnormal erythropoiesis
- Body iron levels are controlled solely by intestinal iron absorption
- Dietary non-heme iron (ferric Fe3+), is reduced by the ferrireductase Dcytb to ferrous iron (Fe2+) for transport across
the membrane of enterocytes mainly via DMT1
- Most iron required for erythropoiesis is recycled by macrophages from aged or damaged red blood cells
- If recycling cannot satisfy the demand, iron stored in hepatocytes is released
- When serum iron is not used for erythropoiesis, it is stored in the liver for later use
- When serum iron levels exceed the buffering capacity of transferrin at about 60% saturation, non-transferrin-bound iron
appears. Non-transferrin-bound iron is imported into hepatocytes
- Exposure to high altitude, severe blood loss, or the production of too few or malfunctioning erythrocytes cause hypoxia,
which the bone marrow aims to compensate by increased erythropoiesis. EPO release by the kidney triggers red blood
cell proliferation and terminal differentiation > it controls the rate of erythropoiesis
- When erythropoiesis intensifies, dietary iron absorption and iron release from stores must increase
- Anaemia of inflammation is a multifactorial, acquired disorder or iron homeostasis associated with infections,
malignancies and other causes of inflammation. The causes for these mild to moderate anaemias are multifactorial
- Inflammation induces proteins that limit iron supplied for erythropoiesis
- Dietary iron restriction diminished transferrin saturation and hepatic iron stores. These parameters are sensed by the
liver and regulates hepcidin levels
- The concentration of circulating hepcidin is determined by the liver
o The exact mechanism of how the liver senses and responds to changes in iron remains an question
, - Diminished hepcidin expression has been recognised as one of the key mechanisms responsible for the increased iron
absorption
- Hepcidin decreases duodenal iron absorption
Fox Young – Chapter 10: Iron
Introduction:
- Iron deficiency remains one of the most common nutrition disorders worldwide, affect a large proportion of children and
women in the developing world
- It also remains as a key nutrient deficiency of significant prevalence in virtually all developed countries
Role of iron in biological functions:
- Iron exists in two oxidation states; Fe2+ = ferrous form and Fe3+ = ferric form
- Haemoglobin > composed of four heme units; plays an essential role in oxygen transport from the lungs to tissues in
erythrocytes
o In severe anaemia, Hb content of RBCs is reduced, decreasing oxygen delivery to tissues and leading to
chronic tissue hypoxia
- Myoglobin > single heme group with a single globin chain
o Found in the muscle where it transports, and stores oxygen needed for muscle contraction
- Cytochromes
o Contain heme and are essential to respiration and energy metabolism
o Cytochromes serve as electron carriers in transforming ADP to ATP, the primary energy storage compound
Metabolism and regulation of iron:
- Iron-containing compounds in the body are grouped into functional iron (in which iron serves a metabolic or enzymatic
function), transport iron (bound to transferrin) and storage iron (ferritin and hemosiderin)
- Transport of iron:
o Iron is transported from the intestine to tissue by transferrin (plasma transport protein), Tf has a high affinity
for Fe3+ (ferric) and binds two iron atoms per molecule
o Transferrin transports iron from intestine, storage sites and Hb breakdown sites and delivers it to other cells
through surface receptors specific for transferrin (transferrin receptor)
o The receptors bind the transferrin-iron complex at the cell surface and carry the complex into the cell, where
iron is released
o A low transferrin saturation indicated undersupply of iron or deficiency; a high transferrin saturation indicates
oversupply of iron
o The expression of transferrin receptors on tissues is highly regulated in response to the availability of iron
§ In an iron-rich environment > number of transferrin receptors decreases
§ In an iron-poor environment > number of transferrin receptors increase because it demands iron
- Storage of iron
o Major iron storage compounds are ferritin and hemosiderin, found primarily in the liver, spleen and bone
marrow
o In the liver, iron is stored mainly in parenchymal cells or hepatocytes
o Stored iron is used primarily for the production of Hb and for meeting other cellular needs for iron
o Ferritin is also located in the serum in trace amounts in proportion to body iron stores and is a useful indicator
of iron status
o Ferritin is an acute phase protein and increases with inflammation
o Full term infants are born with a substantial store of iron, which usually can meet the infants needs until 6
months of age > solid food containing iron
- Iron turnover and loss
o The production and destruction of erythrocytes accounts for most of the turnover of iron in the body and is
essential for maintaining iron homeostasis
o Daly iron turnover in an adult is 20-25 mg
o Most of the iron from degraded erythrocytes is recaptured for the synthesis of haemoglobin
o Iron loss via faeces, skin, sweat and urine
- Absorption of iron
o Iron can be very toxic > iron overload can lead to organ dysfunction and failure
o Homeostasis of iron depends on regulated dietary iron absorption instead of excretion of iron
o Heme iron; meat, poultry and fish
o Non-heme; plant and animal sources and iron in supplements
o Non-heme iron in ferrous state (Fe2+) enters enterocyte from the gut lumen through DMT1 (iron in ferric state
needs to be reduced to the ferrous state to be transported by DMT1
§ Nonheme iron is stored as ferritin or exported across the membrane through ferroportin
o Heme iron enters the enterocyte via a heme importer
o Iron absorption is influenced by the biochemical form of iron in the gut lumen (heme or nonheme), iron status
of the individual, and bioavailability of the iron source
o Absorption of heme iron is significantly greater than nonheme iron and is less affected by the overall
composition of the diet and iron status of the individual
o But iron status of the individual and iron bioavailability alter nonheme iron absorption up to 10-15 fold
o Individuals with little or no iron stores absorb a greater fraction of nonheme iron from the diet, whereas
individuals with sufficient iron stores absorb less iron from the diet
- Regulation of iron homeostasis
o Two key mechanisms that regulate iron homeostasis:
§ Iron regulator proteins (IRPs) > essential for cellular regulation
§ Hepcidin > essential for systematic regulation
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