Vitamin A deficiency
Encyclopedia
Vitamin A deficiency is a lack of vitamin A
in humans. It is common in developing countries but rarely seen in developed countries. Night blindness is one of the first signs of vitamin A deficiency. Xerophthalmia
and complete blindness can also occur since Vitamin A has a major role in phototransduction
. Approximately 250,000 to 500,000 malnourished children in the developing world go blind each year from a deficiency of vitamin A, approximately half of which die within a year of becoming blind. The United Nations
Special Session on Children in 2002 set the elimination of vitamin A deficiency by 2010. The prevalence of night blindness due to vitamin A deficiency is also high among pregnant women in many developing countries. Vitamin A deficiency also contributes to maternal mortality and other poor outcomes in pregnancy
and lactation
.
Vitamin A deficiency also diminishes the ability to fight infections. In countries where children are not immunized, infectious disease like measles
have higher fatality rates. As elucidated by Dr. Alfred Sommer
, even mild, subclinical deficiency can also be a problem, as it may increase children's risk of developing respiratory and diarrheal infections, decrease growth rate, slow bone development, and decrease likelihood of survival from serious illness.
Vitamin A deficiency is estimated to affect approximately one third of children under the age of five around the world. It is estimated to claim the lives of 670,000 children under five annually. Approximately 250,000-500,000 children in developing countries become blind each year owing to vitamin A deficiency, with the highest prevalence in Southeast Asia and Africa. According to the World Health Organization (WHO), vitamin A deficiency is under control in the United States, but in developing countries vitamin A deficiency is a significant concern.
Night blindness is the difficulty for the eyes to adjust to dim light. Affected individuals are unable to distinguish images in low levels of illumination. People with night blindness have poor vision in the darkness, but see normally when adequate light is present.
VAD affects vision by inhibiting the production of rhodopsin, the eye pigment responsible for sensing low light situations. Rhodopsin is found in the retina and is composed of retinal (an active form of vitamin A) and opsin (a protein). Because the body cannot create retinal in sufficient amounts, a diet low in vitamin A will lead to a decreased amount of rhodopsin in the eye, as there is inadequate retinal to bind with opsin. Night blindness results.
Night blindness caused by VAD has been associated with the loss of goblet cells in the conjunctiva, a membrane covering the outer surface of the eye. Goblet cells are responsible for secretion of mucus, and their absence results in xerophthalmia, a condition where the eyes fail to produce tears. Dead epithelial and microbial cells accumulate on the conjunctiva and form debris that can lead to infection and possibly blindness.
Decreasing night blindness requires the improvement of vitamin A status in at risk populations. Supplements and fortification of food have been shown to be effective interventions. Supplement treatment for night blindness includes high doses of vitamin A (200,000 IU) in the form of retinyl palmitate to be taken by mouth, which is administered two to four times a year. Intramuscular injections are poorly absorbed and are ineffective in delivering sufficient bio-available vitamin A. Fortification of food with vitamin A is costly, but can be done in wheat, sugar, and milk. Households may circumvent expensive fortified food by altering dietary habits. Consumption of yellow-orange fruits and vegetables rich in carotenoids, specifically beta carotene, provides pro-vitamin A precursors that will prevent VAD related night blindness.
The major cause is diets which include few animal sources of pre-formed vitamin A. Breast milk
of a lactating mother with vitamin A deficiency contains little vitamin A
, which provides a breast-fed child with too little vitamin A
.
In addition to dietary problems, there are other causes of vitamin A deficiency. Iron
deficiency can affect vitamin A uptake. Excess alcohol consumption can deplete vitamin A, and a stressed liver may be more susceptible to vitamin A toxicity. People who consume large amounts of alcohol should seek medical advice before taking vitamin A supplements. In general, people should also seek medical advice before taking vitamin A supplements if they have any condition associated with fat malabsorption such as pancreatitis
, cystic fibrosis
, tropical sprue
& biliary obstruction.
The reason for the increased infection rate in vitamin A deficient populations is due to the T-killer cells which require retinoids to proliferate correctly (Athanassiades1981). Retinoic acid binds the promoter region of specific genes and so activates the transcription process and therefore cell replication (Baron 1981). A vitamin A deficient diet will have a very limited surplus of retinol and so cell proliferation and replication will be suppressed, contributing to a reduced number of T-cells and lymphocytes. Suppression of these will result in a lack of immune reaction if pathogens become present in the body and consequently a greater susceptibility to incubation of disease.
VAD and infections aggravate each other and therefore with infection the vitamin A levels are depleted which in turn reduces intestinal absorption of vitamin A (WHO 1982). Very often seen with vitamin A deficiency is protein energy malnutrition (PEM). With PEM the synthesis of retinol binding protein (RBP) is decreased, consequently the uptake of retinol is reduced (Combs, 1991). This leads to an inability to utilise any vitamin A present as the RBP is absent and so the retinol cannot be transported to the liver maximising the VAD (Ikekpeazu 2010).
forms, generally as vitamin A palmitate.
, Helen Keller International
, Micronutrient Initiative
, UNICEF, USAID, and the World Bank
. Joint GAVA activity is coordinated by the Micronutrient Initiative.
Vitamin Angels
has committed itself to eradicating childhood blindness due to Vitamin A deficiency on the planet by the year 2020. Operation 20/20 was launched in 2007 and will cover 18 countries. The program gives children two high dose vitamin A and anti-parasitic supplements (twice a year for four years), which provides children with enough of the nutrient during their most vulnerable years in order to prevent them from going blind and suffering from other life-threatening diseases caused by Vitamin A Deficiency.
About 75 per cent of the vitamin A required for supplementation activity by developing countries is supplied by the Micronutrient Initiative
with support from the Canadian International Development Agency.
An estimated 1.25 million deaths due to vitamin A deficiency have been averted in 40 countries since 1998.
In 2008 it was estimated that an annual investment of US$60 million in vitamin A and zinc supplementation combined would yield benefits of more than US$1 billion per year, with every dollar spent generating benefits of more than US$17. These combined interventions were ranked by the Copenhagen Consensus
2008 as the world’s best development investment.
Vitamin A
Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
in humans. It is common in developing countries but rarely seen in developed countries. Night blindness is one of the first signs of vitamin A deficiency. Xerophthalmia
Xerophthalmia
Xerophthalmia is a medical condition in which the eye fails to produce tears. It may be caused by a deficiency in vitamin A and is sometimes used to describe that lack, although there may be other causes....
and complete blindness can also occur since Vitamin A has a major role in phototransduction
Visual phototransduction
Visual phototransduction is a process by which light is converted into electrical signals in the rod cells, cone cells and photosensitive ganglion cells of the retina of the eye....
. Approximately 250,000 to 500,000 malnourished children in the developing world go blind each year from a deficiency of vitamin A, approximately half of which die within a year of becoming blind. The United Nations
United Nations
The United Nations is an international organization whose stated aims are facilitating cooperation in international law, international security, economic development, social progress, human rights, and achievement of world peace...
Special Session on Children in 2002 set the elimination of vitamin A deficiency by 2010. The prevalence of night blindness due to vitamin A deficiency is also high among pregnant women in many developing countries. Vitamin A deficiency also contributes to maternal mortality and other poor outcomes in pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
and lactation
Lactation
Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, however it predates mammals. In humans the process of feeding milk is called breastfeeding or nursing...
.
Vitamin A deficiency also diminishes the ability to fight infections. In countries where children are not immunized, infectious disease like measles
Measles
Measles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
have higher fatality rates. As elucidated by Dr. Alfred Sommer
Alfred Sommer (ophthalmologist)
Alfred Sommer is a prominent American ophthalmologist and epidemiologist at the Johns Hopkins Bloomberg School of Public Health. His research on vitamin A in the 1970s and 1980s revealed that dosing severely vitamin A deficient children with an inexpensive, large dose vitamin A capsule twice a...
, even mild, subclinical deficiency can also be a problem, as it may increase children's risk of developing respiratory and diarrheal infections, decrease growth rate, slow bone development, and decrease likelihood of survival from serious illness.
Vitamin A deficiency is estimated to affect approximately one third of children under the age of five around the world. It is estimated to claim the lives of 670,000 children under five annually. Approximately 250,000-500,000 children in developing countries become blind each year owing to vitamin A deficiency, with the highest prevalence in Southeast Asia and Africa. According to the World Health Organization (WHO), vitamin A deficiency is under control in the United States, but in developing countries vitamin A deficiency is a significant concern.
Signs and symptoms
The most common cause of blindness in developing countries is vitamin A deficiency (VAD). The World Health Organization (WHO) estimates 13.8 million children to have some degree of visual loss related to VAD. Night blindness and its worsened condition, xerophthalmia, are markers of VAD, as VAD can also lead to impaired immune function, cancer, and birth defects.Night blindness is the difficulty for the eyes to adjust to dim light. Affected individuals are unable to distinguish images in low levels of illumination. People with night blindness have poor vision in the darkness, but see normally when adequate light is present.
VAD affects vision by inhibiting the production of rhodopsin, the eye pigment responsible for sensing low light situations. Rhodopsin is found in the retina and is composed of retinal (an active form of vitamin A) and opsin (a protein). Because the body cannot create retinal in sufficient amounts, a diet low in vitamin A will lead to a decreased amount of rhodopsin in the eye, as there is inadequate retinal to bind with opsin. Night blindness results.
Night blindness caused by VAD has been associated with the loss of goblet cells in the conjunctiva, a membrane covering the outer surface of the eye. Goblet cells are responsible for secretion of mucus, and their absence results in xerophthalmia, a condition where the eyes fail to produce tears. Dead epithelial and microbial cells accumulate on the conjunctiva and form debris that can lead to infection and possibly blindness.
Decreasing night blindness requires the improvement of vitamin A status in at risk populations. Supplements and fortification of food have been shown to be effective interventions. Supplement treatment for night blindness includes high doses of vitamin A (200,000 IU) in the form of retinyl palmitate to be taken by mouth, which is administered two to four times a year. Intramuscular injections are poorly absorbed and are ineffective in delivering sufficient bio-available vitamin A. Fortification of food with vitamin A is costly, but can be done in wheat, sugar, and milk. Households may circumvent expensive fortified food by altering dietary habits. Consumption of yellow-orange fruits and vegetables rich in carotenoids, specifically beta carotene, provides pro-vitamin A precursors that will prevent VAD related night blindness.
Causes
Breast milk
Breast milk, more specifically human milk, is the milk produced by the breasts of a human female for her infant offspring...
of a lactating mother with vitamin A deficiency contains little vitamin A
Vitamin A
Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
, which provides a breast-fed child with too little vitamin A
Vitamin A
Vitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
.
In addition to dietary problems, there are other causes of vitamin A deficiency. Iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...
deficiency can affect vitamin A uptake. Excess alcohol consumption can deplete vitamin A, and a stressed liver may be more susceptible to vitamin A toxicity. People who consume large amounts of alcohol should seek medical advice before taking vitamin A supplements. In general, people should also seek medical advice before taking vitamin A supplements if they have any condition associated with fat malabsorption such as pancreatitis
Pancreatitis
Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...
, cystic fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
, tropical sprue
Tropical sprue
Tropical sprue is a malabsorption disease commonly found in the tropical regions, marked with abnormal flattening of the villi and inflammation of the lining of the small intestine.It differs significantly from coeliac sprue.-Symptoms and signs:...
& biliary obstruction.
Rates of infection
Along with poor diet there is a large amount of infection and disease present in many developing communities. Infection is very draining on vitamin A reserves and this vitamin A deficit leaves the individual more susceptible to infection (Combs, 1991); increased documentation of xerophthalmia has been seen after an outbreak of measles and the varying stages of xerophthalmia become a good reference point for the extent of deficiency (with mortality increasing with severity of the eye disease). In a longitudinal study of preschool Indonesian children it was found that susceptibility to disease increased nine times when severe VAD was present (Dole 2009).The reason for the increased infection rate in vitamin A deficient populations is due to the T-killer cells which require retinoids to proliferate correctly (Athanassiades1981). Retinoic acid binds the promoter region of specific genes and so activates the transcription process and therefore cell replication (Baron 1981). A vitamin A deficient diet will have a very limited surplus of retinol and so cell proliferation and replication will be suppressed, contributing to a reduced number of T-cells and lymphocytes. Suppression of these will result in a lack of immune reaction if pathogens become present in the body and consequently a greater susceptibility to incubation of disease.
VAD and infections aggravate each other and therefore with infection the vitamin A levels are depleted which in turn reduces intestinal absorption of vitamin A (WHO 1982). Very often seen with vitamin A deficiency is protein energy malnutrition (PEM). With PEM the synthesis of retinol binding protein (RBP) is decreased, consequently the uptake of retinol is reduced (Combs, 1991). This leads to an inability to utilise any vitamin A present as the RBP is absent and so the retinol cannot be transported to the liver maximising the VAD (Ikekpeazu 2010).
Treatment
Treatment of vitamin A deficiency can be undertaken with both oral and injectableInjection (medicine)
An injection is an infusion method of putting fluid into the body, usually with a hollow needle and a syringe which is pierced through the skin to a sufficient depth for the material to be forced into the body...
forms, generally as vitamin A palmitate.
- As an oral form, the supplementation of vitamin AVitamin AVitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
is effective for lowering the risk of morbidity, especially from severe diarrheaDiarrheaDiarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
, and reducing mortalityMortality rateMortality rate is a measure of the number of deaths in a population, scaled to the size of that population, per unit time...
from measlesMeaslesMeasles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
and all-cause mortality. Studies have shown that vitamin A supplementation of children under five who are at risk of vitamin A deficiency can reduce all‐cause mortality by 23 per cent. Some countries where vitamin A deficiency is a public health problem address its elimination by including vitamin A supplements available in capsule form with National Immunization Days (NIDs) for polio eradication or measlesMeaslesMeasles, also known as rubeola or morbilli, is an infection of the respiratory system caused by a virus, specifically a paramyxovirus of the genus Morbillivirus. Morbilliviruses, like other paramyxoviruses, are enveloped, single-stranded, negative-sense RNA viruses...
. Vitamin A capsules cost about US$0.02. The capsules are easy to handle; they don’t need to be stored in a refrigerator or vaccine carrier. When the correct dosage is given, vitamin AVitamin AVitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
is safe and has no negative effect on seroconversionSeroconversionSeroconversion is the development of detectable specific antibodies to microorganisms in the blood serum as a result of infection or immunization. Serology is used to determine antibody positivity...
rates for Oral Polio Vaccine or measles vaccine. However, because the benefit of vitamin A supplements is transient, children need them regularly every four to six months. Since NIDs provide only one dose per year, NIDs-linked vitamin A distribution must be complemented by other dose programs to maintain vitamin AVitamin AVitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
in children Maternal high supplementation benefits both mother and breast-fed infant: high dose vitamin A supplementation of the lactating mother in the first month postpartum can provide the breast-fed infant with an appropriate amount of vitamin AVitamin AVitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
through breast milkBreast milkBreast milk, more specifically human milk, is the milk produced by the breasts of a human female for her infant offspring...
. However, high-dose supplementation of pregnant women should be avoided because it can cause miscarriageMiscarriageMiscarriage or spontaneous abortion is the spontaneous end of a pregnancy at a stage where the embryo or fetus is incapable of surviving independently, generally defined in humans at prior to 20 weeks of gestation...
and birth defects.
- Food fortification is also useful for improving vitamin A deficiency. A variety of oily and dry forms of the retinol esters, retinyl acetates and retinyl palmitateRetinyl palmitateRetinyl palmitate, or vitamin A palmitate, is the ester of retinol and palmitic acid, with formula C36H60O2.Palmitate is the major component of palm oil...
are available for food fortificationFood fortificationFood fortification or enrichment is the process of adding micronutrients to food. It can be purely a commercial choice to provide extra nutrients in a food, or sometimes it is a public health policy which aims to reduce numbers of people with dietary deficiencies in a population.Diets that lack...
of vitamin AVitamin AVitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
. MargarineMargarineMargarine , as a generic term, can indicate any of a wide range of butter substitutes, typically composed of vegetable oils. In many parts of the world, the market share of margarine and spreads has overtaken that of butter...
and oilOilAn oil is any substance that is liquid at ambient temperatures and does not mix with water but may mix with other oils and organic solvents. This general definition includes vegetable oils, volatile essential oils, petrochemical oils, and synthetic oils....
are the ideal food vehicles for vitamin A fortification. They protect vitamin AVitamin AVitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
from oxidation during storage and prompt absorption of vitamin AVitamin AVitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
. β-carotene and retinyl acetate or retinyl palmitateRetinyl palmitateRetinyl palmitate, or vitamin A palmitate, is the ester of retinol and palmitic acid, with formula C36H60O2.Palmitate is the major component of palm oil...
are used as a form of vitamin AVitamin AVitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
for vitamin A fortification of fat-based foods. Fortification of sugarSugarSugar is a class of edible crystalline carbohydrates, mainly sucrose, lactose, and fructose, characterized by a sweet flavor.Sucrose in its refined form primarily comes from sugar cane and sugar beet...
with retinyl palmitateRetinyl palmitateRetinyl palmitate, or vitamin A palmitate, is the ester of retinol and palmitic acid, with formula C36H60O2.Palmitate is the major component of palm oil...
as a form of vitamin AVitamin AVitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
has been used extensively throughout Central AmericaCentral AmericaCentral America is the central geographic region of the Americas. It is the southernmost, isthmian portion of the North American continent, which connects with South America on the southeast. When considered part of the unified continental model, it is considered a subcontinent...
. Cereal flours, milk powder, and liquid milk are also used as food vehicles for vitamin A fortification.
- Dietary diversification can also control vitamin A deficiency. Non-animal sources of vitamin AVitamin AVitamin A is a vitamin that is needed by the retina of the eye in the form of a specific metabolite, the light-absorbing molecule retinal, that is necessary for both low-light and color vision...
which contain pre-formed vitamin A account for greater than 80% of intake for most individuals in the developing world. The increase in consumption of vitamin A-rich foods of animal origin in addition to fruits and vegetables has beneficial effects on vitamin A deficiency. Researchers at the Agricultural Research ServiceAgricultural Research ServiceThe Agricultural Research Service is the principal in-house research agency of the United States Department of Agriculture . ARS is one of four agencies in USDA's Research, Education and Economics mission area...
have been able to identify genetic sequences in corn that are associated with higher levels of beta-caroteneBeta-caroteneβ-Carotene is a strongly-coloured red-orange pigment abundant in plants and fruits. It is an organic compound and chemically is classified as a hydrocarbon and specifically as a terpenoid , reflecting its derivation from isoprene units...
, the precursor to vitamin A. They found that breeders can cross certain variations of corn to produce a crop with an 18-fold increase in beta-carotene. Such advancements in nutritional plant breeding could one day aid in the illnesses related to vitamin A deficiency in developing countries.
Global Initiatives
Global efforts to support national governments in addressing vitamin a deficiency are led by the Global Alliance for Vitamin A (GAVA), which is an informal partnership between A2Z, the Canadian International Development AgencyCanadian International Development Agency
The Canadian International Development Agency was formed in 1968 by the Canadian government. CIDA administers foreign aid programs in developing countries, and operates in partnership with other Canadian organizations in the public and private sectors as well as other international organizations...
, Helen Keller International
Helen Keller International
Helen Keller International combats the causes and consequences of blindness and malnutrition by establishing programs based on evidence and research in vision, health and nutrition. Founded in 1915 by Helen Keller and George Kessler, the organization’s mission is to save the sight and lives of the...
, Micronutrient Initiative
Micronutrient Initiative
The Micronutrient Initiative is an international not for profit agency based in Canada that works to eliminate vitamin and mineral deficiencies in developing countries...
, UNICEF, USAID, and the World Bank
World Bank
The World Bank is an international financial institution that provides loans to developing countries for capital programmes.The World Bank's official goal is the reduction of poverty...
. Joint GAVA activity is coordinated by the Micronutrient Initiative.
Vitamin Angels
Vitamin Angels
Vitamin Angels is a non-profit, non-governmental organization focused on bringing essential nutrition to children around the world through vitamin supplementation.-Mission:...
has committed itself to eradicating childhood blindness due to Vitamin A deficiency on the planet by the year 2020. Operation 20/20 was launched in 2007 and will cover 18 countries. The program gives children two high dose vitamin A and anti-parasitic supplements (twice a year for four years), which provides children with enough of the nutrient during their most vulnerable years in order to prevent them from going blind and suffering from other life-threatening diseases caused by Vitamin A Deficiency.
About 75 per cent of the vitamin A required for supplementation activity by developing countries is supplied by the Micronutrient Initiative
Micronutrient Initiative
The Micronutrient Initiative is an international not for profit agency based in Canada that works to eliminate vitamin and mineral deficiencies in developing countries...
with support from the Canadian International Development Agency.
An estimated 1.25 million deaths due to vitamin A deficiency have been averted in 40 countries since 1998.
In 2008 it was estimated that an annual investment of US$60 million in vitamin A and zinc supplementation combined would yield benefits of more than US$1 billion per year, with every dollar spent generating benefits of more than US$17. These combined interventions were ranked by the Copenhagen Consensus
Copenhagen Consensus
Copenhagen Consensus is a project that seeks to establish priorities for advancing global welfare using methodologies based on the theory of welfare economics. It was conceived and organized by Bjørn Lomborg, the author of The Skeptical Environmentalist and the then director of the Danish...
2008 as the world’s best development investment.
Epidemiology
Further reading
- UNICEF, Vitamin A Supplementation: A Decade of Progress, UNICEF, New York, 2007.
- Flour Fortification Initiative, GAIN, Micronutrient Initiative, USAID, The World Bank, UNICEF, Investing in the Future: A United Call to Action on Vitamin and Mineral Deficiencies, 2009.