Vitamin A deficiency

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Prevalence of vitamin A deficiency, 1995-2005 Prevalence-of-vitamin-a-deficiency-in-children.png
Prevalence of vitamin A deficiency, 1995-2005

Vitamin A deficiency (VAD) or hypovitaminosis A is a lack of vitamin A in blood and tissues. [1] It is common in poorer countries, especially among children and women of reproductive age, but is rarely seen in more developed countries. [1] Vitamin A plays a major role in phototransduction, so this deficiency impairs vision, often presenting with nyctalopia (night blindness). [1] In more severe VAD cases, it can progress to xerophthalmia, keratomalacia, and complete blindness. [1]

Contents

Vitamin A deficiency is the leading cause of preventable childhood blindness worldwide and is a major cause of childhood mortality. [1] Each year, approximately 250,000 to 500,000 malnourished children in the developing world go blind from a VAD, with about half of whom dying within a year of losing their sight. [2] Addressing VAD has been a critical focus of global health initiatives, including Sustainable Development Goal 2: to end hunger, achieve food security and improved nutrition and promote sustainable agriculture. [3]

In pregnant women, VAD is associated with a high prevalence of night blindness and poor maternal health outcomes including an increased risk of maternal mortality and complications during pregnancy and lactation. [4] [5] [6] [7] VAD also affects the immune system and diminishes the body's ability to fight infections. [1] In countries where children are not immunized, VAD is linked to higher fatality rates from infectious diseases such as measles. [1] Even mild, subclinical deficiency can also be a problem, as it may increase children's risk of developing respiratory and diarrheal infections, decrease growth, impair bone development, and reduce their likelihood of surviving serious illnesses. [6]

Globally, VAD is estimated to affect about one-third of children under the age of five, causing an estimated 670,000 deaths in children under five annually. [8] [9] It is most prevalent in sub-Saharan Africa (48 percent) and South Asia (44 percent). [8] Although VAD is well-managed in many high income nations, it remains a significant concern in resource-poor settings. Public health interventions, such as vitamin A supplementation, reached 59% of targeted children in 2022, highlighting the ongoing need for comprehensive efforts to combat VAD. [8]

Signs and symptoms

Vitamin A deficiency is the most common cause of blindness in developing countries. The WHO estimated in 1995 that 13.8 million children had some degree of visual loss related to VAD. [10] Night blindness and its worsened condition, xerophthalmia, are markers of Vitamin A deficiency; collections of keratin in the conjunctiva, known as Bitot's spots, and ulceration and necrosis of cornea keratomalacia can be seen. Conjunctival epithelial defects occur around lateral aspect of the limbus in the subclinical stage of VAD. These conjunctival epithelial defects are not visible on a biomicroscope, but they take up black stain and become readily visible after instillation of kajal (surma); this is called "Imtiaz's sign". [11]

Night blindness

A process called dark adaptation typically causes an increase in photopigment amounts in response to low levels of illumination. This occurs to an enormous magnitude, increasing light sensitivity by up to 100,000 times its sensitivity in normal daylight conditions. VAD affects vision by inhibiting the production of rhodopsin, the photopigment 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).

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. [12]

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 massive 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. [13] Intramuscular injections are poorly absorbed and are ineffective in delivering sufficient bioavailable vitamin A. Fortification of food with vitamin A is costly, but can be done in wheat, sugar, and milk. [14] Households may circumvent expensive fortified food by altering dietary habits. Consumption of yellow-orange fruits and vegetables rich in carotenoids, specifically beta-carotene, provides provitamin A precursors that can prevent VAD-related night blindness. However, the conversion of carotene to retinol varies from person to person and bioavailability of carotene in food varies. [15] [16]

Infection

Along with poor diet, infection and disease are common in many developing communities. [1] Infection depletes vitamin A reserves which in turn make the affected individual more susceptible to further infection. [1] Increased incidence of xerophthalmia has been observed after an outbreak of measles, with mortality correlated with severity of eye disease. [1] In longitudinal studies of preschool children, susceptibility to disease increased substantially when severe VAD was present. [1] While VAD can make measles worse, Vitamin A supplements do not prevent measles, high doses may be dangerous, and vaccines remain the most effective was to prevent the disease. [17]

The reason for the increased infection rate in vitamin A deficient individuals is that killer T-cells require the retinol metabolite retinoic acid to proliferate correctly. [1] Retinoic acid is a ligand for nuclear retinoic acid receptors that bind the promoter regions of specific genes, [18] thus activating transcription and stimulating T cell replication. [1] Vitamin A deficiency will often entail deficient retinol intake, resulting in a reduced number of T-cells and lymphocytes, leading to an inadequate immune response and consequently a greater susceptibility to infections. [1] In the presence of dietary deficiency of vitamin A, VAD and infections reciprocally aggravate each other. [1]

Causes

In addition to dietary problems, other causes of VAD are known. Iron deficiency can affect vitamin A uptake. Other causes include fibrosis, pancreatic insufficiency, inflammatory bowel disease, and small-bowel bypass surgery. [19] Protein energy malnutrition is often seen in VAD. This is because suppressed synthesis of retinol binding protein (RBP) due to protein deficiency leads to reduced retinol uptake. [20]

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.

Other causes of vitamin A deficiency are inadequate intake, fat malabsorption, or liver disorders. Deficiency impairs immunity and hematopoiesis and causes rashes and typical ocular effects (e.g., xerophthalmia, night blindness). [21] 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, and biliary obstruction.

Diagnosis

Initial assessment may be made based on clinical signs of VAD. [22] The most common sign of VAD is night blindness, but VAD might also present with conjunctival xerosis, Bitot spots (foamy lesions), corneal xerosis, or corneal ulcerations. [23]

A VAD deficiency diagnosis is confirmed with laboratory findings. Several methods of assessing bodily vitamin A levels are available, with plasma retinol levels being the most common method of assessing VAD in individuals [24] . A plasma or serum retinol level below 0.70 μmol/L suggests subclinical vitamin A deficiency in both children and adults, while a level below 0.35 μmol/L indicates a severe deficiency of vitamin A [24] .

Other biochemical assessments include measuring serum retinol levels, serum zinc, plasma retinol ester levels, plasma and urinary retonioic acid levels, and vitamin A in breast milk. [22] [24] While liver biopsies are regarded as the gold standard for assessing total body vitamin A, they are rarely used outside of research settings because of the risks associated with the procedure. [23] Additionally, conjunctival impression cytology can be used to assess the presence of xerophthalmia which is strongly correlated with VAD status (and can be used to monitor recovery progress). [22] [25]

Vitamin A sources

This section is an excerpt from Vitamin A § Sources.[ edit ]
Food

μg RAE (2001) [26] per 100 g [27]

cod liver oil 30,000
beef liver (cooked)4,970–21,145
chicken liver (cooked)4,296
butter (stick)684
cheddar cheese 316
egg (cooked)140

Vitamin A is found in many foods. [27] Vitamin A in food exists either as preformed retinol – an active form of vitamin A – found in animal liver, dairy and egg products, and some fortified foods, or as provitamin A carotenoids, which are plant pigments digested into vitamin A after consuming carotenoid-rich plant foods, typically in red, orange, or yellow colors. [28] Carotenoid pigments may be masked by chlorophylls in dark green leaf vegetables, such as spinach. The relatively low bioavailability of plant-food carotenoids results partly from binding to proteins – chopping, homogenizing or cooking disrupts the plant proteins, increasing provitamin A carotenoid bioavailability. [28]

Vegetarian and vegan diets can provide sufficient vitamin A in the form of provitamin A carotenoids if the diet contains carrots, carrot juice, sweet potatoes, green leafy vegetables such as spinach and kale, and other carotenoid-rich foods. In the U.S., the average daily intake of β-carotene is in the range 2–7 mg. [29]

Some manufactured foods and dietary supplements are sources of vitamin A or β-carotene. [28] [26]

Prevention and treatment

Treatment of VAD can be undertaken with both oral vitamin A and injectable forms, generally as vitamin A palmitate.

Although synthetic vitamin A supplementation is a useful and effective treatment for VAD, a 2017 review (updated in 2022) reported that synthetic vitamin A supplementation may not be the best long‐term solution for vitamin A deficiency, but rather food fortification, improved food distribution programs, and crop improvement, such as for fortified rice or vitamin A-rich sweet potato, may be more effective in eradicating vitamin A deficiency. [35]

Public health initiatives

Some countries where VAD 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 measles. When the correct dosage is given, vitamin A is safe and has no negative effect on seroconversion rates for oral polio or measles vaccines. [48] Additionally, the delivery of vitamin A supplements, during integrated child health events such as child health days, has helped ensure high coverage of vitamin A supplementation in a large number of least developed countries. Child health events enable many countries in West and Central Africa to achieve over 80% coverage of vitamin A supplementation. [49] According to UNICEF data, in 2013 worldwide, 65% of children between the ages of 6 and 59 months were fully protected with two high-dose vitamin A supplements.Since NIDs provide only one dose per year, NIDs-linked vitamin A distribution must be complemented by other programs to maintain vitamin A in children. [50] [51]

Global efforts to support national governments in addressing VAD are led by the Global Alliance for Vitamin A (GAVA), which is an informal partnership between Nutrition International, Helen Keller International, UNICEF, WHO, and CDC. About 75% of the vitamin A required for supplementation of preschool-aged children in low- and middle-income countries is supplied through a partnership between Nutrition International and UNICEF, with support from Global Affairs Canada. [2] An estimated 1.25 million deaths due to vitamin A deficiency have been averted in 40 countries since 1998. [2]

Related Research Articles

<span class="mw-page-title-main">Carotene</span> Class of compounds

The term carotene (also carotin, from the Latin carota, "carrot") is used for many related unsaturated hydrocarbon substances having the formula C40Hx, which are synthesized by plants but in general cannot be made by animals (with the exception of some aphids and spider mites which acquired the synthesizing genes from fungi). Carotenes are photosynthetic pigments important for photosynthesis.

<span class="mw-page-title-main">Vitamin</span> Nutrients required by organisms in small amounts

Vitamins are organic molecules that are essential to an organism in small quantities for proper metabolic function. Essential nutrients cannot be synthesized in the organism in sufficient quantities for survival, and therefore must be obtained through the diet. For example, vitamin C can be synthesized by some species but not by others; it is not considered a vitamin in the first instance but is in the second. Most vitamins are not single molecules, but groups of related molecules called vitamers. For example, there are eight vitamers of vitamin E: four tocopherols and four tocotrienols.

<span class="mw-page-title-main">Vitamin A</span> Essential nutrient

Vitamin A is a fat-soluble vitamin that is an essential nutrient. The term "vitamin A" encompasses a group of chemically related organic compounds that includes retinol, retinyl esters, and several provitamin (precursor) carotenoids, most notably β-carotene (beta-carotene). Vitamin A has multiple functions: growth during embryo development, maintaining the immune system, and healthy vision. For aiding vision specifically, it combines with the protein opsin to form rhodopsin, the light-absorbing molecule necessary for both low-light and color vision.

<span class="mw-page-title-main">Retinol</span> Chemical compound

Retinol, also called vitamin A1, is a fat-soluble vitamin in the vitamin A family that is found in food and used as a dietary supplement. Retinol or other forms of vitamin A are needed for vision, cellular development, maintenance of skin and mucous membranes, immune function and reproductive development. Dietary sources include fish, dairy products, and meat. As a supplement it is used to treat and prevent vitamin A deficiency, especially that which results in xerophthalmia. It is taken by mouth or by injection into a muscle. As an ingredient in skin-care products, it is used to reduce wrinkles and other effects of skin aging.

Vitamin deficiency is the condition of a long-term lack of a vitamin. When caused by not enough vitamin intake it is classified as a primary deficiency, whereas when due to an underlying disorder such as malabsorption it is called a secondary deficiency. An underlying disorder can have 2 main causes:

<span class="mw-page-title-main">Golden rice</span> Variety of genetically modified rice

Golden rice is a variety of rice produced through genetic engineering to biosynthesize beta-carotene, a precursor of vitamin A, in the edible parts of the rice. It is intended to produce a fortified food to be grown and consumed in areas with a shortage of dietary vitamin A. Genetically modified golden rice can produce up to 23 times as much beta-carotene as the original golden rice.

β-Carotene Red-orange pigment of the terpenoids class

β-Carotene (beta-carotene) is an organic, strongly colored red-orange pigment abundant in fungi, plants, and fruits. It is a member of the carotenes, which are terpenoids (isoprenoids), synthesized biochemically from eight isoprene units and thus having 40 carbons.

Micronutrients are essential dietary elements required by organisms in varying quantities to regulate physiological functions of cells and organs. Micronutrients support the health of organisms throughout life.

<span class="mw-page-title-main">Xerophthalmia</span> Dry eye

Xerophthalmia is a medical condition in which the eye fails to produce tears. It may be caused by vitamin A deficiency, which is sometimes used to describe that condition, although there may be other causes.

<span class="mw-page-title-main">Retinyl palmitate</span> Vitamin A chemical compound

Retinyl palmitate, or vitamin A palmitate, is the ester of retinol (vitamin A) and palmitic acid, with formula C36H60O2. It is the most abundant form of vitamin A storage in animals.

<span class="mw-page-title-main">Hypervitaminosis A</span> Toxic effects of ingesting too much vitamin A

Hypervitaminosis A refers to the toxic effects of ingesting too much preformed vitamin A. Symptoms arise as a result of altered bone metabolism and altered metabolism of other fat-soluble vitamins. Hypervitaminosis A is believed to have occurred in early humans, and the problem has persisted throughout human history. Toxicity results from ingesting too much preformed vitamin A from foods, supplements, or prescription medications and can be prevented by ingesting no more than the recommended daily amount.

Food fortification is the addition of micronutrients to food products. Food enrichment specifically means adding back nutrients lost during food processing, while fortification includes adding nutrients not naturally present. Food manufacturers and governments have used these practices since the 1920s to help prevent nutrient deficiencies in populations. Common nutrient deficiencies in a region often result from local soil conditions or limitations of staple foods. The addition of micronutrients to staples and condiments can prevent large-scale deficiency diseases in these cases.

Vitamins occur in a variety of related forms known as vitamers. A vitamer of a particular vitamin is one of several related compounds that performs the functions of said vitamin and prevents the symptoms of deficiency of said vitamin.

<span class="mw-page-title-main">Biofortification</span> Breeding crops for higher nutritional value

Biofortification is the idea of breeding crops to increase their nutritional value. This can be done either through conventional selective breeding, or through genetic engineering. Biofortification differs from ordinary fortification because it focuses on making plant foods more nutritious as the plants are growing, rather than having nutrients added to the foods when they are being processed. This is an important improvement on ordinary fortification when it comes to providing nutrients for the rural poor, who rarely have access to commercially fortified foods. As such, biofortification is seen as an upcoming strategy for dealing with deficiencies of micronutrients in low and middle-income countries. In the case of iron, the WHO estimated that biofortification could help cure the 2 billion people suffering from iron deficiency-induced anemia.

<span class="mw-page-title-main">Nutrition International (organization)</span> Nonprofit organization

Nutrition International, formerly the Micronutrient Initiative (MI), is an international not for profit agency based in Canada that works to eliminate vitamin and mineral deficiencies in developing countries. Although often only required by the body in very small amounts, vitamin and minerals – also known as micronutrients – support an array of critical biological functions including growth, immune function and eye function, as well as foetal development of the brain, the nervous system, and the skeletal system. Micronutrient deficiency is a form of malnutrition and is a recognized health problem in many developing countries. Globally, more than two billion people live with vitamin and mineral deficiencies.

Retinyl acetate is a natural form of vitamin A which is the acetate ester of retinol. It has potential antineoplastic and chemopreventive activities.

Hans Konrad Biesalski is a German physician and professor of biological chemistry and nutritional medicine at the University of Hohenheim.

Artificial rice is a grain product made to resemble rice. It is usually made from broken rice, sometimes with the addition of other cereals, and often fortified with micronutrients, including minerals, such as iron and zinc, and vitamins, such as vitamin A and vitamin B.

<span class="mw-page-title-main">Child health and nutrition in Africa</span>

Child health and nutrition in Africa is concerned with the health care of children through adolescents in the various countries of Africa. The right to health and a nutritious and sufficient diet are internationally recognized human rights that are protected by international treaties. Millennium Development Goals (MDGs) 1, 4, 5 and 6 highlight, respectively, how poverty, hunger, child mortality, maternal health, the eradication of HIV/AIDS, malaria, tuberculosis and other diseases are of particular significance in the context of child health.

Joanne Katz is an epidemiologist, biostatistician, and Professor of International Health at the Johns Hopkins Bloomberg School of Public Health. She holds joint appointments in the Departments of Biostatistics, Epidemiology and Ophthalmology within the School of Medicine. Her expertise is in maternal, neonatal, and child health. She has contributed to the design, conduct and analysis of data from large community-based intervention trials on nutritional and other interventions in Indonesia, Philippines, Bangladesh, Nepal, and other countries.

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