Clinical Severe subclinical Moderate subclinical | Mild subclinical VAD under control No data available |
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] Nyctalopia (night blindness) is one of the first signs of VAD, as the vitamin has a major role in phototransduction; [1] but it is also the first symptom that is reversed when vitamin A is consumed again. Xerophthalmia, keratomalacia, and complete blindness can follow if the deficiency is more severe. [1]
Vitamin A deficiency is the world's leading cause of preventable childhood blindness, [1] and is critical to achieving Millennium Development Goal 4 to reduce child mortality. About 250,000 to 500,000 malnourished children in the developing world go blind each year from a deficiency of vitamin A, around half of whom die within a year of becoming blind. [2] The United Nations Special Session on Children in 2002 set a goal of the elimination of VAD by 2010. [3]
The prevalence of night blindness due to VAD is also high among pregnant women in many developing countries. VAD also contributes to maternal mortality and other poor outcomes in pregnancy and lactation. [4] [5] [6] [7]
VAD also diminishes the ability to fight infections. [1] In countries where children are not immunized, infectious diseases such as measles have higher fatality rates. [1] As elucidated by 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. [6]
VAD is estimated to affect about one-third of children under the age of five around the world. [8] It is estimated to claim the lives of 670,000 children under five annually. [9] Around 250,000–500,000 children in developing countries become blind each year owing to VAD, with the highest prevalence in Southeast Asia and Africa. According to the World Health Organization (WHO), VAD is under control in the United States, but in developing countries, VAD is a significant concern. Globally, 65% of all children aged 6 to 59 months received two doses of vitamin A in 2013, fully protecting them against VAD (80% in the least developed countries). [10]
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. [11] 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". [12]
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. [13]
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. [14] 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. [15] 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. [16] [17]
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]
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]
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; 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. 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. 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]
Initial assessment may be made based on clinical signs of VAD. [22] 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] [23] Several methods of assessing bodily vitamin A levels are available, with HPLC the most reliable. [23] Measurement of plasma retinol levels is a common laboratory assay used to diagnose VAD. Other biochemical assessments include measuring plasma retinyl ester levels, plasma and urinary retonioic acid levels, and vitamin A in breast milk. [22]
Food | |
---|---|
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. [25] 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. [26] 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. [26]
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. [27]
Some manufactured foods and dietary supplements are sources of vitamin A or beta-carotene. [26] [24]
Despite the US setting an adult upper limit of 3,000 μg/day, some companies sell vitamin A (as retinal palmitate) as a dietary supplement with amounts of 7,500 μg/day. Two examples are WonderLabs and Pure Prescriptions. [28] [29]Treatment of VAD can be undertaken with both oral vitamin A and injectable forms, generally as vitamin A palmitate.
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] In 2013, the prevalence of vitamin A deficiency was 29% in low-income and middle-income countries, remaining highest in sub-Saharan Africa and South Asia. [46] A 2017 review (updated in 2022) found that vitamin A supplementation in children five years old and younger in 70 countries was associated with a 12% reduction in mortality rate. [47] The review 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. [47]
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. Carotenes contain no oxygen atoms. They absorb ultraviolet, violet, and blue light and scatter orange or red light, and (in low concentrations) yellow light.
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.
Vitamin A is a fat-soluble vitamin and an essential nutrient for animals. The term "vitamin A" encompasses a group of chemically related organic compounds that includes retinol, retinal, retinoic acid, and several provitamin (precursor) carotenoids, most notably beta-carotene. Vitamin A has multiple functions: it is essential for embryo development and growth, for maintenance of the immune system, and for vision, where it combines with the protein opsin to form rhodopsin – the light-absorbing molecule necessary for both low-light and color vision.
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:
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. Vitamin A deficiency causes xerophthalmia, a range of eye conditions from night blindness to more severe clinical outcomes such as keratomalacia and corneal scars, and permanent blindness. Additionally, vitamin A deficiency also increases risk of mortality from measles and diarrhea in children. In 2013, the prevalence of deficiency was the highest in sub-Saharan Africa, and South Asia.
β-Carotene (beta-carotene) is an organic, strongly coloured 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. Among the carotenes, β-carotene is distinguished by having beta-rings at both ends of the molecule. β-Carotene is biosynthesized from geranylgeranyl pyrophosphate.
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.
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.
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.
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 or enrichment is the process of adding micronutrients to food. It can be carried out by food manufacturers, or by governments as a public health policy which aims to reduce the number of people with dietary deficiencies within a population. The predominant diet within a region can lack particular nutrients due to the local soil or from inherent deficiencies within the 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.
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.
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.
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.
Jagannath Ganguly (1921–2007) was an Indian biochemist known for his researches on Vitamin A and fatty acids, which assisted in the better understanding of their metabolism in humans. Born on the 1 April 1921, he authored a book, Biochemistry of Vitamin A, which details the physiological, biochemical and nutritional characteristics of the organic compound. The Council of Scientific and Industrial Research, the apex agency of the Government of India for scientific research, awarded him the Shanti Swarup Bhatnagar Prize for Science and Technology, one of the highest Indian science awards, in 1963, for his contributions to biological sciences. He died on 12 December 2007.
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. 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.