Vitamin A deficiency

Vitamin A deficiency
Classification and external resources
Specialty endocrinology
ICD-10 E50
ICD-9-CM 264.9
DiseasesDB 13902
eMedicine med/2381
Patient UK Vitamin A deficiency
MeSH D014802
Prevalence of vitamin A deficiency, 1995

Vitamin A deficiency (VAD) or hypovitaminosis A is a lack of vitamin A in blood and tissues. It is common in poorer countries but rarely seen in more developed countries. Nyctalopia (night blindness) is one of the first signs of VAD. Xerophthalmia, keratomalacia, and complete blindness can also occur since Vitamin A has a major role in phototransduction.

Vitamin A deficiency is the leading cause of preventable childhood blindness and is critical to achieving Millennium Development Goal 4 to reduce child mortality.[1] 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 whom die within a year of becoming blind. The United Nations Special Session on Children in 2002 set a goal of the elimination of VAD by 2010.

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.[2][3][4][5]

VAD also diminishes the ability to fight infections. In countries where children are not immunized, infectious diseases like measles have higher fatality rates. 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.

VAD is estimated to affect approximately one third of children under the age of five around the world.[6] It is estimated to claim the lives of 670,000 children under five annually.[7] Approximately 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).[1]

Signs and symptoms

The common cause of blindness in developing countries is VAD. The World Health Organization (WHO) estimates 13.8 million children to have some degree of visual loss related to VAD.[8] Night blindness and its worsened condition, xerophthalmia, are markers of VAD, as it can also lead to impaired immune function, cancer, and birth defects. Collections of keratin in the conjunctiva, known as Bitot's spots, are also seen. Imtiaz's sign is the earliest ocular sign of VAD. Conjunctival epithelial defects occur around lateral aspect of the limbus in subclinical stage of VAD. These conjunctival epithelial defects are not even 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".[9]

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.[10]

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.[11] 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.[12] 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 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.[13][14]

The richest animal sources of Vitamin A (retinol) are livers like beef liver (one ounce provides around 8,000 IUs [15]) and Cod Liver Oil (one teaspoon provides around 4,500 IUs [16]).

Vitamin A deficiency is one of several hypovitaminoses implicated in follicular hyperkeratosis.


The major cause is roughage which include few animal sources of pre-formed vitamin A. In addition to dietary problems, there are other causes of VAD. 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 and biliary obstruction.

Infection rates

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

Global initiatives

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 A2Z, the Canadian International Development Agency, 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 VAD 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 VAD.[27]

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.[28]

An estimated 1.25 million deaths due to VAD have been averted in 40 countries since 1998.[29]

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.[30] These combined interventions were ranked by the Copenhagen Consensus 2008 as the world’s best development investment.[30]


Disability-adjusted life year for vitamin A deficiency per 100,000 inhabitants in 2002.[31]
  no data
  less than 35
  more than 400

See also


  1. 1 2 3 "Vitamin A Deficiency and Supplementation UNICEF Data". Retrieved 2015-04-07.
  2. "WHO Vitamin A deficiency | Micronutrient deficiencies". Retrieved 2008-03-03.
  3. Latham, Michael E. (1997). Human Nutrition in the Developing World (Fao Food and Nutrition Paper). Food & Agriculture Organization of the United. ISBN 92-5-103818-X.
  4. Sommer, Alfred (1995). Vitamin a Deficiency and Its Consequences: A Field Guide to Detection and Control. Geneva: World Health Organization. ISBN 92-4-154478-3.
  5. "A world fit for children" (PDF). Retrieved 2008-03-03.
  6. World Health Organization, Global prevalence of vitamin A deficiency in populations at risk 1995–2005, WHO global database on vitamin A deficiency.
  7. Black RE et al., Maternal and child undernutrition: global and regional exposures and health consequences, The Lancet, 2008, 371(9608), p. 253.
  8. J S Rahi, S Sripathi, C E Gilbert, A Foster. Childhood blindness due to VAD in India: regional variations. Archives of Disease in Childhood. 72: 330–333, 1995.
  10. Underwood, Barbara A. Vitamin A Deficiency Disorders: International Efforts to Control A Preventable “Pox.” J. Nutr. 134: 231S–236S, 2004.
  11. Sommer A, Muhilal, Tarwotjo I, Djunaedi E and Glover J (1980b) Oral versus intramuscular vitamin A in the treatment of xerophthalmia. Lancet 1: 557–559.
  12. Arroyave G, Mejia LA and Aguilar JR (1981) The effect of vitamin A fortification of sugar on the serum vitamin A levels of preschool Guatemalan children: a longitudinal evaluation. J. Nutr. 34: 41–49.
  13. Borel P, Drai J, Faure H, Fayol V, Galabert C, Laromiguière M, Le Moël G (2005). "Recent knowledge about intestinal absorption and cleavage of carotenoids". Annales de Biologie Clinique (in French). 63 (2): 165–77. PMID 15771974.
  14. Tang G, Qin J, Dolnikowski GG, Russell RM, Grusak MA (2005). "Spinach or carrots can supply significant amounts of vitamin A as assessed by feeding with intrinsically deuterated vegetables". The American Journal of Clinical Nutrition. 82 (4): 821–8. PMID 16210712.
  17. Beaton GH et al. Effectiveness of vitamin A supplementation in the control of young child morbidity and mortality in developing countries. United Nations Administrative Committee on Coordination, Sub-committee on Nutrition State-of-the-Art Series: Nutrition Policy Discussion Paper No. 13. Geneva, 1993.
  18. "Distribution of vitamin A during national immunization days" (PDF). Retrieved 2008-03-03.
  19. "WHO Vitamin A supplementation". Retrieved 2008-03-03.
  20. Stoltzfus RJ, Hakimi M, Miller KW, et al. (1993). "High dose vitamin A supplementation of breast-feeding Indonesian mothers: effects on the vitamin A status of mother and infant". J. Nutr. 123 (4): 666–75. PMID 8463867.
  21. edited by Lindsay Allen ... (2006). Guidelines on Food Fortification With Micronutrients. Geneva: World Health Organization. ISBN 92-4-159401-2.
  22. Food and Agriculture Organization of the United Nations (1996). Food Fortification: Tech & Quality Control (Food & Nutrition Papers). Bernan Assoc. ISBN 92-5-103884-8.
  23. Ye, X; Al-Babili, S; Klöti, A; Zhang, J; Lucca, P; Beyer, P; Potrykus, I (2000). "Engineering the provitamin A (beta-carotene) biosynthetic pathway into (carotenoid-free) rice endosperm". Science. 287 (5451): 303–5. doi:10.1126/science.287.5451.303. PMID 10634784.
  24. One existing crop, genetically engineered "golden rice" that produces vitamin A, already holds enormous promise for reducing blindness and dwarfism that result from a vitamin-A deficient diet. – Bill Frist, physician and politician, in a Washington Times commentary – November 21, 2006
  25. " Vitamin A Deficiency". Archived from the original on 2008-02-18. Retrieved 2008-03-14.
  26. "A New Approach that Saves Eyesight and Lives in the Developing World". USDA Agricultural Research Service. May 3, 2010.
  28. Micronutrient Initiative, Annual Report 2009–2010, p. 4.
  29. "Micronutrient Deficiencies-Vitamin A". World Health Organization. Retrieved 2008-04-09.
  30. 1 2 Copenhagen Consensus 2008, Results, press release, May 30, 2008.
  31. "Mortality and Burden of Disease Estimates for WHO Member States in 2002" (xls). World Health Organization. 2002.

Further reading

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