Population at Risk and Consequences of Vitamin A Deficiency

Definition of vitamin A deficiency 

WHO/UNICEF.  The Indicators of VAD (Vitamin A Deficiency) and their use in monitoringintervention programmes. World Health Organization, Geneva, VAD is not simply defined. 

With reference to WHO statement:

WHO defines it as tissue concentrations of vitamin A low enough to have adverse health consequences even if there is no evidence of clinical xerophthalmia.

In addition to the specific signs and symptoms of xerophthalmia and the risk of irreversible blindness, non-specific symptoms include increased morbidity and mortality, poor reproductive health, increased risk of anaemia, and contributions to slowed growth and development. Because these non-specific adverse consequences may occur from other nutrient deficits as well, it is difficult to attribute non-ocular symptoms specifically to VAD in the absence of biochemical measurements reflective of vitamin A status.

Geographic distribution and magnitude

WHO/UNICEF and WHO/NUT mapped the global distribution of VAD and categorised countries by degree of significance as a public health problem on the basis of both clinical and moderate and severe sub-clinical (prevalence of low blood levels of retinol) indicators of deficiency.

WHO. Global prevalence of vitamin A deficiency. MDIS Working Paper #2. World Health Organization, Geneva. 

In the early 1990s, WHO estimated that about 3 million children had some form of xerophthalmia annually and, on the basis of blood levels, another 250 million were sub-clinically deficient. 

The magnitude of the sub-clinical estimate is currently being reevaluated to quantitatively establish a benchmark for measuring prevalence trends. The actual number of sub-clinical deficiencies based on the prevalence of low serum levels of retinol, however, remains uncertain because of the confounding and poorly quantitative role of infections.

Katz, J. Clustering of xerophthalmia within households and villages. Int. J. Epidemiol., stated:

Epidemiologic studies repeatedly report clustering of VAD, presumably resulting from concurrent occurrence of several risk factors. This clustering may occur among both neighbourhoods and households. 

Age and gender

Sommer, A. VAD and its consequences: A field guide to their detection and control. 3rd ed. Geneva, World Health Organization, 1994 stated:

VAD can occur in individuals of any age. However, it is a disabling and potentially fatal public health problem for children under 6 years of age. VAD-related blindness is most prevalent in children under 3 years of age. 

Beaton, G.H.  Effectiveness of vitamin A supplementation in the control of young child morbidity and mortality in developing countries. ACC/SCN State-of-the-art Series, nutrition policy discussion paper no. 13. United Nations Administrative Committee on Coordination, Subcommittee on Nutrition. Geneva, World Health Organization. stated:

This period is characterised by high requirements for vitamin A to support early rapid growth, the transition from breast-feeding to dependence on other dietary sources of the vitamin, and increased frequency of respiratory and gastrointestinal infections. The increased mortality risk from concurrent infections extends at least to 6 years of age and is associated with both clinical and sub-clinical VAD. 

There is little information regarding the health consequences of VAD in school-age children.

Bloem, M.W., Matzger, H. & Huq, N. 1994. Vitamin A deficiency among women in the reproductive years: an ignored problem. Proceedings of the 16th IVACG Meeting, October, 1994, Chiang Rai, Thailand. and Christian, P. 1998. Night blindness of pregnancy in rural Nepal—nutritional and health risks. Int. J. Epidemiol stated:

The prevalence of Bitot's spots (i.e., white foamy patches on the conjunctiva) may be highest in this age group but their occurrence may reflect past more than current history of VAD. Women of reproductive age are thought also to be vulnerable to VAD during pregnancy and lactation because they often report night blindness   

Wallingford, J.C. & Underwood, B.A. 1986. Vitamin A deficiency in pregnancy, lactation, and the nursing child. In: Baurenfeind JC, ed. Vitamin A deficiency and its control and Newman, V. 1994. Vitamin A and breast-feeding: a comparison of data from developed and developing countries. Food and Nutrition Bulletin stated:

and because their breast-milk is frequently low in vitamin A. 

Christian, P. 1998. Night blindness of pregnancy in rural Nepal—nutritional and health risks. Int. J. Epidemiol stated:

Not all night blindness in pregnant women, however, responds to vitamin A. 

WHO. 1995. Physical status: The use and interpretation of anthropometry. Report of a WHO Expert Committee. WHO Technical Report. Series 854. Geneva, World Health Organization stated:

There is no consistent, clear indication in humans of a gender differential in vitamin A requirements during childhood. Growth rates and presumably the need for vitamin A from birth to 10 years for boys are consistently higher than those for girls. 

National Academy Sciences, Food and Nutrition Board, Institute of Medicine. 1990. Nutrition during pregnancy. Part II. Nutrient supplements. p. 336-341. Washington, DC, National Academy Press stated:

In the context of varied cultural and community settings, however, variations in gender-specific child-feeding and care practices are likely to subsume a small gender differential in requirements to account for reported gender differences and prevalence of xerophthalmia. Pregnant and lactating women require additional vitamin A to support maternal and foetal tissue growth and lactation losses, additional vitamin A which is not needed by other post-adolescent adults. 

Risk factors

Mele, L. 1991. Nutritional and household risk factors for xerophthalmia in Aceh, Indonesia: a case-control study. Am. J. Clin. Nutr., and Erdman, J. Jr. 1988. The physiologic chemistry of carotenes in man. Clin. Nutr., 7: 101-106 stated:

VAD is most common in populations consuming most of their vitamin A needs from provitamin carotenoid sources and where minimal dietary fat is available. About 90 percent of ingested preformed vitamin A is absorbed, whereas the absorption efficiency of provitamin A carotenoids varies widely depending on the type of plant source and the fat content of the accompanying meal. Where it is possible to increase dietary fat, this will likely improve the absorption of vitamin A activity from the diet.

Marsh, R.R., Talukder, A., Baker, S.K. & Bloem, M.W. 1995. Improving food security through home gardening: A case study from Bangladesh. In: Technology for rural homes: research and extension experiences . UK, AERDD, University of Reading stated:

In areas with endemic VAD, fluctuations in the incidence of VAD throughout the year reflect the balance between intake and need. Periods of general food shortage (and specific shortages in vitamin A–rich foods), peak incidence of common childhood infectious diseases (diarrhoea, respiratory infections, and measles), and periodic seasonal growth spurts affect the balance. Seasonal food availability can influence VAD prevalence by directly influencing access to pro-vitamin A sources; for example, the scarcity of mangoes in hot arid months followed by the glutting of the market with mangoes during harvest seasons.   

Sinha, D.P. & Bang, F.B. 1973. Seasonal variation in signs of vitamin A deficiency in rural West Bengal children. Lancet, ii: 228–231 stated

Seasonal growth spurts in children frequently follow seasonal post harvest increases in energy and macronutrient intakes. These increases are usually obtained from staple grains (e.g., rice) and tubers (e.g., light-coloured yams) which are not good sources of some micronutrients (e.g., vitamin A to support the growth spurt). 

Mele, L. 1991. Nutritional and household risk factors for xerophthalmia in Aceh, Indonesia: a case-control study. Am. J. Clin. Nutr., 53: 460–1465, 
Johns, T., Booth, S.L. & Kuhnlein, H.V. 1992. Factors influencing vitamin A intake and programmes to improve vitamin A status. Food and Nutrition Bulletin, 14: 20–33, 
Johns, T., Booth, S.L. & Kuhnlein, H.V. 1992. Factors influencing vitamin A intake and programmes to improve vitamin A status. Food and Nutrition Bulletin, 14: 20–33, and 
Zeitlan, M.F. 1992. Mothers' and children's intakes of vitamin A in rural Bangladesh. Am. J. Clin. Nutr., 56: 136–147, according to them:

Food habits and taboos often restrict consumption of potentially good food sources of vitamin A (e.g., mangoes and green leafy vegetables). Culture-specific factors for feeding children, adolescents, and pregnant and lactating women are common. 

Mahadevan, I. 1961. Belief systems in food of the Telugu-speaking people of the Telengana region. Indian J. Soc. Work,, 21: 387–396 stated:

Illness- and childbirth-related proscription of the use of specific foods pervade in many traditional cultures.

Such influences alter short- and long-term food distribution within families. However, some cultural practices can be protective of vitamin A status and they need to be identified and reinforced.

Morbidity and mortality

Sommer, A. 1994. VAD and its consequences: A field guide to their detection and control. 3rd ed. Geneva, World Health Organization, 1994 stated:

The consequences of VAD are manifested differently in different tissues. In the eye, the symptoms and signs, together referred to as xerophthalmia, have a long, well-recognised history and have until recently been the basis for estimating the global burden from the disease. 

Although ocular symptoms and signs are the most specific indicators of VAD, they occur only after other tissues have impaired functions that are less specific and less easily assessed.

Beaton, G.H. 1993. Effectiveness of vitamin A supplementation in the control of young child morbidity and mortality in developing countries. ACC/SCN State-of-the-art Series, nutrition policy discussion paper no. 13. United Nations Administrative Committee on Coordination, Subcommittee on Nutrition. Geneva, World Health Organization and Ghana VAST study team. 1993. Vitamin A supplementation in northern Ghana: effects on clinic attendance, hospital admissions, and child mortality. Lancet, 342: 7–12 stated:

The prevalence of ocular manifestations (i.e., xerophthalmia or clinical VAD) is now recognised to far underestimate the magnitude of the problem of functionally significant VAD. Many more preschool-age children and perhaps older children and women who are pregnant or lactating have their health compromised when they are sub-clinically deficient. In young children, sub-clinical deficiency, like clinical deficiency, increases the severity of some infections, particularly diarrhoea and measles, and the risk of dying.  

Barreto, M.L. 1994. Effect of vitamin A supplementation on diarrhoea and acute lowerrespiratory- tract infections in young children in Brazil. Lancet, 344: 228–231 and Bhandari, N., Bhan, M.K. & Sazawal, S. 1994. Impact of massive dose of vitamin A given to preschool children with acute-diarrhoea on subsequent respiratory and diarrhoeal morbidity. BMJ, 309: 1404-7 stated:

The incidence and prevalenc of diarrhoea may also increase with sub-clinical VAD. Metaanalyses conducted by three independent groups using data from several randomised trials provide convincing evidence that community-based improvement of the vitamin A status of deficient children 6 months to 6 years of age reduces their risk of dying by 20–30 percent on average.  

Mele, L. 1991. Nutritional and household risk factors for xerophthalmia in Aceh, Indonesia: a case-control study. Am. J. Clin. Nutr., 53: 460–1465,
Fawzi, W.W. 1993. Vitamin A supplementation and child mortality. A meta-analysis. JAMA, 269: 898-903,
Glasziou, P.P. & Mackerras, D.E.M. 1993. Vitamin A supplementation in infectious diseases: a meta-analysis. BMJ, 306: 366-70, 
Fawzi, W.W. 1993. Vitamin A supplementation and child mortality. A meta-analysis. JAMA, 269: 898-903.,
Glasziou, P.P. & Mackerras, D.E.M. 1993. Vitamin A supplementation in infectious diseases: a meta-analysis. BMJ, 306: 366-70,
Menon, K. & Vijayaraghavan, K. 1979. Sequelae of severe xerophthalmia: a follow-up study. Am. J. Clin. Nutr., 33: 218-20.
Hussey, G.D. & Klein, M. 1990. A randomised controlled trial of vitamin A in children with severe measles. N. Engl. J. Med., 323: 160–164.
West, K.P. 1997. Impact of weekly supplementation of women with vitamin A or betacarotene on foetal, infant and maternal mortality in Nepal. In: Report of the XVIII International Vitamin A Consultative Group Meeting. p. 86. 22-26 September. Cairo, Egypt.

Mortality in children who are blind from keratomalacia or who have corneal disease is reported to be from 50 percent to 90 percent and measles mortality associated with VAD is increased up to 50 percent. Limited data are available from controlled studies of the possible link between morbidity history and vitamin A status of pregnant and lactating women.

WHO/UNICEF. Indicators of VAD and their use in monitoring intervention programmes. WHO/NUT/96.10. pp. 66. World Health Organization, Geneva, 
Ghana VAST study team. 1993. Vitamin A supplementation in northern Ghana: effects
on clinic attendance, hospital admissions, and child mortality. Lancet, 342: 7–12. 
Barreto, M.L. 1994. Effect of vitamin A supplementation on diarrhoea and acute lowerrespiratory- tract infections in young children in Brazil. Lancet, 344: 228–231.
Bhandari, N., Bhan, M.K. & Sazawal, S. 1994. Impact of massive dose of vitamin A given to preschool children with acute-diarrhoea on subsequent respiratory and diarrhoeal morbidity. BMJ, 309: 1404-7
WHO 1995. The Vitamin A and Pneumonia Working Group. Potential interventions for the prevention of childhood pneumonia in developing countries: a meta-analysis of data from field trials to assess the impact of vitamin A supplementation on pneumonia morbidity and mortality. Bulletin of the World Health Organization. 73: 609–619. Four of them

There are discrepancies in the linkage between incidence and severity of infectious morbidity of various aetiologies and vitamin A status. The weight of evidence supports an association of VAD with severity of an infection once acquired, except for respiratory diseases, which are nonresponsive. 

Hussey, G.D. & Klein, M. 1990. A randomised controlled trial of vitamin A in children with severe measles. N. Engl. J. Med., 323: 160–164 stated:

The severity of the pneumonia associated with measles, however, is an exception because it decreases with treatment with vitamin A supplements. 

Alvarez, J.O. 1995. Urinary excretion of retinol in children with acute diarrhea. Am. J. Clin. Nutr., 61: 1273–1276.
Solomons, N.W. & Keusch, G.T. 1981. Nutritional implications of parasitic infections. Nutr. Revs., 39: 149–161.
Feachem, R.G. 1987. Vitamin A deficiency and diarrhoea: a review of interrelationships and their implications for the control of xerophthalmia and diarrhoea. Tropical Disease Bulletin, 84: R1–R16.

Infectious diseases depress circulating retinol and contribute to vitamin A depletion. Enteric infections may alter absorptive-surface area, compete for absorption-binding sites, and increase urinary loss. 

Stephensen, C.B. 1994. Vitamin A is excreted in the urine during acute infection. Am. J. Clin. Nutr., 60: 388–392.
Thurnham, D.I. & Singkamani, R. 1991. The acute phase response and vitamin A status in malaria. Transactions of the Royal Society of Tropical Medicine and Hygiene, 85: 194-199.
Curtale, F., Pokhrel, R.P., Tilden, R.L. & Higashi, G. 1995. Intestinal helminths and xerophthalmia in Nepal. J. Tro. Pediatr., 41: 334–337.
Sommer, A. & West, K.P. Jr. 1996. Infectious morbidity. In: Vitamin A Deficiency, Health, Survival, and Vision. p.19-98. New York, Oxford University Press.

Febrile systemic infections also increase urinary loss and metabolic utilisation rates and may reduce apparent retinol stores if fever occurs frequently. In the presence of latent deficiency, disease occurrence is often associated with precipitating ocular signs. 

Hussey, G.D. & Klein, M. 1990. A randomised controlled trial of vitamin A in children with severe measles. N. Engl. J. Med., 323: 160–164.
Sommer, A. & West, K.P. Jr. 1996. Infectious morbidity. In: Vitamin A Deficiency, Health, Survival, and Vision. p.19-98. New York, Oxford University Press.
Foster, A. & Yorston, D. 1992. Corneal ulceration in Tanzanian children: relationship between measles and vitamin A deficiency. Transactions of the Royal Society of Tropical Medicine and Hygiene, 86: 54–455.
Arroyave, G. 1961. Serum and liver vitamin A and lipids in children with severe protein malnutrition. Am. J. Clin. Nutr., 1961, 9:180–185.

Measles virus infection is especially devastating to vitamin A metabolism, adversely interfering with both efficiencies of utilisation and conservation. Severe protein-energy malnutrition affects many aspects of vitamin A metabolism, and even when some retinyl ester stores are still present, malnutrition – often coupled with infection – can prevent transport-protein synthesis, that results in immobilisation of existing vitamin A stores.

Ross, C. & Gardner, E.M. 1994. The function of vitamin A in cellular growth and differentiation, and its roles during pregnancy and lactation. In: Allen L, King J., Lönnerdal B, eds. Nutrient Regulation during Pregnancy, Lactation, and Infant Growth. P. 187-200. New York, Plenum Press. 
Eskild, L.W. & Hansson, V. 1994. Vitamin A functions in the reproductive organs. In: Blomhoff R, ed. Vitamin A in Health and Disease. p. 531–559.
Morriss-Kay, G.M. & Sokolova, N. 1996. Embryonic development and pattern formation. FASEB J., 10: 961–968.
Wallingford, J.C. & Underwood, B.A. 1986. Vitamin A deficiency in pregnancy, lactation, and the nursing child. In: Baurenfeind JC, ed. Vitamin A deficiency and its control. p.101–152. New York, Academic Press.
Bates, C.J. 1983. Vitamin A in pregnancy and lactation. Proc. Nutr. Soc., 42: 65–79.
Takahashi, Y. 1975. Vitamin A deficiency and foetal growth and development in the rat. J. Nutr., 105: 1299–1310, they wrote:

The compromised integrity of the epithelium, together with the possible alteration in hormonal balance at severe levels of deficiency, impairs normal reproductive functions in animals.  

Wallingford, J.C. & Underwood, B.A. 1986. Vitamin A deficiency in pregnancy, lactation, and the nursing child. In: Baurenfeind JC, ed. Vitamin A deficiency and its control. p.101–152. New York, Academic Press.
Public Affairs Committee of the Teratology Society. 1987. Teratology society position paper: Recommendations for vitamin A use during pregnancy. Teratology, 35: 269–275.

Controlled human studies are, of course, lacking. In animals and Humans, congenital anomalies can result if the foetus is exposed to severe deficiency or large excesses of vitamin A at critical periods early in gestation (first trimester) when foetal organs are being formed. 

West, K.P. 1997. Impact of weekly supplementation of women with vitamin A or betacarotene on foetal, infant and maternal mortality in Nepal. In: Report of the XVIII International Vitamin A Consultative Group Meeting. p. 86. 22-26 September. Cairo, Egypt.

Reproductive performance measured by infant outcomes in one community-based clinical intervention trial, however, was not influenced by vitamin A status. 

Underwood, B.A. 1994. The role of vitamin A in child growth, development and survival. In: Allen L et al., eds. Regulation during pregnancy, lactation, and infant growth. p. 195-202. New York, Plenum,

The growth of children may be impaired by VAD. Interventions with vitamin A only have not consistently demonstrated improved growth in community studies because VAD seldom occurs in isolation of other nutrient deficiencies that also affect growth and may be more limiting. 

IVACG. 1998. IVACG statement on vitamin A and iron interactions. Washington, DC, International Vitamin A Consultative Group stated that:

A lack of vitamin A can affect iron metabolism when deficiencies of both nutrients coexist and particularly in environments that favour frequent infections.

Suharno, D. 1993. Supplementation with vitamin A and iron for nutritional anaemia in pregnant women in West Java, Indonesia. Lancet, 342: 1325–1328 and Sijtsma, K.W. 1993. Iron status in rats fed on diets containing marginal amounts of vitamin A. Br. J. Nutr., 70: 777–785 stated:

Maximum haemoglobin response occurs when iron and vitamin A deficiencies are corrected together. VAD appears to influence the availability of storage iron for use by haematopoietic tissue.

With all these statements by authors, by which each of them expressed their statements based on their own research and studies they had done, the WHO said:

However, additional research is needed to clarify the mechanisms of the apparent interaction.