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New issues in developing effective approaches for the prevention and control of vitamin a deficiency

Abstract
Introduction
Assessment and analysis
Prevalence
Requirements
Causes of vitamin a deficiency
Consequences of vitamin a deficiency
Supplementation
Fortification
Food-diversification programmes
Using vitamin A capsule programme evaluation to monitor progress in food-diversification and food-fortification programmes
The future
Acknowledgements
References

Martin W. Bloem, Saskia de Pee, and Ian Darnton-Hill

Martin Bloem and Saskia de Pee are affiliated with Helen Keller International in Jakarta, Indonesia. Ian Darnton-Hill is the project director for Opportunities for Micronutrient Interventions (OMNI), a fully US Agency for International Development-funded project managed by John Snow, Inc., in Arlington, Virginia, USA.

Abstract

Even mild to moderate vitamin A deficiency is now recognized as an important factor in child health and survival. This has given increased emphasis to the goal of virtually eliminating vitamin A deficiency and its consequences, including blindness, by the end of the decade. The implications of vitamin A deficiency, however, vary according to the group at risk, and this needs to be addressed when looking at ways to achieve the goal. In preschool children, vitamin A deficiency can lead to increased risk of mortality and morbidity and to blindness. In pregnant and lactating women, it can lead to night-blindness and appears to have implications for maternal morbidity and mortality. Although the immediate health consequences for schoolchildren and adolescents are not completely known, they are probably less dramatic. Nevertheless, it is clear that there is a cross-generational cycle leading to and perpetuating vitamin A deficiency in affected communities. This also has implications when addressing prevention and control strategies. The existing, somewhat successful approach has been to target children aged six months to six years; it is implicit that this criterion is used to measure progress towards the end-of-decade goals. A broader, complementary, life-cycle approach to vitamin A deficiency is now appropriate in many countries. There is increasing emphasis on such approaches, i.e., fortifying foods with vitamin A and improving the diet, which address the whole population at risk. A mix of interventions will give governments the chance to shift from a subsidized vitamin A capsule programme to more sustainable, non-subsidized, consumer-funded vitamin A interventions, although in an appreciable number of countries, supplementation with vitamin A will be a necessity for some years to come. Guidelines to assist governments in such transitions are a high priority.

Introduction

Vitamin A deficiency has been known to be the underlying cause of xerophthalmia for many centuries. The recognition of the clinical signs has obscured the fact that subclinical vitamin A deficiency is prevalent among large segments of the populations of many countries. This deficiency critically affects the health and well-being of these societies, since a series of large intervention trials has shown that even mild to moderate vitamin A deficiency is an important factor in child health and survival [1].

The United Nations, through UNICEF, convened the World Summit for Children in September 1990 to discuss a plan of action for improving the condition of women and children worldwide. Over 70 heads of state ratified a global plan of action, which included 27 social and health goals to be achieved by the year 2000. The plan details how the rights of women and children to adequate and dignified survival and development can be guaranteed. Among the other goals were nutrition goals, including the virtual elimination of vitamin A deficiency and its consequences, including blindness. Two years later, the World Declaration and Plan of Action for Nutrition of the International Conference of Nutrition at Rome in December 1992 reaffirmed the goal of eliminating vitamin A deficiency before the end of the decade.

The question of why, amidst an abundance of plant sources of provitamin A, children still become blind from vitamin A deficiency was first raised by H.A.P.C. Oomen in Indonesia in the early part of this century. Lack of knowledge and lack of care were found to be the major underlying causes. However, it has recently become evident that the bioavailability of provitamin A from plant foods, especially from dark-green leafy vegetables and to some extent also from fruits and tubers, is much lower than what has been assumed [2-4]. In general, currently used food-composition tables overestimate the vitamin A content of dark-green leafy vegetables by a factor of approximately 4 to 6 [3, 4] and that of fruits by a factor of approximately 2 [3]. The degree of overestimation can range from as little as 1 to as much as 15, depending upon several factors, such as the method used for analysing carotene content, the food source of carotenoids, the preparation methods used, and the condition of the child (host) consuming the carotene source. However, whether it is a factor of 3 or a factor of 10, in countries where large segments of the population are dependent on dark-green leafy vegetables as their only source of vitamin A, there will be a high prevalence of subclinical vitamin A deficiency.

The implications of such vitamin A deficiency, however, vary according to the group at risk. In pre-school children, vitamin A deficiency can lead to increased risk of mortality and morbidity and to blindness. In pregnant and lactating women, it can lead to night-blindness and appears to have implications for maternal morbidity and mortality [5]. Although the immediate health consequences for schoolchildren and adolescents are not completely known, they are probably less dramatic (table 1).

The goal of this overview is to consider the implications of recognizing vitamin A deficiency as a potential problem in all age groups of a society rather than solely as a problem of pre-school children. This new paradigm - a life-cycle approach to vitamin A deficiency - will demonstrate the need for new strategies.

Assessment and analysis

The challenge of “virtually eliminating vitamin A deficiency and its consequences” has made governments face the need to determine the existence, severity, and extent of vitamin A deficiency in their populations. The reliability of such assessment depends on the validity and interpretation of the measures of vitamin A status employed. Vitamin A intake should be a leading indicator of vitamin A status at the population level, as a lack of vitamin A in the diet is the main underlying cause of vitamin A deficiency. However, because of the overestimation of dark-green leafy vegetables and fruits as a source of vitamin A, among other limitations, dietary methodology has not proven to be a very useful assessment tool.

Serum retinol levels, although not considered a reliable index of the subclinical vitamin A status of individuals, have proven to be a useful indicator at a population level, thus demonstrating that indicators used for population-based assessment can be of limited value for individual-based assessment but can still be useful for characterizing a population. In contrast to subclinical vitamin A deficiency, which is prevalent in large portions (30%-70%) of affected populations, clinical vitamin A deficiency (xerophthalmia) is clustered in the lowest socio-economic strata of villages and communities in poorer countries. Nevertheless, the prevalence of xerophthalmia can still be used to identify vitamin A deficiency in a population, because a population with an overall high prevalence of xerophthalmia will have an overall high prevalence of vitamin A deficiency. Xerophthalmia can be viewed as the tip of the iceberg for vitamin A deficiency (table 2).

Cut-off points are applied to laboratory findings for individual-based screening to estimate the prevalence of the condition of interest, in this case vitamin A deficiency. The only conventional and widely accepted biochemical criterion for the identification of populations at risk is a prevalence of 5% or more of serum retinol levels less than 10 mg/dl. A serious drawback of this approach is the tendency to regard only individuals below the cut-off as affected, and to focus intervention on those who meet the definition for the indicator, when in fact a much greater proportion of the population is affected. One way to avoid this pitfall is to present the entire distribution of the laboratory findings against a reference or standard distribution (which should be in a population largely free from vitamin A deficiency). The proper application of the prevalence of an indicator below a certain cut-off point is to view its prevalence as an index of the severity of the deficiency in the population.

Prevalence

Vitamin A deficiency is one of the most frequent nutritional deficiency disorders in the world. The World

TABLE 1. Public health implications of vitamin A deficiency according to risk group

Variable	Infants (6-12 mo)	Pre-school children	School-children	Adolescents	Pregnant women	Lactating women
Mortality	+	+	?	+	+	+
Severity of morbidity	-	+	?	?	+	+
Mild anaemia	±	+	+	+	+	+
Growth	?	±	?	?	?	-

TABLE 2. Biological indicators of vitamin A status

Indicator	Infants	Pre-school children	School-children	Adolescents	Pregnant women	Lactating women
Clinical signs	-	+	Night-blindness, Bitot’s spots	Night-blindness?	Night-blindness	Night-blindness
Serum retinol	+	+	+	+	+	+
Breastmilk vitamin A	Indirect indicator?
Vitamin A - related morbidity		+			+	+

Health Organization (WHO) has estimated that over 250 million children worldwide have deficient vitamin A stores [1]. The highest prevalence of vitamin A deficiency is found in pre-school children and in pregnant and lactating women, but subclinical vitamin A deficiency has also been shown to be common in school-children and adolescents in some settings. Almost all country prevalence data relate to vitamin A deficiency in pre-school children, which means that prevalence data from other age groups are frequently not available (table 1).

Requirements

Vitamin A is the generic term for all compounds that have the biological activity of retinol. In animals vitamin A exists largely in the preformed state as retinol or as its related compounds. In plants vitamin A occurs in the precursor or provitamin forms as carotenoids, which animals convert into preformed vitamin A after consuming them in the diet. The most widely distributed carotenoid is b-carotene. The relative amounts of vitamin A consumed as provitamins from plant sources and as preformed vitamin A from animal sources differ considerably in various parts of the world (table 3). In the average Western diet, about half of the vitamin A activity comes from plant carotenes. The remainder of the dietary vitamin A is obtained as preformed vitamin A from animal sources. In much of the developing world, up to 90% of the vitamin A in the diet is of plant origin. Sources of the provitamin A carotenoids include dark-green leafy vegetables, deep-yellow vegetables, and deep-yellow fruits. Sources of preformed vitamin A include liver, fish liver oil extracts, and egg yolks.

The apparent vitamin A activity of plant foods was recently been found to be much lower than had been assumed [2,3]. An intervention study among school-children in Indonesia found that the apparent vitamin A activity of leafy vegetables and carrots was 23% of what had been assumed (95% confidence interval, 8% to 46%), and that the vitamin A activity of fruits was 50% of what had been assumed (95% confidence interval, 21% to 100%) [3]. These proportions were confirmed in a recent intervention study among breastfeeding women in Vietnam [7]. Vitamin A from plant sources largely comes from leafy vegetables and to a much smaller extent from roots, tubers, and fruits. In fact, recent analysis of cross-sectional data from women in Indonesia confirmed that the apparent vitamin A activity of plant foods was 16% to 23% of what had been previously assumed [4]. Therefore, we have chosen a factor of approximately five for adjusting vitamin A intake from plant foods.

TABLE 3. Available supply of vitamin A according to WHO region

Region	Vitamin A (mg RE/day)a			Incidence of xerophthalmia
	Vegetable	Animal	Total
South-East Asia	378 (75)	53	431 (128)	1.45
Africa	654(130)	122	776 (255)	1.04
Western Pacific	781 (156)	216	997 (372)	0.13
Eastern Mediterranean	591(118)	345	936 (463)	0.12
Americas	519 (104)	295	814(400)	0.06

Source: ref. 6.

a. Numbers in parentheses are adjusted for bioavailability.

Table 3 shows the vitamin A intake and the xe-rophthalmia rates by region. The gross figures do not show a significant correlation between the total vitamin A intake and reported rates of xerophthalmia (Spearman rank test, R=.60, p=.285). However, the adjusted vitamin A intake for the new conversion factor correlates significantly with the prevalence rates of xerophthalmia (Spearman rank test, R=.90, p=.038).

Causes of vitamin a deficiency

Figure 1 shows the conceptual framework of the causes of vitamin A deficiency. The conceptual framework of the causes of xerophthalmia is in principle the same. However, the role of contributing factors such as infection and protein-energy malnutrition is more important. The main causes of vitamin A deficiency in the developing world are insufficient intake of vitamin A and poor bioavailability of provitamin A sources (vegetables and fruits). Important contributing factors to vitamin A deficiency are the increased requirements for vitamin A at certain stages in the life cycle (early childhood, pregnancy, and lactation) and during infection.

However, this simplified list does not address the many varied physiological, sociocultural, and geographic factors that also define the vitamin A status of a population. The conceptual framework clearly shows the role of the contributing factors. Coexisting health status affects vitamin A status both by affecting the metabolic processes and by reducing intake. The clustering of xerophthalmia, now widely described, points to the importance of sociocultural factors such as intrahousehold distribution. The different prevalence in boys and girls points to the impact of sex and intrahousehold distribution of food.

FIG. 1. Conceptual framework of causes of vitamin A deficiency

Consequences of vitamin a deficiency

Vitamin A deficiency and child mortality

Irreversible blindness is among the most dramatic consequences of vitamin A deficiency. As a result, there has been considerable emphasis on xerophthalmia, the eye changes due to vitamin A deficiency, and the most visible consequences of vitamin A deficiency. Nutritionists have tended to consider xerophthalmia a problem for those working in blindness prevention, whereas those involved in blindness prevention have considered it a problem for nutritionists. More recently, though, on the basis of the work of Sommer and others, vitamin A has become recognized as having an essential role in the prevention of childhood mortality and disability [1].

A series of eight controlled, community-based trials has been carried out since the first trial in Aceh [8-15]. Findings from all these trials were submitted to a comprehensive meta-analysis on the effectiveness of vitamin A supplementation in reducing child morbidity and mortality [16]. The reported impact has ranged from a 50% reduction in mortality rates among children under five years of age (Tamil Nadu) to no effect (Sudan). The meta-analysis, which included 8 of 10 formal field trials, showed a 23% reduction in mortality (95% confidence interval, 15% to 29%) for children aged 6 to 72 months. Estimated 95% confidence intervals were established under two models: a fixed effects model (R =.77; 95% confidence interval, .71 to .84) and a random effects model (R =. 77; 95% confidence interval, .68 to .88).

Adequate vitamin A status prevents nutritional blindness and contributes significantly to child health and survival. Vitamin A plays an important role in preventing nutritional blindness and in reducing morbidity and mortality, from mid-infancy through the early school-age years, particularly from measles and diarrhoea.

Vitamin A deficiency and morbidity

The various studies on the association between vitamin A deficiency and morbidity have not had very consistent results [17-26]. This maybe explained by the fact that morbidity studies are hard to carry out. Under-and overreporting, differences in definitions and severity, and differences in underlying factors such as malnutrition make these studies more difficult than studies on mortality, which have, among other things, the clearly defined end point of death. However, the lack of findings cannot be attributed only to poor methods, since studies of the effects of improvements in water supplies and excreta disposal were able to detect a reduction of 22% in morbidity rates using similar methods.

Increased morbidity and mortality occur at levels of vitamin A deficiency less severe and chronic than those required for night-blindness and xerophthalmia. Therefore, the definition of vitamin A deficiency for public health purposes must be revised and made more sensitive to milder degrees of deficiency.

Vitamin A deficiency and measles

Measles deserves separate consideration because it is a viral disease that infects and damages epithelial tissues throughout the body, and because it has been shown that measles plays an important role in corneal blindness. A relationship between measles and vitamin A has been recognized since the early 1930s [27]. It is now well known that measles can bring serum concentrations of vitamin A in well-nourished children to below those observed in non-infected malnourished children. Mean serum retinol levels have been shown to be significantly lower in children with corneal lesions than in those with normal corneas. Several studies have evaluated the treatment of severe measles with vitamin A [27-29]. In these trials, mortality was at least 50% lower among children who had been treated with large doses of vitamin A at admission. In each trial, the clinical severity of measles complications was lower among those who survived.

Vitamin A deficiency increases the severity, complications, and risk of death from measles. Improving vitamin A status before the onset of measles (prophylaxis), or after measles occurs (treatment), markedly reduces the severity of complications and associated mortality. Improving the vitamin A status of children with vitamin A deficiency and treating all cases of measles with vitamin A, even in populations in which xerophthalmia is rare, can substantially reduce childhood disease and mortality.

Vitamin A deficiency and women

Although vitamin A deficiency is a serious and dangerous deficiency in childhood, it has recently been recognized that its impact goes well beyond this age group. Publications from Indonesia and Malawi, and now Nepal, have shown that vitamin A deficiency in pregnancy is associated with anaemia, low vitamin A content of breastmilk, transmission of the human immunodeficiency virus (HIV) from mother to child [30-32], and probably a reduction in maternal mortality [5]. Stoltzfus et al. [31] showed that a high dose of vitamin A was an efficacious way to improve the vitamin A status of both mother and child. Suharno et al. [30] demonstrated the extent to which improvement in vitamin A status contributes to the treatment of anaemia in pregnancy. Semba et al. [32] showed that the mean vitamin A status of mothers who transmitted HIV to their infants was lower than that of mothers who did not transmit HIV. These reports are of less public health importance when vitamin A deficiency in women is not very prevalent. A recent analysis from Bangladesh, however, showed that the prevalence of night-blindness among mothers was even higher than among pre-school children. Children of mothers with night-blindness showed a statistically significant increase in morbidity after potential confounding factors had been controlled [33]. Similar results have been reported in Nepal [34,35]. A recent study by West et al. [12] showed that vitamin A or b-carotene supplementation to pregnant women may reduce maternal mortality by up to 50%.

It is well recognized that vitamin A deficiency clusters in households and is more likely to occur in siblings, and that children from the same household exhibit similar vitamin A status. It is, therefore, not surprising that this cluster effect extends to other vulnerable family members, notably women of reproductive age. It takes one to two years for a healthy adult to show signs of vitamin A deficiency, thereby making it likely that many of these mothers have been nutritionally compromised since their early childhood. In life-cycle terms, this means that young girls are starting out with low liver stores of vitamin A and never have a chance to catch up. By the time they are 18 and married, they too will give birth to children with low vitamin A stores. These children, a majority of whom are breastfed exclusively for the first months of life, then complete the generational cycle of vitamin A deficiency. Older and malnourished women in such societies have also been found to be at risk for night-blindness, which reinforces the above-mentioned hypothesis and emphasizes the need to take a life-cycle approach to vitamin A deficiency.

Vitamin A deficiency is prevalent among women in areas where vitamin A deficiency is endemic. Vitamin A deficiency in women has negative effects on the health status of both mothers and their offspring. Therefore, programmes should be developed to improve the vitamin A status of women, starting in early childhood and continuing during the reproductive years, for the sake of both their own and their children’s health. Vitamin A interventions in pregnant women may reduce maternal mortality by up to 50%.

Vitamin A deficiency and anaemia

Vitamin A and its derivatives are important not only for the normal functioning of the eye but also for the normal differentiation of other cell systems in the body, including parts of the haematological system. Arrays of epidemiological studies have indicated that vitamin A deficiency and anaemia often coexist, and that there are significant associations between serum retinol and biochemical indicators of iron status [36-44]. A study of pregnant Indonesian women showed that 100% of the anaemic women were cured by combination therapy of vitamin A with iron, whereas only 40% were cured by vitamin A alone and only 60% by iron alone [40]. This clearly has important programmatic and policy implications. Recent work from Nepal by Stoltzfus et al. [45] showed that vitamin A supplementation improved only mild anaemia, and only in those women who were not infected by worms.

Improvement of iron status, when combined with vitamin A supplementation, will have an even greater impact on the prevalence of anaemia than the separate application of only one of these strategies. Vitamin A deficiency should be tackled by a combination of strategies, including dietary diversification, food fortification, vitamin A supplementation, and other public health measures such as promotion of breastfeeding and control of infectious disease, to achieve the virtual elimination of vitamin A deficiency (table 4).

Supplementation

The rationale for supplementation with high doses of vitamin A (retinol) rests on the fact that this fat-soluble nutrient can be stored in the body, principally in the liver. Periodic high-dose supplementation is intended to protect against vitamin A deficiency and its consequences by building up a reserve of the vitamin for periods of reduced dietary intake or increased needs [46].

TABLE 4. Strategies to combat vitamin A deficiency according to risk group

Strategy	Infants (0-6 mo)	Pre-school children	School-children	Adolescents	Pregnant women	Lactating women
Breastfeeding	++	+
Universal distribution of high-dose vitamin A	±	+	Not yet	Not yet	-	Postpartum
Low-dose vitamin A	+	+	+	+	+	+
Food-based	-	+	+	+	+	+
Fortification	+	+	+	+	+	+

High-dose vitamin A supplements for pre-school children, lactating women, and high-risk populations

The human liver has an enormous capacity to store vitamin A, allowing sufficient stores in the body to be laid down through periodic administration of large doses of the vitamin. The dose of vitamin A must be large enough to offer protection but not so large as to produce side effects. For individuals one year of age and older, administration of 200,000 IU (approximately 60,000 mg) of vitamin A will provide adequate protection for four to six months. There is now considerable experience with vitamin A supplementation programmes in countries such as Bangladesh and India, and they are known to be effective and safe. When vitamin A is administered in recommended doses, there are no serious or permanent adverse effects; such side effects as may occasionally occur (e.g., for infants, a tense or bulging fontanelle or vomiting) are minor and transitory and do not require specific treatment [46].

All mothers in high-risk regions should also receive a high dose of vitamin A within eight weeks of delivery. The capsule should be delivered as soon as possible after delivery, since this will increase the vitamin A levels in breastmilk [31]. It now appears this may also have beneficial effects for the mother herself [5].

Infants and children who have infections such as diarrhoea, measles, respiratory infections, and chickenpox or who are severely malnourished have an increased risk of vitamin A deficiency. Furthermore, work from Bangladesh, Indonesia, and Nepal has shown that severe vitamin A deficiency is clustered. It is, therefore, recommended that these children receive a high dose of vitamin A.

Low-dose vitamin A supplementation

Both severe vitamin A deficiency and excessive vitamin A are teratogenic in animals, although this observation has not been confirmed in humans. Adequate maternal vitamin A status ensures protection from the adverse consequences of either too much or too little vitamin A for the mother, foetus, and newborn [47]. Where habitual vitamin A intakes are low, a pregnant woman and her developing foetus are expected to benefit without risk from a daily vitamin A intake of 10,000 IU or a weekly intake of 25,000 IU from diet or supplementation or a combination of both. It has been suggested by Underwood and others (e.g., at the International Congress of Nutrition in Montreal in 1997) that these somewhat more physiological doses may have an added advantage over the high-dose regimens. A weekly dose was the method used in a recent study in Nepal showing an impact of both vitamin A and carotene separately on maternal mortality [5]. This also suggests that the form of the supplement may be relevant.

Fortification

Micronutrient interventions, particularly fortification, have been identified by the World Bank as among the most cost-effective of all health interventions [48]. There is a wealth of experience in the fortification of foods, and it has been a major factor in the control of micro-nutrient deficiencies in the industrialized world [49]. Until recently it was presumed that fortification was not a suitable intervention in the less industrialized countries, as the experience in developing countries has not always been encouraging [50]. There are now enough successful examples to suggest this is no longer true. Mora and Dary* list 17 countries in Latin America that now fortify with at least one micronutrient and sometimes more.

*Mora JO, Dary 0. Strategies for prevention of micronutrient deficiency through food fortification. Lessons learned from Latin America. Presented at the 9th World Congress of Food Science and Technology, Budapest, Hungary, 1995.

Vitamin A fortification has been important in reducing deficiencies of vitamin A, especially in Latin America, where sugar is fortified. Other vehicles have included fats and oils, tea, cereals, monosodium glutamate and instant noodles, as well as milk and milk powder, whole wheat, rice, salt, soya bean oil, and infant formulas [51]. For example, margarine is currently fortified with vitamin A in Brazil, Chile, Colombia, El Salvador, Mexico, the Philippines, and other countries around the world, including virtually all developed countries. In India red palm oil is added to other edible oils, and vitamin A-fortified soya bean oil is being tested in Brazil [52].

The most successful experience with vitamin A, outside the industrialized world where margarine and milk have been most important, is with sugar in Central and South America. Sugar was first fortified in Guatemala over 25 years ago. Despite the demonstrated success of the programme in the early 1970s, with increases in the status of recipients’ vitamin A levels and, indirectly, haemoglobin levels, the programme faltered in the 1980s [53]. This was due to a lack of continuing government commitment, indifference from the producing sector, economic limitations, and, presumably, a lack of self-sustainability (in terms of passing on costs, etc.), so that it could not continue without some public-sector involvement. It has now been revitalized, although some technical improvements are still needed. In a start-up programme in Bolivia, in a partnership between government, donors (US Agency for International Development/OMNI, UNICEF), and a commercial firm, sustainability has yet to be assured, although there are currently plans for scaling up nationally by the private sector. Sugar has been fortified with vitamin A in Costa Rica, El Salvador, Guatemala, Honduras, and Panama [51]. Zambia has reached agreement to fortify its sugar in 1998. Other countries, such as the Philippines and Uganda, are also interested.

An interesting programme using whole wheat was developed in Bangladesh with technical assistance and support from the US Agency for International Development through Helen Keller International. Wheat being the less preferred staple, the fortification programme would have been automatically targeted to the poor. It became, however, an example of a technically feasible, properly developed programme that failed politically because it did not adequately involve the policy makers and those most affected [54]. The Philippines is currently testing vitamin A fortification of wheat flour.

In both Indonesia and the Philippines, fortifying monosodium glutamate (MSG) with vitamin A had been shown to be technically feasible and had been properly developed by consumption, taste, and impact trials [55, 56]. It did not proceed because of a variety of technical, political, and food-industry reservations. Fortification of rice and other cereals is also technically feasible as a pilot, but the fortification of rice with vitamin A has not proceeded to the national level. In Brazil it is still at the stage of bioavailability testing [51]. In Venezuela, on the other hand, pre-cooked corn flour, used to make arepas, a staple food in the national diet, has been successfully fortified with vitamin A, iron, thiamine, riboflavin, and niacin [57].

Success in fortifying with vitamin A has depended on sustained political commitment (both in-country and, initially, by donors), persistence with technical development of fortificant technologies to overcome problems, and increased awareness of the health consequences of vitamin A deficiency by governments as well as involvement of the private sector. It has, however, now been shown to be effective in a variety of settings [51-53, 58].

Food-diversification programmes

Since inadequate intake of vitamin A is the main cause of vitamin A deficiency, the solution lies in providing adequate amounts of the vitamin to populations at risk. Vitamin A in foods consists of provitamin A sources and preformed vitamin A sources. Foods containing preformed vitamin A are expensive and beyond the regular reach of the poor, but alternative, less expensive sources of provitamin A are easily available. Home gardening is a traditional family food production system widely practised in many developing countries [59-61].

Despite this, vitamin A deficiency remains a public health problem in many of these countries. Provitamin A carotenoids are the major source of dietary vitamin A, with plant sources providing more than 80% of the total vitamin A intake. The intervention studies mentioned above have shown that leafy vegetables and carrots improve vitamin A status, but not as much as previously thought [3]. Fruits, including pumpkin and sweet potato, improve vitamin A status more than vegetables. This, the lower bioavailability of vitamin A in vegetables and fruits, and probably also the seasonal variability of production of vegetables and fruits in home gardens, are factors underlying the causes of vitamin A deficiency in these regions. However, vegetables and fruits are more than a possible source of vitamin A; the various carotenoids and other micronutrients they contain are important, because consumption of vegetables and fruits is associated with lower risk of degenerative diseases. A recent study in Nepal also showed that b-carotene had an effect on reducing maternal mortality, which is not the case for vitamin A [5].

It is, therefore, essential to maximize the effectiveness of home gardening as a strategy to combat vitamin A deficiency. Anecdotal experience suggests that home gardening (as a method of improving nutrition) has been generally successful at the pilot phase but has not often been scaled up successfully. Recent experience in Bangladesh, however, has demonstrated a successful example [60]. The International Union of Nutritional Sciences (IUNS) Committee II/B Food Gardening for Nutrition Improvement has made the following recommendations:

» Diversify food production

- Where possible, include orange fruits, roots, and tubers;
- Where possible, introduce animal husbandry, such as poultry and fish;

- Deworming;

- Providing zinc supplements (which may improve carotene bioconversion, but this needs further research);

- Maximizing nutrient intake and reducing the effect of matrix and absorption inhibitors by choice of foods and choice of preparation methods;

- Using techniques of breeding, selection, and genetic engineering to improve carotene content and bioavailability.

Using vitamin A capsule programme evaluation to monitor progress in food-diversification and food-fortification programmes

For two decades now, at least four countries in South-East Asia (Bangladesh, India, Indonesia, and Vietnam) have had programmes implementing universal supplementation of vitamin A capsules, which, according to the World Bank, is one of the most cost-effective of health interventions. Although prophylactic vitamin A dosing does not address the underlying cause of vitamin A deficiency, the nutritional aim is to improve vitamin A status for several months by increasing liver stores and tissue concentrations of retinol, thereby reducing the risk and severity of vitamin A deficiency and its devastating sequela of blindness, as well as reducing the increased morbidity and mortality from infectious diseases as a consequence of vitamin A deficiency, while minimizing the risk of acute hypervita-minosis A.

Several studies have shown that high-potency vitamin A supplementation has an efficacy of 90% under controlled circumstances [62-65]. The reasons that the efficacy of vitamin A capsules is not 100% may be an inability of 200,000 IU to protect individuals who are at particularly high risk (repeated infections, virtual absence of dietary sources, or severe deficiency initially) for the full six months or programme-related issues (inadequate administration, misrecording, or partial delivery of the intended dose). The likely cause of early recurrence of vitamin A deficiency after a high-dose vitamin A capsule is poor dietary intake of vitamin A combined with infectious diseases.

Since the efficacy of vitamin A capsules is 90%, the effectiveness will reflect differences in programme performance under “real-life” circumstances. The theoretical effectiveness, or the expected reduction, is the product of efficacy and coverage. Two recent studies in the region studied the effectiveness of vitamin A capsule programmes [64,65]. A study from Bangladesh found an effectiveness of 25%, with coverage of 48% in rural areas, and a higher effectiveness of 61%, with coverage of 93% in urban areas. The expected reductions under these circumstances were 90% × 48% = 43% and 90% × 93% =83%, respectively [1]. The lower effectiveness is most probably due to the low dietary vitamin A intake and high rate of infectious disease among pre-school-aged children in Bangladesh. The effectiveness of the vitamin A capsule programme was associated with the time lag between the distribution of the capsule and the moment of measurement of the impact. This implies that vitamin A supplementation would be more effective when given every four months.

During the past 10 years, substantial progress has been made, particularly in reducing the prevalence of vitamin A deficiency. The analysis of both the Bangladesh and Vietnam experiences showed that in terms of high effectiveness (Vietnam) or of a high time-response effectiveness (Bangladesh), the reduction in vitamin A deficiency in those countries has been mainly an effect of the vitamin A capsule programme, and that the underlying problem of lack of vitamin A in the diet (through fortification or through foods in the diet) has still not been solved. The governments, however, are now in the process of phasing out the vitamin A capsule programme, because the national prevalence of vitamin A deficiency is currently below the level that has been used to define the existence of a public health problem.

As the intake of vitamin A-rich sources in the diet increases as a result of fortification, changing diets, or both, the efficacy of vitamin A capsule supplementation will decrease (in Europe there is no impact of vitamin A supplementation on morbidity, mortality, or blindness). As a consequence, the effectiveness of the vitamin A capsule programme will decline with maintained coverage rates. Measuring the effectiveness of vitamin A capsules is much simpler than measuring the shift in a variety of fortified products or natural sources of vitamin A. Work is currently under way to measure the relative cost-effectiveness of different interventions. In the past, sustainability has not always been factored in, nor has the changing burden of costs (moving from donors to consumers).

The future

Several countries (Indonesia, India, and the Philippines) have made serious progress, at least at the national level, in eliminating xerophthalmia. All still have significant problems with vitamin A deficiency, as detected by serum retinol surveys. It is known that this must be having an impact on both morbidity and mortality of young children. However, it is likely that schoolchildren, adolescents, and women (especially pregnant and lactating women) will also show signs of vitamin A deficiency upon examination. The previous, largely successful approach has been to address children six months to six years of age (and it is implicit that this is the criterion being used to measure progress towards the end-of-decade goals). It is becoming clear that a broader, complementary life-cycle approach to vitamin A deficiency is now appropriate in many countries.

Over the last few years, there has been increasing emphasis on approaches such as fortifying foods with vitamin A and improving the diet of the population at risk. A mix of interventions will give governments the chance to shift from a subsidized vitamin A capsule programme to more sustainable, non-subsidized, consumer-funded vitamin A interventions. In an appreciable number of countries, supplementation with vitamin A will be a necessity for some years to come. Nevertheless, governments are seeking guidelines for phasing out the vitamin A capsule programme when fortification and other approaches emerge. Monitoring food-based strategies and fortification programmes is much more costly and perhaps not very cost-effective. Guidelines to assist governments in such transitions are a high priority.

Acknowledgements

This publication was made possible through support provided by the Office of Health and Nutrition, Bureau for Global Programs, Field Support and Research, US Agency for International Development, under the terms of contract no. HRN-5122-C-00-3025-00. The opinions expressed herein are those of the authors and do not necessarily reflect the views of the US Agency for International Development.

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