Adequate intake of nutritious foods is a prerequisite to achieving and maintaining good health and well-being. Millions of people worldwide, however, are unable to achieve this. An estimated 852 million people do not eat sufficient food to meet their energy requirements and are consequently undernourished. Many more people suffer from ‘hidden hunger’: 150 million are vitamin-A-deficient, almost 2 billion are iodine-deficient, between 4 and 5 billion are iron-deficient¹ and about 2.7 billion are zinc-deficient². This imbalance between ‘overt’ and ‘hidden’ hunger is underlined in the report of the United Nations Millennium Project's Task Force on HungerReference Sanchez and Swaminathan³, where the authors call for further investments in agriculture and confirm the major role that agricultural research has played in reducing hunger. Indeed, the advent of the Green Revolution in the 1960s – in which high-yielding crop varieties were introduced and combined with more intense use of inputs, such as irrigation and agrochemicals – was instrumental in increasing the food supply in developing countries. The general concern today is less about whether there is sufficient food in the world, but rather how to distribute and ensure access for those in need without compromising their independence, self-reliance and dignity.Footnote †

Historically, the control of micronutrient malnutrition has been under the domain of public health, rather than agriculture, despite the same underlying cause: an inadequate intake of a balanced diet. This was because clinical deficiencies were widespread and control was driven by the medical model that focused on the provision of therapeutic and preventive pharmaceutical supplements, such as iron or iron–folate tablets to pregnant women or of vitamin A capsules to older infants and young children. More recently food fortification has come to the fore: for example, salt iodisation; flour fortification with iron; and fortification of sugar and cooking oil with vitamin A.

Pharmaceutical supplementation and food fortification gained acceptance as viable options once it was deemed they were very cost-effective^25–Reference Horton⁷. Yet, as with all interventions, impact depends on coverage. The further the programme is from urban centres and the more it targets people at the margin of society, the more difficult and expensive it is to increase coverage². Rural people, and to a certain extent the urban poor, tend to eat less processed food; thus they are often not reached by food fortification programmes, especially where both the food industry and food market infrastructure are immature. Likewise, a weak health infrastructure coupled with discrimination can limit the effectiveness and efficiency of pharmaceutical supplementation programmes. Moreover, both fortification and supplementation programmes require financial commitment year on year, either directly by the government or donors, or indirectly through voluntary measures (e.g. donated labour/time or absorbing the marginal cost of fortification) or higher prices for fortified foodstuffs. Monitoring the fortificant levels in food or the coverage of either programme imposes additional administrative burdens.

Because micronutrient malnutrition is the consequence of a lack of access to adequate quality food and the existing interventions are not easy to implement in all areas, a new initiative was started recently in which food quality is recognised as an important agricultural objective. The means to fulfil this objective includes breeding crops – notably staple foods – both for higher yields and higher micronutrient content, an approach known as ‘biofortification’Reference Bouis^8, Reference Welch and Graham⁹. This approach has multiple advantages, including the fact that it capitalises on the regular daily intake of a consistent amount of food staple by all family members, and, because staple foods predominate in the diets of the poor, this strategy implicitly targets low-income householdsReference Nestel, Bouis, Meenakshi and Pfeiffer¹⁰. Biofortification also provides a feasible means of reaching micronutrient-deficient populations in relatively remote rural areas. (For example, subsequent to the introduction of modern wheat varieties to India in the mid-1960s, adoption rates exceeded 70% within 10 yearsReference Heisey, Lantican and Dubin¹¹.) Thus biofortification can deliver naturally fortified foods to people with limited access to commercially marketed fortified foods that are more readily available in urban areasReference Nestel, Bouis, Meenakshi and Pfeiffer¹⁰. Because farmers will not adopt new crops unless they provide an agronomic and/or economic advantage, the strategy is to introduce high zinc content as a standard trait for releases of new varieties (that have desirable agronomic properties) or to introduce the zinc-rich trait into new releases of popular varieties. As such, there will be only marginal costs for distribution and marketing.

Zinc deficiency (ZnD) is one of the five leading risk factors that contribute to the burden of disease in developing countries with high mortality rates². Despite this, the extent and severity of ZnD have not received the attention given to others, notably iodine, iron and vitamin AReference Hotz and Brown^{12, 13}, largely because of the difficulty in measuring zinc status. With a better understanding of the consequences of ZnD and the development of proxy indicators for deficiency, concerted efforts are now being made to control ZnD. One of these is to breed crops for higher zinc content, a goal of the HarvestPlus programme.Footnote *

To provide a common framework for estimating the effectivenessFootnote † and cost-effectiveness of zinc biofortification, and to compare biofortification with conventional fortification and pharmaceutical supplementation programmes, Stein et al. Reference Stein, Meenakshi, Qaim, Nestel, Sachdev and Bhutta¹⁴ developed a model based on disability-adjusted life years (DALYs). This model can be used to measure both the current burden of ZnD and the likely impact of biofortification, and it also enables economic analyses of the related costs and benefits. The present paper reports the outcome of the first application of this framework, to the introduction of zinc-rich wheat and zinc-rich rice in India to control ZnD. Because the specific varieties are still at the stage of research and development (R&D), the analysis is necessarily carried out as an ex-ante study.

The International Zinc Nutrition Consultative GroupReference Hotz and Brown¹² estimates that 26% of the Indian population is at risk of inadequate zinc intakes. Clearly ZnD in India is a public health problem that warrants a detailed analysis, and the present paper starts with this. It then goes on to show the potential impact of zinc biofortification on the burden of ZnD in India. The focus is on wheat and rice given that India is divided into predominantly wheat-eating and rice-eating states (Fig. 1¹⁵).

Fig. 1 Average per capita consumption of cereals (kg month^− 1) in rural India, per state, 1999/2000¹⁵ (P. – Pradesh; D & N – Dadra and Nagar; J & K – Jammu and Kashmir)

A ‘recommended action’ of the World Health Report² is that ‘cost-effectiveness analyses should be used to identify high, medium and low priority interventions to prevent or reduce risks, with highest priority given to those interventions that are cost-effective and affordable’ (p. 11). Therefore, in the third and final step, the cost-effectiveness of zinc biofortification is analysed. The latter is significant because biofortification is proposed as a complementary intervention to conventional fortification and preventive pharmaceutical supplementation; thus it is important to know whether biofortification uses scarce resources as efficiently as the existing interventions.

Methods

The burden of ZnD in India was quantified using the DALY method, in which morbidity is assigned a weight and combined with information on mortality to give a common measure of ill healthReference Stein, Meenakshi, Qaim, Nestel, Sachdev and Bhutta^14, Reference Murray and Lopez^16, Reference Zimmermann and Qaim¹⁷. Four per cent of all under-fives mortality can be prevented if all children have sufficient intakes of absorbable zincReference Jones, Steketee, Black, Bhutta and Morris¹⁸. The known adverse health outcomes from ZnD that do not necessarily result in death are diarrhoeaReference Bahl, Baqui, Bhan, Bhatnagar, Black and Brooks^19, Reference Bhutta, Bird, Black, Brown, Gardner and Hidayat²⁰, pneumoniaReference Bhutta, Black, Brown, Gardner, Gore and Hidayat²¹ and stuntingReference Brown, Peerson, Rivera and Allen²². The target groups for these conditions included both infants (below 1 year of age) and children (1–5 years of age). The incidence rates, disability weights and durations used for each condition are shown in Table 1Reference Stein, Meenakshi, Qaim, Nestel, Sachdev and Bhutta^{14, 23, 24}. To derive the remaining life expectancy in the case of child mortality and for duration of stunting, which was considered a permanent condition, standard life tables for India were used²⁵. The size of the target groups were taken from Census of India data^{26, 27}.

Table 1 Data used to calculate disability-adjusted life years lost due to ZnD in India

ZnD – zinc deficiency; N/A – not applicable.

* Fraction of target group that experiences the health outcome.

† Extent of disability that is caused by the health outcome (perfect health corresponds to a weight of 0, death to a weight of 1).

Source: reference 14, ‡reference 23, §reference 24.

The 55th survey of the Indian National Sample Survey Organisation¹⁵ – which is a representative survey that included 120 000 households – was used to compute zinc intakes. Household-level data on the quantities and volumes of the foodstuffs and beverages consumed in the preceding month were multiplied by their respective zinc content using Indian food composition tablesReference Gopalan, Rama Sastri and Balasubramanian²⁸.Footnote * For the few foods for which national composition values were not available, the corresponding zinc values in the US food composition table were used²⁹; given the small number of less important food items concerned, a potential bias because of underlying differences in the zinc content of the soil is expected to be insignificant. The survey data for household composition and the energy requirements of IndiansReference Gopalan, Rama Sastri and Balasubramanian²⁸ in different age and gender groups were used to compute the zinc intake per adult equivalent in each household (i.e. the assumption is that there is no general, nationwide and persistent bias in the distribution of food within the householdsReference Behrman^30, Reference Behrman and Deolalikar³¹). The estimated zinc intake of individual household members was then calculated as a proportion of the adult equivalent.

Future consumption of biofortified wheat and rice will lead to higher zinc intakes and reduce the incidence of deficiency-related health conditions. To anticipate changes in zinc intakes, the food composition values of zinc for wheat and rice were replaced with the assumed increases in zinc contents through biofortification; the latter were used to derive projected zinc intakes. As neither biofortified wheat nor biofortified rice has been released, the projected increases in zinc contents were estimated by the plant breeders at the International Rice Research Institute and the International Maize and Wheat Improvement Centre based on the variation in zinc concentrations found in the germplasm screening. The plant breeders and other experts also estimated potential coverage rates for both crops 20 years after release (Fig. 2). Because of the multiple sources of uncertainty arising from these estimations, an optimistic–pessimistic scenario approach was chosen (Table 2) to increase the reliability of the resultsReference Walker and Fox-Rushby³²; for the potential coverage rate, a further sensitivity analysis was carried out to determine the lowest bound at which zinc biofortification can still be considered cost-effective.

Fig. 2 The time frame and adoption rates for the analysis of zinc biofortification (for the example of zinc-rich wheat). *The assumption is that some of the advanced lines released by the International Rice Research Institute and the International Maize and Wheat Improvement Centre are suitable for immediate cultivation in India. Additional biofortified varieties are then released in the course of the country-specific activities. It is also assumed that the varieties with the biggest potential coverage are adapted first. Also see Tables 2 and 3 (R&D – research and development; act. – activities)

Table 2 Assumptions about the success of zinc biofortification of wheat and rice

PPM – parts per million.

Source: *I Ortiz-Monasterio and †G Barry (personal communication, 2006).

Current zinc intakes together with the potential zinc intakes from biofortified wheat and rice (which were simulated based on the food consumption data, the food composition information and the expected zinc content in wheat and rice; Table 2) and the estimated average requirements for zinc for individuals consuming unrefined, cereal-based dietsReference Hotz and Brown¹² were used to calculate separate efficacy ratios at the individual level for both scenarios. These efficacy ratios are based on the notion that a given absolute increase in zinc intake will have a bigger impact on the health of a very deficient individual than on the health of an almost sufficient individual: the more deficient a person is, the higher the efficacy of a given increment in zinc intakeReference Stein, Meenakshi, Qaim, Nestel, Sachdev and Bhutta¹⁴. To calculate new incidence and mortality rates, mean efficacy ratios were derived for the target groups. These new rates were used to recalculate the burden of ZnD in India with biofortification for the two scenarios. The difference to the number of DALYs lost in the status quo is the impact of biofortification.

Finally, the number of DALYs that could be saved through biofortification was juxtaposed on the costs of biofortifying wheat and rice to determine the cost-effectiveness of the intervention. The costs for the optimistic scenario were derived from the HarvestPlus budget³³ as the development of the new varieties is being funded through this programme; for the pessimistic scenarios these figures were doubled, making this a conservative assumption. The expected time required for R&D was estimated by the lead plant breeders (G Barry and I Ortiz-Monasterio, personal communication, December 2004) (Table 3). The time horizon of the analyses was set at 30 years, which is a common time frame for economic analyses because after that time discounting levels the impact of future events. In the present context, it also covers the life cycle of the biofortified crops from the initial R&D until the maximum assumed coverage of these crops (Fig. 2). To discount future costs and benefits to the base year, a 3% rate was usedReference Stein, Meenakshi, Qaim, Nestel, Sachdev and Bhutta¹⁴. R&D costs were attributed to the main target countries according to their respective production shares.Footnote * Potentially, other countries can also benefit from biofortified wheat or rice, but costs tend to be underestimated ex-ante. This warrants a cautious approach when projecting costs into the future. Also, the actual adoption of biofortified varieties is still an open issue.

Table 3 Assumptions about costs of zinc biofortification of wheat and rice

R&D – research and development.

Source: Based on reference 32, I Ortiz-Monasterio and G Barry (personal communication, 2004).

Results

The current burden of ZnD in India amounts to 2.8 million DALYs lost, 2.7 million from mortality and 140 000 from morbidity, 70% of which occurs among infants (Fig. 3). With zinc biofortification of wheat and rice 0.6 million DALYs can be saved each year in the pessimistic scenario, while 1.4 million DALYs can be gained annually under the optimistic assumptions. This corresponds to a reduction of the burden of ZnD of 20 and 51%, respectively (Table 4). Yet, while the biggest burden of ZnD is borne by infants, the biggest health gain through biofortification occurs among children aged 1–5 years (Fig. 4). If these health benefits are set against the costs to be incurred for zinc biofortification of wheat and rice for India, and if all values are discounted to the base year, saving one healthy life year through biofortification costs $US 7.31 under the pessimistic assumptions or as little as $US 0.73 in the optimistic scenario.

Fig. 3 Number of disability-adjusted life years (DALYs) lost due to the different health outcomes of zinc deficiency (a) and number of DALYs lost by the two target groups (b)

Table 4 Potential impact of zinc biofortification on the burden of ZnD in India

ZnD – zinc deficiency; DALY – disability-adjusted life year; N/A – not applicable.

Fig. 4 The reduction of the burden of zinc deficiency through biofortification by age group

Expressed in mortality figures only, the annual burden of ZnD in India is 95 500 deaths; with zinc biofortification 18 350 and 48 100 lives can be saved in the pessimistic and optimistic scenario, respectively. Juxtaposing the net present cost and the (undiscounted) number of infant and child deaths that can be averted within the 30-year time frame yields a cost of $US 115 per life saved in the pessimistic scenario, while under optimistic assumptions saving one life through zinc biofortification costs only $US 12 (Table 5).

Table 5 Cost-effectiveness of zinc biofortification of wheat and rice over 30 years

DALY – disability-adjusted life year.

* Internal rate of return (if one DALY is valued at $US 1000).

Discussion

The results show that ZnD imposes a heavy burden on public health in India, most of it due to mortality associated with impaired immune function and thus greater susceptibility to infectious diseases. With 2.8 million DALYs lost each year, the burden is lower than the burden of 4 million DALYs lost in India due to iron-deficiency anaemiaReference Stein, Meenakshi, Qaim, Nestel, Sachdev and Bhutta³⁴, but it still poses a problem of a considerable magnitude.Footnote * ZnD has received little public attention, and no systematic interventions are currently in place to control this micronutrient deficiency³⁵. This analysis shows that zinc biofortification of wheat and rice in India may be an effective means to reduce the burden of ZnD. Given the higher natural zinc content in existing wheat varieties and the lower potential increases in biofortified wheat compared with rice, the impact of wheat biofortification is lower than the impact of rice biofortification. Nevertheless, by biofortifying not only rice but also wheat, it may be possible to reduce the burden of ZnD by an additional 2–10%, i.e. by 60 000–290 000 DALYs.Footnote † The impact of zinc biofortification is not completely additive, because if both crops are biofortified some consumers might already achieve sufficiency with the consumption of one crop only and hence biofortification of the other crop does not bring any additional benefit to these individuals.

A limitation of this analysis is the use of household-level rather than individual-level food intake data, because nationally representative food intake data are not currently available. Consequently, the use of adult equivalent weights to attribute a share of the household's overall consumption to each household member only approximates actual individual intakes, and may significantly overestimate infant intakes. However, if maternal zinc status can be improved through (long-term) consumption of zinc-biofortified rice and wheat, it is plausible that the status of her newborn infant will be better than it otherwise would be; consequently, infants may be less at-risk of succumbing to morbidity due to infectious diseases. Our approach is already a notable improvement over previous work (for vitamin A deficiency) that used highly aggregated national average consumption data as the basis for projecting the potential impact of a biofortified cropReference Zimmermann and Qaim¹⁷. It is also an improvement over the use of national food balance data to assess population zinc statusReference Wuehler, Peerson and Brown³⁶, which are production-based and reflect average nutrient availability at the national level only – i.e. the use of household data and adult equivalent weights allows for estimating intakes at a more disaggregated level. Clearly further research with better data is necessary to corroborate the findings. None the less, the approach used here provides important preliminary findings for policy-makers and researchers, and can be regarded as a useful and interesting starting point for further studies.

Showing that an intervention can work (i.e. its efficacy) and quantifying its potential benefits (i.e. in this case the number of healthy life years that can be saved) is necessary, but only a first step. Where resources are limited and funding is scarce, an intervention also needs to be cost-effective compared with alternatives. Scarcity needs to be managed, and in public health such management is paramount. The World Development Report (WDR)⁵ underlines that ‘because interventions can differ so much in cost-effectiveness, making allocative decisions badly in either the public or the private sectors costs lives’ (p. 61). This is also why DALYs were introduced as a unit for measuring health effects: to be able to compare different interventions by what it costs to achieve an additional year of healthy life. The WDR provided a ‘yardstick’ for assessing the cost-effectiveness of public health initiatives by indicating that saving one DALY for less than $US 150 is highly cost-effective. In another publication the World Bank⁶ states that most micronutrient programmes cost less than $US 50 per DALY saved, with iron fortification, iodine fortification and vitamin A supplementation to children under the age of 5 years costing $US 4, $US 8 and $US 9 per DALY saved, respectively. A recent assessment of (hypothetical) zinc fortification in Southeast Asia reports a cost of international $ 14 per DALY avertedReference Tan-Torres Edejer, Aikins, Black, Wolfson, Hutubessy and Evans³⁷.Footnote * The World Health Organization's (WHO) Commission on Macroeconomics and Health³⁸ classified DALY values equal to average per capita income as conservative assumptions and propagated the use of three times the per capita income to value one DALY. The Indian per capita income in 2004 was $US 620³⁹; hence, according to the WHO, health interventions in India can already be considered cost-effective if they save a DALY at a cost of less than $US 1860.

Given that the above yardsticks originate from different years, the issue of inflationary adjustment becomes relevant before any comparisons can be made between the present study and these sources. To convert the nominal $US values given in the sources cited above into real terms, the inflation calculator of the US Bureau of Labor Statistics (http://www.bls.gov/cpi) was used, which is based on the average consumer price index for a given calendar year. 2004 was selected as base year. The resulting new reference values – expressed in constant terms – are reported in Table 6. Against this background the imputed costs of $US 0.73–7.31 for saving one DALY through zinc biofortification of wheat and zinc (Table 5) is extremely low: compared with both other micronutrient interventions and the standards set by the World Bank and the WHO, zinc biofortification may be very cost-effective.Footnote *

Table 6 DALY values and thresholds for cost-effectiveness of health interventions

DALY – disability-adjusted life year; WHO – World Health Organization.

* Source:consumer price index of the US Bureau of Labor Statistics (http://www.bls.gov/cpi).

† These figures are expressed in international $; therefore the cost-effectiveness ratios are relatively higher than those expressed in $US.

In this study DALYs were used to measure the loss of health, but looking at mortality alone can provide a compelling argument for zinc biofortification of wheat and rice: deaths of infants and children can be averted for as little as $US 12–115 per case (Table 5). Another perspective can be gained if the costs of zinc biofortification over 30 years are disaggregated to the per capita level: zinc biofortification would cost only $US 0.0003–0.0009 per citizen in India per year (Table 5). The transition from a cost-effectiveness analysis – or a cost-utility analysis – to a cost-benefit analysis allows for the intervention to be assessed not only in terms of its technical efficiency but also in terms of its allocative efficiency in a context that goes beyond the health sectorReference Walker⁴⁰. In a similar analysis for the Philippines, Zimmermann and QaimReference Zimmermann and Qaim¹⁷ reported internal rates of return (IRRs) of 66–133% for ‘Golden Rice’Footnote ,* which is intended to control vitamin A deficiency. However, they used the annual per capita income of the Philippines of $US 1030 in 2000 to value a DALY. With a somewhat lower but otherwise better comparable DALY value of $US 1000Reference Stein, Meenakshi, Qaim, Nestel, Sachdev and Bhutta¹⁴, the IRRs for zinc biofortification in India are 56–150%.