The most damaging micronutrient deficiencies in the world are the consequence of low dietary intake of iron, vitamin A, iodine and zinc. Vitamin A deficiency (VAD) is prevalent among the poor whose dietr are based mainly on rice or other carbohydrate-rich, micronutrient-poor calory sources. Rice does not contain any β-carotene (provitamin A), which their body could then convert into vitamin A. Dependence on rice as the predominant food source, therefore, necessarily leads to VAD, most severely affecting small children and pregnant women. According to the World Health Organization, dietary VAD causes some 250,000 to 500,000 children to go blind every year. More than half of those children also die within a year of becoming blind. Thus, blindness is only a symptom of much more serious debilitating health problems.

VAD compromises the immune systems of approximately 40 percent of children under five in the developing world, greatly increasing the severeness of common childhood infections, often leading to deadly outcomes. VAD is most severe in Southeast Asia and Africa. For the 400 million rice-consuming poor, the medical consequences are fatal: impaired vision—, in extreme cases irreversible blindness; impaired epithelial integrity, exposing the affected individuals to infections; reduced immune response; impaired haemopoiesis (and hence reduced capacity to transport oxygen in the blood) and skeletal growth; among other debilitating afflictions.

Rice containing provitamin A could substantially reduce the problems described above. This can only be achieved using genetic engineering because there is no provitamin A in the rice seeds, even though it is present in the leaves. Thousands of rice varieties have been screened for this trait without success. Existing coloured rice varieties contain pigments that belong to a different chemical class.

Golden Rice has the potential to complement existing efforts that seek to reduce blindness and other VAD induced diseases. Those efforts include industrial fortification of basic foodstuffs with vitamin A, distributing vitamin supplements, and increasing consumption of other foods rich in vitamin A. Those programmes are successful mainly in urban areas but still around 45% of children around the world are not reached by supplementation programmes. Moreover, these programmes are not economically sustainable. Small countries, like Nepal or Ghana, require about 2 million dollars every year to run the campaigns, in spite of the negligible cost of the vitamin A capsules. A large country like India cannot afford to run country-wide programmes, because the costs becomes prohibitive. There is no guarantee that donors and governments will be able to carry on funding those programmes year after year (UNICEF, Micronutrient Initiative). Biofortified crops, like Golden Rice offer a long-term sustainable solution, because they do not require recurrent and complicated organizational arrangements once they have been deployed.

We must not forget that even if we were able to fill in those existing gaps, at least in part, the problem of malnutrition as such will not be eradicated, as long as the underlying political, economic and cultural issues remain unresolved.

In the United States, the Dietary Reference Intakes are given as three numbers: (1) an estimated average requirement (EAR); (2) a recommended dietary allowance (RDA), and (3) an upper level (UL). For developed countries, the EAR —and thus the RDA (the RDA is derived from the estimated average requirement: RDA = EAR ± 2 standard deviations)— have been derived from the amount of vitamin A needed to provide four months of body stores of the vitamin to a person. For developing countries, the estimated average requirement (EAR) was established as the amount needed to prevent vitamin A deficiency from occurring, as evidenced by the occurrence of night blindness (i.e., how much vitamin A does it take to prevent night blindness). The average amount to prevent a deficiency state is one-half of that needed for adequate storage (i.e. 150 µg).

• Dietary Reference Intake. 2001. National Academy of Science Press, Washington DC.

Potential contribution of Golden Rice to vitamin A deficiency alleviation

It is expected that in countries with high per capita consumption of rice, a locally adapted variety producing less than 30 µg of β-carotene per gram of rice could be able to maintain appropriate levels of vitamin A in the body. Encouraging preliminary bioavailability studies indicate that regular consumption of Golden Rice will be able to provide the RDA in rice-based societies.

The Golden Rice Project is being moved forward at various levels. After the Golden Rice prototype obtained in the year 1999 (Ye et al. 2000) and which accumulated around 1.6 µg/g of β-carotene in the grain, new lines were generated by using tissue-specific promoters in the gene constructs. This led to first Golden Rice 1 (GR1), which produced up to an average of 6 µg/g of β-carotene. The latest development by Syngenta scientists (Paine et al.2005)— is GR2, which produces 31 µg/g— and more β-carotene. Which lines will be used in the end will depend on the final outcome of the ongoing bioavailability studies and regional needs, calculated based on local dietary composition.

We wish that everybody in the world had access to a varied diet, capable of covering all nutrition needs of the population. Yet, a quick reality check teaches us that in many regions of the world this goal will not be achieved any time soon. The reasons for this sad reality are manifold. They are rooted in geographic and climatic limitations, different political, religious and socio-cultural backgrounds and problems. We are happy to see the success of ongoing fortification and supplementation efforts, and we are convinced that Golden Rice will be able to contribute to these programmes and narrow down the existing gaps.

Potential benefits of Golden Rice 2 in a country like Bangladesh
RNI, recommended daily nutrient intake (WHO/FAO); RE, retinol (vitamin A) equivalents. Golden Rice contribution calculated based on 31 µg/g β-carotene (GR2 levels), 1:12 vitamin A/β-carotene conversion, and 25 percent loss during cooking; 400 g of rice were used for adults, 200 g for children. Conservative values were used for consumption, conversion rate and cooking losses. Children 1-3 years of age require only 400 RE.
	Adult women	Children under 7
RNI [RE]	500	450
Contribution from Golden Rice [RE]	775	338
Contribution from other diet [RE]	245	112
RNI coverage [%]	204	112

• Black RE, Morris SS, Bryce J (2003) Where and why are 10 million children dying every year? The Lancet 361:2226-2234.
• Bryce J, El Arifeen S, Pariyo G, Lanata CF, Gwatkin D, Habicht J-P, and the Multi-Country Evaluation of IMCI Study Group (2003) Reducing child mortaility: can public health deliver? The Lancet 362:159-164.
• El Arifeen S, Blum LA, Hoque DME, Chowdhury EK, Khan R, Black RE, Victoria CG, Bryce J (2004) Integrated management of childhood illness (IMCI) in Bangladesh: early findings from a cluster-randomised study. The Lancet 364:1595-1602.
• Jones G, Steketee RW, Black RE, Bhutta ZA, Morris SS, and the Bellagio Child Survival Study Group (2003) How many child deaths can we prevent this year? The lancet 362:65-71.
• Paine JA, Shipton CA, Chaggar S, Howells RM, Kennedy MJ, Vernon G, Wright SY, Hinchliffe E, Adams JL, Silverstone AL, Drake R (2005) A new version of Golden Rice with increased pro-vitamin A content. Nature Biotechnology (published online March).
• 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 287:303-305.

About oil and provitamin A uptake

Dietary fat facilitates carotenoid absorption but a lack of fat is unlikely to play a major role in producing moderate to severe vitamin A deficiency. An early study who found that fat intake was less important than preformed vitamin A in maintaining an adequate status in the blood [1]. Even generous amounts of oil did not prevent 75 percent of dietary carotenoids from being excreted.

In a trial in India [2], added oil was only beneficial to children with better vitamin A status at the outset. Among those who ate meals with no added fat, blood vitamin A levels increased about the same as in those who were deficient and who did receive fat. It is often quoted that 5 grams or more dietary fat is needed in a meal to facilitate provitamin A absorption [3-5]. If taken in adequate amounts, plant sources of provitamin A do protect against moderate to severe vitamin A deficiency, which are the targets of the Golden Rice Project in developing countries. It is important to note that absorption and utilization of provitamin A carotenoids is affected by many factors, the most important being vitamin A status itself.

Hence, people eating Golden Rice regularly would be able to maintain appropriate vitamin A blood levels and thus also absorb sufficient provitamin A from their diets, without added oil. Even though fat content of rice is low, it is the main source of dietary fats in rice-based societies. The simple starchy food matrix of th rice grain and its fat content will facilitate intestinal β-carotene uptake, making Golden Rice most probably an excellent source of the vitamin.

Bibliography
[1] Roels et al. (Journal of Nutrition 65:115-127, 1958
[2] Indian Journal of Medical Research 71:53-56, 1980
[3] Amer Journal of Clinical Nutrition 45:704-716, 1987
[4] Clinical Nutrition 7:101-106, 1988
[5] Food and Nutrition Bulletin 14:34-35, 1992