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22 marzo 2001
Ingo Potrykus

Journal of the American Dietetic Association Volume 101 (March):289-290, 2001

Marion Nestle, Ph.D, Professor and Chair, Department of Nutrition and FoodStudies

New York University, writes in this letter that the suggestion that "golden"rice, bioengineered to contain beta-carotene, could have "a real impact on the health of children living in Southeast Asia" deserves critical scrutiny from nutrition professionals. Nestle says that this rice, although not yet available commercially, has become the "poster child" of the food biotechnology industry's extensive public relations campaign to convince the public that the benefits of genetically engineered agricultural products outweigh any safety, environmental, or social risks they might pose.

National magazines promote golden rice as a means to prevent the more than one million annual deaths and cases of blindness that occur among children in developing countries as a result of vitamin A deficiency. The creation of golden rice appears to confirm the belief that biotechnology is the key to solving world food and nutrition problems.

Consideration of basic principles of nutrition suggests that rice containing beta-carotene is unlikely to alleviate vitamin A deficiency. Nestle says the bioavailability of beta-carotene is quite low-10% or less by some estimates.

To be active, beta-carotene--a pro-vitamin--must be split by an enzyme in the intestinal mucosa or liver into two molecules of vitamin A. Like vitamin A, the pro-vitamin is fat-soluble and requires dietary fat for absorption.

Thus, digestion, absorption, and transport of beta-carotene require a functional digestive tract, adequate protein and fat stores, and adequate energy, protein, and fat in the diet. Many children exhibiting symptoms of vitamin A deficiency, however, suffer from generalized protein-energy malnutrition and intestinal infections that interfere with the absorption of beta-carotene or its conversion to vitamin A. In numerous countries where vitamin A deficiency is endemic, food sources of beta-carotene are plentiful but are believed inappropriate for young children, are not cooked sufficiently to be digestible, or are not accompanied by enough dietary fat to permit absorption.8 In addition to doubts about cost and acceptability,2 biological, cultural, and dietary factors act as barriers to the use of beta-carotene, which explains why injections or supplements of pre-formed vitamin A are preferred as interventions. The extent to which the beta-carotene in golden rice can compensate for these barriers is limited.

Nestle says that vitamin A deficiency is undeniably the single most important cause of blindness among children in developing countries and a substantial contributor to illness and death from infectious diseases.

Nestle goes on to conclude that what all this means is that the short- and long-term effects of supplementation of beta-carotene as a single nutrient-distinct from the foods that contain it-are as yet uncertain. The complexity of the physiological, nutritional, and cultural factors that affect vitamin A status suggest that no single-nutrient added to food can be effective as a remedy for dietary deficiencies. Instead, a combination of supplementation, fortification, and dietary approaches is likely to be needed, along with a substantial commitment to improve socioeconomic status.

Food biotechnology may yet lead to products that improve nutrition and health, but at the moment its benefits remain theoretical. References

1.Ye X, Al-Babili S, Klöti A, Zhang J, Lucca P, Beyer P, Potrykus I. Engineering the provitamin A (beta-carotene) biosynthetic pathway into (carotenoid-free) rice endosperm. Science 2000;287:303-305.

2.Greger JL. Biotechnology: mobilizing dietitians to be a resource. J Am Diet Assoc 2000;100:1306-1307.

3.Council for Biotechnology Information. Biotechnology researchers call it "golden" rice (full-page advertisement). New York Times, October 16, 2000:A9.

4.Nash MJ. Grains of hope. Time Magazine, July 31, 2000:39-46

5.Position of the American Dietetic Association: biotechnology and the future of food. J Am Diet Assoc 1995;95:1429-1432.

6.Olson JA. Carotenoids. In: Shils ME, Olson JA, Shike M, Ross CA, eds. Modern Nutrition in Health and Disease, 9th ed. Philadelphia: Lippincott Williams & Wilkins, 1998: 525-541.

7.Torun B, Chew F. Protein-energy malnutrition. In: Shils ME, Olson JA, Shike M, Ross CA, eds. Modern Nutrition in Health and Disease, 9th ed. Philadelphia: Lippincott Williams & Wilkins, 1998:963-988.

8.Sommer A. Vitamin A deficiency and its consequences: a field guide to detection and control, 3rd ed. Geneva: World Health Organization, 1995.

9.World Health Organization and United Nations Children's Fund. Global prevalence of vitamin A deficiency (Micronutrient Deficiency Informaiton System Working Paper #2). Geneva: World Health Organization, 1995.

10.Food and Agriculture of the United Nations and International Life Sciences Institute. Preventing Micronutrient Malnutrition: A Guide to Food-based Approaches. Washington, DC: International Life Sciences Institute, 1997.

11.Kritchevsky SB. beta-carotene, carotenoids and the prevention of coronary heart disease. J Nutr 1999;129:5-8.

12.Hennekens CH, Buring JE, Manson JE, Stampfer M, Rosner B, Cook NR, et al. Lack of effect of long-term supplementation with beta-carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 1996;334:1145-1149.

13.Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, et al. Effects of a combination of beta-carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 1996;334:1150-1155.

14.Bertram JS. Carotenoids and gene regulation. Nutr Rev 1999;57:182-191.

15.Paolini M, Cantelli-Forti G, Perocco P, Pedulli GF, Abdel-Rahman SZ, Legator MS. Co-carcinogenic effect of beta-carotene. Nature 1999;398:760-761.

16.Palozza P. Prooxidant actiions of carotenoids in biologic systems. Nutr Rev 1998;56:257-265.

17.Filteau SM, Tomkins AM. Promoting vitamin A status in low-income countries. The Lancet 1999;353;1458-1460.


Ingo Potrykus

How much Golden Rice has a child to eat, to prevent vitamin A-deficiency? RDA (Recommended Daily Allowance) of vitamin A for children: 0.3 mg/day. RAE (Retinol Activity Equivalence): converson factor of provitamin A:

a) x12 : US Natl. Acad. Sci. Inst. of Medicin (IOM) January 9, 2001.
b) x 6 : FAO/WHO, 1988.
c) x 4 : Indian Council of Medical Research.

Current prototype Golden Rice lines contain 1.6-2.0 g/g = 1.6-2 mg/kg Assuming 100% bioavailability ( 50% bioavailability) leads to following values:

A child would have to eat the following amount of Golden Rice per day to meet the RDA requirement:

a) 1 800 - 2 250 g, (3 600 - 4 500 g)
b) 900 - 1 125 g, (1 800 - 2 250 g)
c) 600 - 750 g. (1 200 - 1 500 g)

However: Nutritionalists confirm that RDA represents a luxurious recommendation and expect that 30-40% of RDA would successfully defeat mortality, morbidity, and blindness.

a) 540 - 675 g, (1 080 - 1 350 g)
b) 270 - 337 g, ( 540 - 674 g)
c) 180 - 225 g. ( 360 - 450 g)

And further:
Golden Rice is not supposed to provide 100% of the vitamin A-supply, but to help surpassing the border line between malnutrition and sufficient vitamin A supply by complementing other dietary components. According to a rough estimation it should supply 50% of the daily intake (fortification level: 25-30%, Natl. Nutritional Monitoring Board, Hyderabad).

a) 270 - 337 g, ( 540 - 674 g)
b) 135 - 168 g, ( 270 - 336 g)
c) 90 - 112 g. ( 180 - 224 g)

And further:
Golden Rice is at the "proof of concept" state and under further development. We have carried out further transformations aiming at an increase in the provitamin A content. An increase factor of 3-5 appears feasible. Using a factor of 3 leads to:

a) 90 - 112, ( 180 - 224 g)
b) 45 - 56, ( 90 - 112 g)
c) 30 - 38. ( 60 - 76 g)

And further:
Golden Rice technology will be transferred into further basic food crops, and thus probably contribute to further reduction in the amount of rice necessary.
Reliable data will, of course, become available only from nutritional and bioavailability studies with the Golden Rice varieties resulting from the breeding efforts with the local breeding lines, and from field-grown material. This requires undisturbed field experiments Therefore: What is already clear to date, is the fact, that the Greenpeace argument that Golden Rice will not contribute to a solution of the vitamin

A-defiency problem, and, therefore, does not pose a moral challenge to the radical Greenpeace position against field release experiments with Golden Rice, is not more than a fake argument to save a radical position. The moral challenge gains additional weight because Greenpeace has, so far, not presented any concrete scenario for an environmental hazard from Golden Rice beyond the unsubstantiated notion that "release of transgenic plants into the environment poses an unacceptable risk to the environment". In view of the foreseeable benefit from Golden Rice, Greenpeace can be expected to be a bit more concrete with its environmental argument. What is the risk from Golden Rice, which has no selective advantage in whatever environment, and which produces just a few micrograms more of an environmental neutral substance (-carotene) in the endosperm, in addition to the same substance being present in large quantities in all other parts of the natural plant?

How does such a (so far undefined, hypothetical) risk compare to the expected benefit? I believe that the public has a right to a more concrete answer from Greenpeace.

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