Biological availability and efficacy of folates from bioengineered rice

The basic concept of folate rice is to develop a means for rural areas to combat folate deficiency. Folate deficiency is of concern given the relation between folate status and birth defects, ranging in severity from mild back ache to stillbirth, due to a malformation of the neural tube. While western populations benefit from diverse and nutrient rich diets, even these populations are at risk for folate deficiency. One method to alleviate the health burden associated with folate deficiency is to add synthetic folic acid to commonly consumed food items such as breakfast cereals or bread. However, remote, mostly rural communities, do not have free access to folic acid fortification. As such, a rice variety with a high natural folate content that could be grown locally may serve to achieve an adequate folate status. However, since folate rice is a genetically engineered rice variety, public and governmental acceptance depends on scientific evidence that the folates contained within these rice grains are released into the bloodstream when consumed. This is because some genetically engineered food items have been criticized as a result of their limited influence on nutrient status. It is therefore of paramount importance to evaluate the impact of folate rice consumption on folate status. Given the need for strict control of nutrient intake and regulatory constraints, a rodent feeding trial was devised to evaluate the efficacy of folate rice as a dietary folate source. Due to the complexity of folate metabolism and body distribution, a long term study was performed including regular evaluation of folate status, folate related clinical parameters and general health. These results were compared between groups receiving no folate, a small amount of folate present in 'normal' rice, a larger amount of folate in either folate rice or folic acid fortified rice or ample folate as an optimal scenario. To quantify the biological outcome of folate rice consumption, an analytical method was developed to measure the amount of folates in 2 separate blood fractions, i.e. plasma and red blood cells. Given the low concentrations in which folates are present, a sensitive method using liquid chromatography coupled to tandem mass spectrometry was used. Since the term folate signifies several different molecules with different chemical and biological properties, the developed method required the measurement of individual folate species. Also, to exclude the influence of folates which might be present in the rodent diets used during the rodent trial, a separate method was developed to determine the folate concentration in the rodent diets used. Due to the necessity of folates for DNA-synthesis in white blood cells, the influence of folate concentration and speciation on the functioning of the immune system was investigated as well.

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