Genetic engineering offers promising new approaches to improve dietary iron intake

Using selective plant breeding and genetic engineering could be used to reduce the incidence of iron deficiency worldwide by improving the quality of dietary iron, conclude authors of a Seminar in this week’s edition of The Lancet.

Dr Michael Zimmerman, Laboratory for Human Nutrition, Swiss Federal Institute of Technology, Zurich, and colleagues have reviewed published literature worldwide, mainly from the last five years, to prepare the Seminar, which looks at the issue of nutritional iron deficiency in both industrialised and developing countries.

The authors say: “Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estimated 2 billion people…the high prevalence of iron deficiency in the developing world has substantial health and economic costs, including poor pregnancy outcome, impaired school performance, and decreased productivity.”

The World Health Organisation (WHO) estimates that 39% of children younger than five years, 48% of children between five and 14 years, 42% of all women, and 52% of pregnant women in developing countries are anaemic, with half having iron deficiency anaemia. WHO also believes that the frequency of iron deficiency in developing countries is around 2.5 times that of anaemia which is not iron deficiency related.

Dietary iron bioavailability (the measure of iron which can be absorbed from food) is low in populations consuming monotonous plant-based diets with little meat – ie. many developing countries. In an analysis of ten developing countries, the median value of physical productivity losses per year due to iron deficiency was around US $0.32 per head, or 0.57% of gross domestic product (GDP) for those nations. In the WHO Africa subregion, it is estimated that if iron fortification reached 50% of the population, it would avert 570,000 disability adjusted life years (DALYs- an international standard for measuring the effects of disability).

Iron deficiency has many reported consequences – children deficient in iron have higher susceptibility to upper respiratory tract infections, and anaemia which can affect their brain, motor activity and general performance in school, whilst adult manual laborers in developing countries were found to be less productive when iron-deficient, and left untreated for hookworm and other infections.

The three main strategies for correcting iron deficiency are supplementation (provision of iron without food), fortification of foods, and the relatively new approach of genetic engineering and plant breeding. The authors say: “Although dietary modification and diversification is the most sustainable approach, change of dietary practices and preferences is difficult, and foods that provide highly bioavailable iron (such as meat) are expensive.”

Supplementation can be targeted to high risk groups and be cost-effective; yet the logistics of distribution and absence of compliance are major limitations. Untargeted supplementation in children in tropical countries, mainly in areas of high transmission of malaria, is associated with increased infections.

Fortification is, say the authors, “probably the most practical, sustainable and cost-effective long-term solution to control iron deficiency at the national level.” The low incidence of iron deficiency anaemia in adolescent and young women in the USA might be at least partly due to consumption of iron-fortified wheat flour. Types of iron used for fortification vary depending on the situation, but in most cases cereal flour is fortified with ferrous sulphate, ferrous fumarate or several other common types of iron. Fortifying powdered milk has also been shown to benefit children in developing countries, with Chile reporting that the frequency of anaemia decreased from 27% to 9% after a powdered milk fortification programme.

However, while fortification is common and has proven benefits, loss of iron from both wheat and rice during the milling process means that keeping the levels of iron acceptable (40mg/kg) is difficult. This is where the authors believe genetic engineering can play a key role – eg. The iron content in rice can be increased two- to three-fold by introduction of the ferritin gene from the soy bean. Another problem – the reduction of bioavailable iron due to high phytate content – could also be solved by introducing genes which increase the activity of phytase enzymes to break down the phytate.

The authors conclude by calling for more data on the functional consequences of iron deficiency, eg. on immune function and cognition in infants and children. Due to the risks of untargeted supplementation in malaria-endemic countries, new strategies are urgently needed to provide additional dietary iron to susceptible infants and children that might not be reached by universal fortification programmes.

They conclude: “Selective plant breeding and genetic engineering are promising new approaches to improve dietary iron bioavailability, however a major challenge is to show that they can increase iron content to nutritionally useful levels and that the additional iron is bioavailable.”