Evaluating iron and zinc bioavailability from biofortified potatoes to reduce malnutrition in the Andean highlands.

Iron and zinc deficiency are global problems, with high prevalence in Asia, Sub-Saharan Africa and South America. While iron and zinc supplementation and food fortification programmes have been shown to be efficacious in certain situations, their implementation requires good infrastructure, significant investment and safe delivery systems. The development of crops with enhanced levels of bioavailable iron and zinc - so called biofortification - is a sustainable and cost-effective complementary strategy that has the potential to provide sufficient iron and zinc for resource poor rural and urban communities, such as those in the Andean highlands. There has been significant effort within the international community to breed new varieties of staple crops that have enhanced levels of iron and/or zinc. It is however difficult to predict whether the additional iron and zinc in biofortified crops would be bioavailable - that is effectively absorbed from the diet into the body to improve iron and zinc status. The risk in breeding these biofortified crops is that the investment in crop development will have limited impact if the iron and zinc is not bioavailable.
Iron and zinc biofortified potato are an ideal crop to contribute to a reduction in iron and zinc deficiencies in the Andean highlands for two major reasons. Firstly, unlike cereals and legumes, potatoes have very low levels of phytates which inhibit iron bioavailability, and this is combined with a relatively high concentration of vitamin C which promotes iron absorption - an ideal combination to maximize bioavailability. Secondly, potatoes are the major staple in the diet amongst the iron and zinc-deficient Andean population, and are largely consumed without other foods. Thus, while various strategies including agricultural diversification have potential to alleviate micronutrient deficiencies and should be considered in an integrated approach, biological, cultural and economic factors suggest that the introduction of iron and zinc biofortified potatoes may be an effective approach to have a significant contribution to reducing iron and zinc deficiencies. Quantifying the bioavailability of iron and zinc at this time is critical.
The bioavailability of iron and zinc from biofortified crops can only be meaningfully quantified through human dietary intervention studies in which foods made from the biofortified crops are labelled with stable isotopes of iron or zinc, which are subsequently quantified human tissues to provide a measure of bioavailability. These studies are technically challenging, but of the utmost importance for the success of biofortification strategies.
To quantify the potential impact of the introduction of biofortified potatoes, data from the human studies will be used within a Disability Adjusted Life Year (DALY) modelling approach. This method has been successfully applied to assess the potential impact of other biofortified crops to alleviate micronutrients deficiencies. Furthermore, we will use data from the proposed research along with that from other studies to develop iron dietary intake guidelines for low and middle-income countries.
If we find compelling evidence through the human intervention studies and the subsequent DALY modeling that iron and zinc biofortified potatoes can contribute to alleviation of iron and zinc deficiencies in low and middle income countries, it will provide the justification for investment from the international donor community and national research programmes for further development and selection of clones of diploid and tetraploid potatoes that have enhanced iron and zinc content, and their transfer to national agricultural research programmes in south America, Asia and Africa. Subsequently, these programmes and their associated extension programmes and NGOs will ensure the introduction of biofortified potatoes to small scale farmers in regions of high iron and zinc deficiencies.

Iron bioavailability studies: We will compare bioavailability of iron from a non-fortified potato variety with a biofortified potato that has significantly higher iron content (p<0.001) though the use of a randomized cross-over intervention study. Female volunteers will consume both biofortified potato extrinsically labelled with 58FeSO4 and a nonfortified potato labelled with 57FeSO4. Forty women with marginal iron status (plasma ferritin < 25 ng/ml) will be selected from an initial screening of 180 women. Every woman will receive 2 different types of test meals in a series of 20 servings for 10 d each. Blood samples will be collected during screening and on days 1, 15, 26 and 40 and the amount of 58Fe and 57Fe incorporated into haemoglobin and serum ferritin quantified.

Zinc bioavailability study: We will compare bioavailability of zinc from a non-fortified potato variety with that of a biofortified potato that has significantly higher zinc content (p<0.001) with a crossover study. Volunteers will be randomly assigned to receive first either the biofortified or the nonfortified potato, and receive the second meal 30 days later. Zinc absorption from two meals will be measured using the double stable isotope technique. Every volunteer will be given an i.v. infusion of 70zinc and two test meals of 300 g cooked potato labelled extrinsically with 67zinc separated by 3-4 hr. A spot urine sample will be collected 96 hours after each set of test meal and the ratio of the two isotopes measured in order to calculate absorption of zinc from the test meal.

Modelling and Impact assessment: Data on bioavailability will be used in a Disability Adjusted Life Year model to assess the potential impact of biofortified potatoes to alleviate iron and zinc deficiencies in the Andean Highlands and low and middle-income countries elsewhere. Additional modelling will be undertaken to derive recommendations for dietary iron and zinc intake for low and middle-income countries

The ultimate target beneficiaries of the proposed research are resource-poor people in low and middle-income countries who lives are blighted through iron and zinc deficiencies. Iron deficiency is widely considered to be the largest nutritional deficiency worldwide and the major cause of anaemia. Iron deficiency anaemia (IDA) is estimated to affect 1.24 billion people, the majority of whom are children and women from resource-poor countries [1]. Deficiency due to dietary iron intake is frequently exacerbated by concomitant parasitic and bacterial infections and contributes to over 120 000 maternal deaths a year. IDA irreparably limits the cognitive development of children and leads to poor outcomes in pregnancy [1]. Zinc has a role in over 300 enzymes in the majority of metabolic pathways in humans. Zinc deficiency leads to multiple and complex physiological disorders and impairment of growth and cognitive development of children. Extent of deficiency has been estimated to be up to 30% of the population of low and middle-income countries [2]. Despite considerable investment in the past 25 years in nutrition interventions with iron and zinc supplementation and food fortification, it has been challenging to significantly decrease the burden of these micronutrient deficiencies in resource-poor countries. A strategy of biofortification in which sufficient micronutrients are delivered as part of the diet has been widely advocated, and there is evidence that this approach can be sustainable and effective. Iron and zinc biofortified potatoes may have an important role to play in communities in which potatoes are the major component of the diet, exemplified by those in the Andean Highlands, but may also contribute to alleviating deficiencies in other communities in which potatoes are an important component of a more diverse diet.

The successful introduction of biofortified potatoes into these communities will take several years. The proposed research will have more immediate impact on several groups of other intermediate beneficiaries:

Donor agencies: The results of the proposed study are critical to justify further investment in potato biofortification by donor agencies, including Bill and Melinda Gates Foundation, The World Bank, bilateral aid agencies and the European Union. CIP in collaboration with national research programmes, NGOs and farmers have spent more than fifteen years selecting iron and zinc biofortified diploid potatoes. Further significant investment is required to develop elite biofortified potatoes for introduction into Africa and Asia. However, the proposed bioavailability studies and subsequent impact assessment are required to justify investment.

Public health workers and nutrition scientists: The results of the proposed research will inform nutrition scientists and public health workers whether biofortified potatoes have the potential to contribute to the alleviation of iron and zinc deficiencies, and specifically how much potatoes need to be consumed in a single meal and how frequently to make a significant difference to iron and zinc status.

Plant breeders and crop scientists: The results of the proposed research will provide specific target for iron and zinc content for breeders, enabling effective decisions about how much additional effort is required to produce breeding line with marginal increases in iron and zinc.

Research scientists and nutritionists: The programme will provide training in undertaking human intervention studies and iron and zinc stable isotope studies for scientists in Peru. This will include protocol design, obtaining ethics and the specific aspects of working with stable isotopes, and diet intake assessment.

[1] Stellae at al (2018) Proceedings of Nutrition Society, 10th July https://doi.org/10.1017/S0029665118000460. [2] Wessells and Brown (201) Plos One doi.org/10.1371/journal.pone.0050568