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IZiNCG Awarded New Grant from the Bill & Melinda Gates Foundation to Evaluate the Nutritional Impact of Multiply-Fortified Salt Among Women of Reproductive Age in India 

IZiNCG Awarded New Grant from the Bill & Melinda Gates Foundation to Evaluate the Nutritional Impact of Multiply-Fortified Salt Among Women of Reproductive Age in India 

IZiNCG is pleased to announce the receipt of a grant from the Bill & Melinda Gates Foundation to evaluate the nutritional impact of quintuply-fortified salt vs. standard iodised salt for the improvement of micronutrient status among non-pregnant women of reproductive age in Haryana, India. This project is a collaborative effort primarily between IZiNCG, the Postgraduate Institute of Medical Education and Research (PGIMER), and the Haryana State Government.

Why women of reproductive age?

Women of reproductive age (WRA) and young children are particularly vulnerable to multiple micronutrient deficiencies, and prevalences of deficiency remain unacceptably high in India. The 2015-2016 National Family Health Survey revealed that over half of non-pregnant WRA in India are anaemic. A recent survey of 866 WRA in Haryana demonstrated the co-occurrence of multiple micronutrient deficiencies: 75% of WRA had iron deficiency, 80% had folate insufficiency, and 82% had vitamin B12 deficiency (unpublished observations).  Although plasma zinc concentrations were not assessed, the high prevalence of stunting and the low level of absorbable zinc in the national food supply are suggestive of a high prevalence of zinc deficiency.

 

Why zinc, iron, vitamin B12 and folate?

Zinc, iron, vitamin B12, and folate are critically important for several biological processes related to a healthy pregnancy and the optimal growth and development of the foetus and offspring. Thus, deficiencies in these micronutrients are associated with several adverse health outcomes ranging from preterm and small-for-gestational-age births, neural tube defects, stunting and childhood diarrhoea.  These health problems are widespread in India where more than 3.5 million infants are born preterm each year, nearly 10% of children under 5 have had diarrhoea in the previous 2 weeks, and 38% of children under 5 are stunted. A recent analysis estimated that the prevalence of neural tube defects in South Asia is 32 per 10,000 live births. Clearly, there is an urgent need to improve the micronutrient status of Indian WRA and their children.

Photo credit: World Bank Photo Collection

Photo credit: World Bank Photo Collection

Salt as a novel vehicle for multiple micronutrient fortification

Micronutrient fortification of a staple food or condiment can be an effective strategy for improving the micronutrient status of a population, as the approach is cost-effective, utilises existing delivery systems, can deliver multiple micronutrients simultaneously, and does not require behaviour change by the population.

Salt is an attractive vehicle for multiple micronutrient fortification in India, as it is universally consumed in fairly consistent amounts. India already has excellent coverage of iodized salt and has recently scaled up the distribution of salt fortified with iodine and iron (double-fortified salt).

Extensive research conducted in various settings has shown that double-fortified salt significantly improves iron status in nutritionally vulnerable groups. With new technology developed by the University of Toronto, it is now possible to fortify salt with multiple micronutrients, including zinc, vitamin B12, and folic acid, in addition to iron and iodine.

While salt fortified with encapsulated ferrous fumarate is already being produced at scale and extensively consumed by large populations in India, the planned study proposes to conduct a head-to-head comparison with ferric pyrophosphate likely in combination with citric acid and trisodium citrate (to enhance iron absorption) in an encapsulated medium that is under development and test whether sensory qualities could be improved further.

Plan for the study 

The study will be conducted in two phases. Phase 1 will include formative research involving a dietary assessment to ascertain habitual salt intake and dietary intake of micronutrients; qualitative research to understand salt procurement, storage, and utilization practices; as well as sensory and acceptability testing of the quintuply-fortified salts.

Phase 2 will be a double-blind, randomised controlled efficacy trial where 750 women of reproductive age will be randomised to 1 of 3 groups: 1) quintuply fortified salt with iron in the form of encapsulated ferrous fumarate; 2) quintuply fortified salt with iron in the form of ferric pyrophosphate; and 3) iodised salt. In brief, participating women will be provided with the assigned study salt on a monthly basis for 12 months and blood samples will be taken at baseline, 6 months, and 12 months. The primary outcome will be micronutrient status as measured by the change in biomarkers of zinc, iron, folate, vitamin B12 and iodine status. Secondary outcomes to be assessed include DNA damage, essential fatty metabolism and cognition. 

If proven efficacious, MFS has the potential not only to improve the micronutrient status of WRA, but also lead to improved perinatal outcomes, and better micronutrient status in their offspring. Together with our collaborators, IZiNCG is excited to initiate this study!

 

Collaborators: PGIMER, Haryana State Government, SWACH Foundation, WHO Southeast Asia, the University of Toronto, Tata Trusts/ The India Nutrition Initiative, ETH Zürich, JVS Foods, St. John’s Research Institute, University of Colorado Denver, University of California Davis, Eurofins, University of Otago, University of Nottingham, VitMin laboratory.

 

Read more:

Strategies for promoting zinc nutrition

Zinc supplementation during pregnancy

Zinc Fortification Task Force 

Case study: Addressing Zinc Deficiency Through Wheat Flour Fortification in Cameroon

Case study: Addressing Zinc Deficiency Through Wheat Flour Fortification in Cameroon

As part of a series of case-studies on population-level zinc interventions, Ann Tarini (Independent Consultant), Ismael Teta, Alex Ndjebayi and Jules Guintang Assiene (Helen Keller International, Cameroon) and Reina Engle-Stone (UC Davis) have summarised the Cameroon experience of implementing wheat flour fortification to address zinc deficiency in a new IZiNCG brief.

Food fortification is one of three main strategies to address zinc deficiency in a population. This six page brief covers key program milestones, the rationale for wheat flour fortification, early program impact, a commentary on sustainability, and key lessons learned.

But perhaps most importantly, it highlights the power of data. Prior to 2009, no information was available on the status of zinc and several other micronutrients in Cameroon. In 2009, the Ministry of Public Health conducted a National Micronutrient Survey; the availability of data on plasma zinc concentration enabled the identification of zinc deficiency as a public health problem, and dietary intake data helped identify possible fortification vehicles along with their potential impact. The measurement of plasma zinc concentrations in the two major urban centers in 2012 enabled inference about program impact. And without monitoring data, it would not have been possible to identify and address the faltering of the program in 2016.

We hope Cameroon’s experience can provide inspiration and guidance to other countries considering zinc fortification.

Related:

IZiNCG Research Projects: Zinc Fortification Task Force

IZiNCG Technical Brief no. 4: Zinc Fortification

IZiNCG Technical Document no. 2

Zinc Fortification Task Force initiates efforts to enhance the impact of zinc fortification interventions

Zinc Fortification Task Force initiates efforts to enhance the impact of zinc fortification interventions

Why a Zinc Fortification Task Force?

Fortification of staple foods and/or condiments with zinc appears to be a promising strategy for improving zinc status at the population level in low- and middle-income countries because of its relatively low cost and long-term sustainability. The motivation for establishing a Zinc Fortification Task Force is to progress IZiNCG’s position and recommendations related to zinc fortification, taking into account recent evidence, existing global guidelines, and the fact that mandatory zinc fortification is in place in more than 30 countries. The Task Force harnesses the perspectives of the Food Fortification Initiative, the Global Alliance for Improved Nutrition and Helen Keller International together with IZiNCG.

 

IZiNCG’s current stance on zinc fortification 

A review in IZiNCG’s 2009 Technical Document no. 2 summarised evidence showing that fortifying staple foods with zinc increases total daily zinc absorption, does not adversely affect the absorption of other minerals, is not associated with adverse effects and is a relatively low-cost intervention (1). Therefore, IZiNCG’s recommendation following this review was that countries should consider including zinc in mass and targeted fortification programs in populations at high risk of zinc deficiency. However, the review also pointed to the paucity of evidence on the efficacy and effectiveness of fortification programs, and that only a few studies had found a positive impact on plasma/serum zinc or functional indicators of zinc status.

Recent reviews

A 2016 Cochrane review of zinc fortification concluded the same: given the relatively small number of trials and participants, further investigation of the effects of zinc fortification was needed (2). However, the Cochrane review excluded many studies on the basis that zinc was not the only nutrient which differed between intervention and control groups, despite plasma/serum zinc being measured as an outcome. While such comparisons may be useful from an epidemiological perspective, they may not fully capture the real-world context.  For example, 34 countries have mandatory zinc fortification in place, with zinc being part of a premix with several other micronutrients. In a very recent review of large-scale food fortification on vitamin A, iodine, iron and folic acid status and health outcomes, this “real-world impact” was at the centre (3). However, this latter review excluded trials with less than 1000 participants, which would be too limiting in the case of available publications on zinc fortification.

School meal_WB photo.jpg

Planned work of the taskforce 

The overarching goal of the task force is to assess the efficacy and effectiveness of zinc fortification interventions, and to identify opportunities to enhance impact. The first activity is to produce an update to the previous zinc fortification systematic reviews, summarising the additional evidence now available on zinc fortification. In addition to determining the impact of zinc fortification on zinc-related biochemical and functional outcomes, the review will attempt to answer the following other questions: 

  • What is the adequate dosage and duration of exposure required to show an effect?

  • What proportion reduction in zinc deficiency can we expect to see as a result of zinc fortification, and which groups may require additional/complementary interventions? 

  • Which indicators should be recommended for evaluating zinc fortification programs?

  • What do we know about novel/alternative vehicles for zinc fortification? 

In parallel, the Zinc Fortification Task Force also wants to capture the lessons learnt and identify knowledge and resource gaps in countries with existing national zinc fortification programs. Which evidence did they act on? Which barriers are they facing? Likewise, the Task Force plans to explore the perspectives of countries with a high burden of zinc deficiency without zinc fortification in place, and the feasibility of zinc fortification as a successful strategy in such settings. 

We hope that the results from the activities in this first phase of the Zinc Fortification Task Force will be available by July 2020, and that this effort will help inform renewed global commitments to food fortification. 

 

References

  1. Hess SY, Brown KH. Impact of zinc fortification on zinc nutrition. Food Nutr Bull. 2009 Mar;30(1 Suppl):S79-107. 

  2. Shah D, Sachdev HS, Gera T, De-Regil LM, Peña-Rosas JP. Fortification of staple foods with zinc for improving zinc status and other health outcomes in the general population. Cochrane Database Syst Rev. 2016 Jun 9;(6):CD010697.

  3. Keats EC, Neufeld LM, Garrett GS, Mbuya MNN, Bhutta ZA. Improved micronutrient status and health outcomes in low- and middle-income countries following large-scale fortification: evidence from a systematic review and meta-analysis. Am J Clin Nutr. 2019 Jun 1;109(6):1696-1708.

Read more about strategies for promoting zinc nutrition here.

BIZIFED2 – Biofortification with Zinc and Iron for Eliminating Deficiency in Pakistan

BIZIFED2 – Biofortification with Zinc and Iron for Eliminating Deficiency in Pakistan

In her guest blog for IZiNCG, Dr Heather Ohly introduces an exciting new research project led by the University of Central Lancashire

Biofortificationis a process by which the nutritional quality of food crops is improved through conventional plant breeding techniques and addition of nutrient-rich fertilisers. An increasing body of evidence suggests that it may be a cost-effective and sustainable approach to reduce micronutrient deficiencies (1).

Tightly controlled human feeding studies (efficacy trials) have demonstrated that consumption of biofortified crops can lead to increased micronutrient status (2). However, a limited number of effectiveness studies have demonstrated similar improvements under ‘real world’ conditions.

The most recent national nutrition survey in Pakistan indicated that over 40% of women were zinc deficient and 20% had iron deficiency anaemia (3). It was identified as a priority country for investment by HarvestPlus and a new variety of biofortified wheat (Zincol-2016) was released in 2016. It contains significantly higher concentrations of zinc and iron, compared to standard varieties which have been released in South Asia.

We recently completed a foundation study (known as BiZiFED) to investigate the impact of biofortification as a strategy to alleviate zinc deficiency in Pakistan (4). The findings will be available soon via our website.

Bagging the wheat grain for our foundation study RCT

Bagging the wheat grain for our foundation study RCT

BIZIFED2is a much larger study led by Professor Nicola Lowe from the University of Central Lancashire, in collaboration with University of Nottingham, London School of Hygiene & Tropical Medicine, Kings College London, Khyber Medical University, British Geological Survey and the Abaseen Foundation.

We received £1.9 million from UK Research and Innovation, through the Global Challenges Research Fund (GCRF) and awarded by the Biotechnology and Biological Sciences Research Council (BBSRC). This funding is for two years from 1stApril 2019.

BIZIFED2 is the first large-scale investigation into the potential of biofortified wheat to reduce zinc and iron deficiencies among adolescent girls and children in Pakistan. Adolescence is a critical time in the life-course to influence maternal and neonatal outcomes, and the health of future generations.

The project will be conducted in a low resource community on the outskirts of Peshawar, Khyber Pakhtunkhwa Province (KPK). The diet is vegetable based and wheat is the staple food crop. Wheat flour is purchased locally and used for making chapatti and roti, which are consumed with every meal.

Study community in KPK showing brick kiln workers

Study community in KPK showing brick kiln workers

The programme of work includes three Work Packages:

WP1 – A trial effectiveness study of the potential of biofortified wheat (Zincol-2016) to improve zinc and iron status among adolescent girls and children living in a low resource community in Pakistan.

WP2 – A spatial modelling study to integrate soil and crop data, together with environmental covariates, to enable prediction and mapping of the variation in wheat grain zinc concentration due to soil properties, farmer management and wheat variety.

WP3 – A mixed methods study to understand the socio-cultural factors and market systems that affect the sustainable uptake of biofortified wheat in Pakistan.

 

For more information please contact Dr Heather Ohly, Research Fellow in Global Nutrition, University of Central Lancashire by email: HOhly1@uclan.ac.uk or follow our website.

Research team meeting in Islamabad in 2018

Research team meeting in Islamabad in 2018

References

1.    Lockyer S, White A and Buttriss JL. Biofortified crops for tackling micronutrient deficiencies – what impact are these having in developing countries and could they be of relevance within Europe? Nutrition Bulletin 2018; 43: 319-357. doi:10.1111/nbu.12347

2.     Saltzman A, Birol E, Oparinde A, Andersson MS, Asare-Marfo Det al. Availability, production, and consumption of crops biofortified by plant breeding: current evidence and future potential. Annals of the New York Academy of Sciences2017; 1390: 104-114. doi:10.1111/nyas.13314

3.     Bhutta Z, Soofi S, Zaidi S, Habib A, Hussain M. Pakistan National Nutrition Survey, 2011: https://ecommons.aku.edu/pakistan_fhs_mc_women_childhealth_paediatr/262

4.     Ohly H, Broadley MR, Joy EJ, Khan MJ, McArdle H et al. The BiZiFED project: Biofortified zinc flour to eliminate deficiency in Pakistan. Nutrition Bulletin 2019; 44: 60-64. doi:10.1111/nbu.12362

ORS and zinc deserve equal investment to defeat diarrheal disease

ORS and zinc deserve equal investment to defeat diarrheal disease

In a guest blog for IZiNCG, Hope Randall, Digital Communications Officer at PATH’s Defeat Diarrheal Disease (DefeatDD) Initiative asks you to get behind a proposal to add co-packaged oral rehydration solution + zinc to national essential medicines lists.

ORS and zinc TW.jpg

The World Health Organization (WHO) recommends both oral rehydration solution (ORS) and zinc as the gold standard treatment for diarrhea, yet awareness of and access to both remains remarkably low. This is even truer of zinc than of ORS. 

Important nutrients like zinc, that are key for healthy growth and development, become depleted when a child has diarrhea. A vicious cycle of malnutrition and repeated infections is a common struggle for children who survive. Zinc helps ameliorate these effects in a child’s body, reducing the duration and severity of diarrhea and prevents future episodes for up to three months. Zinc also picks up where ORS leaves off, decreasing mortality or treatment failure by 40%. 

Low awareness is a key barrier to combined use of these medicines—only about a third of the children who need ORS get it—but use of zinc as a diarrhea treatment is even lower, with low awareness contributing to additional logistical barriers like facility stock-outs. And even in the rare event that the stars of awareness and availability are aligned, there is still affordability to contend with.  

Sometimes the simplest solutions are the most powerful. PATH and other global stakeholders are advocating for more countries to follow in the footsteps of Ghana, Zambia, Kenya, Senegal, and Vietnam to include co-packaged ORS + zinc into their national essential medicines lists for children. 

AllStar_Macro_3_TW_V2.1.jpg

Many countries include ORS and zinc in their national lists as separate medicines, which is a good beginning. But adding co-packaged ORS + zinc as a single entity to the list holds greater potential to boost awareness and uptake of the WHO-recommended combined treatment for diarrhea. 

The listing helps prioritize the co-pack in country expenditures, procurement and supply, and training of healthcare providers. Essentially, it creates an enabling environment for greater use of both medicines together, and all at a lower cost to families: in some countries, co-packaged ORS + zinc is estimated to be 46% more affordable than purchasing both medicines separately. Ultimately, that means greater healing and protection of children from the destructive impact of diarrheal infections.

And if two medicines are what it takes to protect children from the effects of diarrhea, it seems right to think of them as a non-negotiable package deal. Parents shouldn’t have to choose between them. Learn more about how to get involved.

Digging deeper into the relationship between zinc and environmental enteric dysfunction 

Digging deeper into the relationship between zinc and environmental enteric dysfunction 

Julie Long from the University of Colorado, Denver shares insights from a recently published study investigating zinc absorption from micronutrient powders (MNP) in Bangladeshi toddlers at risk of environmental enteric dysfunction.

 "Apart from contributing to the generation of knowledge, getting involved in this study was a memorable experience for me, as working with children of this age is always lots of fun and challenging at the same time. Julie, Novo and I had to spend long hours in the Clinical Trial Unit, but it never felt boring." – Dr. Prasenjit Mondal

Many young children in low-resource settings, such as Bangladesh, have malnutrition with poor growth and high rates of stunting.  Deficiencies of micronutrients are also high, including for iron and zinc.  Zinc deficiency, which causes poor growth, is prevalent in Bangladesh, with rates of nearly 50% in young children.  In recent years, there has also been increasing recognition of the role of the subclinical disorder environmental enteric dysfunction (EED) on this poor growth. EED causes gastrointestinal dysfunction, nutrient malabsorption and inflammation.   

As of current, the WHO recommends point-of-use fortification with MNP that contain 5 mg of zinc for children in setting where anemia rates are greater than 20%. It is unclear if the 5 mg of zinc in MNP is sufficient to meet the needs of children with EED and zinc deficiency, as children with both of these conditions are suspected to have higher requirements.

This question led researchers at the University of Colorado Denver and the International Centre for Diarrhoeal Disease Research, Bangladesh to collaborate on a project to answer the following:

·      How do children with EED absorb zinc and is 5 mg enough to meet their needs?

·      What dose of zinc in MNP is needed to meet the estimated requirements of children at risk for EED?

Researchers recruited toddlers at risk for EED from the peri-urban slums in Dhaka, Bangladesh. Children were randomized to receive MNP with 0, 5, 10, or 15 mg of zinc. Upon enrollment, toddlers’ gut function was measured using the lactulose:mannitol ratio (L:M). Absorbed zinc from a day’s total intake (including MNP of assigned dose) was measured, using stable zinc isotope tracers. Researchers also measured total dietary zinc and phytate, and assessed intestinal inflammation. 

Although the investigators intended to identify children with both normal and abnormal gut function, results indicated that virtually all children had evidence of gut dysfunction, i.e. consistent with EED. Zinc absorption was remarkably lower for all MNP doses. The data indicated that a MNP dose of at least 10 mg would be needed to meet requirements. This is in contrast to infants in the U.S. who were found to be able to meet zinc requirements with only ~ 3-4 mg/day.  Secondary analysis of biomarkers of intestinal and systemic inflammation were also high for most enrolled children. 

The extent to which zinc absorption was impaired for these children was greater than predicted. The results suggest that children at risk for EED and zinc deficiency likely need MNP with more than 5 mg of Zn to meet their nutritional needs to support healthier growth and development. 

Read more about IZiNCG’s ZiPT Trial, which also addresses the question of zinc dose in MNPs, here.

Read more about zinc supplementation here.

Photo credit: World Bank Photo Collection

IZiNCG Practical Tips for collecting blood in the field for assessment of plasma or serum zinc concentration

IZiNCG Practical Tips for collecting blood in the field for assessment of plasma or serum zinc concentration

The second edition of IZiNCG Practical Tips: Collecting blood in the field for assessment of plasma or serum zinc concentration is now available on our website.

The document briefly covers the following topics:

  • Precautions to prevent transmission of infectious agents when handling blood samples 

  • Practices and supplies to avoid zinc contamination of samples 

  • Tips for blood collection technique 

  • Tips for processing samples 

  • Tips for aliquoting of samples in the field laboratory 

  • Tips for sample analyses 

  • Information on reference laboratories

  • Tips for statistical analyses 

  • List of trace element-free blood collection supplies 

  • Image examples of field laboratory hoods

  • Example laboratory protocols for the analysis of plasma/serum zinc by flame atomic absorption spectrophotometry and inductively coupled plasma–optical emission spectrometry (ICP-OES) 

Please contact IZiNCG with any questions or comments regarding this brief.

Determining the risk of zinc deficiency: Assessment of dietary zinc intake - Second Edition published!

Determining the risk of zinc deficiency: Assessment of dietary zinc intake - Second Edition published!

Assessing the prevalence of inadequate dietary zinc intakes provides information on the risk of zinc deficiency in a population. 

Determining the risk of zinc deficiency: Assessment of dietary zinc intake takes you through the five main steps of assessing the adequacy of dietary zinc intake. These steps are:

  1. Determine the survey design

  2. Select a representative population sample

  3. Determine food intakes

  4. Estimate dietary intake of absorbable zinc

  5. Determine the prevalence of inadequate zinc intakes

Updates in this Second Edition of IZiNCG Technical Brief no. 3 include instructions for calculation of absorbable zinc, including a worked example, and a section on additional resources.

All of IZiNCG’s Technical Briefs are available here.