Portable X-ray fluorescence of zinc applied to human toenail clippings

Could toenail zinc content assessed by portable X-ray fluorescence be a field friendly biomarker of zinc status? Professor David Fleming of Mount Allison University describes where the science is at.

Zinc deficiency is a widespread problem which has been associated with a variety of serious health effects. Diagnosing zinc deficiency at the individual level is, unfortunately, a somewhat thorny issue. Currently, there is no single method of determining zinc status which is both simple and reliable. The best option is probably the measurement of plasma (or alternatively serum) zinc concentration [1,2]. This approach, however, requires a sequence of non-trivial steps pertaining to the sample acquisition, storage, and analysis (usually at a distant lab). Other reliable or potentially useful biomarkers of zinc status have been noted, including zinc concentration in urine and hair [1,2]. These approaches also have drawbacks.

Zinc concentration in nail was recently described as an “emerging biomarker” by the Biomarkers of Nutrition for Development (BOND) zinc expert panel [2]. This designation indicates that nail zinc concentration has a theoretical association with zinc status, but requires further study. This need for additional development was reinforced in a Technical Brief from IZiNCG, which provided an overview of assessing zinc exposure using hair or nail zinc [3]. 

Toenail clippings ready for measurement by portable X-ray fluorescence (Photo: David Fleming)

We recently conducted a study involving the measurement of zinc concentration in toenail clippings using two different methods: portable X-ray fluorescence (XRF) and inductively coupled plasma-mass spectrometry (ICP-MS) [4]. Of the two methods, portable XRF is a relatively new approach to zinc biomarker analysis, while ICP-MS may be considered a “gold standard”. We measured single toenail clippings from 60 different individuals living in Atlantic Canada (the population was drawn from the Atlantic PATH cohort [5]). The clippings were measured first by portable XRF, a non-destructive technique, and then by ICP-MS. The population average zinc concentration was found to be 85 µg/g from ICP-MS. The portable XRF technique was very sensitive to detecting zinc in the clippings and provided a reasonable estimate of zinc concentration. Using the XRF output spectrum to determine a normalized zinc signal, we found a correlation coefficient r = 0.68 between the XRF results and the ICP-MS zinc concentrations. Looking forward, correlation between the two methods might be improved by measuring multiple points on each clipping when using XRF – in our study, only a single point on each clipping was assessed by XRF.

Single toenail clipping in portable X-ray fluorescence instrument (Photo: David Fleming)

Single toenail clipping (Photo: David Fleming)

The portable XRF approach presents a number of potential advantages for the analysis of zinc concentration in nail clippings. Measurements could be made in a field setting and results provided quickly. Sample preparation is minimal, operating conditions are simple, and the technique is relatively inexpensive. If the correlation of XRF results with ICP-MS concentrations could be improved, portable XRF might therefore be an especially attractive approach for assessing zinc concentration in nail clippings. The other critical issue here, of course, is whether zinc concentration in nail is truly representative of an individual’s zinc status. That remains an open question which will require additional study to resolve. If zinc concentration in nail is eventually upgraded from “emerging biomarker” to “useful biomarker”, we anticipate that portable XRF will receive a great deal of attention and become a potentially important component of public health initiatives targeting zinc deficiency.

References

[1] N.M. Lowe, K. Fekete, T. Decsi, Methods of assessment of zinc status in humans: a systematic review, Am. J. Clin. Nutr. 89 (2009) 2040S-2051S.

[2] J.C. King, K.H. Brown, R.S. Gibson, N.F. Krebs, N.M. Lowe, J.H. Siekmann, D.J. Raiten, Biomarkers of nutrition for development (BOND) – zinc review, J. Nutr. 146 (2016) 858S-885S.

[3] International Zinc Nutrition Consultative Group (IZiNCG) Technical Brief No. 8, Assessing population zinc exposure with hair or nail zinc (2018), https://www.izincg.org/technical-briefs

[4] D.E.B. Fleming, S.L. Crook, C.T. Evans, M.N. Nader, M. Atia, J.M.T. Hicks, E. Sweeney, C.R. McFarlane, J.S. Kim, E. Keltie, A. Adisesh, Portable X-ray fluorescence of zinc applied to human toenail clippings, J. Trace Elem. Med. Biol. 62 (2020) 126603.

[5] E. Sweeney, Y. Cui, V. DeClercq, P. Devichand, C. Forbes, S. Grandy, J.M.T. Hicks, M. Keats, L. Parker, D. Thompson, M. Volodarsky, Z.M. Yu, T.J.B. Dummer, Cohort profile: the Atlantic partnership for tomorrow’s health (Atlantic PATH) study, Int. J. Epidemiol. 46 (2017) 1762-1763i.

Preventive and Therapeutic Zinc Interventions and Diarrhea Outcomes in Laotian Children

In this guest blog for IZiNCG, Dr Maxwell A Barffour and Dr Guy-Marino Hinnouho provide insights from a recent publication titled Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial.

Background

Over 500,000 young children die from complications of diarrhea each year, with a disproportionately higher burden (>90%) in low- and middle-income countries. Since, 2004, the World Health Organization and UNICEF have recommended the use of therapeutic zinc, along with oral rehydration therapy (ORS), for the treatment of acute diarrhea episodes [1, 2]. This strategy, which requires the use of 20 mg zinc, given daily for 10-14 days during diarrhea episodes, is supported by results of several trials and reviews, which collectively indicate that in children 6 months and older, adjunctive treatment of diarrhea with zinc reduces diarrhea severity. Specifically, the evidence suggests that therapeutic zinc shortens the duration of diarrhea and reduces the number of episodes progressing to persistent diarrhea [3]. Limited evidence also suggests that therapeutic zinc may reduce the incidence of new diarrhea episodes in the 2-3 months following treatment initiation [4].

There are several limitations to a therapeutic approach to zinc supplementation. Because this strategy requires appropriate recognition of diarrhea, motivation to seek treatment and access to a health care facility, coverage is often low [5, 6]. In addition, this strategy has not been shown to affect other functional outcomes related to zinc deficiency, such as physical growth and risk of pneumonia. Hence a goal of this study was to compare the health benefits of therapeutic and preventive strategies for delivering zinc. Furthermore, when delivered as a preventive supplement, zinc may be given as a single zinc-alone supplement, or as part of a multiple micronutrient powder (MNP). Generally, MNP formulations are deemed more desirable because of the ability to target multiple micronutrient deficiencies. However, some evidence suggests that because zinc interacts with other nutrients, zinc delivered as  part of  MNP may not be as effective as zinc delivered alone. Therefore, an additional goal of this study was to compare  two preventive zinc strategies (i.e. zinc alone or MNP) with respect to their effect on diarrhea outcomes.

Photo credit: Sonja Hess

Study Design and Study Population

This blog summarizes a study published in the Journal of Global Health which aimed to assess the benefits of two preventive zinc supplementation regimens and a therapeutic zinc supplementation for diarrhea, on the incidence and duration of diarrhea episodes [7]. The trial was implemented from September 2015 through April 2017 in rural communities in Khammouane Province, Lao PDR. The province was selected because of the  high prevalence of stunting [8], a proxy indicator of zinc deficiency. In addition, the province had no existing programs delivering micronutrient interventions at the time of the study. A pilot survey completed in 2015 found that ~62% of children (6- 23 months) were zinc deficient (plasma zinc concentrations <65 μg/dL).

The study included children 6-23 months at enrollment [9]. Children were randomly assigned to one of four groups, namely a preventive zinc group (7mg zinc /d as dispersible tablet), a therapeutic zinc group (20 mg/d for 10 days) given in relation to diarrhea episodes, and a daily preventive MNP group (containing 10 mg zinc, 6 mg iron + 13 other micronutrients). A fourth group, the control group, received a daily placebo powder, and in addition, a placebo tablet during diarrhea episodes. Each child was followed for up to 9 months, or until lost to follow-up. Reported diarrhea episodes were assessed during weekly home visit. Diarrhea was defined as 3 or more lose stools in a 24-hr period. 

Photo credit: Maxwell Barffour

Photo credit: Maxwell Barffour

Relevant baseline characteristics and compliance

Overall, 3407 eligible children were enrolled and randomized into one of the four groups (i.e. therapeutic zinc (n=851), preventive zinc (n=852), MNP (n=852) and control (n=852)). About 87% of the children enrolled completed the scheduled 9 months of follow-up. The participants who completed the study were similar to those who did not with respect to age and other baseline characteristics including anemia. 

The mean age of participating children was 14 months, and the prevalence of stunting (40%), and anemia (55%) suggested a population with a high prevalence of chronic malnutrition. Most of the children (>70%) were breastfed at the time of the baseline survey. Reported adherence to the daily preventive supplements was 92%. Diarrhea treatment was initiated for ~87% of all diarrhea episodes, and on average, 7 out of the 10 tablets were given to children who needed treatment for diarrhea. 

Main results

Overall, 2013 children (representing ~60% of the study population) experienced at least one diarrhea episode during the course of the follow-up. The overall incidence of acute diarrhea was low ( <1 episode per 100 days at risk) and each episode lasted about 2 days. There was no overall difference in either the diarrhea incidence or duration across the four groups. Because previous studies have established that the impact of zinc on diarrhea tended to vary by age, a goal of this study was to also assess evidence of such age variation. We found that older children (i.e. those 18 months of age and above) tended to benefit from the therapeutic zinc supplementation. In this age group, the duration of diarrhea was significantly lower in those who received the therapeutic zinc compared to the control group. Similarly, the incidence of recurrent diarrhea episodes (i.e. episodes occurring after a prior diagnosis) was significantly reduced among the therapeutic zinc group compared to the control group. The preventive zinc and the MNP  had no impact on diarrhea incidence or duration, regardless of the child’s age. Also, noteworthy, the MNP was not associated with an overall adverse effect on diarrhea incidence or duration.

Concluding remarks

Finding of this study suggest that therapeutic zinc may confer protective benefits against diarrhea in this population, especially if delivered to older children. It is plausible that the observed impact seen in older children may be due to a zinc-dependent enhancement in adaptive immune response. Contrary to evidence from several prior studies and systematic reviews, preventive zinc did not have an impact on diarrhea in this population. This lack of effect may have been due to the fact that the overall incidence of diarrhea in this population was relatively lower than those observed in other populations. Finally, the  MNP, which contained a daily iron dose of 6 mg was not associated with an overall increase in the diarrhea incidence. It is worth mentioning that in children with genetic hemoglobinopathies, the MNP was associated with a small increase in diarrhea incidence. Overall, the findings from this study highlight the need for continuing research to find optimal strategies for improving nutritional and health status in this population.

Additional findings  from the Lao Zinc Study

The Lao zinc study was also designed to assess  treatment effect on micronutrient status, anemia and physical growth.  Below is a summary of findings as published in the Journal of Pediatrics [10]:

• Therapeutic zinc had no impact on zinc, iron or vitamin A status.

• Preventive zinc significantly improved zinc status.

• MNP improved zinc  and iron status.

• MNP had a marginal positive impact on hemoglobin and anemia, with a significant impact among children who were anemic at baseline.

Photo credit: Maxwell Barffour

Relevant references

1.         WHO, U., Clinical management of acute diarrhoea in children: WHO/UNICEF joint statement. Geneva: World Health Organization; 2004. http://www.who.int/maternal_child_adolescent/documents/who_fch_cah_04_7/en/, 2004.

2.         World Health Organization; UNICEF., Zinc supplementation in the management of diarrhoea.http://www.who.int/elena/titles/zinc_diarrhoea/en/ 2016. Accessed 2016 September 28.

3.         Lazzerini, M. and H. Wanzira, Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev, 2016. 12: p. Cd005436.

4.         Baqui, A.H., et al., Effect of zinc supplementation started during diarrhoea on morbidity and mortality in Bangladeshi children: community randomised trial. BMJ, 2002. 325(7372): p. 1059.

5.         Sabot, O., et al., Scaling up oral rehydration salts and zinc for the treatment of diarrhoea. Bmj, 2012. 344: p. e940.

6.         Ram, P.K., et al., Declines in case management of diarrhoea among children less than five years old. Bull World Health Organ, 2008. 86(3): p. E-f.

7.         Barffour MA, Hinnouho GM, Wessells KR, et al. Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial. J Glob Health. 2020;10(1):010424. doi:10.7189/jogh.10.010424

8.         Bureau., M.o.H.a.L.S., Lao People's Democratic Republic Special, 2011–12 - Lao Social Indicator Survey (MICS/DHS) Final Report (English) Vientiane: Ministry of Health and Lao Statistics Bureau. 2012.

9.         Wessells, K.R., et al., Comparison of two forms of daily preventive zinc supplementation versus therapeutic zinc supplementation for diarrhea on young children’s physical growth and risk of infection: study design and rationale for a randomized controlled trial. BMC Nutrition, 2018. 4(1): p. 39.

10.       Barffour, M.A., et al., Effects of Daily Zinc, Daily Multiple Micronutrient Powder, or Therapeutic Zinc Supplementation for Diarrhea Prevention on Physical Growth, Anemia, and Micronutrient Status in Rural Laotian Children: A Randomized Controlled Trial. J Pediatr, 2018.

Contact:

Maxwell A Barffour, Missouri State University, MaxwellABarffour@missouristate.edu

Read more on this topic:

Preventive zinc supplementation in children

Zinc as part of the treatment of diarrhea

The ZiPT trial

World Breastfeeding Week 2020

World Breastfeeding Week is always a good opportunity to highlight the importance of breastfeeding for adequate zinc nutrition.

Promotion and support of appropriate breastfeeding practices is a recommended strategy to enhance the zinc status of infants and young children, for two main reasons:

1. Breastmilk is an important source of bioavailable zinc

2. Breastfeeding protects against diarrhea, which causes excessive zinc losses.

And 3. Support breastfeeding for a healthier planet! (the #WBW2020 theme)

Safe and appropriate complementary foods should be introduced at 6 months of age, with continued, frequent, on-demand breast feeding until at least 2 years of age as described in the WHO publication Guiding Principles for Improved Complementary Feeding Practices. To ensure the nutrient needs for zinc are met, a variety of foods that includes meat, poultry, fish or eggs should be provided daily or as often as possible.

Relevant IZiNCG publications:

IZiNCG Technical Brief no. 5 Preventing zinc deficiency through diet diversification and modification

In IZiNCG Technical Document #2 Dietary intervention strategies to enhance zinc nutrition: Promotion and support of breastfeeding for infants and young children

New IZiNCG Technical Brief: A Field-Friendly Method for Measuring Dietary Phytic Acid Species in Plant-based Foods

IZiNCG Technical Brief no. 11 is now available! The brief describes a low-tech, low-cost Polyacrylamide Gel Electrophoresis method for measuring phytic acid.

Dietary phytic acid reduces zinc absorption and is an important cause of zinc deficiency, especially for populations in low-income countries where diets rely on unrefined cereals and legumes. In order to estimate the risk of zinc deficiency or to establish dietary zinc recommendations in a population, measuring the phytate content of food is required 

Phytic acid, myo-inositol hexaphosphate (IP6)

In addition to phytic acid, or myo-inositol hexaphosphate (IP6), its breakdown product IP5 can also negatively impact zinc absorption. However other, less-phosphorylated inositol phosphates (IP4 onwards) have a much lower effect. Therefore, analytical methods must have the ability to separate out phytic acid and its breakdown products.  

The current gold standard for analysis of phytic acid and its breakdown products is analysis by high-performance liquid chromatography (HPLC). This method requires specialized, expensive equipment and highly trained technicians.

Polyacrylamide Gel Electrophoresis (PAGE) methods are common in many laboratories. A PAGE method has been developed that has an adequate detection level for typical levels of phytic acid in foods, provides adequate separation and quantification of phytic acid and less-phosphorylated inositol phosphates, is high-throughput, low-cost (10% of HPLC), widely available, and does not require substantial expertise or training.

This new Technical Brief provides an overview of the PAGE method in comparison to HPLC. It is also accompanied by a Practical Tips document describing the method in more detail, targeted at laboratory technicians.

Other Technical Briefs on on dietary assessment and phytic acid from IZiNCG:

Technical Brief no. 3 Determining the prevalence of zinc deficiency: Assessment of dietary zinc intake

Technical Brief no. 5 Preventing zinc deficiency through diet diversification and modification

Technical Brief no. 7 Tools to assess dietary zinc intake in populations

Newsletter No. 4 is out!

We have summarized updates from IZiNCG in our Newsletter No. 4! Despite delays and challenges, we are pleased to report progress on many projects and the publication of a new IZiNCG Technical Brief.

We would also like to thank you for visiting our website for news and resources. IZiNCG aims to pool together the talents and experience of the world's leaders in zinc nutrition and become a global resource for the best science, strategic thinking, and policy recommendations to control zinc deficiency.

Our small group cannot achieve this mission without the help, collaboration and direction from our wider nutrition and health community. We would love your feedback, whether you are a student or a program director!

You can contact us on secretariat@izincg.org, or by using this contact form.

With kind regards,

Christine McDonald (Director) and Mari Manger (Deputy Director)

Photo credit: Dominic Chavez, World Bank

NEW IZiNCG TECHNICAL BRIEF: ADJUSTING PLASMA OR SERUM ZINC CONCENTRATIONS FOR INFLAMMATION

A new technical brief is now available, outlining when and how plasma/serum zinc concentrations should be adjusted for inflammation. 

Plasma or serum zinc concentration (PZC) is considered the best available biomarker of population zinc status. However, PZC may be depressed in the presence of inflammation, and in settings with a high burden of infection, this could lead to artificially high estimates of the prevalence of nutritional zinc deficiency.

C-reactive protein (CRP) and alpha-1-acid glycoprotein (AGP) are two acute phase proteins most commonly assessed to measure inflammation.  As part of the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anaemia (BRINDA) project, an analysis was carried out to answer the following questions:

1. Is there a need to adjust PZC for inflammation to estimate the prevalence of nutritional zinc deficiency in preschool-aged children or women of reproductive age?

2. Is it necessary to adjust PZC for CRP, AGP or both?

3. How do the different adjustment approaches compare?

This new technical brief summarises the findings from this analysis. The reader can refer to the full journal article for further information. For more reading about the measurement of plasma or serum zinc concentrations, refer to previous IZiNCG Technical Briefs and Technical Documents, IZiNCG Practical Tips, and the Biomarkers of Nutrition for Development (BOND) - Zinc Review.

Phytase added to SQ-LNS increased zinc absorption

In their guest blog for IZiNCG, Sarah Zyba and Ryan Wessells from UC Davis describe the findings from a randomized controlled trial where the addition of exogenous phytase to small-quantity lipid-based nutrient supplements (SQ-LNS) increased absorption of zinc from a meal of millet-based porridge containing SQ-LNS in young Gambian children.

Young children in low- and middle- income countries like The Gambia are at risk for zinc deficiency because of high rates of infection and dietary zinc inadequacy common in these settings (1). Additional zinc can be provided to young children through supplementation, large-scale food fortification of staple foods, or the home fortification of complementary foods with products such as multiple micronutrient powders, fortified blended foods (e.g. Supercereal Plus) or small-quantity lipid-based nutrient supplements (SQ-LNS). SQ-LNS are typically a peanut and milk powder-based paste, fortified with vitamins and minerals and designed to be added to complementary foods (2).

However, many of the complementary foods eaten with SQ-LNS are cereal-based and high in phytate. Phytate is a phosphorus storage molecule that also binds minerals such as calcium, iron and zinc (3). Phytate is not easily digested by humans, which causes low absorption of minerals, including zinc, from foods or meals that are high in phytate. Phytase, an enzyme which breaks down phytate, can free phytate-bound zinc in the diet making it more available for absorption. Phytase is naturally found in some foods, such as wheat, in small amounts. Phytase can also be added to foods during the manufacturing process. 

The primary objective of this study was to assess the effect that adding phytase to SQ-LNS had on zinc absorption. We did this by using a dual stable zinc isotope tracer method (4,5). Two SQ-LNS products were manufactured by Nutriset SAS; one was a standard formulation without phytase and one was the same formulation with 550 FTU (phytase units) of phytase added at the point of manufacture. In a collaboration between the University of California, Davis Institute for Global Nutrition, and the Medical Research Council Unit, The Gambia, we conducted a crossover double-blind randomized controlled trial in Keneba, The Gambia to test these two products.

Field staff during a training session before data collection began. Photo credit: Sarah Zyba

Thirty healthy young children 18 – 24 months of age participated in the study. For two consecutive days, children received a standard breakfast and lunch, which both consisted of a millet-based porridge and 10 g SQ-LNS.  On one day, they received the SQ-LNS product with phytase, and the other day they received SQ-LNS without phytase; the order that they received the two products was randomly assigned. To measure zinc absorption from the test meals, we gave the children oral doses of two different stable zinc isotopes (Zn-67 and Zn-70) while they ate the meals; one stable zinc isotope was given with meals containing SQ-LNS with phytase, and the other stable zinc isotope was given with meals containing SQ-LNS without phytase. At the end of the second day, children received an IV infusion of a third stable zinc isotope (Zn-68). Urine samples were then collected for several days.

Field staff preparing test meals. Photo credit: Sarah Zyba

The ratio of the oral isotopes to the IV isotope (i.e. Zn-67:Zn-68 and Zn-70:Zn-68) in the urine was used to determine the fraction, or percent, of zinc absorbed from each of the test meals. By collecting weighed food records, we were also able to calculate the total amount of zinc absorbed (in mg) from millet-based porridge test meals containing SQ-LNS with or without phytase.

A study participant being fed a test meal by his mother. Photo credit: Sarah Zyba.

A study participant receiving an oral zinc stable isotope from a study fieldworker. Photo credit: Sarah Zyba

We found that the addition of phytase increased the fractional absorption of zinc from test meals containing a millet-based porridge and SQ-LNS from 8.6% to 16.0%. The total amount of zinc absorbed from the test meals more than doubled from 0.5 mg to 1.1 mg when phytase was added to the SQ-LNS.  

This shows that reducing the amount of phytate in the diet by adding phytase to SQ-LNS at the point of manufacture may be an important strategy to increase zinc absorption among young children. Further studies should be conducted to determine the longer-term impact of SQ-LNS with phytase on biomarkers of zinc status and functional outcomes of zinc deficiency.

A publication with more details of the methods and results from this study can be found here.

For more information, please contact Dr. Ryan Wessells, University of California, Davis at krwessells@ucdavis.edu. 

References

1.     Brown KH, Rivera JA, Bhutta Z, Gibson RS, King JC, Lönnerdal B, Ruel MT, Sandtröm B, Wasantwisut E, Hotz C. International Zinc Nutrition Consultative Group (IZiNCG) technical document #1. Assessment of the risk of zinc deficiency in populations and options for its control. Food Nutr Bull 2004;25:S99–203.

2.     Arimond M, Zeilani M, Jungjohann S, Brown KH, Ashorn P, Allen LH, Dewey KG. Considerations in developing lipid-based nutrient supplements for prevention of undernutrition: experience from the International Lipid-Based Nutrient Supplements (iLiNS) Project. Matern Child Nutr 2015;11 Suppl 4:31–61.

3.     Lonnerdal B. Phytic acid-trace element (Zn, Cu, Mn) interactions. Int J Food Sci Tech 2002;37:749–58.

4.     Lopez de Romana D, Salazar M, Hambidge KM, Penny ME, Peerson JM, Krebs NF, Brown KH. Longitudinal measurements of zinc absorption in Peruvian children consuming wheat products fortified with iron only or iron and 1 of 2 amounts of zinc. Am J Clin Nutr 2005;81:637–47.

5.     Islam MM, Woodhouse LR, Hossain MB, Ahmed T, Huda MN, Peerson JM, Hotz C, Brown KH. Total zinc absorption from a diet containing either conventional rice or higher-zinc rice does not differ among Bangladeshi preschool children. J Nutr 2013;143:519–25.

Further reading on strategies to increase zinc absorption:

Gibson RS, Anderson VP. A review of interventions based on dietary diversification or modification strategies with the potential to enhance intakes of total and absorbable zinc. Food Nutr Bull. 2009 Mar;30(1 Suppl):S108-43.

Gibson RS, Raboy V, King JC. Implications of phytate in plant-based foods for iron and zinc bioavailability, setting dietary requirements, and formulating programs and policies. Nutr Rev. 2018 July 13.

Bangkok Micronutrient Forum 5th global conference postponed

Dear colleagues,

Please note the decision to postpone the Micronutrient Forum conference to be held next month:

“Due to guidance from the Government of Thailand, in response to the threat of the novel coronavirus (COVID-19) in Southeast Asia, we are postponing the Micronutrient Forum 5th Global Conference and the Second Global Summit on Food Fortification to a later, as-yet-unspecified date.”

IZiNCG will work closely with the micronutrient forum to ensure that the great scientific programme, including our symposium Advancing efforts to improve zinc nutrition globally, can be enjoyed at a later date.

Read more:

https://micronutrientforum.org/postponement-of-the-micronutrient-forum-5th-global-conference-and-second-global-summit-on-food-fortification/

Fortified Rice for School Children in Cambodia. The FORISCA project.

In their guest blog for IZiNCG, Khov Kuong (DFPTQ, Fisheries Administration, Ministry of Agriculture, Forestry and Fisheries) and Frank Wieringa (the French National Research Institute for Sustainable Development (IRD)) share the findings from the newly published FORSICA project.

Zinc deficiency is highly prevalent in Cambodia. The 2014 Micronutrient Survey in Cambodia found that >60% of the women of reproductive age and under-five children had plasma zinc concentrations <9.9 mmol/L, indicative of zinc deficiency [1]. Other indicators for zinc deficiency, such as stunting prevalence, are highly prevalent too, which the latest Demographic Health Survey (2014) reporting 1 in 3 children being stunted [2]. Although there are few data available, it is likely that zinc status is poor in other age groups in Cambodia, such as in school-aged children. 

To improve zinc status of the Cambodian population, the use of zinc-fortified rice is a tempting solution. The consumption of rice in Cambodia is very high, with >60% of daily energy intake coming from rice. Also, zinc-fortified rice is very stable, without zinc being lost over time, or when using different rice cooking techniques [3]. And rice fortified with zinc, iron, and B-vitamins was found to be highly acceptable in Cambodia [4]. Before the start of the FORISCA ((Fortified Rice for School Children in Cambodia) project, we tested the organoleptic qualities of different types of fortified rice on mothers and school teachers. Interestingly, over 80% of the mothers were capable of picking out correctly the fortified rice out of a sample of 3 plates of rice. But the fortified rice scored high on different aspects of organoleptic qualities, such as smell and taste. 

As the United Nations World Food Program (WFP) in Cambodia was exploring possibilities to improve nutritional status of school children in Cambodia through use of fortified foods in school meal programs, we took the opportunity to test the impact of introducing fortified rice on micronutrient status, morbidity and cognitive development in school children. Together with the US-based NGO PATH, and co-funded by the United States Department of Agriculture (USDA), WFP-DSM consortium and IRD, we recruited almost 10,000 school children within the FORISCA project. The FORISCA project was developed together with the Government of Cambodia’s Ministry of Education, Youth and Sports, The Ministry of Agriculture, Forestry and Fisheries and the National Fortification Board. The aim of the project was two-fold. First, to test whether a daily breakfast with multiple-micronutrient fortified rice could reduce anemia prevalence, improve micronutrient status and improve functional outcomes such as cognitive development and incidence of infectious diseases. The second aim was to test whether different types of fortified rice (i.e. cold extruded vs hot extruded) had different efficacy in improving micronutrient status. For this aim, 3 different types of fortified rice where tested, with different micronutrient composition and different fabrication techniques. 

The micronutrient content of the different fortified rice groups tested in the FORISCA project, per 100 g of uncooked blended rice.

Within the FORISCA project, school children were given a standard breakfast, 6 days per week, for 6 months. The breakfast consisted of rice (~100 g dry rice per child per day), with a sauce of tomatoes, oil (fortified with vitamin A) and fish (~5 g per child per day). Breakfast was prepared every morning in the school kitchen, and meals were distributed over the classes. 

Schools were allocated to receive either normal rice, or one of the 3 different types of fortified rice tested. Children would receive their breakfast at 7 in the morning, and class would start thereafter. Children were assessed for anthropometry, cognitive development and micronutrient status at baseline, midline (after 3 months) and at endline. 

Baseline micronutrient status confirmed our suspicion that zinc status was poor in school-aged children in Cambodia, with >80% of the school children having low plasma zinc concentrations [5]. Severe zinc deficiency, defined as a plasma zinc concentration <7.6 mmol/L) was present in ~50% of the school children. Six-month consumption of rice fortified with zinc significantly reduced the prevalence of zinc deficiency in the children, with the fortified rice with the highest zinc content, (Nutri-Rice) having the greatest reduction. At endline of the study, the prevalence of zinc deficiency and severe deficiency had not changed in the group receiving ordinary rice, and remained very high at 93% and 54% respectively. In contrast, in the Nutri-Rice group, the prevalence of zinc deficiency and severe zinc deficiency had decreased to 66% and 25% respectively. In the Ultra-Rice Improved group of school children, which was the fortified rice with the lowest fortification level of zinc, the prevalence of zinc deficiency and severe zinc deficiency was reduced too as compared to the placebo group, but to a lesser extent than in the Nutri-Rice group (to 83% and 37% respectively). 

We calculated that the zinc fortified rice contributed between 29% (Ultra-Rice improved) and 53% (Nutri-Rice) of the Recommended Daily Allowance (RDA) of the school children over the 6 month intervention period. Clearly, the higher zinc content of the Nutri-Rice contributed to the greater impact on zinc status. But even with ~50% of the RDA covered by the fortified breakfast, 25% of the children remained severely zinc deficient. Given the very high prevalence of zinc deficiency in this population, the amount of zinc in the fortified rice could easily be doubled, to cover 100% of the RDA. Vitamin A status was improved also in the children who received rice fortified with vitamin A, with children in the Ultra-Rice improved and Nutri-Rice groups having a risk for marginal vitamin A status that was 1/5 and 1/4 respectively of children receiving normal rice [6].

The prevalence of anemia in the school children was lower than expected, at 16% [6]. Surprisingly, the prevalence of iron deficiency was very low, with <2% of the children having iron deficiency, and hence, the fortified rice had little impact on anemia prevalence or on improving iron status. Sub-clinical inflammation also played a role here, as in children without inflammation, there was a tendency towards higher haemoglobin concentrations in all the groups receiving fortified rice. 

Another surprising outcome of the FORISCA project was the increase in hookworm infection in the children receiving fortified rice. At baseline, all children were dewormed. However, after 6 months, up to 30% of the children were re-infected, and the re-infection rate was higher in the children receiving fortified rice than in the children receiving normal rice[7]. The re-infection rate was highest in the children receiving the fortified rice with the highest iron content, making us believe that the iron in the fortified rice played a role in enabling the re-establishment of the hookworm infection. Also, as hookworm re-infection rate tended to be higher in the cold-extruded fortified rice groups, bioavailability of iron might have been different between the cold- and hot-extruded rice varieties. 

Finally, despite the differences in zinc content of the 3 groups of fortified rice, both types of extruded fortified rice (cold vs hot extruded rice) were effective in improving zinc status and therefore production method appears not to be an important factor in determining the impact on zinc status of fortified rice. 

The WFP in Cambodia is currently assessing the expanded use of fortified rice in the school meal program, and the aim is to have a rice fortified breakfast for all the children participating in the school meal program, meaning that almost 250,000 children will hopefully receive a fortified rice meal soon.

REFERENCES

1.         Wieringa FT, Dahl M, Chamnan C, Poirot E, Kuong K, Sophonneary P, Sinuon M, Greuffeille V, Hong R, Berger J, et al: The High Prevalence of Anemia in Cambodian Children and Women Cannot Be Satisfactorily Explained by Nutritional Deficiencies or Hemoglobin Disorders. Nutrients 2016, 8.

2.         Cambodia Demographic and Health Survey 2014. [https://dhsprogram.com/pubs/pdf/FR312/FR312.pdf]

3.         Kuong K, Laillou A, Chea C, Chamnan C, Berger J, Wieringa FT: Stability of Vitamin A, Iron and Zinc in Fortified Rice during Storage and Its Impact on Future National Standards and Programs-Case Study in Cambodia. Nutrients 2016, 8.

4.         Khanh Van T, Burja K, Thuy Nga T, Kong K, Berger J, Gardner M, Dijkhuizen MA, Hop le T, Tuyen le D, Wieringa FT: Organoleptic qualities and acceptability of fortified rice in two Southeast Asian countries. Ann N Y Acad Sci 2014, 1324:48-54.

5.         Kuong K, Tor P, Perignon M, Fiorentino M, Chamnan C, Berger J, Burja K, Dijkhuizen MA, Parker M, Roos N, Wieringa FT: Multi-Micronutrient Fortified Rice Improved Serum Zinc and Folate Concentrations of Cambodian School Children. A Double-Blinded Cluster-Randomized Controlled Trial. Nutrients 2019, 11.

6.         Perignon M, Fiorentino M, Kuong K, Dijkhuizen M, Burja K, Parker M, Chamnan C, Berger J, Wieringa FT: Impact of Multi-Micronutrient Fortified Rice on Hemoglobin, Iron and Vitamin A Status of Cambodian Schoolchildren: a Double-Blind Cluster-Randomized Controlled Trial.Nutrients 2016, 8:doi:10.3390/nu8010029.

7.         de Gier B, Campos Ponce M, Perignon M, Fiorentino M, Khov K, Chamnan C, de Boer MR, Parker ME, Burja K, Dijkhuizen MA, et al: Micronutrient-Fortified Rice Can Increase Hookworm Infection Risk: A Cluster Randomized Trial. PLoS One 2016, 11:e0145351.

IZiNCG Symposium at Micronutrient Forum 5th Global Conference March 2020

The Micronutrient Forum 5th Annual Conference will be held in Bangkok from March 23rd to 27th 2020. The theme is Building new Evidence and Alliances for Improving Nutrition, and our colleagues at the Micronutrient Forum are promising their best conference yet!

If you are going to Bangkok, please mark Wednesday March 25th from 12.30 to 2pm in your calendar now for IZiNCG’s Symposium titled Advancing Efforts to Improve Zinc Nutrition Globally. We will present on recent developments and opportunities for action in assessment of zinc status, advances in the delivery of additional zinc to vulnerable populations, and progress in the use of therapeutic zinc as part of diarrhoea treatment. One of the presentations will share preliminary findings from the Zinc in Powders Trial, where data collection is on track to finish by January 30, 2020.

See you there?

Update: The Micronutrient Forum 5th Annual Conference has been postponed and will now take place between November 8-13, 2020.

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 Punjab, 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

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.

Last edited 24.03.2020.

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

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

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.

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

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

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

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

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

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.

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. 

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

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

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!

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.