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Zinc absorption

Phytase added to SQ-LNS increased zinc absorption

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

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

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 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

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.

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