Systematic review of factors influencing zinc bioavailability

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Systematic review of factors influencing zinc bioavailability Dr Nicola M Lowe International Institute of Nutritional Sciences and Food Safety Studies University of Central Lancashire. COST: Modifying the composition of plant foods for better mineral nutrition. June 4-5 th 2012

Overview Context- importance of improving zinc bioavailability from a global perspective EURRECA network- systematic review of factors affecting zinc absorption Concluding comments

Global Context Middle and low income countries Stunting, severe wasting and intrauterine growth restriction together are responsible for 2.2 million deaths and 21% of disability-adjusted life years for children under 5 years old. Deficiencies of vitamin A and zinc are estimated to be responsible for 0.4 million deaths (Black et al. Lancet 2008) Pakistan Pakistan, 370,000 child deaths per year linked to malnutrition. 44% children are stunted 32% underweight 42% women 37% children are zinc deficient. (National Nutrition Survey 2011) Baghbanan- a rural village in NW PK 38% of children under five years old found to be underweight 40% of children under five years are stunted (Lowe et al unpublished data)

Dietary patterns in Baghbanan, NW Pakistan 90 80 70 84,2 76,3 69,3 81,6 60 50 43,9 40 30 20 10 0 7,9 27,2 27,2 9,6 21,1 9,6 5,3 0,9 6,1 6,1 6,1 7,9 2 1,8 1,8 1,8 0 1,8 0,9 Milk Meat Legumes/ pulses Fruits Vegetables 0 Daily 1-2 times 3-4times None Ocassinaly (Lowe et al unpublished data)

Improving zinc bioavailability Improve quality of complementary foods Quality-micronutrient content and bioavailability Increase intake of animal products? Developing countries- not possible Alternative strategies Supplementation Fortification biofortification Food processing fermentation Germination GM Crops

EURRECA European Micronutrient Recommendations Aligned Priority micronutrients: Zn, Fe, I, Folate, B12

Background The dietary reference values (DRV s) for zinc are based on estimates of zinc requirements, however there is a large variation in the values set by expert panels across Europe. There are many explanations for this high degree of variation, including differences in research data used, expert opinion and the methodology employed. One of the aims of the Eurreca Network of Excellence is to harmonise the approach to setting DRV s.

Step 1: Establishing selection criteria Step 2: Setting up a Committee of experts Step 3: Establishing best practice methods Step 4: Collecting available scientific data Step 5: Integrating evidence into requirements Step 6: Deriving DRV from requirements Step 7: Identifying the most appropriate policy options Identification of which Micronutrient Population group Health outcome Purpose Composition Goal Collation via evidence on: Intake Status Health outcomes (Systematic) review procedure Intake-status-health Bioavailability, interactions Factorial estimates Inter-individual variability Health space Dose-response Factorial approach & bioavailability Individual variability Multiple micronutrients Factorial approach & bioavailability Scaling Global approach I-S-H Dose response model Criteria for policy instruments feasability (cost) effectiveness Equity EURRECA Micronutrient Requirement Process Flow chart: aims to facilitate the scientific alignment of micronutrient requirements = 7 steps. Matthys et al 2011 Int J Vitam Nutr Res. Step 8: Implementing policy instruments and evaluating their impact

Factorial approach for setting DRV S = Basal losses (e.g. faeces, sweat) Zn + Bioavailability factor (fractional absorption) Requirement for maintenance & growth Zn Factors affecting absorption have an impact on dietary recommendations Zn

Systematic Review Questions: What are the key factors that affect zinc gains in all population groups? How well is zinc absorbed from meals and whole diets? Search protocol designed by UEA Ovid Embase Ovid Medline Cochrane Central Inception to Dec 2010 Reference lists searched.

Systematic Review- population groups Screened and sorted Human studies Adults and Elderly Pregnant and Lactating women Children and Adolescents Infant Language Data extracted and meta-analysis where possible

20 for meta-analysis

Results of Systematic review in Adult and Elderly populations Dietary component Number of studies Phytate 30 Inhibitor Micronutrients 16 Ca-?inhibitor Folic acid- no effect Iron- no effect Tin- inhibitor Ascorbic acid -? Summary of effect on Zn absorption Zn (food and supplements) 10 Subject to homeostatic control Proteins 13 Zn absorption enhanced from animal protein Human Milk vs cows Milk vs whey based Formula Oxalate 1 No affect Fat/Cholesterol 1?enhancer Tea 1 No affect Maillard Browning 1 Inhibitor Dairy 1 Enhancer 2 Zn absorption enhanced from human milk

All studies- overall effect

Grouping by P:Zn molar ratio P:Zn P:Zn ratio for high P meal is >15, and for the low Zn meal is <15 P:Zn ratio for high P meal is >15, and for the low Zn meal is >15 P:Zn ratio for high P and low P meal is <15

Grouping by single meal vs diet

Saturation transport model Miller et al J Nutr 2007 Model developed from a biochemical and physiological understanding of the absorption process Absorbed zinc is modelled as a function of both dietary zinc and phytate. Variables modelled were the total daily dietary zinc (TDZ) and phytate (TDP) ingested and total daily absorbed zinc (TAZ) from all the meals over an entire day

Fit of data to trivariate model (Miller et al J Nutr 2007) >80% of the variability in absorbed zinc is explained

Conclusions Phytate potent inhibitor of zinc absorption Meta analysis reveal an overall effect of 14% reduction in fractional zinc absorption from a high phytate vs low diet Use of modelling techniques/algorithms may be useful in setting DRVs for Zn Research priorities More data required for other potential inhibitors Improved strategies to increase Zn content and bioavailability in developing countries More data for infant populations Genetic variations in the metabolism of Zn Casgrain et al. AJCN 2010 91(S) Hambidge AJCN 2010 91(S)

Global context

Acknowledgements http://www.eurreca.org/ University of East Anglia Susan Fairweather-Tait, Kate Ashton, Amélie Casgrain, Rachel Collings, Linda Harvey and Lee Hooper designed and developed the review protocol and search strategy University of Zaragoza, Spain Sylvia Bel Luis Moreno

Thank you for your attention UClan Team Fiona Dykes Victoria Moran Fiona Nicky Victoria Marisol Warthon- Medina Anna Sol Anna Skinner Sujata Patel Questions?