Harmonization of Approaches to Nutrient Reference Values Applications to Young Children and Women of Reproductive Age (2018) / Chapter Skim
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4 Applying Methodological Approaches to Nutrient Reference Values for Young Children and Women of Reproductive Age: An Assessment of Exemplar Nutrients
4 Applying Methodological Approaches to Nutrient Reference Values for Young Children and Women of Reproductive Age: An Assessment of Exemplar Nutrients
Pages 73-120
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From page 73... ...
This chapter summarizes the committee's application of its proposed framework for deriving NRVs for these exemplar nutrients. The committee did not carry out an analysis for the two population subgroups for each nutrient.
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From page 74... ...
4. Derive two key reference values, the average requirement (AR)
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From page 75... ...
The committee did not carry out analyses for both young children and women of reproductive age for all three nutrients. Rather, the three nutrients were selected to illustrate the application of the framework across age groups.
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From page 76... ...
Shifts in endogenous fecal losses are the primary mechanism for maintaining whole body zinc homeostasis. When the amount of dietary zinc declines, endogenous fecal losses also decline to reestablish zinc balance, at least initially.
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From page 77... ...
Plasma zinc is thought to be a component of this pool. However, a moderate reduction in dietary zinc of 3–5 mg per day reduces plasma zinc concentrations only if the limited intake is continued for several months or if endogenous losses are increased because of diarrheal disease.
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From page 78... ...
Animal studies conducted in the 1980s suggested that calcium could inhibit zinc absorption because of the formation of an insoluble calciumzinc-phytate complex. However, later studies in humans confirmed that calcium did not impede zinc absorption when dietary zinc intake was adequate, regardless of whether phytate concentration was either low or high (Hunt and Beiseigel, 2009)
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From page 79... ...
Dose–Response Estimates The dose–response estimate is not used to estimate zinc NRVs because the primary indicator of zinc status, plasma zinc concentrations, remains constant over a wide range of zinc intakes. Consistent with the evidence cited above, a review of studies of zinc status at the population level showed that serum zinc concentrations remained unchanged from diets providing between 3 and 60 mg zinc/d (Gibson et al., 2008)
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From page 80... ...
Factorial Approach Given the aforementioned limitation of the balance method, and because there is no known biomarker of dietary zinc or a selected health outcome that is sensitive to variations in dietary zinc, the factorial approach is the only method that can be used to estimate the physiological zinc requirement. This approach requires estimating the amount of absorbed zinc needed to replace endogenous zinc losses, as well as estimating the endogenous zinc losses, including both endogenous fecal zinc (EFZ)
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From page 81... ...
1.00 3.30 1.86 2.93 NOTE: EFSA = European Food Safety Authority; IOM = Institute of Medicine; IZiNCG = International Zinc Nutrition Consultative Group; WHO = World Health Organization. Conversion of Physiological Zinc Requirements as Determined by the Factorial Approach to ARs and RIs for Adult Men and Women The estimated AR is the amount of dietary zinc that will replace total endogenous losses.
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From page 82... ...
SOURCE: EFSA NDA Panel, 2014a. itself is based on 650 individual measurements from 18 publications, the European Food Safety Authority (EFSA)
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From page 83... ...
EFSA also based its estimate on the amount of breast milk consumed as well; it concluded that 2.0 mg zinc is required daily based on an average breast milk volume of 0.80 L/d and with a zinc concentration of 2.5 mg/L. All four authoritative bodies used the factorial approach to estimate the AR for absorbed zinc for infants 6 to 12 months and children 1 to 18 years
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From page 84... ...
84 TABLE 4-3 Estimated Physiological Requirements for Absorbed Zinc, ARs (mg/d) , and for the RIs During Childhood by Age Group and Gender WHO IOM Physiol Physiol Wt requirements AR RI Wt requirements AR RI Age, Sex (kg)
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From page 85... ...
(mg/d) 6–11 mo 9 0.84 3 4 7–11 mo 2.4 2.9 1–3 12 0.53 2 3 1–3 11.9 1.074 3.6 4.3 4–8 21 0.83 3 4 4–6 19.0 1.390 4.6 5.5 7–10 28.7 1.869 6.2 7.4 9–13 38 1.53 5 6 11–14 M 44 2.635 8.9 9.4 11–14 F 45 2.663 8.9 9.4 14–18 M 64 2.52 8 10d 15–17 M 64 3.544 11.8 12.5 14–18 F 56 1.98 7 9d 15–17 F 56 2.969 9.9 10.4 NOTE: AR = average requirement; EFSA = European Food Safety Authority; IOM = Institute of Medicine; IZiNCG = International Zinc Nutrition Consultative Group; Physiol = physiological; RI = recommended intake; WHO = World Health Organization; wt = weight.
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From page 86... ...
Thus, increasing dietary zinc intakes from zinc supplements or fortified foods may improve tissue zinc levels and growth in vulnerable populations subsisting on cereal-based diets (Ariff, 2014; Chomba, 2015)
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From page 87... ...
Breast milk zinc appears to be relatively similar among women with different zinc intakes, owing to the redistribution of tissue zinc from uterus involution, and the release of zinc to maternal tissues resulting from the decline in blood volume during early lactation. However, breast milk volume, and thus breast milk zinc concentrations, do change over time.
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From page 88... ...
During Pregnancy and Lactation by WHO, the IOM, IZiNCG, and EFSA WHOa IOMb IZiNCGb EFSAb Pregnancy Lactation Pregnancy Lactation Pregnancy Lactation Pregnancy Lactation AR RI AR RI AR RI AR RI AR RI AR RI AR RI AR RI -- 3.4 -- 5.8 9.5 11 10.4 12 8.0 10 7.0 9 +1.3 +1.6 +2.4 +2.9 4.2 5.3 6.0 4.3 NOTE: EFSA = European Food Safety Authority; IOM = Institute of Medicine; IZiNCG = International Zinc Nutrition Consultative Group; WHO = World Health Organization. a WHO made RI recommendations for each trimester and for 0–3, 3–6, and 6–12 months lactation.
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From page 89... ...
. But, as stated previously, plasma zinc concentrations remain constant over a range of dietary zinc intakes from 4 to 60 mg/d (Gibson et al., 2008)
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. Unfortunately, these biomarkers are also limited in their sensitivity and/or specificity for assessing whole body zinc status, and thus, would not be useful for estimating dietary zinc requirements.
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Reviews addressing dietary factors influencing zinc absorption and physiological losses among various population subgroups are needed. In reference to the four steps for setting NRVs outlined in Figure 3-4, these are the issues regarding zinc recommendations: • Currently, systematic reviews of dietary zinc requirements are lacking.
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From page 92... ...
In addition to data gaps identified and listed in the findings, including the need to continue to search for a reliable biomarker of zinc status that is more sensitive to changes in dietary zinc than plasma/serum zinc concentrations, studies are needed to help identify the potential influence of genetic polymorphisms (i.e., genetic variations) on individual dietary zinc requirements.
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From page 93... ...
Whole Body Iron Utilization and Status Iron absorption is a tightly regulated function; its efficiency is determined in the absence of disease by the size of body iron stores. The iron status of healthy populations is usually measured using serum ferritin level as a biomarker.
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From page 94... ...
Using food preparation techniques that enhance iron absorption, such as cooking in iron pots, may increase iron intake. Iron Bioavailability Iron is absorbed either as heme iron, which is found in meat and fish, or as nonheme iron, as found in plant foods.
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. Assessment of Strengths and Weaknesses in Methodologies to Derive Iron ARs Although attempts have been made to define a dose–response relationship between iron intake and an iron status biomarker or selected health outcome, too many uncertainties remain.
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and status • Difficulty in measuring adaptive and functional responses to varia tions in iron intake • Lack of sensitive and specific markers to determine iron status • Confounding by other dietary and lifestyle factors and by responses to infection and inflammation • Inadequate characterization of iron deficiency anemia and the rela tive role of iron deficiency and other causes of anemia The Factorial Approach In the absence of a sensitive biomarker or health outcome for defining a dose–response relationship for iron intake, the factorial approach is the preferred method for estimating physiological iron requirements. This approach involves estimating the quantity of absorbed iron needed to replace iron losses.
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19 11.4 7 6.5 (≥ 19 y) NOTE: AR = average requirement; Aus/NZ = nutrient reference values for Australia and New Zealand; D-A-CH = Nutrition Societies of Germany, Austria, and Switzerland; EFSA = European Food Safety Authority; IOM = Institute of Medicine; NDA = nutrition, novel foods, and allergens; NL = Netherlands Food and Nutrition Council; NNR = Nordic Nutrition Recommendations; tri = trimester; UK COMA = United Kingdom Committee on Medical Aspects of Food and Nutrition Policy; WHO/FAO = World Health Organization/Food and Agriculture Organization.
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From page 98... ...
took a unique approach to estimating iron requirements by using the whole-body iron loss data derived from isotope studies (Hunt et al., 2009)
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From page 99... ...
EFSA, however, in its determination of an iron intake for pregnancy, did not include an iron allocation for expanding the hemoglobin mass based on evidence that the efficiency of iron absorption increases exponentially up to about 10 mg/d during the last 6 weeks of pregnancy (Barrett et al., 1994; Whittaker et al., 1991)
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From page 100... ...
. When using the factorial approach to calculate additional iron needed to support lactation, some agencies do not account for increased iron losses in breast milk.
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From page 101... ...
NOTE: AR = average requirement; D-A-CH = Nutrition Societies of Germany, Austria, and Switzerland; EFSA = European Food Safety Authority; IOM = Institute of Medicine; NDA = nutrition, novel foods, and allergens; NL = Netherlands Food and Nutrition Council; NNR = Nordic Nutrition Recommendations; RI = recommended intake; UK COMA = United K ingdom Committee on Medical Aspects of Food and Nutrition Policy; WHO/FAO = World Health Organization/Food and Agriculture Organization. The Nordic Council of Ministers (2012)
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From page 102... ...
The model has since been refined and updated and an interactive modeling tool published. • The lack of agreement for reference values is caused largely by the choice of bioavailability factor used to convert physiologi cal requirements into dietary intakes, which results from limited information on iron absorption from complete diets, as well as assumptions about storage iron at conception.
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From page 103... ...
There are challenges for setting an iron UL, but the value is es sential for evaluating the safety of food iron fortification and other public health programs. PROPOSED SOLUTIONS FOR IRON Although authoritative bodies have adopted the factorial method globally, there remains wide variation in NRVs determined for women of reproductive age, mainly attributable to different calculations used to transform physiological requirements into dietary intakes.
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From page 104... ...
Supplementation and food fortification with folic acid reduce the prevalence of NTDs in women of reproductive age, especially in regions where folate status is poor and there is a high baseline prevalence of NTDs. Recognition of this issue has mobilized the global community around recommendations for folic acid requirements, supplementation, and fortification.
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From page 105... ...
Because of this difference in bioavailability between folate and folic acid, the amount of folate present in the diet is calculated as µg food folate + 1.7 × µg folic acid; the sum is expressed as dietary folate equivalents (DFEs)
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From page 106... ...
. The biomarkers used by different authoritative bodies to derive ARs for folate for women of reproductive age, and the AR value themselves, are summarized in Table 4-7.
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From page 107... ...
AR DFE (µg/d) 400 400 220 300 400 220 NOTE: AR = average requirement; D-A-CH = Nutrition Societies of Germany, Austria, and Switzerland; DFE = dietary folate equivalents; EFSA = European Food Safety Authority; IOM = Institute of Medicine; NNR = Nordic Nutrition Recommendations; RBC = red blood cell; WHO/FAO = World Health Organization/Food and Agriculture Organization.
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From page 108... ...
108 TABLE 4-8 Values Used by Authoritative Bodies to Derive ARs for Young Children and Women of Reproductive Age IOM WHO/FAO D-A-CH Aus/NZ EFSA Premenopausal women Intake to maintain biomarkers 320 320 220 320 250 (DFEa µg/d) Bioavailability factor (%)
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From page 109... ...
Children 4–8 years Extrapolation factor Weight0.75 Weight0.75 Weight0.75 Weight0.75 Weight0.75 Growth factor 0.15 0.15 0.15 -- 0.38 AR (DFE µg/d) 160 160 106 F, 94 M 160 110 F, 160 M NOTE: AI = adequate intake; AR = average requirement; Aus/NZ = Australia/New Zealand; D-A-CH = Nutrition Societies of Germany, Austria, Switzerland; EFSA = European Food Safety Authority; IOM = Institute of Medicine; WHO/FAO = World Health Organization/Food and Agriculture Organization.
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From page 110... ...
. The IOM and WHO/FAO folate recommendations for infants aged 6 to 12 months are based on data derived from studies that measured intake from breast milk and/or formula, leading to an estimated intake of 80 µg/ day to maintain normal levels of serum and erythrocyte folate.
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From page 111... ...
Derivation of Safe Upper Levels of Intake The UL set by the IOM at 1 mg/day, using an uncertainty factor of 5, has been adopted by other authoritative bodies. The UL for young children is adjusted downward to 300–400 µg/day of folic acid.
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From page 112... ...
• It is unlikely that local adjustments will need to be made for re quirements that depend on breast milk folate concentration. Folate requirements are not affected by maternal status or intake, or bio availability from different foods (except for the higher bioavailabil ity of folic acid in fortified foods)
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From page 113... ...
. Thus, avoiding excessive intakes and monitor ing folate status may be especially important in populations with a high prevalence of vitamin B12 deficiency since there is some evi dence that a high folic acid intake may exacerbate B12 deficiency.
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APPLICATIONS OF NUTRIENT REFERENCE VALUES IN LOW- AND MIDDLE-INCOME COUNTRIES Applications of NRVs for populations living in low- and middle-income countries include formulation of food and nutrition policies; the development of targeted intervention programs, such as food assistance or fortification programs; nutrition education; and the evaluation or monitoring of population health (NASEM, 2018)
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From page 115... ...
2018. Folate status in women of reproductive age as basis of neural tube defect risk assessment.
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:768-772. EFSA NDA Panel (European Food Safety Authority Panel on Dietetic Products, Nutrition, and Allergies)
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2012. A historical review of progress in the assessment of dietary zinc intake as an indicator of population zinc status.
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2013. EURRECA -- Estimating zinc requirements for deriving dietary reference values.
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2006. Nutrient reference values for Australia and New Zealand.
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1991. Iron absorption during normal human pregnancy: A study using stable isotopes.
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