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APPENDIX B Derivation of Criteria for Interpreting Iron Intake in Women As discussed in Chapter 5, when nutrient require- ments are symmetrically distributed around the mean, the probability assessment approach is relatively insensi- tive to the shape of the requirement distribution. This is not true when the distribution is markedly asymmet- rical, as for iron requirements of menstruating women. For this reason, it is important to estimate the charac- teristics of the distribution of iron requirements for this group. In agreement with the FAD/WHO Expert Group (FAD/WHO, 1970), the iron losses are divided into two components: basal losses via the skin, urine, and feces (excreted iron rather than unabsorbed iron) and the losses in the menses. The need for absorbed iron to balance these losses is then estimated using the upper limit of absorption of dietary iron that can be expected in persons ingesting a mixed diet, who are in need of iron, but maintaining body iron stores. The development of these components of the final estimate is described below. An isotopic technique has been used to measure basal iron losses for adult men under various conditions (Green et al., 1968). For the purpose of this appendix, the data obtained with this technique have been extrapo- lated to women on the basis of relative metabolic size, as reflected by basal metabolic rate (BAR). The mean basal iron loss derived in this manner is approximately 0.67 mg/day. mere are few data on the variability of these losses, other than those in the original studies of men. A coefficient of variation (CV) of approxi- mately 15% used for this exercise results in a range 115

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116 from about 0.47 to 0.87 mg/day. For simplicity' a basal loss of 0.87 mg/day was accepted for all wa~en--a small overestimation of actual need. Iron content of the menses is the major factor affect- ing the distribution of iron needs among menstruating women. Several studies have established that there is considerable variation among women but a similarity from cycle to cycle for individual women. Thus, losses for a population of women should be fairly similar to the distribution of iron requirements used in the probability approach. Suitable data on iron losses have been provided in the reports of two large population studies (Cole et al., 1971; Hallberg et al., 1966), which are supported by the findings from a number of smaller studies (see Beaton, 1974). A simple examination of the distribution of observed iron losses would lead to an underestimate of both loss and requirements of women replete with iron because women with high blood losses tend to have low hemoglobin levels (i.e., a tendency toward anemia). To circumvent this, the distribution of blood losses was con- verted to iron losses by using a standard hemoglobin concen- tration rather than the hemoglobin level of the study sub- ject. The resultant distributions for the two studies were then merged and found to be in good agreement. A log-normal distribution model that fit the data reasonably well (Beaton, 1974) was used for modeling. Expressed in terms of natural logarithms, the menstrual iron loss distribution may be de- scribed as having a mean of -0.81 and a standard deviation of 0.84. Iron absorption is a regulated process, and within the limits of bioavailability of dietary iron, the body will absorb sufficient iron to meet one's needs and will reject (i.e., absorb with lower efficiency) iron above these needs. Since the objective is to estimate the lowest intake of dietary iron that will maintain iron balance in relation to known losses, there is a need to estimate the upper limit of iron absorption. As iron depletion increases, the effi- ciency of iron absorption also increases. After reviewing various kinds of information, the FAG/ WHO (1970) committee suggested that the upper limit of absorption was approximately 20% among subjects consuming diets relatively rich in meat and other animal proteins. Since the nature of different diets affects iron bioavaila- bility (Monsen et al., 1978), the upper limit suggested by the FAD/WHO committee was much lower for subjects consuming

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117 predominantly cereal diets. The 20% upper limit absorption figure is appreciably higher than the commonly quoted aver- age iron absorption of adult men. Nonetheless, it hen been used in the models presented in this report. To examine the effect of defining the requirement in terms of some iron-depleted state (e.g., mild anemia), one need only alter the estimate of the upper limit of iron absorption by increasing it. To apply this model in the assessment of intake, the following algorithms were adopted: Available iron = 0I x UL, where 0I = observed intake (mean intake for the frequency interval) and UL = upper limit of absorption, i.e., 20% for the iron replete state. Iron available to meet menstrual loss = (OI x UL) - 0.87, where 0.87 mg/day is the assumed basal loss of iron (see comments above), and the position in the normal dis- tribution (Z score) is calculated as: Z = Ln [(OI x UL) - 0.87] - (-0.81), 0.84 where -0.81 is the mean of the distribution of logarithms of menstrual iron losses, 0.84 is the standard deviation of that distribution, and the probability that the observed intake would be inadequate to meet iron losses is computed by an algorithm describing the cumulative area under the normal distribution curve to the right of Z. This phase of the calculation is identical with that used for nonloga- rithmic distribution models. Beaton (1974) attempted to validate this model by com- paring predicted prevalences of inadequate intake with pre- dicted response to iron administration. He based the latter on the probability of response associated with observed hematocrit, using data from a population study by Garby et _. (1969a,b). There was reasonable agreement when hema- tologic data from Nutrition Canada and from the Ten-State Nutrition Survey were examined by a probability approach and then compared with assessments based on dietary data from 1-week studies. The model described above has been used to estimate dietary iron requirements in the recent revision of Recommended Nutrient Intakes for Canadians, which contains further discussion on this topic (Health and Welfare, Canada, 1983). With this model, the current Canadian recommended

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118 intake of iron (14 mg/day) would be adequate to meet the needs of all but approximately 5% of menstruating women, whereas the U.S. recommended intake (18 mg/day) would meet the predicted needs of all but about 2% to 3% of women. REFERENCES Beaton, G. H. 1974. Epidemiology of iron deficiency. Pp. 477-528 in A. Jacobs and M. Worwood, eds. Iron in Biochemistry and Medicine. Academic Press, New York. Cole, S. R., W. Z. Billewicz, and A. M. Thomson. 1971. Sources of variation in menstrual blood loss. J. Obstet. Gynaecol. Br. Commonw. 78:933-939. FAD/WHO (Food and Agriculture Organization/World Health Organization). 1970. Requirements of Ascorbic Acid, Vitamin D, Vitamin B12, Folate, and Iron. Report of a Joint FAD/WHO Expert Group. WHO Technical Report Series No. 452. FAO Nutrition Meetings Report Series No. 47. World Health Organization, Geneva. Garby, L., L. Irnell, and I. Werner. 1969a. Iron defi- ciency in women of fertile age in a Swedish community. II. Efficiency of several laboratory tests to predict the response to iron supplementation. Acta Med. Scand. 185:107-111. Garby, L., L. Irnell, and I. Werner. 1969b. Iron de~i- ciency in women of fertile age in a Swedish community. III. Estimation of prevalence based on response to iron supplementation. Acta Med. Scand. 185:113-117. Green, R., R. Charlton, H. Seftel, T. Bothwell, F. Mayet, B. Adams, C. Finch, and M. Layrisse. 1968. Body iron excretion in man: A collaborative study. Am. J. Med. 45:336-353. Hallberg, L., A.-M. Hogdahl, L. Nilsson, and G. Rybo. 1966. Menstrual blood loss--a population study: Variation at different ages and attempts to define normality. Acta Obstet. Gynaecol. Scand. 45:320-351.

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119 Health and Welfare, Canada. 1983. Recommended Nutrient Intakes for Canadians. Compiled by the Committee for the Revision of the Dietary Standard for Canada. Bureau of Nutritional Sciences, Food Directorate, Health Pro- tection Branch, Department of National Health and Welfare. Canadian Government Publishing Centre, Ottawa. Monsen, E. R., L. Hallberg, M. Layrisse, D. M. Hegsted, J. D. Cook, W. Hertz, and C. A. Finch. 1978. Esti- mation of available dietary iron. Am. J. Clin. Nutr. 31:134-141.