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Appendix E Letter Report: Review of Issues Related to Iron Status in Women During U.S. Army Basic Combat Training Submitted December 1995



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--> Appendix E Letter Report: Review of Issues Related to Iron Status in Women During U.S. Army Basic Combat Training Submitted December 1995

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--> INSTITUTE OF MEDICINE NATIONAL ACADEMY OF SCIENCES 2101 CONSTITUTION AVENUE, N.W. WASHINGTON, DC 20418 FOOD AND NUTRITION BOARD COMMITTEE ON MILITARY NUTRITION RESEARCH FAX (202) 334-1737 (202) 334-2316 December 19, 1995 Brig. General R. Zajtchuk Commanding General U.S. Army Medical Research and Materiel Command (SGRD-ZA) Fort Detrick Frederick, MD 21702-5012 Dear General Zajtchuk: At the specific request of Harris R. Lieberman, Ph.D., Chief, Military Nutrition Division, U.S. Army Research Institute of Environmental Medicine (USARIEM) and Grant Officer Representative of the U.S. Army Medical Research and Materiel Command (the Command) for Grant No. DAMD 17-94-J-4046 to the National Academy of Sciences for support of the Food and Nutrition Board's (FNB) Committee on Military Nutrition Research (CMNR), members of the CMNR met in Washington, D.C. on November 13, 1995. The purpose of this meeting was to provide additional scientific guidance to the staff of the Military Nutrition Division in reviewing their recent research related to iron deficiency in military women during U.S. Army Basic Combat Training. The CMNR was requested to perform this review as part of its task to provide scientific support to USARIEM, which has the mission to perform military nutrition and related research. Prior to the meeting, the CMNR reviewed (1) Nutritional Assessment of Cadets at the U.S. Military Academy: Part 1. Anthropometric & Biochemical Measures (Friedl et al., 1990); (2) Nutritional Assessment of Cadets at the U.S. Military Academy: Part 2. Assessment of Nutritional Intake (Klicka. et al., 1993); (3) Relationship between Iron Status and Physical Performance in Female Soldiers during U.S. Army Basic Combat Training (Westphal et al., 1995); (4) Health, Performance, and Nutrition Status of U.S. Army Women during Basic Combat Training (Draft manuscript, K. A. Westphal, K. E. Friedl, M. A. Sharp, N. King, T. R. Kramer, K. L. Reynolds, and L. J. Marchitelli, U.S. Army Research Institute of Environmental Medicine, 1995); and (5) the recent FNB report, Iron Deficiency Anemia (IOM, 1993). These materials are

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--> appended to the report with the materials presented to the CMNR for review at the meeting and a list of meeting participants. The Committee on Military Nutrition Research's role at the meeting was to review the previously published Army technical reports and new material presented at the meeting. The Committee was asked to write a formal report that included responses to nine questions posed by Dr. Lieberman and MAJ Karl E. Friedl, Ph.D., and to evaluate, comment upon, and make specific recommendations regarding these studies and proposed research plans. Drs. John L. Beard and Sean Lynch served as special consultants to the CMNR for this project. These consultants participated in the meeting and the initial discussion with the Committee regarding this report. The report was written by the CMNR and represents the Committee's views concerning the issues. This report has two parts. Part I is this letter that contains the conclusions and general recommendations of the CMNR. Part II includes the specific answers to the questions posed by the Army representatives. This report of the CMNR has been reviewed in accordance with National Research Council (NRC) guidelines by a separate anonymous scientific review panel. This report is thus based on executive session discussions by the Committee and is a thoughtfully developed presentation incorporating the scientific opinion of the CMNR and the comments of the anonymous peer review panel of the NRC. Conclusions and Recommendations The CMNR presents the following conclusions and recommendations to the U.S. Army Medical Research and Materiel Command regarding iron deficiency in military women during U.S. Army Basic Combat Training (BCT). Conclusions It is the view of the CMNR that iron status is an important issue for military women. From the preliminary data presented at this meeting, the potential for some compromise in physical performance has been demonstrated with low iron stores. Of equal military concern are the possible effects on cognitive performance that may result from impaired iron nutrition. Therefore, additional research should be conducted on the most susceptible groups of military women. It is important to determine whether the compromised iron status observed in women in BCT affects performance; therefore, initial studies should emphasize this issue, using an iron supplement that has the greatest potential for preventing or correcting decrements in iron status with appropriate nutrition counseling stressing the importance of taking such supplements, to help assure compliance with the study design. Following this determination, it then will be

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--> important to determine whether appropriate nutrition education methods can achieve similar results. Since the stresses of military training are an approximation of the anticipated stresses of actual combat, it is important to collect and evaluate broadly all pertinent information from women involved in rigorous, physically stressful military training. Any analysis of iron status must take into consideration the possible presence of any concurrent infectious or inflammatory processes, which are known to affect rapidly the results of clinical laboratory parameters used to measure iron status. Recommendations As a result of the review and discussion of related information, the CMNR recommends that: Intervention studies be conducted with women in BCT to identify cognitive and physical performance decrements that may be related to iron status. An evaluation of the most appropriate approaches to correcting deficits in iron status be made (i.e., nutrition education versus iron supplements). An analysis of existing data be conducted using models of iron deficiency previously recommended for the NHANES II and III studies. A screening program for military women be established to identify the extent of deficits in iron status and periods of greatest vulnerability, in order that remedial steps can be instituted where appropriate. Enlistment of any individual with iron deficiency anemia be delayed until this medically-reversible condition has been corrected. Future Research Considerations Evaluate the effectiveness of dietary intervention using nutrition education in maintaining iron status. Evaluate the impact of dieting measures to meet weight standards on iron status and the potential for nutrition educational approaches to assist women in maintaining iron status when restricting calorie consumption. If a relationship between iron status and physical and cognitive performance is found, determine the measure of iron deficiency that best correlates with performance and the extent of iron deficiency that results in a compromised performance. In conjunction with monitoring iron status of military women, survey the impact of iron (and other macro- and micronutrient) status on immune function and the impact of iron status on the cardiovascular and pulmonary systems.

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--> If studies confirm instances of compromised iron status (in individuals who are free of active infections or inflammatory processes), evaluate various delivery systems to minimize or eliminate deficits in iron status such as: a diet naturally high in iron (along with nutrition education), and periodic nutritional supplements of iron (e.g., daily, weekly) (following a review of the dosage and effectiveness [as well as risk of complications such as gastrointestinal side-effects] as reported in the scientific literature). If such delivery systems prove to be ineffective, consider the evaluation of other interventions, such as: iron delivered orally in a hydrodynamically balanced solution (Cook et al., 1990), and the safety and effectiveness of oral heme iron. The CMNR is pleased to provide this review as part of the Committee's continuing response to the U.S. Army Medical Research and Materiel Command. The Committee always welcomes comments and suggestions from you or your staff regarding how these reports can better serve the needs of the Army. Sincerely, Robert O. Nesheim, Ph.D. Chairman, Committee on Military Nutrition Research Attachments cc: COL J. T. Hiatt MAJ K. E. Friedl F. W. Hagge H. R. Lieberman K. I. Shine K. Hein A. A. Yates S. J. Carlson

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--> References Cook, J.D., M. Carriaga, S.G. Kahn, W. Schalch, and B.S. Skikne. 1990. Gastric delivery system for iron supplementation. Lancet 335:1136–1139. Friedl, K.E., L.J. Marchitelli, D.E. Sherman, and R. Tulley. 1990. Nutritional assessment of cadets at the U.S. Military Academy: Part 1. Anthropometric & biochemical measures. Technical report T4-91. Natick, Mass.: U.S. Army Research Institute of Environmental Medicine. IOM (Institute of Medicine). 1993. Iron Deficiency Anemia: Recommended Guidelines for the Prevention, Detection, and Management among U.S. Children and Women of Childbearing Age. A report of the Committee on the Prevention, Detection, and Management of Iron Deficiency Anemia Among U.S. Children and Women of Childbearing Age, Food and Nutrition Board. Washington, D.C.: National Academy Press. Klicka, M.V., D.E. Sherman, N. King, K.E. Friedl, and E.W. Askew. 1993. Nutritional assessment of cadets at the U.S. Military Academy: Part 2. Assessment of Nutritional Intake. Technical report T94-1. Natick, Mass.: U.S. Army Research Institute of Environmental Medicine. Westphal, K.A., L.J. Marchitelli, K.E. Friedl, and M.A. Sharp. 1995. Relationship between iron status and physical performance in female soldiers during U.S. Army Basic Combat Training [abstract]. Fed. Am. Soc. Exp. Biol. J. 9(3):A361.

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--> Part II Answers to the Nine Specific Questions Presented to the CMNR by the Army Representatives The answers to the nine specific questions posed to the CMNR are: 1. Do the data from recent research studies indicate that there is a problem related to iron deficiency in Army women in U.S. Army Basic Combat Training (BCT)? Two recent military studies offer evidence that a significant number of female trainees has suboptimal iron stores. In one, a significant fraction of women cadets at the U.S. Military Academy (USMA) was observed to have below normal values of one or more markers of iron status (hematocrit [Hct], hemoglobin [Hgb], serum ferritin, iron saturation, serum iron, and total iron-binding capacity). In the other study conducted at Fort Jackson, new army recruits entered BCT with below normal serum ferritin values, which were reduced even further during the course of 8 weeks of BCT. Such information indicates suboptimal iron status, though other indices did not change (notably Hct and Hgb). It is not known whether the subjects' physical or cognitive performance was impaired as a result of this deficiency in body iron stores, though data in the literature have linked diminished iron status to possible impairment of these functions. The USMA results suggest a high incidence of chronically impaired iron stores. Due to disparity in the definitions of iron status, it is not yet possible to directly compare the BCT results, which indicated rapid depletion of iron stores under conditions of demanding physical activity, with those of the USMA study, which involved female cadets. 2. Do the data indicate that the incidence of iron deficiency or low iron stores among military women is different from what exists in women with the same demographic characteristics in the civilian population? Given available data, it seems clear that a sizable fraction of the population of both military and civilian women exhibit a significant degree of diminished iron storage, but it is not yet possible, due to disparity in the definitions of iron status, to compare directly the relative degrees of compromised iron status. Profiles of iron status of military women entering BCT were similar to those of civilian women with comparable demographic characteristics, as presented in preliminary form at the meeting (NHANES III, Personal communication, A. C. Looker, National Center for Health Statistics, 1995).

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--> The NHANES III defined iron deficiency according to two separate models or sets of criteria. The ''Ferritin'' model defines iron deficiency as abnormal levels of two or more of the following: serum ferritin concentration, percent transferrin saturation (TS), and red blood cell (RBC protoporphyrin concentration. The Mean Cell Volume (MCV) model defines iron deficiency as abnormal levels of two or more of the following: MCV, TS, and RBC protoporphyrin. For women ages 20 to 49, the cutoff levels (as determined by the 2.5th percentile values) were: serum ferritin concentration less than 12 ng/ml, TS less than 15 percent, RBC protoporphyrin concentration greater than 70 μg/dL, and MCV less than 85 fl. Iron deficiency anemia was defined as a Hgb concentration less than 118 g/L accompanied by two or more of the Ferritin or MCV model criteria for iron deficiency. According to data from Phase I of NHANES III (Personal communication, A. C. Looker, National Center for Health Statistics, 1995; Dallman et al., in press), the prevalence of iron deficiency among non-African American women ages 20 to 49 was 9 to 10 percent (comparable data for African-American women are not yet available), whereas the prevalence of iron deficiency anemia was 3 to 4 percent among non-African American women ages 20 to 49. In comparison, a followup survey of iron status among female Army enlisted women, average age 21 years (data not available by ethnic group) at the beginning of BCT utilized a serum ferritin concentration of less than 12 ng/ml as the criterion for iron deficiency and a combination of low serum ferritin and Hgb of less than 120 g/L as the criteria for iron deficiency anemia (thus, these definitions would include some women who would be excluded using NHANES criteria). Seventeen percent of new female recruits surveyed fit these criteria for iron deficiency, while 8 percent could be classified as having iron deficiency anemia. A survey of a similar population at the end of BCT showed that, by that time, 33 percent were iron deficient, and 26 percent were anemic (the prevalence of iron deficiency with and without anemia did not differ significantly between African American and non-African American recruits) (Personal communication, LTC A. Cline, U.S. Army Research Institute of Environmental Medicine, 1995). Studies in civilian women athletes show reductions in iron stores with physical training (Lyle et al., 1992), similar to those observed in women recruits undergoing BCT. In general, however, military women are more vulnerable than civilian women to developing depleted iron stores due to the demands placed on them for vigorous physical activity. A careful comparison has not yet been made, and it is thus not possible to conclude whether the military population of women differs from the civilian population regarding iron status. Regardless, compromised iron status should be of great concern to the Army because of the need to maintain military personnel in a high state of physical and mental readiness.

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--> 3. In terms of military readiness, would military women benefit from a nutritional intervention? Military readiness can be compromised by severely depleted iron stores. At present, the degree of iron depletion necessary to cause meaningful decrements in physical and cognitive performance is unknown. Hence, it is not possible to conclude that an intervention would improve military readiness until the degree of decrement is correlated with performance. Some available data suggest that physical performance is impaired by subnormal iron status (Westphal et al., 1995), but the literature is not conclusive regarding the level of suboptimal stores necessary for impairment (Edgerton et al., 1979; Gardner et al., 1977). Too few data exist to evaluate whether cognitive performance in military women is affected by poor iron status. Iron deficiency anemia has been associated with lowered scores on tests of discrimination learning in infants and children, suggestive of disturbances in attentional processes. To date, most studies have failed to document significant relationships between iron deficiency and cognitive changes in the absence of anemia (Pollitt et al., 1986) but sufficient controversy remains to merit further research. The negative impact of significant physical stress on iron status is well documented (Haymes and Lamanca, 1989). With the demonstrated reduction in iron status during BCT, it is possible that iron status might be further diminished during combat duty. Since no data are currently available to evaluate this possibility, this issue demands further investigation. In particular, the impact on iron status of physical exercise of the intensity experienced during BCT and combat needs to be evaluated. It is important that measures to correct low iron status be accomplished on an individual basis. Iron fortification levels in cereal grain products have been designed to meet the needs of most individuals without causing harm associated with too much iron intake. As reviewed by the IOM (1993), excess iron stores have been linked, at least theoretically, to an increased incidence of ischemic heart disease, as well as several types of cancers and neurological disorders. There is evidence that excess dietary iron may also interfere with absorption of dietary zinc (Zn) and copper (Cu) and iron supplementation may cause gastrointestinal side-effects. For these reasons, blanket iron supplementation of all military women is not prudent. 4. Are there additional medical considerations related to iron status in military women that need to be addressed? Yes. Examples include reproductive health, function of the immune, cardiovascular and pulmonary systems, and the greater consequences of blood loss, such as through blood donation or wounds. In most studies, these potential problems have not been thoroughly investigated.

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--> 5. Should there be periodic screening of military women for anemia or iron deficiency? Yes. Annual screening (detection) should evaluate iron status and identify both iron deficiency and iron deficiency anemia (by including an initial measurement of serum ferritin). Those identified with low serum ferritin values should be further evaluated by other criteria such as Hgb, Hct, RBC protoporphyrin, and possibly circulating transferrin receptors. Infectious diseases and inflammatory processes are known to alter the results of laboratory indicators of iron nutrition, and therefore the presence of any such medical problem must be identified and noted at the time of screening. Evaluation of the status of other nutrients that may result in anemias, such as vitamin B6 , vitamin B12 , and folate should be performed on an annual basis as well. Screening should be done in the following manner: a)   At the time of initial entry into service. Those persons with a clear-cut diagnosis of iron deficiency anemia (the exact criteria to confirm this diagnosis must be defined for this military purpose, including any possible racial differences) should have their enlistment deferred until this correctable medical condition can be reversed by proper therapy. Since 53 percent of active duty Army women are classified as belonging to a minority group (44 percent of Army women are African American) (IOM, 1995), racial differences in diagnostic criteria for iron deficiency anemia need to be considered for accession and treatment. b)   Upon completion of BCT. Those individuals with iron deficiency or iron deficiency anemia should receive appropriate medical treatment, and be monitored until laboratory results show a return to normal values. Current recommendations for treatment include a daily 6-week course of high dose supplemental iron with nutritional counseling, followed by monitoring of Hgb and either continuation of the high dose or adjustment to a maintenance level (LSRO, 1991). c)   In women on active military duty, at the time of their required annual Pap Smear exam (IOM, 1995). Those individuals with iron deficiency or iron deficiency anemia should receive appropriate medical treatment. d)   At the time of any initial prenatal visit, and throughout any pregnancy, as previously recommended (IOM, 1993).

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--> Those women with laboratory evidence of iron deficiency or iron deficiency anemia should receive appropriate medical treatment. e)   At the time of a woman's 4–6 week post-partum, visit. Those with iron deficiency or iron deficiency anemia should receive appropriate medical treatment. f)   Women who are identified clinically as being at high risk for developing iron deficiency should be screened at more frequent, medically-defined intervals. g)   Results from all screening studies related to iron nutrition should be entered into an individual's medical records and assessed clinically on a longitudinal basis. 6. In military personnel with low iron stores as well as anemia, is there an impairment of military readiness that is gender specific? Iron deficiency anemia can be expected to have adverse effects on the military performance of both men and women, depending in part upon its severity. Performance deficits in both men and women due to compromised iron status have been demonstrated most clearly during exercise of prolonged duration, such as long distance running (Newhouse and Clement, 1988). Iron deficiency anemia may also have an adverse impact upon recovery from serious wounds or injuries, especially those that involve large blood loss. Mild iron deficiency without anemia has been shown to produce decrements in physical performance in rats (Zinker et al., 1993); however, comparable experiments have not been carried out in humans. Research in this area should be expanded. It is clear that women experience a far greater variability than men in the status of their iron stores. This problem is partially due to variable menstrual blood losses, parity, pregnancy, and any terminations of pregnancy. In addition, dietary intake of iron (and energy) tends to be lower in women than in men. Self-imposed dieting is more prevalent among women (Klicka et al., 1993) and adds to the risk for lowered iron stores. BCT also impacts the iron stores of women to a greater degree than those of men (Moore et al., 1993). Voluntary blood donation has a greater impact on the iron status of women than it does on men (LSRO, 1991). Iron nutrition may be an issue in achieving gender-neutral job standards for military occupational specialties (MOS's).

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--> 7. Are there additional analyses that should be conducted with the data in Friedl et al., 1990; Klicka et al., 1993; Westphal et al., 1995; or Westphal et al. [draft manuscript], 1995 on iron status issues in women in BCT? For future studies, are there additional specific analyses that should be considered? In evaluating the data presented in Army technical reports (Friedl et al., 1990; Klicka et al., 1993; Westphal et al., 1995; Westphal et al. [draft manuscript], 1995) and in future studies, consideration should be given to using NHANES II and III models for identifying iron deficiency and iron deficiency anemia. Two such models which are established are the Ferritin model and the MCV model. The ferritin model includes the use of data on serum ferritin, the percent TS, and RBC protoporphyrin levels. The MCV model uses the MCV, percent TS, and RBC protoporphyrin values. The rationale for using these models is described in the report, Summary of a Report on Assessment of the Iron Nutritional Status of the United States Population (Expert Scientific Group, 1995). In studies where a sufficient number of observations are available, consideration might also be given to using an analysis of the iron storage status of the whole population based on the model developed by Cook and colleagues (1986). The inclusion of a new assay for detecting a deficiency of iron stores (the circulating transferrin receptor concentration) should also be considered. The concentration of this specific protein appears to be a direct measure of tissue iron demand and has the particular advantage of not being affected by infections. Concurrent infections reduce the reliability of measures of ferritin, TS, and erythrocyte protoporphyrin as indicators of iron deficiency (Cook et al., 1993; Flowers et al., 1989; Skilme et al., 1990). Therefore, additional analyses must consider the presence of coexisting problems of infection and inflammation. With the data from the completed studies, analyses should be extended where possible and appropriate to include the impact of ethnic and lifestyle factors, such as smoking and alcohol consumption. Future studies should also consider the impact of aspirin and other non-steroidal, anti-inflammatory drugs on gastric blood loss. 8. What are the CMNR recommendations regarding the proposed intervention study? In the proposed intervention study, if the primary objective is to determine the effect of compromised iron status on physical and cognitive performance, then the CMNR recommends consideration that a prospective intervention trial using iron supplements be conducted initially. If this study indicates clear positive effects on performance, then a subsequent study could be designed to evaluate nutrition education (i.e., dietary intervention without supplementation)

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--> as an alternative method for increasing iron intake. For the intervention trial, the following design changes are recommended: Objectives: a)   to determine whether iron deficiency and/or iron deficiency anemia affects selected military performance measures in participating subjects; b)   to determine whether correction of iron deficiency will improve selected military performance measures; c)   to determine whether a 60 mg or smaller iron supplement (dose to depend on a thorough review of iron supplementation research) will correct any observed iron deficiencies in participating subjects; and d)   to determine whether participating subjects will tolerate a 60 mg daily elemental iron supplement. Type of Study: Prospective intervention trial with placebo controls. Study Population: If at all possible, the desired study population should be BCT personnel. Such trainees have been shown to be at greatest risk for developing iron deficiency or iron deficiency anemia during training. In addition, the use of this population would provide data comparable to those generated in previous Army studies. The use of advanced individual training (AIT) personnel is less desirable because they have just been subjected to 8 weeks of BCT. Studies have demonstrated that measures of iron status tend to stabilize by 12 weeks, and physiological adaptation or compensatory reaction may take place (Blum et al., 1986; Rajaram et al., 1991). Moreover, no complete studies have been done previously in AIT personnel. Design of Study: A 2 x 2 randomized, ethnically balanced block factorial design of 8-week duration in BCT volunteers is recommended, with a stratified assignment of subjects to inadequate iron stores (IIS) and adequate iron stores (AIS) groups. The CMNR assumes that no person who is classified with iron deficiency anemia will be included (as discussed in the response to Question 5). Within each stratum subjects will be randomized to placebo versus intervention groups. Intervention will consist of a daily supplement containing 60 mg, or less of elemental iron in the form of ferrous sulfate tablets. Ideally, iron tablets should be taken in the fasting state with a glass of orange juice. Counseling on this point and on the importance of adherence is essential. Compliance must be enforced and monitored. Power analysis should be performed to determine the sample size required to demonstrate statistically significant effects.

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--> Group hematology: IIS: Hgb ≤ 12 g/dL   Ferritin < 20 ug/L   TS ≤ 16% AIS: Hgb ≥ 12 g/dL.   Ferritin > 20 ug/L   TS > 16% What is Measured: a)   Hematologic responses; b)   cognitive and physical performance variables should be emphasized, such as i)   endurance performance (e.g., 2 mile run) in the physical tests and ii)   cognitive tests, particularly those involving attention; c)   full recording of infectious illnesses and inflammatory conditions incurred during the study; plus useful laboratory markers such as RBC Sedimentation Rates, G reactive protein, and plasma haptoglobin; and d)   side effects, i)   especially gastrointestinal and ii)   if a 60 mg daily iron supplement is used, zinc and copper status should be monitored since there is some evidence to suggest that excess iron supplementation may interfere with the absorption of dietary zinc and copper (IOM 1993). Depending on the results of this intervention, a subsequent intervention should be conducted to evaluate the efficacy of a nutritional education program in correcting iron deficiency. Design of such a program should be based in part on a careful evaluation of dietary habits of subjects in earlier studies, particularly with respect to iron intake, restricted eating and food preferences. 9. Emphasis of the meeting on November 13, 1995 was on data collected during BCT, should there be additional research with military women dealing with iron status in military women in general? Yes. Data should be collected to investigate the iron status of career military women, as recommended in the answer to Question 5 regarding screening.

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--> References Blum, S.M., A.R. Sherman, and R.A. Boileau. 1986. The effects of fitness-type exercise on iron status in adult women. Am. J. Clin. Nutr. 43:456–463. Cook, J.D., B.S. Skikne, S.R. Lynch, and M.E. Reusser. 1986. Estimates of iron sufficiency in the U.S. population . Blood 68:726–731. Cook, J.D., M. Carriaga, S.G. Kahn, W. Schalch, and B.S. Skikne. 1990. Gastric delivery system for iron supplementation. Lancet 335:1136–1139. Cook, J.D., B.S. Skikne, and R.D. Baynes. 1993. Serum transferrin receptor. Annu. Rev. Med. 44:63–74. Dallman, P., A. C. Looker, C.L. Johnson, and M. Carroll. In Press. Influence of age on laboratory criteria for the diagnosis of iron deficiency anemia and iron deficiency in infants and children. In Proceedings of Symposium on Iron Nutrition in Health and Disease, L. Halberg, ed. London: John Lubbey and Company. Edgerton, V.R., G.W. Gardner, Y. Ohira, K.A. Gunawardina, and B. Senewiratne. 1979. Iron-deficiency anemia and its effect on worker productivity and activity patterns. Br. Med. J. 2:1546–1549. Expert Scientific Working Group of the Life Sciences Research Office, FASEB. 1988. Summary of a report on assessment of the iron nutritional status of the United States population. Am. J. Clin. Nutr. 42:1318–1330. Flowers, C.H., B.S. Skilme, A.M. Covell, and J.D. Cook. 1989. The clinical measurement of serum transferrin receptor. J. Lab. Clin. Med. 114:368–377. Friedl, K.E., L.J. Marchitelli, D.E. Sherman, and R. Tulley. 1990. Nutritional assessment of cadets at the U.S. Military Academy: Part 1. Anthropometric & biochemical measures. Technical report T4-91. Natick, Mass.: U.S. Army Research Institute of Environmental Medicine. Gardner, G.W., V.R. Edgerton, B. Senewiratne, R.J. Barnard, and Y. Ohira. 1977. Physical work capacity and metabolic stress in subjects with iron deficiency anemia. Am. J. Clin. Nutr. 30:910–917. Haymes, E.M., and J.J. Lamanca. 1989. Iron loss in runners during exercise: Implications and recommendations. Sports Medicine 7:277–285. IOM (Institute of Medicine). 1993. Iron Deficiency Anemia: Recommended Guidelines for the Prevention, Detection, and Management among U.S. Children and Women of Childbearing Age. A report of the Committee on the Prevention, Detection, and Management of Iron Deficiency Anemia Among U.S. Children and Women of Childbearing Age, Food and Nutrition Board. Washington, D.C.: National Academy Press. IOM. 1995. Recommendations for Research on the Health of Military Women . A report of the Committee on Defense Women's Health Research. Washington, D.C.: National Academy Press. Klicka, M.V., D.E. Sherman, N. King, K.E. Fried), and E.W. Askew. 1993. Nutritional assessment of cadets at the U.S. Military Academy: Part 2. Assessment of nutritional intake. Technical report T94-1. Natick, Mass.: U.S. Army Research Institute of Environmental Medicine. LSRO (Life Sciences Research Office). 1991. Guidelines for the Assessment and Management of Iron Deficiency in Women of Childbearing Age. Prepared for Center for Food Safety and Applied Nutrition, Food and Drug Administration, U.S. Department of Health and Human Services. Bethesda, Md.: Life Sciences Research Office, Federation of American Societies for Experimental Biology. Lyle, R.M., C.M. Weaver, D.A. Sedlock, S. Rajaram, B. Martin, and C.L. Melby. 1992. Iron status in exercising women: The effect of oral iron therapy vs. increased consumption of muscle foods. Am. J. Clin. Nutr. 56a:1049–1055.

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--> Moore, R.J., K.E. Friedl, R.T. Ttilley, and E.W. Askew. 1993. Maintenance of iron status in healthy men during an extended period of stress and physical activity. Am. J. Clin. Nutr. 58:923–927. Newhouse, I.J., and D.B. Clement. 1988. Iron status in athletes. Sports Med. 5:337–352. Pollitt, E., C. Saco-Pollitt, R.L. Leibel, and F.E. Viteri. 1986. Iron deficiency and behavioral development in infants and preschool children. Am. J. Clin. Nutr. 43:555–565. Rajaram, S., C.M. Weaver, R.M. Lyle, D.A. Sedlock, and C.L. Melby. 1991. Effect of oral iron therapy vs. increased consumption of muscle foods on iron status in exercising women [abstract]. Fed. Am. Soc. Exp. Biol. J. 5:A1656. Skikne, B.S., C.H. Flowers, and J.D. Cook. 1990. Serum transferrin receptor: A quantitative measure of tissue iron deficiency. Blood 75:1870–1876. Westphal, K.A., L.J. Marchitelli, K.E. Friedl, and M.A. Sharp. 1995. Relationship between iron status and physical performance in female soldiers during U.S. Army Basic Combat Training [abstract]. Fed. Am. Soc. Exp. Biol. J. 9(3):A361. Zinker, B.A., P.R. Dallman, and G.A. Brooks. 1993. Augmented glucoregulatory hormone concentrations during exhausting exercise in mildly iron-deficient rats. Am. J. Physiol. 265(4 Pt 2):R863–871.

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--> Review of Issues Related to Iron Status in Women during U.S. Army Basic Combat Training November 13–14, 1995 Foundry Building Room 2004 1055 Thomas Jefferson Street, N.W. Washington, D.C. 20007 (202) 334–1911 PARTICIPANTS November 13, 1995 Presentation Session, 9:00 a.m.–1:00 p.m. Closed Discussion Session, 1:00 p.m.–5:00 p.m. November 14, 1995 Executive Session, 8:30 a.m.–12:00 p.m. Committee Members (All sessions except where noted) Robert O. Nesheim, Ph.D. (Chair) Salinas, CA William R. Beisel, M.D. The Johns Hopkins School of Hygiene and Public Health Baltimore, MD Gail E. Butterfield, Ph.D. (available by fax to review report) Palo Alto Veterans Administration Medical Center, and Program in Human Biology, Stanford University Palo Alto, CA John D. Fernstrom, Ph.D. University of Pittsburgh School of Medicine Western Psychiatric Institute and Clinic Pittsburgh, PA G. Richard Jansen, Ph.D. Department of Food Science and Human Nutrition Colorado State University Fort Collins, CO Robin B. Kanarek, Ph.D. (available by fax to review report) Department of Psychology Tufts University Medford, MA Orville A. Levander, Ph.D. Nutrient Requirements and Functions Laboratory USDA, ARS/BHNRC Beltsville, MD Gilbert A. Leveille, Ph.D. (available by fax to review report) Research and Technical Services Nabisco Foods Group East Hanover, NJ

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--> John E. Vanderveen, Ph.D. (Presentation and Executive Sessions) Food and Drug Administration Washington, DC Douglas W. Wilmore, M.D. (available by fax to review report) Department of Surgery Brigham and Women's Hospital Boston, MA Johanna T. Dwyer (Presentation and Closed Discussion Sessions) Frances Stem Nutrition Center and Department of Medicine Tufts Medical School and New England Medical Center Boston, MA Special Consultants (Presentation and Closed Discussion sessions except where noted) John L. Beard, Ph.D. Department of Nutrition The Pennsylvania State University University Park, PA James D. Cook, M.D., M.Sc. (did not attend; did not receive airline ticket) Division of Hematology University of Kansas Medical Center Kansas City, KS Sean Lynch, M.D. Hematology and Oncology, Veterans Administration Medical Center Eastern Virginia Medical School Hampton, VA Elaine R. Monsen, Ph.D. (available by fax to review report) Department of Nutritional Sciences University of Washington Seattle, WA Military Representatives (Presentation session only) LTC Alana Cline Military Nutrition Division Occupational Health & Performance Directorate U.S. Army Research Institute of Environmental Medicine Natick, MA MAJ Karl E. Friedl, Ph.D. U.S. Army Medical Research and Materiel Command Fort Detrick Frederick, MD LTC Dale Hill Army Surgeon General's Office Falls Church, VA Harris R. Lieberman, Ph.D. Military Nutrition Division U.S. Army Research Institute of Environmental Medicine Natick, MA

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--> Speaker (Presentation session only) Anne Looker, Ph.D., R.D. Chief of Nutrition Statistics Branch National Center for Health Statistics Hyattsville, MD Staff (All sessions) Bernadette M. Marriott, Ph.D. Sydne J. Carlson, Ph.D. Allison A. Yates, Ph.D., R.D. Susan M. Knasiak