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Body composition and in vivo neutron activation
ED TO IALS Body composition and in vivo neutron activation Abbreviations: DEXA = d u a l e n e r g y x-ray a b s o r p t i o m e t r y ; ECW = e x t r a c e l l u l a r w a t e r ; FFM = f a t - f r e e mass; I V N A = in v i v o n e u t r o n a c t i v a t i o n ; TBW = t o t a l b o d y w a t e r
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ver the past few decades, research to establish indirect methods to determine human body composition has been extensive. Numerous methods have emerged, and many are based on a two-compartment model, fat and fat-free mass. In the two-compartment model, the chemical composition of the fat-free body is assumed to be relatively constant, with a density of 1.1 gm/ml at 37° C, a water content of 72% to 74%, and a potassium content of - 7 0 mmol/kg in men and 50 to 60 mmol/kg in women. Fat that is anhydrous and potassium free has a density of 0.900 gm/ml at 37° C. 1 However, methods based on the two-compartment models may have limitations when used in individuals who have changes in hydration or bone mineralization caused by aging, gender, disease, excess adipose tissue, and ethnicity, because the assumptions become invalid. 2-4 More recently, the development of multicompartment models has paralleled the development of new methods that include DEXA, total body electrical conductivity, neutron activation analysis, and bioelectric impedance, along with the traditional measures of TBW, potassium, and density. A four-compartment model divides the body into its constituents of fat, water, mineral, and protein, while a six-component model is divided into fat, protein, water, glycogen, mineral osseous, and cell mineral. The multicompartment models are advantageous over the traditional two-compartment models because they allow more complete analysis of the chemical components, and fewer assumptions are made. Without valid two-compartment models, the field of body composition has lacked a criterion method by which to validate new body composition methods. 5 Quantification of the human body poses numerous problems, because it cannot be measured directly in vivo. Direct measurement techniques imply J Lab Clin Med 1996;127:414-5. Copyright © 1996 by Mosby-Year Book, Inc. 0022-2143/96 $5.00 + 0 5/1/71157
414
noninvasive measurement of a specific structural or chemical mass in vivo and do not refer to the analysis of isolated tissue9 Indirect methods quantify compartments based on experimental models (e.g., the two-compartment model). Fat mass can not be measured directly; thus is indirectly measured by using known relationships between fat and other directly measured compartments. 6 This can result in spurious estimates of fat mass. Also, evaluation of fat mass by subtracting FFM from body weight can create large errors of estimate because of the magnification of small systemic errors in estimating FFM. The degree of propagation of error depends inversely on the fat content of the body] IVNA is a direct analytic technique based on nuclear reactions rather than chemical reactions. 1 IVNA has been considered a criterion method for the past three decades. IVNA systems deliver a moderated beam of fast neutrons to the subject and capture these neutrons by using atoms of the target elements in the body to create unstable isotopes. 1 The interaction of neutrons with tissue creates new physical states within some elements, which will emit one or more ~/-rays of characteristic energy when the isotopes revert to a stable condition. Radiation from the subject emits an energy level that identifies the element, and the activity indicates its abundance. 1 This method has been refined and expanded so that 11 elements (C, O, H, N, Ca, P, Mg, Na, C1, I, and Cd) are now measurable in vivo. Three chemical compartments (protein, mineral, and fat) can be estimated from these elements. 6 The neutron activation systems are calibrated against various phantoms, which are used to evaluate the precision of the instruments. If the isotope has a very short half-life (e.g., nitrogen 15, lifetime of 10 to 15 seconds) then the "y-raycounting must proceed simultaneously and is referred to as prompt gamma neutron activation analysis; when the -/-ray emissions are longer (e.g., calcium 49, half-life of 8.7 minutes), the technique is referred to as delayed gamma neutron activation analysis. 6
J Lab Clin Med Volume 127, Number 5
The overall accuracy of estimates of IVNA has been determined by examining the relationship between body weight calculated by summing the measured and derived amounts of the major elements and the actual body weight and the body weight calculated from six chemical components at the molecular level and actual body weight. 6 These results revealed that an excellent correlation (r = 0.97) between the actual body weight (62.6 _+ 9.4 kg) and calculated body weight (61.0 _+ 9.3 kg) can be determined by summing the six components for the 20 subjects, and the study found body density values of 1.039 _+ 0.018 gm/ml 3 and 1.041 _+ 0.017 gm/ml 3, respectively. The assumptions of this model are that the proportions of C, N, and Ca are known and constant within lipid, protein, and bone mineral, respectively, s Although considerable work has been conducted with IVNA, the precision of this technique is not known. The reliability studies on IVNA have been tested with phantom calibrations, and the measurement reliability for IVNA in human subjects has been evaluated in only 2 healthy subjects. The paper by Ma et al. 8 in this issue of the JOURNAL provides the reliability of IVNA for six total body elements in 5 male, weight-stable patients with AIDS. In these patients, IVNA was used to measure total body N, Ca, C1, Na, P, and C on three different occasions. In addition, TBW (3H20), ECW (35804 and NaBr), and D E X A were measured. Healthy subjects also had their TBW, ECW, and D E X A measurements taken three times for means of comparison. The reliability of the IVNA techniques was very high in the AIDS population; it ranged from 0.99 for total body C1 to 0.84 for total body phosphorus, and it agreed with the phantom calibration. Both patients with AIDS and healthy volunteers had a similar reliability for measuring percent fat and total body Ca by DEXA. The reliability values for measuring ECW in patients with AIDS by 35804 and NaBr were 0.66 and 0.68, respectively, and these were lowest values among all measurements. These authors suggest that the differences in the transmem-
Editorial
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brane distributions of these tracers may vary as a function of the disease. 8 Percent fat was larger when measured by IVNA than by DEXA. The tracer dilution of TBW had reliability similar to that of IVNA and D E X A in both the patients with AIDS and the healthy volunteers. The contribution of this article is that it provides valuable information regarding the measurement precision of IVNA, and this will enhance the application of power analysis to study designs requiring IVNA measurements. JILL KANALEY, PhD Department of Health and Physical Education Syracuse University 820 Comstock Ave., Rm 201 Syracuse, N Y 13244
REFERENCES
1. Eukaski LC. Methods for the assessment of human body composition: traditional and new. Am J Clin Nutr 1987;46: 537-56. 2. Baumgartner RN, HeymsfieldSB, Lichtman S, Wang J, Pierson RN Jr. Body composition in elderly people: effect of criterion estimates on predictive equations. Am J Clin Nutr 1991;53:1345-53. 3. HeymsfieldSB, Wang J, Lichtman S, Kamen Y, Kehayias J, Pierson RN. Body composition in elderly subjects: a critical appraisal of clinical methodology. Am J Clin Nutr 1989; 50(suppl):l167-75. 4. Mazariegos M, Wang A, Gallagher D, et al. Differencesbetween young and old females in the five levels of body composition and their relevanceto the two-compartmentchemical model. J Gerontology 1994;49:M201-8. 5. Lohman TG, Going SB. Multicomponent models in body composition research: opportunities and pitfalls. In: Ellis JK, Eastman JD, eds. Human body composition. New York: Plenum Press, 1993:53-8. 6. HeymsfieldSB, Waki M. Body composition in humans: advances in the development of multicompartment chemical models. Nutr Rev 1991;49:97-107. 7. KehayiasJT, HeymsfieldSB, LoMonte AF, Wang J, Pierson RN Jr. In vivo determination of body fat by measuring total body carbon. Am J Clin Nntr 1991;53:1339-44. 8. Ma K, Kotler DP, Wang J, Thornton JC, Ma R, Pierson RN Jr. Reliabilityof in vivoneutron activationanalysisfor measuring body composition: comparisonswith tracer dilution and dualenergyx-rayabsorptiometry.J LABCLINMED 1996;127:420-7.
O
ver the past few decades, research to establish indirect methods to determine human body composition has been extensive. Numerous methods have emerged, and many are based on a two-compartment model, fat and fat-free mass. In the two-compartment model, the chemical composition of the fat-free body is assumed to be relatively constant, with a density of 1.1 gm/ml at 37° C, a water content of 72% to 74%, and a potassium content of - 7 0 mmol/kg in men and 50 to 60 mmol/kg in women. Fat that is anhydrous and potassium free has a density of 0.900 gm/ml at 37° C. 1 However, methods based on the two-compartment models may have limitations when used in individuals who have changes in hydration or bone mineralization caused by aging, gender, disease, excess adipose tissue, and ethnicity, because the assumptions become invalid. 2-4 More recently, the development of multicompartment models has paralleled the development of new methods that include DEXA, total body electrical conductivity, neutron activation analysis, and bioelectric impedance, along with the traditional measures of TBW, potassium, and density. A four-compartment model divides the body into its constituents of fat, water, mineral, and protein, while a six-component model is divided into fat, protein, water, glycogen, mineral osseous, and cell mineral. The multicompartment models are advantageous over the traditional two-compartment models because they allow more complete analysis of the chemical components, and fewer assumptions are made. Without valid two-compartment models, the field of body composition has lacked a criterion method by which to validate new body composition methods. 5 Quantification of the human body poses numerous problems, because it cannot be measured directly in vivo. Direct measurement techniques imply J Lab Clin Med 1996;127:414-5. Copyright © 1996 by Mosby-Year Book, Inc. 0022-2143/96 $5.00 + 0 5/1/71157
414
noninvasive measurement of a specific structural or chemical mass in vivo and do not refer to the analysis of isolated tissue9 Indirect methods quantify compartments based on experimental models (e.g., the two-compartment model). Fat mass can not be measured directly; thus is indirectly measured by using known relationships between fat and other directly measured compartments. 6 This can result in spurious estimates of fat mass. Also, evaluation of fat mass by subtracting FFM from body weight can create large errors of estimate because of the magnification of small systemic errors in estimating FFM. The degree of propagation of error depends inversely on the fat content of the body] IVNA is a direct analytic technique based on nuclear reactions rather than chemical reactions. 1 IVNA has been considered a criterion method for the past three decades. IVNA systems deliver a moderated beam of fast neutrons to the subject and capture these neutrons by using atoms of the target elements in the body to create unstable isotopes. 1 The interaction of neutrons with tissue creates new physical states within some elements, which will emit one or more ~/-rays of characteristic energy when the isotopes revert to a stable condition. Radiation from the subject emits an energy level that identifies the element, and the activity indicates its abundance. 1 This method has been refined and expanded so that 11 elements (C, O, H, N, Ca, P, Mg, Na, C1, I, and Cd) are now measurable in vivo. Three chemical compartments (protein, mineral, and fat) can be estimated from these elements. 6 The neutron activation systems are calibrated against various phantoms, which are used to evaluate the precision of the instruments. If the isotope has a very short half-life (e.g., nitrogen 15, lifetime of 10 to 15 seconds) then the "y-raycounting must proceed simultaneously and is referred to as prompt gamma neutron activation analysis; when the -/-ray emissions are longer (e.g., calcium 49, half-life of 8.7 minutes), the technique is referred to as delayed gamma neutron activation analysis. 6
J Lab Clin Med Volume 127, Number 5
The overall accuracy of estimates of IVNA has been determined by examining the relationship between body weight calculated by summing the measured and derived amounts of the major elements and the actual body weight and the body weight calculated from six chemical components at the molecular level and actual body weight. 6 These results revealed that an excellent correlation (r = 0.97) between the actual body weight (62.6 _+ 9.4 kg) and calculated body weight (61.0 _+ 9.3 kg) can be determined by summing the six components for the 20 subjects, and the study found body density values of 1.039 _+ 0.018 gm/ml 3 and 1.041 _+ 0.017 gm/ml 3, respectively. The assumptions of this model are that the proportions of C, N, and Ca are known and constant within lipid, protein, and bone mineral, respectively, s Although considerable work has been conducted with IVNA, the precision of this technique is not known. The reliability studies on IVNA have been tested with phantom calibrations, and the measurement reliability for IVNA in human subjects has been evaluated in only 2 healthy subjects. The paper by Ma et al. 8 in this issue of the JOURNAL provides the reliability of IVNA for six total body elements in 5 male, weight-stable patients with AIDS. In these patients, IVNA was used to measure total body N, Ca, C1, Na, P, and C on three different occasions. In addition, TBW (3H20), ECW (35804 and NaBr), and D E X A were measured. Healthy subjects also had their TBW, ECW, and D E X A measurements taken three times for means of comparison. The reliability of the IVNA techniques was very high in the AIDS population; it ranged from 0.99 for total body C1 to 0.84 for total body phosphorus, and it agreed with the phantom calibration. Both patients with AIDS and healthy volunteers had a similar reliability for measuring percent fat and total body Ca by DEXA. The reliability values for measuring ECW in patients with AIDS by 35804 and NaBr were 0.66 and 0.68, respectively, and these were lowest values among all measurements. These authors suggest that the differences in the transmem-
Editorial
415
brane distributions of these tracers may vary as a function of the disease. 8 Percent fat was larger when measured by IVNA than by DEXA. The tracer dilution of TBW had reliability similar to that of IVNA and D E X A in both the patients with AIDS and the healthy volunteers. The contribution of this article is that it provides valuable information regarding the measurement precision of IVNA, and this will enhance the application of power analysis to study designs requiring IVNA measurements. JILL KANALEY, PhD Department of Health and Physical Education Syracuse University 820 Comstock Ave., Rm 201 Syracuse, N Y 13244
REFERENCES
1. Eukaski LC. Methods for the assessment of human body composition: traditional and new. Am J Clin Nutr 1987;46: 537-56. 2. Baumgartner RN, HeymsfieldSB, Lichtman S, Wang J, Pierson RN Jr. Body composition in elderly people: effect of criterion estimates on predictive equations. Am J Clin Nutr 1991;53:1345-53. 3. HeymsfieldSB, Wang J, Lichtman S, Kamen Y, Kehayias J, Pierson RN. Body composition in elderly subjects: a critical appraisal of clinical methodology. Am J Clin Nutr 1989; 50(suppl):l167-75. 4. Mazariegos M, Wang A, Gallagher D, et al. Differencesbetween young and old females in the five levels of body composition and their relevanceto the two-compartmentchemical model. J Gerontology 1994;49:M201-8. 5. Lohman TG, Going SB. Multicomponent models in body composition research: opportunities and pitfalls. In: Ellis JK, Eastman JD, eds. Human body composition. New York: Plenum Press, 1993:53-8. 6. HeymsfieldSB, Waki M. Body composition in humans: advances in the development of multicompartment chemical models. Nutr Rev 1991;49:97-107. 7. KehayiasJT, HeymsfieldSB, LoMonte AF, Wang J, Pierson RN Jr. In vivo determination of body fat by measuring total body carbon. Am J Clin Nntr 1991;53:1339-44. 8. Ma K, Kotler DP, Wang J, Thornton JC, Ma R, Pierson RN Jr. Reliabilityof in vivoneutron activationanalysisfor measuring body composition: comparisonswith tracer dilution and dualenergyx-rayabsorptiometry.J LABCLINMED 1996;127:420-7.