Alcohol, Vol. 12, No. 6, pp. 553-558, 1995 Copyright © 1995 ElsevierScienceInc. Printed in the USA. All rights reserved 0741-8329/95 $9.50 + .00
Pergamon 0741-8329(95)02001-K
Application of Bioelectric Impedance Methodology and Prediction Equations to Determine the Volume of Distribution for Ethanol JAMES
L. Y O R K l A N D
JUDITH
ANN
HIRSCH
Research Institute on Addictions, 1021 Main Street, Buffalo, N Y 14203 and Department o f Physiology, State University o f N e w York at Buffalo, Buffalo, N Y 14214 R e c e i v e d 9 M a r c h 1995; A c c e p t e d 22 M a y 1995 YORK, J. L. AND J. A. H1RSCH. Application of bioelectric impedance methodology and prediction equations to determine the volume of distribution for ethanol. ALCOHOL 12(6) 553-558, 1995.-In large-scale epidemiologic studies of drinking behavior there is a need for simple and reliable estimates of the body water compartment of subjects. This, in turn, provides an estimate of the volume of distribution of ingested ethanol and a better estimate of tissue exposure levels than the use of total body weight as the volume of distribution for alcohol. The volume of distribution for ethanol (total body water, TBW) was estimated in a racially mixed group of 276 alcoholics and 166 nonalcoholics (aged 20-59 years) by means of bioelectric impedance methodology (BIA) and by means of prediction equations based upon age, body weight, and height. Estimations of mean TBW from BIA were found to be only slightly higher (1-4°/0) than those provided by the prediction equations. TBW values generated from both prediction equations were also highly correlated with TBW values obtained by impedance methodology, with the highest correlations observed in females (particularly black) and in alcoholics (particularly female). Alcohol
Alcoholics
Total body water
Bioelectric impedance
O W I N G to the pronounced water solubility of the ethanol molecule and its low solubility in fat or minerals, the total body water (TBW) comprises the compartment (volume of distribution) into which ingested ethanol is distributed (7). This principle has, in fact, served as the basis for the use of ethanol dilution to determine the size of the body water compartment (11). Approximately 50% and 60% of the total body weight is water in adult, middle-aged females and males, respectively (21). Because body water is continuous with the blood, which is approximately 81°70 water by volume (3), concentrations of ethanol in the serum are identical to those in other aspects of the body water. Thus, in the absence o f actual blood alcohol measures (BAC), an estimation of the dilution of ethanol into the body water mass may provide a relative estimate of the BAC (6,22,24,25), provided the rate of alcohol intake and the gradual disappearance of ethanol via metabolism are taken into account. In turn, estimates of the BAC provide the best
Anthropometric measures
estimates of tissue exposures and of the biological impact of alcohol on drinking occasions. A number of current studies have applied the principles cited above to refine the understanding of gender differences in alcohol consumption practices (4,28) and the response to alcohol challenges (6). Because the body water compartment is smaller in adult women than in adult men, a standard challenge with alcohol (e.g., one drink) will produce a higher BAC in women, on the average, than in men. Because of the difficulty involved in the direct determination of total body water by means of isotope dilution, researchers have utilized prediction equations derived from disitometry or isotope dilution studies to estimate the body water content of subjects. These equations are sex specific and include one or more of the factors of age, height, and weight (15,23). Moore and coworkers (15) derived their equation from pooled data obtained from five studies on 132 men and 88 women who resided in the New England area. The parabolic functions they recom-
Requests for reprints should be addressed to James L. York, Ph.D., Research Institute on Addictions, 1021 Main Street, Buffalo, NY 14203. 553
554
YORK A N D H I R S C H TABLE 1 BODY COMPOS|TION ESTIMATES-FEMALES Black Alcoholic (n = 25) Anthropometric measures Age Height(cm) Weight(kg) BSA (kg-cm) BMI(kg/m 2) Skinfolds (mm) Biceps Triceps Shank-medial Shank-lateral Quadriceps Hamstrings Estimates of total body water Bioelectric Impedance Equation (Moore)* Equation (Watson 1)t Equation (Watson 2):~ Correlation with impedance (r2; slope) Moore equation Watson equation l Watson equation 2 Estimates of percent fat Bioelectric impedance Durnan & Wormersly equation§ Biceps Triceps Biceps + triceps
White Nonalcoholic (n = 19)
Alcoholic (n = 44)
Nonalcoholic (n = 48)
36.5 163.7 65.2 1.70 25.5
(1.4) (1.1) (3.1) (0.04) (1.5)
33.1 163.0 75.0 1.80 28.5
(1.5) (1.8) (3.9) (0.04) (1.9)
36.1 162.8 62.2 1.66 23.4
(1.2) (1.0) (2.0) (0.03) (0.7)
35.0 162.9 67.1 1.72 25.3
(1.4) (0.9) (1.8) (0.02) (0.7)
9.7 16.8 13.5 11.3 22.3 24.4
(1.1) (1.8) (1.2) (1.4) (2.4) (2.6)
12.1 20.8 15.6 12.9 24.0 26.8
(1.7) (2.0) (1.7) (1.4) (3.8) (4.2)
11.9 t6.6 15.6 12.9 24.0 26.7
(0.7) (0.9) (0.9) (0.7) (1.2) (1.5)
13.6 21.8 20.0 19.1 32.6 34.0
(1.1) (1.2) (1.4) (1.4) (1.8) (1.8)
32.5 31.0 31.5 31.1
(1.1) 2 (0.7) 3 (0.8) 3 (0.8) 3
35.1 34.0 33.8 33.6
(1.3) 1 (1.0) 1 (1.0) ~ (1.0) ~
31.9 30.2 30.6 30.3
(0.7) 3,4
31.9 31.9 31.9 31.6
(0.6) 3,4 (0.5) 2 (0.5)2 (0.5)2
(0.6)4 (0.5)4 (0.5)4
0.94;0.92 0.97;0.90 0.95;0.68
0.90; 1.09 0.94; 1.03 0.89;0.75
0.67;0.99 0.77;0.87 0.73;0.62
0.54;0.88 0.59;0.79 0.51;0.56
30.7 (0.9) 3
35.2 (1.4) 1
30.4 (0.8) 4
33.3 (1.0) 2
30.5 (1.1)4 27.8 (1.7) 4 28.9 (1.4) 4
33.4 (1.5) 2 30.8 (1.7) 2 31.8 (1.7) 2
32.9 (0.7) 3 28.5 (0.9) 3 30.3 (0.8) 3
33.6 (1.0) I 32.3 (1.0) 1 33.0 (0.9) ~
Values in parentheses are SEM. BSA = Body surface area [BSA = 0.007184 × weight (kg)°4zs × height (cm)°725]; BMI = body mass index [weight (kg)/height (m)2]; TBW = total body water (liters or kilograms).
Superscripts assigned to estimates of percent Fat and TBW refer to rank order among the four subgroups. *Moore equation: TBW = weight (kg) × (69.81 - 0.26 x weight - 0.12 × age(yrs). tWatson equation 1: TBW = -2.097 + 0.1069 × height (cm) + 0.2466 × weight (kg). ~:Watson equation 2: TBW = 14.46 + 0.2549 x weight (kg). §Predicts density from skinfolds(s) with age- and gender-specific slopes and intercepts [D = c - M × (log(skinfold))], and uses Siri equation to estimate body fat from density [%Fat = (4.95/D - 4.50) × 100].
m e n d e d (see legend to Tables 1 a n d 2) utilize only body weight and age as variables. T h e linear equations o f W a t s o n a n d coworkers (23) i n c o r p o r a t e age, weight, a n d height into one equation. These equations were derived f r o m d a t a pooled from several E u r o p e a n a n d A m e r i c a n isotope dilution studies o n subjects aged from 17 to 84 years (458 men, 265 women). The purpose o f the present study was to c o m p a r e T B W values o b t a i n e d f r o m these prediction equations with the T B W values o b t a i n e d by bioelectric i m p e d a n c e m e t h o d o l o g y , which provides a measure o f whole body i m p e d a n c e t h a t is highly correlated with the volume o f total body water (8,17). A seco n d goal was to determine the usefulness o f the prediction equations in s u b p o p u l a t i o n s segregated by gender, race, a n d alcoholism status. METHOD
Subjects The 442 subjects described here (Tables l a n d 2) participated in a larger study to determine the residual impact o f
alcohol abuse o n muscle a n d m o t o r system p e r f o r m a n c e measures (26-28). T h e alcoholic subjects were recruited from local alcoholism t r e a t m e n t centers a n d were screened for m a j o r medical p r o b l e m s or polydrug abuse. These subjects h a d been alcohol free for a m e a n of 35 days before reporting to our l a b o r a t o r y for tests a n d measurements. The nonalcoholic subjects were o b t a i n e d for the most part by the n o m i n a t i o n m e t h o d ; t h a t is, these subjects were acquaintances (neighbors, relatives, friends, workmates) o f the alcoholics a n d had n o history o f alcoholism or drug abuse problems. This racially mixed group o f subjects ranged in age from 20 to 59 years.
Anthropometric and Body Composition Measures Height (shoeless) a n d weight were determined using a physicians scale ( H e a l t h o m e t e r , C o n t i n e n t a l Scale C o r p o r a t i o n , Bridgeview, IL). Lang Skinfold calipers were used to assess biceps a n d triceps skinfold thicknesses. Bioelectric i m p e d a n c e m e t h o d o l o g y ( R J L Systems Body C o m p o s i t i o n Analyzer BIA101, Detroit, MI) was used to assess total body water a n d
ESTIMATION OF TOTAL BODY WATER
555
percent b o d y fat. Software supplied by the m a n u f a c t u r e r (program version 1.0) c o n t a i n e d age- a n d sex-specific equations for the c o m p u t a t i o n s o f T B W , and, f r o m that, calculation o f lean body mass a n d percent b o d y fat. T h e equations were generated by the m a n u f a c t u r e r f r o m d a t a o b t a i n e d f r o m isotope dilution procedures to d e t e r m i n e b o d y water. T h e details and validity o f the bioelectric i m p e d a n c e (BIA) procedure are described in detail elsewhere (9,12,13,27). Statistical Analyses
The statistical significance of the differences a m o n g the means o f the four s u b g r o u p s was d e t e r m i n e d by m e a n s o f a two-way A N O V A (race x alcoholic status). D a t a f r o m men a n d w o m e n were treated separately because o f the wellestablished gender differences in body water content. Bivariate correlations between body water estimates o b t a i n e d by means of B I A m e t h o d o l o g y vs. prediction equations based on anthropometric data were calculated with the N u m b e r Cruncher Statistical Software package. The statistical significance o f the differences between any two correlations was tested by
t r a n s f o r m i n g the r values into Z scores a n d p e r f o r m i n g t-tests for differences in m e a n s (14). RESULTS A nthropometric Measures
With the exception o f the black alcoholics, all subgroups within each gender fell in the mid-30s age range. Heights were quite similar within the four male or within the four female subgroups. Body weights, however, were slightly lighter for all alcoholic subgroups within each sex a n d within each race. A 2 × 2 A N O V A (race × alcoholism diagnosis) was perf o r m e d on data for each sex separately. In w o m e n , m a i n effects o f race a n d o f alcohol diagnosis were significant for body weight, BSA, a n d B M I measures (all larger in blacks a n d nonalcoholics, p < 0.05). Nonalcoholic black females were noticeably heavier t h a n the other female subgroups, yielding also a slightly higher B M I for that subgroup. The tendency for alcoholic subjects to be leaner t h a n nonalcoholics was also evident in the skinfold data, with significant m a i n effects o f
TABLE 2 BODY COMPOSITION ESTIMATES-MALES Black Alcoholic (n = 102) Anthropometric measures Age Height(cm) Weight(kg) BSA (kg-cm) BMl(kg/m 2) Skinfolds (mm) Biceps Triceps Shank-medial Shank-lateral Quadriceps Hamstrings Estimates of total body water Bioelectric impedance Equation (Moore)* Equation (Watson 1)t Equation (Watson 2):~ Correlation with impedance (r2; slope) Moore equation Watson equation 1 Watson equation 2 Estimates of percent fat Bioelectric impedance Durnan & Wormersly equation§ Biceps Triceps Biceps + triceps
White Nonalcoholic (n = 30)
Alcoholic (n = 105)
Nonalcoholic (n = 69)
40.3 172.6 76.7 1.90 25.7
(1.3) (0.7) (1.5) (0.02) (0.4)
35.9 175.6 83.1 1.98 27.1
(1.2) (1.3) (2.7) (0.04) (0.8)
36.8 173.5 79.6 1.93 26.4
(0.8) (0.6) (1.5) (0.02) (0.5)
34.1 175.0 81.8 1.97 26.8
(1.0) (0.9) (2.0) (0.03) (0.6)
7.5 11.4 7.1 7.4 12.8 14.8
(0.4) (0.5) (0.3) (0.3) (0.6) (0.7)
8.7 13.3 9.2 9.0 16.6 18.7
(1.0) (1.2) (!.2) (0.6) (1.2) (1.4)
8.9 13.3 9.4 9.2 15.8 16.5
(0.5) (0.6) (0.4) (0.4) (0.7) (0.7)
8.7 14.5 10.2 10.4 15.4 17.6
(0.6) (0.7) (0.5) (0.5) (0.7) (1.0)
43.1 41.7 42.9 43.1
(0.6) 4
46.2 44.5 45.9 46.1
(1.1) I (0.9) j (1.0) t (1.0)'
45.0 43.0 44.3 44.5
(0.6) 3 (0.5) 3 (0.5) 3 (0.6) 3
46.0 44.1 45.6 45.8
(1.0) 2 (0.6) 2 (0.7) 2 (0.7) 2
(0.5)4 (0.5) 4 (0.5) 4
0.69;0.66 0.71;0.76 0.33;0.66
0.69;0.67 0.66;0.73 0.64;0.72
0.67;0.63 0.62;0.71 0.39;0.72
0.57;0.40 0.67;0.55 0.64;0.53
22.2 (0.7) 2
23.1 (1.3) I
21.7 (0.9) 3.4
21.7 (0.9) 3,4
25.0 (0.4) 4 24.0 (0.5) 3 24.6 (0.4) 4
25.1 (1.1) 2,3 23.7 (1.3) 4 24.6 (1.1)3
25.6 (0.6) I 24.1 (0.6) 2 25.0 (0.6) 2
25.1 (0.7) 2,3 24.4 (0.7) ~ 25.1 (0.6) I
Values in parentheses are SEM. BSA = body surface area [BSA = 0.007184 × weight (kg)°425 × height (cm)°725]; BMI = body mass index [weight (kg)/height (m)2]; TBW = total body water (liters or kilograms). Superscripts assigned to estimates of percent Fat and TBW refer to rank order among the four subgroups. *Moore equation: TBW = weight (kg) × (79.45 - 0.24 × weight - 0.15 × age(yrs) tWatson equation 1: TBW = 2.447 - 0.09516 x age (yrs) + 0.1074 x height(cm) + 0.3362 × weight (kg). *Watson equation 2: TBW = 20.03 - 0.1183 × age (yrs) + 0.3626 x weight (kg). §Predicts density from skinfolds(s) with age- and gender-specific slopes and intercepts [D = c - m X (log(skinfold))], and uses Siri equation to estimate body fat from density [°/0fat = (4.95/D - 4.50) × I00].
556 alcohol diagnosis for all of the skinfold measures (all p < 0.01). In men also, weights were significantly lower for the alcoholics [F(1, 302) = 5.07, p < 0.02, main effect of alcohol diagnosis]. The slightly lower BMI and biceps skinfold for the alcoholics were not statistically significant, but the triceps skinfold was significantly smaller for the alcoholic subjects, F(1, 302) = 4.29, p < 0.04, and for blacks, F(1, 302) = 4.28, p < 0.04. There were no race x alcohol diagnosis interactions for these anthropometric measures or for any of the other measures listed in Table 2.
Estimates of Adiposity The skinfold values also indicated different distributions of fat in black females vs. white females. Fat was distributed relatively uniformly across subcutaneous sites in upper and lower extremities in whites, but was more concentrated in the torso area of blacks, emphasizing the need for suprailliac skinfold measures. For instance, it can be seen that the estimates (Durnin and Womersley equation) (5) of percent body fat based upon biceps or triceps measures underestimate the percent fat in the black females, as compared to the measures from body weight, BMI, or BIA methodology. The same pattern may be seen in black males but to a lesser degree than in the females. The tendency toward leanness in alcoholic subgroups is, likewise, associated with the loss of fat from the subcutaneous sites in upper and lower limbs in whites, but is characterized more by loss of fat from the midsection in the blacks. In female subgroups, the estimates of percent body fat from BIA agreed for the most part with the skinfold measures, again suggesting greater leanness in alcoholic subjects [F(1, 132) = 11.81, p < 0.001, main effect of alcohol diagnosis]. In men, no noteworthy differences in percent body fat were noticeable between alcoholics and controls, using the BIA approach. The predictions of percent body fat from skinfold measures (Durnin and Womersley equation) were quite similar regardless of the specific skinfold examined. Only a small range of values was observed among the four male subgroups (23.7-25.6) and these values were all slightly greater than the corresponding value obtained using BIA methodology (range 21.7-23.1). The mean percent fat for all men from BIA was 22.2 vs. a mean of 24.8 obtained when biceps plus triceps equations were utilized. For women, a greater range of values for percent fat was observed (range 30.4-35.2 from BIA vs. 27.8-36.6 from skinfold equations). In general, both impedance and skinfold measures yielded lower body fat measures for alcoholic subgroups, but the differences were statistically significant only in women. Correlations of the percent fat values obtained from B1A with those obtained from the Durnin and Womersley prediction equations yielded r ~ values of 0.32 (all men) and 0.43 (all women) when biceps plus triceps combined were used. Similar correlations (0.35 and 0.44, respectively) were obtained when the value obtained from the biceps prediction equation was regressed against the BIA estimate of percent body fat. Use of the triceps equation values vs. BIA values yielded the lowest correlations (r 2 = 0.21 for all men and 0.34 for all women)
BIA Analysis of TBW As expected, the BIA estimate of TBW for women was about 75O7o of the value obtained for men. The actual numbers generated via BIA (mean 32.5L for women, 45.2L for men) are quite similar to mean values obtained by the "gold stan-
YORK A N D H I R S C H dard" technique of radioisotope dilution on similar age groups (21,23). For males, the mean values of TBW obtained using the equations of either Moore and coworkers (mean 43.2) or Watson and coworkers (mean 44.6) were slightly smaller than those obtained via BIA (mean 45.2), but the rank order o f the four male subgroups was identical for all three measures (Table 2). Somewhat similar to males, BIA estimates of TBW for women (mean 32.9) were slightly larger than those obtained from either the Moore equation (mean 31.8) or the Watson equation (mean 31.9). The rank orders of the four subgroups were also somewhat similar for all three measures, with the largest TBW values observed in the nonalcoholic blacks, a finding similar to that in males. Correlations of both the Moore and Watson values (ordinate) with the BIA estimates (abscissa) of TBW were highest for females, particularly the black females (Tables 1 and 2). All the correlations listed in the table were highly significant (p < 0.001). Correlations for all females of BIA vs. Watson equation were r 2 = 0.78, with r 2 = 0.71 for the Moore equation. Correlations for all men of BIA vs. Watson equation were r 2 = 0.66, with r 2 = 0.64 for the Moore equation. Thus, slightly higher correlations with BIA values were obtained using the Watson equation. This was not surprising, considering that the Watson equation factored in the variable of height, which was not included in the formula of Moore and coworkers. Watson and coworkers have also derived an equation that utilizes only weight and age. The predictions of TBW from the second Watson equation (Watson 1, Tables 1 and 2) yields mean values for TBW that are nearly identical to the body water values obtained from the full equation (Watson 1). Moreover, the r 2 values (equation value vs. impedance value) obtained from the Watson 2 equation were 0.74 for all women combined and 0.63 for all men combined, quite similar to the r 2 values obtained from the Watson 1 equation. Noteworthy, and unexpected, were the relatively low r 2 values obtained from Watson 2 for the black alcoholic and white alcoholic male subgroups. The r 2 value increased to 0.63 when the black and white alcoholics were combined (Table 3). Table 3 also portrays the significantly higher correlations o f the Watson and Moore TBW values with impedance-derived TBW values for the black female and alcoholic female subgroups.
TABLE 3 INFLUENCE OF RACE AND ALCOHOLISM DIAGNOSIS ON CORRELATIONS (r 2) OF EQUATION-DERIVED TOTAL BODY WATER (TBW) VALUES WITH BIOELECTRICAL IMPEDANCE-DERIVED (BIA) TBW VALUES
Men
Women
Black White Alc Nonalc Black White Alc Nonalc (132) (174) (207) (99) (44) (92) (69) (67) Moore Watson 1 Watson2
0.70 0.71 0.68
0.60 0.68 0.64 0.67 0.60 0.63
0.57 0.66 0.63
0.88 0.95 0.92
0.57* 0.71 0.68 0.66* 0.85 0.75~ 0.60* 0.82 0.68t
Data from men and women were treated separately. /-tests were performed on black vs. white, or alcoholic (Alc) vs. nonalcoholic (Nonalc) subgroups. The number of subjects studied is indicated in parentheses. *tlndicate significantly higher correlations with BIA values in black vs. white women (*all p < 0.001) and in alcoholic vs. nonalcoholic women (tall p < 0.05), t-tests on z-scores.
E S T I M A T I O N O F T O T A L BODY W A T E R
557
DISCUSSION Correlation coefficients obtained by regressing raw triceps skinfold values against percent fat obtained from BIA yielded r 2 values of 0.29 for all men and 0.33 for all women (p < 0.001). By comparison, correlations of BIA estimates o f percent fat vs. BMI yielded r 2 values of 0.52 for both men and women (p < 0.001). These findings suggest that BMI may be the better predictor of percent fat in both men and women. An earlier study (19) found very little difference in the correlation of percent body fat (from underwater weighing) with triceps skinfold or BMI measures, with r 2 ranging from 0.49 to 0.59. However, in interpreting the data on percent fat, it should be recognized that TBW is the entity that is correlated with BIA. Lean body mass is calculated using sl~andard conversion factors (18) and then a subtraction of LBM from total body weight is performed to estimate total fat and from that, percent fat content. In general, BMI values have not been found to be highly correlated with BIA measures of fatness (20). In interpreting these findings, it should be considered that the BIA procedure yields TBW values that are highly correlated with TBW values obtained through isotope dilution [e.g., r 2 = 0.96 (10); r 2 = 0.90 (13); r 2 = 0.91 (12)1. In con~rast, the correlation coefficients of T B W obtained from the Moore (15) and Watson (23) equations with TBW obtained from dilution studies were much lower (for Watson, r "~ = 0.70 for males, 0.73 for females; for Moore, r 2 = 0.37 for males, 0.42 for females). We observed similar correlations among the four male subgroups (r 2 values) for the equationderived vs. impedance-derived values. In contrast, the correlations were much higher for black females (Table 1) than for white females, and we have no explanation to offer for those findings at this time. In the absence of a direct measure of TBW by means of isotope dilution, the findings presented here are of limited value for determining the validity of the TBW estimates in the different subpopulations listed in Tables 1 and 2. Notwithstanding this caution, the mean estimates of
TBW obtained via BIA or via the equation of Moore (15) or Watson (23) are quite similar. Surprisingly, the correlations o f equation-derived TBW with impedance-derived T B W were higher for the black subgroups, particularly the females, with the lowest correlations for nonalcoholic white females. The overall conclusion is that both equations tend to provides slightly lower estimations of mean TBW than those determined by BIA, by about 3°/0 in women, and 1o70 (Watson) to 4070 (Moore) in men. Our examination of ethnic differences in fat patterning is limited owing to the absence of trunk fat measures in this study. Moreover, random sampling procedures were not employed in the subject selection process, limiting the application of these findings to the general population. However, the general finding that blacks tend to store excess fat more in the trunk area than in the extremities (2,16) seems to be supported by the data on females. For instance, although estimates of percent body fat from BIA yielded similar values for white controls and for black controls, the leg skinfold thicknesses of the white controls were nearly 1.5 times larger than the white group (Table I). Because similar skinfold thicknesses were observed in the arm for both blacks and whites, it seems likely that trunk skinfolds would have been found to be thicker in blacks, if measured. The caution that this generalization applies only to the deposition of e x c e s s fat is highlighted by the near absence of the above-noted trends in the leaner alcoholic subgroups. The above pattern was also not seen in our generally leaner male subjects. This finding of little difference in fat patterning in lean subjects has also been reported for younger black and white males (1).
ACKNOWLEDGEMENT Supported in part by a grant from the National Institute on Alcoholism and Alcohol Abuse (#RO1-6867).
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