What makes a BIA equation unique? Validity of eight-electrode multifrequency BIA to estimate body composition in a healthy adult population.

BACKGROUND/OBJECTIVES: The validity of bioelectrical impedance analysis (BIA) for body composition analysis is limited by assumptions relating to body shape. Improvement in BIA technology could overcome these limitations and reduce the population specificity of the BIA algorithm. SUBJECTS/METHODS: BIA equations for the prediction of fat-free mass (FFM), total body water (TBW) and extracellular water (ECW) were generated from data obtained on 124 Caucasians (body mass index 18.5-35 kg/m(2)) using a four-compartment model and dilution techniques as references. The algorithms were validated in an independent multiethnic population (n=130). The validity of BIA results was compared (i) between ethnic groups and (ii) with results from the four-compartment model and two-compartment methods (air-displacement plethysmography, dual-energy X-ray absorptiometry and deuterium dilution). RESULTS: Indices were developed from segmental R and Xc values to represent the relative contribution of trunk and limbs to total body conductivity. The coefficient of determination for all prediction equations was high (R(2): 0.94 for ECW, 0.98 for FFM and 0.98 for TBW) and root mean square error was low (1.9 kg for FFM, 0.8 l for ECW and 1.3 kg for TBW). The bias between BIA results and different reference methods was not statistically different between Afro-American, Hispanic, Asian or Caucasian populations and showed a similar difference (-0.2-0.2 kg FFM) when compared with the bias between different two-compartment reference methods (-0.2-0.3 kg FFM). CONCLUSIONS: An eight-electrode, segmental multifrequency BIA is a valid tool to estimate body composition in healthy euvolemic adults compared with the validity and precision of other two-compartment reference methods. Population specificity is of minor importance when compared with discrepancies between different reference methods.

Water homeostasis, frailty and cognitive function in the nursing home.

OBJECTIVE: - To develop and test a practical clinical method to assess frailty in nursing homes; - To investigate the relationship between cognitive status of the elderly and the balance between water compartments of their body composition. DESIGN AND SUBJECTS: Cross-sectional study, conducted at two nursing homes in Boston-MA. METHODS: Body mass and height (Ht) were evaluated to calculate BMI (body mass index, in Kg/m²). The cognitive decline was evaluated based on the scores obtained from the Mini-Mental State Examination (MMSE); The extracellular to total body water ratio (ECW/TBW) was calculated after the analysis of TBW from deuterium and tritium dilution and ECW from bromide dilution. Single-frequency BIA analysis data were investigated for resistance (R) and reactance (Xc), plotted in an R/Ht Xc/Ht graph (vectorial analysis-BIVA). The BIVA results of nursing home residents were compared against the data obtained from the NHANES III study. TBW and ECW values were compared with a group of free-living elderly volunteers. RESULTS: The ECW/TBW was significantly higher in nursing home residents than in the free-living individuals. BIVA analysis showed significantly higher Xc/Ht values in the reference subjects. The MMSE did not present a significant correlation with ECW/TBW for either gender. CONCLUSION: We proposed the ECW/TBW ratio and BIVA as surrogate methods for the clinical assessment of frailty. We tested successfully both approaches with nursing home patients and free-living volunteers and compared them to a national data base. The advent of new, portable instruments will enable field tests to further validate our proposed "Frailty Factor" in future studies. We found no correlation between frailty and cognitive decline in the nursing home.

Use of D-T-produced fast neutrons for in vivo body composition analysis: a reference method for nutritional assessment in the elderly.

Body composition has become the main outcome of many nutritional intervention studies including osteoporosis, malnutrition, obesity, AIDS, and aging. Traditional indirect body composition methods developed with healthy young adults do not apply to the elderly or diseased. Fast neutron activation (for N and P) and neutron inelastic scattering (for C and O) are used to assess in vivo elements characteristic of specific body compartments. Non-bone phosphorus for muscle is measured by the (31)P(n, alpha)(28)Al reaction, and nitrogen for protein via the (14)N(n,2n)(13)N fast neutron reaction. Inelastic neutron scattering is used to measure total body carbon and oxygen. Body fat is derived from carbon after correcting for contributions from protein, bone, and glycogen. Carbon-to-oxygen ratio (C/O) is used to measure the distribution of fat and lean tissue in the body and to monitor small changes of lean mass. A sealed, D-T neutron generator is used for the production of fast neutrons. Carbon and oxygen mass and their ratio are measured in vivo at a radiation exposure of less than 0.06 mSv. Gamma-ray spectra are collected using large BGO detectors and analyzed for the 4.43 MeV state of carbon and 6.13 MeV state of oxygen, simultaneously with the irradiation. P and N analysis by delayed fast neutron activation is performed by transferring the patient to a shielded room equipped with an array of NaI(Tl) detectors. A combination of measurements makes possible the assessment of the "quality" of fat-free mass. The neutron generator system is used to evaluate the efficacy of new treatments, to study mechanisms of lean tissue depletion with aging, and to investigate methods for preserving function and quality of life in the elderly. It is also used as a reference method for the validation of portable instruments of nutritional assessment.

Resistance training to counteract the catabolism of a low-protein diet in patients with chronic renal insufficiency. A randomized, controlled trial.

BACKGROUND: Chronic renal insufficiency leads to muscle wasting, which may be exacerbated by low-protein diets prescribed to delay disease progression. Resistance training increases protein utilization and muscle mass. OBJECTIVE: To determine the efficacy of resistance training in improving protein utilization and muscle mass in patients with chronic renal insufficiency treated with a low-protein diet. DESIGN: Randomized, controlled trial. SETTING: Tufts University, Boston, Massachusetts. PATIENTS: 26 older patients with moderate renal insufficiency (17 men, 9 women) who had achieved stabilization on a low-protein diet. INTERVENTION: During a run-in period of 2 to 8 weeks, patients were instructed and their adherence to the low-protein diet (0.6 g/kg of body weight per day) was evaluated. They were randomly assigned to a low-protein diet plus resistance training (n = 14) or a low-protein diet alone (n = 12) for 12 weeks. MEASUREMENTS: Total body potassium, mid-thigh muscle area, type I and II muscle-fiber cross-sectional area, and protein turnover. RESULTS: Mean protein intake was 0.64 +/- 0.07 g/kg per day after stabilization. Total body potassium and type I and II muscle-fiber cross-sectional areas increased in patients who performed resistance training by a mean (+/-SD) of 4% +/- 8%, 24% +/- 31%, and 22% +/- 29%, respectively, compared with those who did not. Leucine oxidation and serum prealbumin levels also improved significantly. Patients assigned to resistance training maintained body weight compared with those who were not. Improvement in muscle strength was significantly greater with resistance training (32% +/- 14%) than without (-13% +/- 20%) (P < 0.001). CONCLUSION: By improving muscle mass, nutritional status, and function, resistance training seems to be effective against the catabolism of a low-protein diet and uremia in patients with renal failure.

Older men and women efficiently absorb vitamin B-12 from milk and fortified bread.

Nothing is directly known about the bioavailability of vitamin B-12 from dairy products or fortified grain products. We directly studied vitamin B-12 absorption from water, milk and fortified bread in adult subjects using (58)Co-labeled vitamin B-12 and a whole body gamma-ray counter/spectrophotometer. Sixteen healthy men and women over the age of 60 y with normal serum levels of vitamin B-12 and normal basal gastric acid secretion were studied. (58)Co vitamin B-12 (0.25 microg) was administered in water, milk or fortified bread to each subject along with 185 kBq (5.0 microCi) (51)Cr as a stool marker. Whole body counting was performed 30 min after ingestion of the radioactive dose and at 7 and 14 d after dosing. Mean absorptions from water, milk and fortified bread were 55, 65 and 55%, respectively, and did not differ. The high body retention of the extrinsic vitamin B-12 label from milk and bread may warrant a greater use of such fortified products in the elderly to ensure vitamin B-12 adequacy.

The effect of gender and body composition method on the apparent decline in lean mass-adjusted resting metabolic rate with age.

BACKGROUND: Declining resting energy expenditure (REE) is a hallmark of normal aging, but the cause of this decline remains controversial. Some, but not all, studies have shown that the decline in REE with age is eliminated after adjustment for fat-free mass (FFM). METHODS: We examined the effect of four body composition methods used to assess FFM (underwater weighing [UWW], bioimpedance analysis [BIA], tritium dilution, and total body potassium [TBK]) on the relationship between REE and age in 30 healthy men and 101 healthy women aged 18 to 87 years. RESULTS: The decline in REE with age was significant in women (-80.3 kJ/d/y, p < .004) but not in men (-46.9 kJ/d/y, p = .328). After adjustment for FFM, the decline in REE with age persisted when FFM was measured by BIA, UWW, or tritium dilution, but no decline was seen when TBK was used to adjust for FFM. In both women and men, fat mass was significantly associated with REE after adjusting for age and FFM. CONCLUSION: It is the decline in cell mass with age, detectable by TBK but not by other methods, rather than any metabolic alteration, that explains the decline in FFM-adjusted REE with age.

In vivo elemental partition analysis using fast neutrons. A tool for testing the efficacy of new clinical interventions.

The nutritional status of patients can be evaluated by monitoring changes in body composition, including depletion of protein and muscle; distribution of adipose tissue; and changes in hydration status, and bone or cell mass. Fast neutron activation (for N and P) and neutron inelastic scattering (for C and O) are used to assess in vivo elements characteristic of specific body compartments. Nonbone phosphorus for muscle is measured by the 31P(n,alpha)28Al reaction, and nitrogen for protein via the (n,2n) fast neutron reaction. The carbon-to-oxygen (C/O) ratio is used to measure distribution of fat and lean tissue in the body and to monitor small changes in lean mass and its quality. In addition to evaluating the efficacy of new treatments, the method is used to study the mechanisms of depletion of lean tissue with aging.

Bone mineral measurements: a comparison of delayed gamma neutron activation, dual-energy X-ray absorptiometry and direct chemical analysis.

A system in vitro consisting of a femur from a cadaver and soft-tissue equivalent material was used to test the agreement between several techniques for measuring bone mineral. Calcium values measured by delayed gamma neutron activation (DGNA) and bone mineral content (BMC) by Lunar, Hologic and Norland dual-energy X-ray absorptiometers (DXA) were compared with calcium and ash content determined by direct chemical analysis. To assess the effect of soft-tissue thickness on measurements of bone mineral, we had three phantom configurations ranging from 15.0 to 26.0 cm in thickness, achieved by using soft-tissue equivalent overlays. Chemical analysis of the femur gave calcium and ash content values of 61.83 g +/- 0.51 g and 154.120 +/- 0.004 g, respectively. Calcium measured by DGNA did not differ from the ashed amount of calcium at any of the phantom configurations. The BMC measured by DXA was significantly higher, by 3-5%, than the amount determined by chemical analysis for the Lunar densitometer and significantly lower, by 3-6%, for the Norland densitometer (p<0.001-0.024), but only 1% lower (not significant) for the Hologic densitometer. DXA instruments showed a decreasing trend in BMC as the thickness increased from 20.5 to 26.0 cm (p<0.05). However, within the entire thickness range (15.0-26.0 cm), the overall influence of thickness on BMC by DXA was very small. These findings offer insight into the differences in these currently available methods for bone mineral measurement and challenge the comparability of different methods.

Insulin-like growth factor I in skeletal muscle after weight-lifting exercise in frail elders.

To assess muscle remodeling and functional adaptation to exercise and diet interventions, 26 men and women aged 72-98 yr underwent a vastus lateralis biopsy before and after placebo control condition, and progressive resistance training, multinutrient supplementation, or both. Type II atrophy, Z band, and myofibril damage were present at baseline. Combined weight lifting and nutritional supplementation increased strength by 257 +/- 62% (P = 0.0001) and type II fiber area by 10.1 +/- 9.0% (P = 0.033), with a similar trend for type I fiber area (+12.8 +/- 22.2%). Exercise was associated with a 2. 5-fold increase in neonatal myosin staining (P = 0.0009) and an increase of 491 +/- 137% (P < 0.0001) in IGF-I staining. Ultrastructural damage increased by 141 +/- 59% after exercise training (P = 0.034). Strength increases were largest in those with the greatest increases in myosin, IGF-I, damage, and caloric intake during the trial. Age-related sarcopenia appears largely confined to type II muscle fibers. Frail elders respond robustly to resistance training with musculoskeletal remodeling, and significant increases in muscle area are possible with resistance training in combination with adequate energy intakes.

Body composition in children and adults by air displacement plethysmography.

OBJECTIVES: Air displacement plethysmography (ADP) may provide a partial alternative to body density (Bd) and therefore body composition measurement compared to conventional hydrodensitometry (Hd) in children. As there are no evaluation studies of ADP in children, this study had a two-fold objective: to compare Bd estimates by ADP and Hd; and to compare fat estimates by both ADP and Hd to fat estimates by another reference method, dual energy X-ray absorptiometry (DXA). SETTING: Obesity Research Center, St. Luke's/Roosevelt Hospital, New York, USA. SUBJECTS: One hundred and twenty subjects (66 females/54 males) who ranged in age from 6-86 y and in body mass index (BMI, kg/m2) from 14.1-40.0 kg/m2 met study entry criteria. STUDY DESIGN: Cross-sectional study of healthy children (age < or = 19 y) and adult group for comparison to earlier studies. Each subject completed ADP, Hd, and DXA studies on the same day. Only subjects with subjectively-judged successful Hd studies were entered into the study cohort. RESULTS: There was a high correlation between Bd by ADP and Hd (Bd Hd = 0.11 + 0.896 x Bd ADP; r = 0.93, SEE = 0.008 g/cm3, P < 0.0001), although the regression line slope and intercept differed significantly from 1 and 0, respectively. Additional analyses localized a small-magnitude Bd bias in the child (n = 48) subgroup. Both ADP and Hd %fat estimates were highly correlated (r > 0.9, P < 0.0001) with %fat by DXA in child and adult subgroups. Bland-Altman analyses revealed no significant %fat bias by either ADP or Hd vs DXA in either children or adults, although a bias trend (P = 0.11) was detected in the child subgroup. CONCLUSION: With additional refinements, the air displacement plethysmography system has the potential of providing an accurate and practical method of quantifying body fat in children as it now does in adults.

Neutron activation analysis determination of body composition.

The nutritional status of patients can be evaluated by monitoring changes in body composition, including the depletion of protein and muscle, adipose tissue distribution and changes in hydration status, bone or cell mass. Neutron activation analysis is a unique reference tool for the in-vivo determination of body composition. In this review we describe the recent changes in the field that followed the advent of new portable generators of fast neutrons, capable of performing elemental analysis in the clinical environment. New models were developed based on the partition of the measurable elements of the body. The recent developments help evaluate new treatments for wasting and obesity, in which change in body composition is the main outcome.

Nutritional alterations and the effect of fish oil supplementation in dogs with heart failure.

Alterations in body composition and nutritional status are common in humans with heart failure and are related, in part, to increases in cytokine concentrations. Cytokines have not been studied previously in dogs with naturally occurring cardiac disease nor has fish oil administration been used in this population to decrease cytokine production. The purposes of this study were to characterize nutritional and cytokine alterations in dogs with heart failure and to test the ability of fish oil to reduce cytokines and improve clinical outcome. Body composition, insulinlike growth factor-1, fatty acids, and cytokines were measured in 28 dogs with heart failure and in 5 healthy controls. Dogs with heart failure then were randomized to receive either fish oil or placebo for 8 weeks. All parameters were measured again at the end of the study period. At baseline, 54% of dogs with heart failure were cachectic and the severity of cachexia correlated with circulating tumor necrosis factor-alpha concentrations (P = .05). Cytokine concentrations at baseline, however, were not significantly increased in dogs with heart failure compared to controls. Baseline plasma arachidonic acid (P = .02), eicosapentaenoic acid (P = .03), and docosahexaenoic acid (P = .004) concentrations were lower in dogs with heart failure than in controls. Fish oil supplementation decreased interleukin-1 beta (IL-1) concentrations (P = .02) and improved cachexia (P = .01) compared to the placebo group. The mean caloric intake of the heart failure dogs as a group was below the maintenance energy requirement (P < .001), but no difference was found in food intake between the fish oil and placebo groups. Insulinlike growth factor-1 concentrations (P = .01) and reductions in circulating IL-1 concentrations over the study period (P = .02) correlated with survival. These data demonstrate that canine heart failure is associated with cachexia, alterations in fatty acids, and reduced caloric intake. Fish oil supplementation decreased IL-1 concentrations and improved cachexia. In addition, reductions in IL-1 predicted survival, suggesting that anticytokine strategies may benefit patients with heart failure.

The relationship between growth hormone kinetics and sarcopenia in postmenopausal women: the role of fat mass and leptin.

Sarcopenia, the decline in body cell mass (BCM) and especially in muscle mass with age, is an important age-related cause of frailty and loss of independence in the elderly. Because the decline in BCM with age parallels a decline in GH secretion from young adulthood to old age, loss of GH secretion has been considered an important contributory cause of sarcopenia in the elderly. To test this hypothesis in a group of healthy postmenopausal women (n = 15; mean +/- SD age, 66.9 +/- 7.8 yr), 24-h GH concentrations and secretory kinetics were correlated with BCM (measured by whole body counting of 40K) and percent body fat (measured by dual energy x-ray absorptiometry or neutron inelastic scattering). Serum leptin levels were determined as a measure of adipocyte mass. Contrary to prediction, GH secretion was lower in women with higher BCM (r = 0.50; P < 0.05), whereas their mean fat mass was higher (r = 0.51, P < 0.05). These data indicate that sarcopenia in postmenopausal women is not associated with reduced GH secretion and is inversely correlated with fat mass. Serum leptin levels were inversely associated with GH secretion (r = -0.67; P < 0.006). Although a causal relationship has not been demonstrated, these data suggest that leptin could modulate GH secretion through its action on the aging hypothalamic-pituitary axis, or that GH regulates leptin secretion.

Assessment of body fat and lean in the elderly by measuring body carbon and oxygen: validation against hydrodensitometry.

Based on the observation that the carbon-to-oxygen ratio (C/O) in tissue is a measure of fat content, we developed a model which correlates C/O to percent body fat. Carbon and oxygen mass and their ratio are measured in vivo by fast neutron inelastic scattering, using a miniature D-T neutron generator, at a radiation exposure of less than 0.06 mSv. We tested the validity of this model against hydrodensitometry with 19 healthy adult volunteers. The method was found to be accurate and insensitive to assumptions about the composition of lean tissue and, therefore, appropriate for studying the elderly and patients with catabolic conditions.

Use of fast neutrons for measuring muscle.

Elemental Partition Analysis (EPA) is a new approach to body composition. A major element of the body is measured and then, by means of other measurements, is partitioned to the contributing body compartments. We developed a model for measuring total body muscle by applying the EPA method to total body phosphorus (TBP). We measure TBP (head excluded) by in vivo fast neutron activation analysis using the reaction 31P(n, alpha)28 Al. The main contributors to TBP are the bone and skeletal muscle. Adipose tissue and the liver contribute less than 3%. We use dual-energy X-ray absorptiometry (DXA) to evaluate the contribution of bone to TBP. Corrections are applied for the small contributions of the liver and adiopose tissue to TBP to derive muscle phosphorous. The technique requires high precision measurements for both TBP (+/- 2%) and DXA (+/- 1%). The total body radiation exposure for measuring human subjects is 0.60 mSv. We observed that nitrogen can also be measured by fast neutron activation analysis through the (n,2n) reaction, simultaneously with TBP.

Cytokine production and nutritional status in hemodialysis patients.

Malnutrition is an important predictor of mortality in patients on chronic hemodialysis, however the pathogenesis of wasting in this population remains unclear. Experimental data suggest that the dialysis procedure per se leads to enhanced catabolism, as well as direct loss of plasma amino acids and proteins into the dialysate. In the present study, the primary hypothesis examined is that hemodialysis-induced cytokine production is associated with reductions in lean body mass and other plasma markers of nutrition. We used the production of interleukin-1 receptor antagonist (IL-1Ra) by peripheral blood mononuclear cells (PBMC) as an indicator of cytokine production. PBMC were obtained pre-dialysis on the first and second sessions of the week in a cohort of 16 patients on chronic hemodialysis using reprocessed cellulose dialyzers who fulfilled rigorous entry criteria designed to eliminate known etiologies of increased cytokine production, e.g. chronic infections. PBMCs were either immediately frozen (cell content) or incubated for 24 hours at 37 degrees C in the presence or absence of endotoxin 10 ng/ml and total IL-1Ra was measured by radioimmunoassay. Nutritional staus was assessed using body mass index (BMI), total body potassium (TBK), anthropometry-derived arm muscle area (AMA), and measurements of plasma albumin, transferrin, total cholesterol, and triglycerides. Over the subsequent 3 months, patients were monitored carefully for pyrogen reactions, hemodynamic stability and intra-interdialytic symptoms. There was a direct correlation of cell content of IL-1Ra with several indices of nutritional status including BMI (r = 0.90, p = 0.0001), AMA (r = 0. 77, p = 0.0008), serum total cholesterol (r = 0.57, p = 0.03) and serum triglycerides (r = 0. 73, p = 0.002). Endotoxin-stimulated IL-1Ra production correlated directly with AMA (r = 0.59, p = 0.02), TBK (r = 0.71, p = 0.01) and serum triglycerides (r = 0.51, p = 0.05). These studies suggest a direct correlation between nutrition and cytokine production, and that malnutrition could depress cytokine production and potentially contribute to reduced immune responsiveness in patients on chronic hemodialysis.

Total body potassium and body fat: relevance to aging.

Understanding the mechanisms that govern sarcopenia (depletion of muscle mass with age) may suggest ways to preserve lean tissue and functional capacity, and to maintain quality of life in the elderly. We investigated the body-composition changes in normal aging in a cross-sectional study of 188 healthy volunteers aged 20-89 y, which examines the differences in body cell mass and fat as a function of age. In aging, the assumptions of indirect body-composition-measurement techniques, such as the "constant" hydration coefficient of lean body mass or the "constant" density of fat-free mass, may not hold. Therefore, we selected body-composition-measurement techniques that are not sensitive to assumptions about the composition of lean tissue. Cellular mass, lean body mass, and fat were assessed "directly" by total body potassium (TBK) measurements and neutron inelastic scattering. Our results show that TBK content declines at a rate of 7.20 +/- 1.00 mg K.kg body wt-1.y-1 for females (r = 0.601, P < or = 0.001) and 9.16 +/- 0.96 mg K.kg body wt-1.y-1 for males (r = 0.710, P < or = 0.001). Body fat measurements by neutron inelastic scattering have shown a significant increase of percentage body fat with age for female volunteers between the ages of 20 and 50 y and a continuous increase for male volunteers throughout adult life.

Adjuvant arthritis as a model of inflammatory cachexia.

OBJECTIVE: To determine whether adjuvant arthritis (AA) leads to changes in body composition and cytokine production similar to those seen in patients with rheumatoid arthritis. METHODS: AA was induced in Lewis rats using Freund's complete adjuvant. Body cell mass was measured by determining the concentration of total exchangeable potassium using 42K gavage. Splenocyte production of interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) was measured by bioassay. Weight and food intake were also measured. RESULTS: Animals that developed AA lost 6% of their body weight by the onset of clinically evident arthritis (day 14; P < 0.01) and lost 20% by the end of the inflammatory phase of AA (day 28; P < 0.0001). Body cell mass fell 24.7 +/- 8.6% (mean +/- SEM) in animals with AA, but did not change significantly in controls (increase of 6.3 +/- 7.9%) (P < 0.03). Pair-fed animals lost one-fourth of the weight lost by the animals with AA (P < 0.01), indicating that anorexia alone does not explain inflammatory cachexia. Weight loss was correlated with TNF alpha production by spleen mononuclear cells (r = 0.68, P < 0.007), and a weaker correlation was seen with IL-1 production (r = 0.45, P < 0.04). CONCLUSION: AA in rats is a useful model of inflammatory cachexia that mimics the human pathophysiology in important ways, and is consistent with cytokine-driven cachexia in chronic inflammatory arthritis.