Special Report
Research and Clinical Advances—1993
A.S.P.E.N. Research Workshop
Body Composition:
STEVEN B.
From the
*Obesity
Research
HEYMSFIELD, MD,*
AND
composition. The workshop had two themes: (1) compartments
of the body and their measurement, and (2) clinical applications
of body composition measurements. There were 12 speakers
of varied backgrounds who gave short lectures followed by
panel discussions. Speakers explored the validity and potential
uses of new body composition methodologies,
including
dual-energy x-ray absorptiometry, multiple frequency bioimpedance analysis, computerized axial tomography, magnetic
The study of body composition is central to many
of human biology research. In particular, body
composition estimates are important in the evaluation
and monitoring of malnourished acute and chronically
ill patients.
Body composition research has a long and esteemed
history in the study of clinical nutrition and medicine.
Over the past several years, important new conceptual
and technologic developments have expanded both the
research and the clinical role of body composition
measurements. These new concepts and methods,
combined with a growing number of books and research
reports, suggest that body composition is emerging as
a distinct scientific discipline.
The growing interest in body composition investigation
led the Board of Directors of A.S.P.E.N. to hold the
1993 research workshop &dquo;Body Composition: Research
and Clinical Advances&dquo; at the annual meeting in San
Diego. The meeting was chaired by Steven Heymsfield,
MD, and Dwight Matthews, PhD. The 1-day meeting had
two themes: (1) compartments of the body and their
measurement, and (2) clinical applications of body
composition measurements. There were 12 speakers of
varied backgrounds who gave short lectures followed
by panel discussions.
areas
resonance
imaging,
nuclear
magnetic
resonance
spectroscopy,
neutron inelastic scattering, and gamma-ray resonance. The
application of these methods to chronically and acutely ill
hospitalized patients was described. The study of body
composition is an emerging distinct research area within the
broad study of human biology. This conference provided an
overview of important new advances in the study of human
body composition. (
Journal of Parenteral and Enteral Nutrition
:91-103, 1994)
18
overview of body composition research and methodology.
The study of body composition consists of three
interconnected areas: the five-level model and its
associated rules, methodology, and intrinsic and extrinsic
factors that influence body composition.1
The five-level model consists of more than 30 major
components organized into atomic, molecular, cellular,
tissue-system, and whole-body levels (Fig. 1). Each level
and component is distinct, and each level has an equation
relating the sum of all components to body weight. For
example, at the molecular level
There is no overlap between components at the same
level. However, connections exist between components
at the same or different levels. For example, fatness
can be characterized by total body carbon, fat, fat cells,
and adipose tissue at the atomic, molecular, cellular,
and tissue-system levels, respectively.
A concept central to the five-level model is that
a steady-state relationship exists during a specified
time period between components at the same or
different body composition levels. For example, at
the molecular level of body composition, total body
water (TBW) is usually about 73% of fat-free body
mass (FFM). Steady-state relations are important in
body composition methodology and will be described
later.
The second area of body composition research is
methodology. The presentation focused on concepts of
COMPARTMENTS OF THE BODY AND THEIR MEASUREMENT
Body Composition Models
I-ieymsfield, MD, Columbia University College
Physicians and Surgeons, New York, provided an
Steven
of
MATMEWS, PHD†
Center, Columbia University College of Physicians and Surgeons, and the†Clinical Research Center, New York
Hospital—Cornell University Medical Center
ABSTRACT. The 1993 ASPEN Research Workshop examined
research and clinical advances in the study of human body
Advances in
DWIGHT
body composition methodology, particularly
to developing body composition models.
Correspondence: Steven B. Heymsfield, MD, Weight Control Unit, 411
West 114th Street, New York, NY 10025.
91
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in relation
All body
92
potassium (Cp) from gamma-ray decay of naturally
occurring potassium 40 (&dquo;KJ. The &dquo;K isotope is a
constant fraction (0.0118%) of total body potassium,
thus allowing estimation of total body potassium from
the gamma-ray decay (1.40 MeV) of total body 4°K.
The second type of body composition method,
Cu
component-based techniques, is shown as Cp
in equation 2. Only about one half of the 30 major body
composition components can be estimated by calculating
an unknown component (Cu) from a property-derived
component (Cp).’ As with property-based methods, either
a statistical equation or a model can be used to estimate
Cu from Cp. An example of a component-based model
method is estimation of FFM with the relatively stable
-
FtG. 1. The five levels of body composition and their respective components, in simplified form, at each level. ECS and ECF are extracellular
solids and extracellular fluid, respectively. From Wang et
with permission.
al,1
composition methods are organized into two main groups
as defined by the following relation:
ratio of FFM/TBW of 1.37.
Some of the commonly used body composition
methods are organized into property-based and component-based methods in Table I.
Until recently, most body composition models were
relatively simple and consisted of only two or three
components. An example is the classic two-component
molecular-level model:
The
The first group of
in
equation 2,
are
as P
Cp
methods. These
methods, shown
property (P)-based
--·
methods involve measurements of a physical property, from which a property-derived component (Cp)
is calculated. The calculation of Cp from a property
can be accomplished by using either a statistically
derived equation or a model equation. The model
methods assume steady-state known relationships
between the property and Cp. An example of a
property-based statistical method is bioimpedance
analysis in which total body resistance (a property)
is used to calculate TBW (Cp) with a statistically
derived prediction equation including terms such as
body weight, height, age, and gender. An example
of a model method is the estimation of total body
Two types of
body composition
simple models were used because the methods
required for solving more complex models with multiple
components were lacking. Over the past several years,
important new or refined body composition techniques
were introduced that created the possibility of estimating
almost all the major components at the five levels of
body composition. Some of the more important of these
developments were as follows:
Estimation of all major elements that body weight
comprises in vivo.~&dquo; These elements can be used to
reconstruct the major chemical components that compose body weight. Until recently, cadaver studies were
the only way of completely analyzing all the major
o
chemical components in vivo.
Dual-energy x-ray absorptiometry now allows quantification of the skeletal mass and density for the whole
body or for specific regions at relatively low cost and
minimal patient risk.55 This development allows for
widespread study of the skeleton, a component that
TABLE I
methods: property-based and component-based
BCM, Body cell mass; BIA. bioimpedance analysis; Cpo property-derived component: Cu, unknown component; e, exchangeable; ECF, extracellular
fluid; ECS, extracellular solids; FFM. fat-free body mass; ICF, intracellular fluid; ~10. osseus mineral; NAA, neutron activation analysis; SM, skeletal
muscle: TBCa, total body calcium; TBK total body potassium; TBN. total body nitrogen: TOBEC, total body electrical conductivity; UWW, underwater
weighing.
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93
until recently could be studied adequately by complex
and costly neutron activation methods.
o
Multicomponent models for estimating compartments
that are relatively simple and inexpensive to apply in
research laboratories have been developed and validated
by more complex and costly methods. 1.7
9
Imaging and spectroscopy methods greatly expand
our capabilities for measuring components
at the
tissue-system level of body composition (eg, skeletal
muscle) as well as biochemical substrates such as
adenosine triphosphate (ATP) and glycogen.8~9
exchange with a much smaller pool of carboxyl and
phosphate oxygen. Schoeller et all’ calculated that the
180-labeled water pool should be < 1 %
greater than
TBW. They determined that the ~H-labeled water space
TBW
maximal exchange possible, their estimates of exchangeable hydrogen in protein included all possible hydrogen,
even that linked into peptide bonds that would not
exchange within the period of TBW measurement. The
true exchangeable hydrogen pool in protein is likely to
be at least a factor of 4 smaller, reducing the estimate
of exchangeable hydrogen of Culebras et al to only 2%
of TBW. Therefore, many of these higher estimates of
TBW measured with 2H-labeled water compared with
180-labeled water may be artifactual and related to the
methods of measurement rather than physiologic.
TBW has been used primarily with the two-compartment model of body composition in which the body is
divided into fat mass (FM) and lean body mass (LBM)
compartments. In 1945, Pace and Rathbun2l determined
the ratio of body water to LBM in guinea pigs to be
0.724. Considering that LBM includes a variety of systems
(eg, viscera, brain, muscle, skin, and bone), we would
not expect a constant determined for the guinea pig to
apply to other species such as humans. Sheng and
Huggins2z reviewed the literature in 1979, and Forbesl2
published a follow-up review in 1987. From these reviews,
it seems that water content ranges from 70% to 78%
of LBM, with a mean value of 73%. This value is critical
for relating measurement of TBW to LBM. Even within
a single species, there must be hydration differences
related to factors such as age, nutrition, and health.
The equation LBM = TBW/0.73 may be in error by
several percentage points depending on the condition
of hydration and distribution of water in the body.23
The TBW tracer dilution method relies on administering an oral or intravenous dose of labeled water and
measuring its dilution in body water after equilibration.
The equilibration process is quick within rapidly perfused
tissues and blood volume, but slower in interstitial
tissues. Although blood and saliva have been used as
sample sites for the tracer dilution, 15,24 the most
commonly used sample is urine. Additional time is
required for the subject to completely clear his or her
bladder and produce urine that has tracer enrichment
equal to that of body water. Depending on perfusion
of the patient and urine outflow, 6 to 10 hours may be
required for a plateau in urine to be reached. There is
little error from tracer loss during this time because of
the slow turnover of water in the body. However, if
the subject is fed before or during the equilibration
period, the water from this input will expand TBW,
dilute the tracer, and contribute to the TBW pool size
measured. Therefore, either the production of urine from
Dwight E. Matthews, PhD, Comell University Medical
College, New York, discussed measurement of TBW and
its relationship to body composition. In 1934, Von Hevesy
and Hoofer&dquo; proposed the use of newly discovered
deuterated water to measure body water in humans,
but it was not until after the report by Dr F. Moore in
194611 that significant interest was given to the use of
2H-water to measure TBW. There have been a variety
of alternative substances used (eg, urea) that disperse
throughout TBW as dilution indicators of TBW, but each
marker suffers from a variety of problems including
nonuniform distribution, disappearance through metabolism, etc.12 The best tracer is the one that is closest in
terms of chemical and physical properties to the
substance being traced. Although there are significant
differences in the properties of hydrogen isotopes, the
isotopes of water have proven far more effective in
tracing water than any other compound. With the
discovery and availability of tritium, 3H-labeled water
began to be used to determine TBW.13 Lifson et al14
used 180-labeled water to measure TBW in mice, but
180-labeled water was long overlooked until 1980 when
Schoeller et al15 described the use of 180-labeled water
as a tracer of TBW in humans. The primary advantage
of 3H-labeled water is its ease of use and measurement,
but it produces a radiation load. Deuterated water is
also cheap to purchase, but it is expensive to measure.
The best sensitivity for measurement of 2H comes from
isotope ratio mass spectrometry. However, the measurement of 2H-labeled water by mass spectrometry is
time consuming and tedious. 180-labeled water is easier
to measure by mass spectrometry, but is too expensive
to
purchase
to use
routinely.
Another drawback with the use of either 3H-labeled
or 2H-labeled water is that the hydrogen atoms in water
are labile and exchange with other labile hydrogen
atoms in the body. Although most hydrogen molecules
in the body do not exchange, some of those attached
to carboxyl, hydroxyl, amino, and other similar groups
do. Culebras and Moore 16 estimated on theoretical
grounds that a maximum of 5% of the protein,
carbohydrate, and fatty acid hydrogen atoms may
exchange with TBW. However, they found <2%
3H-labeled water exchange (determined by desiccation)
in rats.1 With the introduction of ISO-labeled water,
direct dilution measurements could be performed in the
same animals or subjects simultaneously with 110-labeled
and 2H-labeled water. Oxygen in water is estimated to
3% greater than the ig0-labeled water space in
a variety of ~H vs 180
measurement comparisons have been performed with the
application of the doubly labeled water method of
measurement of free living energy expenditure. 18 There
are reports that IH-labeled water (or 3H-labeled water)
overestimates TBW by 4.5% or more.19.20 Because the
estimates of Culebras et all’ were meant to define the
was
normal humans. Since then,
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94
the food source or (better yet) the water from the food
source should be subtracted from the TBW measured.
A meal containing 600 mL of fluid and 1200 kcal would
produce 100 md. of metabolic water for a total load of
700 mL. This fluid load would increase TBW by 1.5%
in a 70-kg man. Even an approximate correction to
TBW for food given before or during the TBW
measurement period would reduce this error substantially. The same correction could also be applied for
measurement of TBW in patients receiving continuous
parenteral or enteral nutrition. Finally, this correction
points out that TBW increases and decreases by perhaps
2% per day going from morning to night with food
intake. When during the day should TBW be measured?
Because the TBW value needed for determination of
LBM should not include extraneous fluid that is being
excreted from the body, the morning postabsorptive
state may be the best time for collection of a urine
sample for TBW determination. Of course, the prior
evening’s meal will contribute to the dilution of the
tracer measured in the morning, and the fluid content
of that evening meal needs to be subtracted.
When a two-compartment model of body composition
is applied, errors described above in TBW are magnified
in the calculation of FM. The magnitude of the error
will depend on the percentage of fat in the body being
measured. The FM error is increased when FM is a
small difference between LBM (determined from TBW)
Wt - TBW/0.73. If FM
and body weight (Wt): FM
sition variables in critically ill patients, and they form
the nucleus of application of body composition measurement methods in clinical nutrition.
Body Cell
Mass and Fluid
Richard Baumgartner, PhD, University of New Mexico
School of Medicine, Albuquerque, discussed measurement of body water pools using bioelectric impedance
analysis (BIA). BIA has advantages over many other
methods of body composition in that it is easy to use,
inexpensive, noninvasive, portable, and requires little
operator training to be performed. BIA refers to
measurement of the electrical conductance (the inverse
of resistance) in the body with a low current.
Conductance is a measure of how well the body conducts
electrical current. Tissues containing little water and
salt, such as fat, are very poor conductors and have a
high resistance to the passage of current through them.
Tissues containing water and salt (eg, blood, visceral
organs, and muscle) are good conductors of electricity.
The BIA method is performed by placing electrodes on
the extremities (a hand and a foot) and measuring the
50-kHz current
conductance of typically a < 1-mA,
between them. Although the BIA technique measures
conductance, that measurement is not directly a measure
of body composition. For example, the dilution of a
water tracer in blood gives a direct measure of TBW,
and the underwater-weighing experiment gives a direct
measurement of body density. However, the conductance
is 20% of body weight, a 2% error in TBW for a 70-kg measurement cannot be related directly to TBW. A
man translates into an 8% error in measurement of FM.
nomogram or regression equation must be developed
As FM increases, the error decreases, and as FM from measurements of TBW or body density and BIA
decreases, the error increases. A 2% TBW error produces conductance.29 Therefore, like skinfold measurements,
a 18% error in the calculation of a 10% body FM.
BIA is very empirical. Each time BIA is applied to a
Fortunately, several of these errors in the TBW new patient population, the regression equation relating
determination can be corrected. We can correct for the BIA and TBW must be reconfilrmed by direct measuregreater than unity TBW dilution space of 2H-labeled ment of TBW or another variable of body composition.
water or 3H-labeled water tracer and for water consumed
Other important factors in the BIA regression equation
or infused during measurement to keep these errors
In theory, these variables
are height and weight.
under 1%. We cannot control for other variables such normalize the length and width of the electrical current
as day-to-day variations in water space and weight.
path because a taller, thinner person presents a longer
However, the worst situation is when FM is assessed path for the current to travel from hand to foot than
in the presence of a fluid imbalance and therefore TBW does a shorter, stockier person. The longer the path,
does not equal 0.73-LBM. Such a hydration error has a the greater the resistance and lower the conductance.
large capacity to distort the FM calculation, especially Numerous papers, both pro and con, have been published
when fat is a low percentage of body weight. It is, of relating BIA measurement to other measures of body
course, in critically ill patients and patients suffering
composition, such as TBW or LBM.19-31 In practice, BIA
malnutrition or eating disorders that both a fluid is a useful technique for routine estimation of body
imbalance and a low FM are likely to occur. Although composition in subjects of normal health. It is less
the two-compartment model may be acceptable for effective in defining accurately alterations of body
assessing LBM and FM in normal or obese healthy composition, because it is in these subjects that more
subjects, it is not acceptable for critically ill subjects complicated alterations occur than can be predicted by
measurement of conductance alone.
with a low FM.
Dr Francis Moore and his colleagues at Harvard
TBW has been incorporated into more complicated
models of four and more compartments in which other defmed a compartment of body water called the body
aspects of body composition are assessed (eg, body cell mass (BCM) as that working, energy-metabolizing
density, total body nitrogen, and body mineral content) portion of the human body and its supporting structure
and in which interior water compartments (eg, extracel- that is the metabolically active tissue in the body.~
lular water [ECW] vs intracellular water [ICW]) have Conceptually, the BCM is equivalent to the ICW pool,
been defmed to clarify individual components., --2- 5-- 21 These and the terms BCM and ICW are often used interchangemodels are required for measurement of body compoably. The BCM defines that portion of the body’s mass
=
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95
that contributes to the resting energy expenditure. In
contrast to TBW, subset compartments of TBW have
been difficult to quantitate. Forbes 12 summarized the
various markers that have been used to define various
body water compartments. None of these markers
measure exactly what is desired. ICW space is not
readily measured directly but has been measured as the
difference between the measurement of TBW and the
measurement of ECW. ECW can be determined by the
dilution of a marker such as bromide or radioactive
sulfate.’ Bromide, for example, dilutes into plasma,
lymph, transcellular water, and dense connective tissue.
An alternative approach has been to measure total body
potassium and relate that back to BCM. Once ICW has
been determined, BCM is set to be ICW plus 33% to
account for other intracellular components such as
protein.
The distribution of water between ICW and ECW has
been of considerable clinical interest. In pathophysiologic
states such as trauma and malnutrition, there is a change
in the transmembrane potential across cells, a change
in electrolyte status, and therefore a shift of fluid
between the intracellular and extracellular compartments.33 The administration and measurement of the
dilution of labeled water and sodium bromide in plasma
defines TBW and ECW (and by difference ICW). Any
imbalance of electrolyte concentrations shifting water
from ICW to ECW can then be evaluated. The problem
to date has been that the determination of water isotopes
and bromide is tedious and expensive, keeping this
aspect of body composition analysis beyond practical
clinical application. In contrast, BIA is simple, easy, and
inexpensive to apply. Early uses of BIA looked only at
the resistance component of the impedance measurement. However, the other half of the impedance
measurement is reactance. Reactance is a term that
relates the relative ability of different frequencies to
pass through a material. The electrical equivalent of
resistance measurement is a simple resistor, and the
electrical equivalent of the reactance measurement is
the capacitor. What evolves therefore is a model in
which the membrane potential of each cell acts as a
miniature capacitor, with the whole-body reactance
measurement being related to the sum of these
measurements. For a constant number of cells, changing
the membrane potential will both shift fluids between
ICW and ECW and change reactance. Therefore, just
as resistance can be related to conductive fluids, ie,
TBW, reactance should relate to capacitive fluids, ie,
ICW. The multifrequency BIA technique has been devised
to evaluate ICW through reactance. The method is based
on the assessment of the dielectric conductive properties
of the cells at two frequencies: a low and a high
frequency. At a low frequency (1 to 5 kHz), the capacitive
effect of cells is sufficient to block conduction through
the cells, and the resistance measured reflects ECW
and its ionic concentration.32.:3?>.3t3
At a high frequency
(>100
kHz), current penetrates the cell membranes,
giving a combined measure of ECW + ICW. For this
method to be applicable, sufficient data must first be
compiled for the various subsets of patients to be studied
to relate direct assessment of TBW/ECW with dual
tracers to the multifrequency BIA measurement.
In Vivo Measurement
of Body Fat and Protein
Joseph J. Kehayias, US Department of Agriculture,
Human Nutrition Research Center on Aging at Tufts
University, Boston, presented important new advances
in the study of fat and protein in vivo. At Dr Kehayias’s
institution, body composition is used to investigate the
changes of energy stores with aging, the causes of LBM
depletion with aging, and the development of ways to
maintain functional capacity and quality of life of the
elderly.
Fat, the
main energy store of the body, is traditionally
assessed either by subtraction of FFM from body weight
or by measuring a physical property of the body, such
as density or skinfold thickness. The need for a more
direct method of measuring total fat and its distribution
applicable to the elderly and the diseased led to the
development of a neutron inelastic scattering technique
for measuring body carbon and oxygen.37 Most of the
body’s carbon is in fat, and total body carbon can
therefore be used to estimate total body fat. Corrections
in total body carbon are applied for the carbon
contribution from nonfat compartments, such as protein,
glycogen, and bone ash. The carbon to oxygen ratio is
a measure of regional fatness and is used to identify
fat distribution patterns as they relate to increased risk
of cardiovascular disease.
Protein is estimated by measuring total body nitrogen
(98% of the body’s nitrogen is in protein). Body nitrogen
can be measured by prompt-gamma neutron capture.
The patient is scanned over a radioactive neutron source
and gamma rays resulting from the neutron interaction
with the body’s nitrogen are detected. The combined
radiation exposure for measuring both fat and protein
is below the usual level for a single chest x-ray. A new
technique is under development for measuring protein
by gamma-ray resonance at a very low radiation
exposure.38
In a catabolic state, the depletion of protein is generally
slower than the loss of cell mass (as measured by total
potassium) or muscle. New studies are directed to the
investigation of changes in cellular function with age
or disease. The role of potassium and sodium ions has
become the focus of this approach.39
Bone Mineral
Henry C. Lukaski, PhD, USDA-ARS Human Nutrition
Research Center, Grand Forks, ND, discussed in vivo
assessment of bone mineral.
Osteoporosis is a serious
increasing public health problem in the United
States, with annual costs of osteoporosis-associated
fractures of approximately $10 billion.&dquo; There is no
current effective treatment for advanced osteoporosis.
and
Risk factors have been identified for the development
of osteoporosis, but they have limited capacity for
predicting bone mass or bone quality. A single measurement of bone mineral status in women at the onset
of menopause, however, has been recommended as an
approach for assessing risk of fracture for use in
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96
decisions.&dquo; Noninvasive techniques are
available for measuring bone mineral content and bone
mineral density, two indices of bone mineral status.
These techniques include single-photon absorptiometry
therapeutic
(SPA), dual-photon absorptiometry (DPA), quantitative
computed tomography, and dual x-ray absorptiometry
(DXA). The original SPA technique was introduced in
1963. It used a monoenergetic photon source, such as
iodine 125, and a sodium iodide scintillation detector
to measure bone mineral content in appendicular or
peripheral skeletal sites, such as the radius and calcaneus
bones. This technique provided a combined measure of
both cortical and trabecular bone, calculated from the
differences in photon absorption between bone and soft
tissue.42 DPA, a modification of SPA, uses a radioisotope
source (gadolinium 153) that emits photons at two
discrete energies and eliminates the need for assuming
constant thickness of soft tissue in the scan path.42
The two-energy photon source permits measurement of
bone mineral content at axial skeletal sites where there
are varying amounts of overlying soft tissue, such as
the hip and spine. Like SPA, DPA converts a three-dimensional body into a two-dimensional image that
provides an integrated measurement of both cortical
and trabecular bone. The measurement of bone mineral
density is expressed as bone mineral content per unit
of bone area (grams per square centimeter).
In contrast to SPA and DPA, quantitative computed
tomography can be used to assess bone mineral status
at both appendicular and axial skeletal SlteS.42 Unlike
SPA and DPA, however, quantitative computed tomography is three-dimensional and directly assesses bone
volume. Therefore, it is the only technique to analyze
separately cortical and trabecular bone mineral content
a
and bone mineral density.
DXA is a two-dimensional projection system similar
in concept to DPA except that an x-ray tube source,
instead of a radioisotope, is used as a photon source.42,43
The DXA systems currently available can be used to
measure bone mineral status both in the peripheral
appendicular skeleton and in axial skeleton sites (which
contain varying proportions of cortical and trabecular
bone). Compared with DPA, DXA has the advantages
of a stable photon source and increased photon flux,
which improve the resolution and precision of the image
and reduce scan time. These characteristics make DXA
the technique of choice for routine assessment of bone
status.
When a beam of x-rays passes through a material of
complex composition, the beam is attenuated in
proportion to the composition of the material, the
thickness of the material, and its individual components. 41
The transmitted intensity of the beam depends on the
intensity of the beam at its source, the x-ray energy,
the composition of the material, and the areal density
of the attenuating material. Energy from an x-ray source
directed through the body undergoes an attenuation or
reduction in intensity that is related to the specific
chemical compounds with which it interacts. Soft tissues,
which contain uTater and organic compounds. restrict
the flux of x-rays less than bone. The unattenuated
energy, as x-ray radiation, is determined with an external
detector. A DXA scanning system includes a source that
emits x-rays collimated into a beam. The beam passes
in a posterior-to-anterior direction through bone and
soft tissue, continues upward, and enters the detector.
The x-ray source and detector are connected to scan
the beam across the patient’s body.
After its initial development in the 1960s and 1970s,
the first commercial DXA system became available in
1987. Three x-ray-based absorptiometry systems are
approved by the Food and Drug Administration and are
in use in the United States and Europe: QDR-1000W
and QDR-2000 (Hologic, Inc, Waltham, MA), DPX (Lunar
Radiation Corp, Madison, WI), and XR-26 (Norland Corp,
Fort Atldnson, WI). Each system uses an x-ray tube as
a photon source, a detector, and an interface with a
computer system for imaging the scanned areas of
interest and for calculating bone mineral content and
bone mineral density. An important aspect of DXA
operation is measurement precision or variability.’ The
precision of DXA has been determined for short-term
and long-term measurements. Repeated measurements
of bone mineral content and bone mineral density made
on a hydroxyapatite lumbar spine phantom have a
within-day precision of better than 0.5% and a betweenday variability of less than 1%. Similarly, the precision
of bone mineral density measurements made in the
spine, femoral neck, and whole body in six women
scanned six times in 1 day, then 9 months later, was
1 % to 2%. The accuracy of DXA measurements of bone
mineral content also has been assessed by comparing
the ash weights of cadaveric lumbar vertebrae with
bone mineral content measured by DXA. The values
were correlated with a slope not different from 1, which
indicates that DXA measures a quantity that is proportional and linearly related to ash weight.&dquo;
The principal uses of DXA have been to measure
bone mineral content and bone mineral density in studies
of aging, ethnicity, and other clinical settings. Crosssectional studies of white and Asian women clearly
indicate an age-dependent decline in lumbar, femoral
neck, and distal radial bone mineral content and bone
mineral density.’ This decline in bone mineral status
was more pronounced in the postmenopausal than in
the premenopausal women. The DXA technique also is
used to evaluate the efficacy of therapy on bone mineral
status. The effectiveness of calcium supplementation&dquo;
and vitamin D supplementation6 on retarding or
increasing regional bone mineral density in women has
been demonstrated with DXA measurements.
Because DPA and DXA use photons at two discrete
energies, it is possible to assess soft tissue (fat and
fat-free mineral-free) masses by using external standards
that simulate fat and fat-free mineral-free tissues. The
precision of DXA determinations of fat and fat-free
mineral-free masses for whole body is 0.5% to 1%.41
DXA and DPA systems yield valid determinations of
whole-body fat, fat-free, and appendicular skeletal masses
in healthy adults.4ï.48 More recently, DXA has been used
successfully
to monitor
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changes
in
body composition
in
97
during weight loss and in patients with
cystic fibrosis.~’
Compared with standard reference methods, DXA
produces accurate estimates (±3%) of human body
composition. The safety of DXA can be assessed in
terms of the radiation dose received by the patient. The
average skin dose is 10 to 30 Gy (10 to 30 [LSv) per
scan.49 The radiation exposure is less for DXA than for
other radiologic methods currently used for bone and
body composition assessment. For comparison, skin
obese
women
AIDS and
exposure from other radiation sources such as environmental background is 35 Gy/week; from dental bitewing
posterior films, 3340 Gy; and from chest x-rays, 80 to
100 Gy. Thus, DXA may be considered a safe procedure
for routine assessment of cross-sectional and longitudinal
assessment of whole-body and regional bone mineral
status and soft tissue composition in healthy subjects
and in patients with metabolic disease. The availability
of DXA instruments greatly enhances body composition
assessment in the evaluation of nutritional status in
clinical studies.
Skeletal Mass
Parenteral Nutrition
Monitoring
During
Home Total
Edward W. Lipkin, MD, PhD, University of Washington,
Seattle, described studies of skeletal mass during home
total parenteral nutrition.5° The studies reported demonstrated a striking heterogeneity in baseline measures
of bone density. Mean bone density of parenteral
nutrition patients was significantly below expected values
on entry into the study at both the distal radius (z
-0.76 ± 0.27) and at the lumbar spine (z score
score
- -1.17 ± 0.27). Mean areal density and morphology
were heterogeneous, with some showing deterioration,
others improvement, and still others no change. The
bone density measures on entry into the study correlated
-.65 and
with duration of parenteral nutrition (r
&horbar;0.64, ~ ~ .02, for wrist and forearm, respectively; r
.06, for lumbar spine) for the group as a
- -.49, p
whole. From longitudinal measures, deterioration of bone
density with time on parenteral nutrition was less evident
but still probable (r
.04,
-.56, -.47, and -.09; p
.09, and .77, respectively). It was concluded from this
study that patients established on parenteral nutrition
frequently have osteopenia and that the group as a
=
=
=
=
=
whole
does
not
demonstrate
normalization
of the
osteopenia over time. It was further concluded that
present parenteral nutrition formulas do not necessarily
cause worsening of bone health and in some cases may
be beneficial to bone. A clear need exists for additional
longitudinal studies of bone density in this patient
population to define the optimal use of parenteral
nutrition in patients with short-bowel syndrome who
might be at risk for, or who already have, established
bone disease.
CLINICAL ASPECTS OF BODY COMPOSITION RESEARCH
Body Composition
and
Energy Expenditure
Michael D. Jensen, MD, Mayo Clinic, Rochester, MN,
described the relationship of body composition to energy
expenditure. A major topic of interest in obesity research
is whether defects in thermogenesis cause or
maintain obesity. To address this issue, we must compare
energy expenditure among individuals of different body
sizes and amounts of body fat. Because lean and obese
subjects have different amounts of both lean and fat
tissue, we must also defme the metabolically active
tissue of lean and obese subjects for comparison of
energy consumption or use.
Daily energy expenditure in humans is commonly
subdivided into the thermic effect of exercise, the
thermic effect of food, and resting energy expenditure.
Body composition is not a critical issue in assessing
the thermic effect of exercise, which is almost completely
determined by the amount of mass moved over a
distance. When studying the thermic effect of food on
obesity, the issue primarily rests on whether fewer
calories are &dquo;wasted&dquo; in lean than in obese individuals.
This issue has been addressed by Segal et al, 51,51 who
have shown that small but significant reductions in the
thermic effect of food are present in obesity. One
component of this thermogenic defect relates to insulin
resistance, and another component may be related to
today
obesity per se.53
When comparing resting energy expenditure between
lean and obese humans, however, body composition has
a major influence on data interpretation. It is not possible
to compare resting energy expenditure in lean and obese
subjects on a &dquo;per weight&dquo; basis. Adipose tissue, kilogram
for kilogram, consumes much less oxygen than
nonadipose tissue. It is therefore necessary to compare
individuals on the basis of metabolically active tissues.
FFM, as assessed by densitometry or by TBW, is
commonly chosen as the basis for making this comparison. Unfortunately, fat-free mass is a less than ideal
denominator. For example, if adipose tissue contains
15% water, a kilogram of body fat would increase body
water by 150 mL. Thus, an individual with 40 kg of fat
would have 6 kg of water associated with that fat, and
this water would be defmed as part of LBM with use
of conventional equations when TBW was measured.
Such an error overestimates the actual metabolically
active tissue of the obese individual and underestimates
resting energy expenditure when normalized for the
measured FFM.
Alternatively, LBM may be assessed by counting the
amount of &dquo;K in the body to determine total body
potassium. Because potassium is concentrated within
cells, body potassium measurement provides an alternative measure of LBM not prone to the error in body
water discussed above. However, it is necessary during
the ~°K measurement to add anthropometric corrections
because increasing amounts of body fat attenuate the
collection of the gamma radiation release from the 40K
decay. Total body nitrogen can be measured by neutron
activation analysis, and total body nitrogen can be
related back to LBM in that protein is associated
primarily with LBM and not with adipose tissue.
Unfortunately, neutron activation analysis is expensive,
complicated, and not widely available for use.
Although there are problems with the direct association
of water with fat in the body, ICW may be used instead
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98
or BCM. TBW is
measured by using standard isotope dilution, and ECW
is measured by using either radiosulfate tracer dilution
or bromide dilution. 12 The resting energy expenditure
can be
compared for lean and obese individuals
normalized for ICW (ie, the difference between TBVV
and ECW. Although ICW may evaluate metabolic tissue
mass, the different types of metabolic tissue are not
addressed. For example, most individuals have similar
amounts of brain, heart, kidney, and visceral tissues.
Differences in body weight largely relate to differences
in terms of fat and muscle masses among individuals.
It has been estimated that internal organs and brain
account for up to 60% of resting energy expenditure,
although they represent only 5% of body weight. In
contrast, skeletal muscle represents a much higher
percentage of body weight but only contributes to 20%
of resting energy expenditure. 54 BCM (via ICW measurement) ignores the different contributions of muscle
and visceral tissue to energy expenditure when large
and small individuals are normalized by BCM. An
alternative is to choose subjects of similar muscle mass
when comparing groups.
The appropriate choice of body composition analysis
can greatly affect the interpretation of resting energy
expenditure measurements between lean and obese
individuals. Simple measures of body composition are
ineffective in relating differences in the metabolic activity
of different tissues and assessing their relative contributions to resting energy expenditure. However, such
an assessment is mandatory when one is trying to defme
differences in metabolic efficiency of lean vs obese
individuals.
to evaluate active metabolic tissue
tis.-13 Resting energy expenditure was 15% higher in the
patients than in age-, sex-, race-, and weight-matched
controls, whereas BCM was 13% lower (a reduction of
one third of the maximal tolerable amount). In addition,
there was an inverse association between IL-1 and usual
dietary energy intake as measured by a food frequency
questionnaire. These data suggest that chronic inflammation
can
lead to disordered metabolism with sub-
sequent catabolism and loss of LBM.
Skeletal Muscle Mass: Estimation by Computerized
Axial Tomography and Other Available Methods
Zi-main Wang, MS, Obesity Research Center, St.
Luke’s/Roosevelt Hospital, Columbia University College
of Physicians and Surgeons, New York, described his
studies of skeletal muscle mass (SM) in healthy men.
Skeletal muscle is the largest nonadipose tissue component of body weight at the tissue-system level (Fig.
- 1),1,12 and skeletal muscle plays a central role in many
physiologic processes.
Although several in vivo measurement methods provide
limited information on skeletal muscle,&dquo; these methods
have not been well validated. Recent studies in
Scandinavia by Sjostrom57 indicate that multiple crosssectional computerized axial tomography (CT) is an
accurate and reproducible method of measuring SM in
vivo. The aim of the studies described by Mr Wang was
to compare CT methods with six other available SM
estimations&dquo;: (1) the neutron activation method, based
on total body potassium and nitrogen; (2) the FFM
method, based on FFM estimates; (3) the creatinine
method, based on 24-hour urinary creatinine excretion;
(4) the 3-methylhistidine (3MH) method, based on
24-hour urinary 3MH excretion; (5) the appendicular
Body Composition, Hormones, Cytokines, and Chronic
skeletal muscle (ASM) method, based on ASM by dual
Disease
energy x-ray absorptiometry;4’ and (6) the anthropometric
Ronenn Roubenoff, MD, MHS, Tufts-USDA Nutrition method, based on cadaver-calibrated anthropometric
Center on Aging, Boston, described the relations between measurements.
Healthy men (n = 26; age [mean ± SD] 34 ± 12
body composition, hormones, cytokines, and chronic
completed the multiscan CT study for SM.
years)
disease. Loss of LBM is a hallmark of aging and of
Compared with CT, neutron activation, FFM, creatinine,
acute and chronic illness. Loss of more than 40% of
lean mass is not compatible with life. The causes of and 3MH methods underestimated SM by an average of
loss of LBM in chronic illness remain obscure, although 21.4%, 9.5%, 13.4%, and 29.5%, respectively. By contrast,
ASM and
methods overestimated skeletal
anorexia, changes in growth hormone, insulin, cortisol, muscle anthropometric
an average of 7.2% and 20.6%, respectively
by
and glucagon production, reduced physical activity, and
<
.01). Mr Wang concluded by emphasizing the
the cytokines interleukin-lb (Ilrl) and tumor necrosis (all p
important new opportunity to study SM in vivo by CT
factor-a (TNF) are implicated.
and magnetic resonance imaging (MRI). The possibility
Recent studies have highlighted the potential role of
exists to develop other methods of estimating SM by
the immune system in altering metabolism.5*.56 The
CT or MRI as the reference methods.
cytokines Ilrl and TNF have been shown to cause using
muscle wasting and catabolism both in vitro an in animal
and Aging: Study by Imaging
models. In addition, there is evidence in animals to Body Composition
Methods
suggest that infusions of these cytokines can increase
Richard N. Baumgartner, PhD, University of New
resting energy expenditure and reduce dietary intake.&dquo;
Recently, a similar association has been shown in adult Mexico, Albuquerque, discussed the study of body
humans with rheumatoid arthritis, an autoinunune
composition and aging. The focus of the presentation
condition in which there is inflammation and hypercy- was the use of the imaging methods CT and MRI.
tokinenia. In these studies, there was a strong
Anatomical body composition refers to the size,
association between resting energy expenditure and location, and relative proportions of various types of
intrinsic production of IL-1 and TNF by Peripheral blood tissues in the body. The introduction of precise imaging
mononuclear cells from patients with rheumatoid arthri- techniques such as CT5ï and MRI~ has made possible
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99
NMR of living tissues was largely confined to low-resolution studies of hydrogen atoms in molecules. With the
development of large-bore superconducting magnets and
pulsed Fourier transform signal-processing techniques,
both the use of NMR for measuring in vivo metabolites
and advanced techniques to produce images from body
proton spectra differences were developed. The latter
is
now
possible.
technique is now called MRI and is the primary medical
whole-body
analysis
although
There is considerable interest in the changes in
use of NMR.~* It is MRI that is used to differentiate fat
anatomical body composition with aging. The changes from water-containing tissue in the study of body
reported to occur with normal aging include the loss composition.&dquo; The NMR signal does not develop from
of SM, atrophy of organs, expansion of adipose tissue all elements. Only elements with isotopes containing an
mass and its redistribution from the extremities to the
odd number of protons or neutrons will possess a
trunk, and loss of bone mass. Each condition may be magnetic moment that can be made to align with or
associated with various underlying pathologies and with against the magnetic field and precess. If a radiofremetabolic and functional consequences. Considerable
quency signal is applied to a nucleus at a frequency
interest is presently being directed in body composition necessary to change its energy state (&dquo;flip&dquo; its magnetic
research toward mechanisms possibly linking these dipole alignment in the magnetic field), it will absorb
changes. Skeletal muscle loss with aging may be partly the energy and go to the higher energy state. When the
caused by alterations in protein metabolism, perhaps radiofrequency energy is removed, some nuclei will
secondary to changes in levels of anabolic hormones, return (flip) to the lower energy state of alignment with
particularly growth hormone, as well as to decreased the magnetic field. This change in alignment results in
physical activity and dietary intake. Low muscle mass emission of radiofrequency energy that can be measured
signifies reduced protein stores for gluconeogenesis and with a receiver coil.6l Thus, the NMR signal is a
hence increased susceptibility to malnutrition given radiofrequency signal generated by the nuclei in a
trauma or disease stresses. The loss of skeletal muscle
magnetic field to which a first radiofrequency signal
is associated with decreased strength and ambulatory has been applied to disturb them. The local environment
capability, increased problems with balance and gait, (the chemical bonds and other atoms attached to the
and increased risk for falls in elderly patients. These nucleus being excited by the NMR experiment) influences
consequences may lead to restriction of physical activity the amount of energy (frequency) required to flip a
resulting in further atrophy of muscle mass. Losses in nucleus and produce a signal. It is these differences
SM may be associated with loss in bone mineral density that allow analytical organic chemists to determine the
also, suggesting common mechanisms underlying structure of an organic compound from an NMR
osteoporosis and muscle wasting in malnutrition and spectrum. When nuclei are placed inside magnets with
during aging. Imaging techniques have been shown to larger magnetic field strengths, more energy is required
be important in the study of obesity also. Visceral to flip them and a radiofrequency pulse of higher
obesity, which can be quantified only with imaging frequency must be applied. The result is that a magnetic
methods, has been shown to be associated in young field of greater strength improves the resolution, and
and middle-aged subjects with a variety of endocrinologic smaller chemical differences among nuclei can be
and metabolic defects including excess free androgens, measured. The common nuclei measured and studied
peripheral insulin resistance, hyperglycemia, hyperlipo- are protons, phosphorus 31, and carbon 13 e8C). Protons
proteinemia, and hypertension. Some studies suggest, and phosphorus 31 are the predominate forms of
however, that these associations are attenuated greatly hydrogen and phosphorus. However, 13C composes only
and are of questionable importance in the elderly.
1 % of the naturally occurring carbon, and its signal
This presentation described the methods used to
is considerably weaker. The primary limitation
strength
analyze CT and MRI images for anatomical body of NMR for the measurement of in vivo metabolism has
composition.5’ The relative accuracy and reliability of been NMR’s poor ability to detect and measure important
these methods were discussed and problems were
elements of organic compounds such as carbon and
identified. The use of imaging methods to quantify
nitrogen. For the most part, special isotopically l3C-laanatomical body composition were illustrated with data beled
compounds must be administered to measure l:3C
from the New Mexico Aging Process Study, the in vivo. Some of these
problems were addressed by Dr
Fels-Emory Abdominal Body Composition Study, and Magnusson in her presentation. However, a general
data from other published literature.
the
is
discussion of NMR and MRI
the accurate in vivo quantification of anatomical body
composition. In vivo analysis by imaging is presently
limited mainly to quantification of the dominant species
of tissues-adipose, muscle, bone, and organ; however,
this can be done with very high precision and accuracy.
Most applications have been restricted to the analysis
of specific regions (eg, the arm, abdomen, or leg),
techniques
1VIR1/Spectroscopy in the Study of Body Composition
Inger Magnusson, PhD, Yale University School
of
CT, discussed MRI and nuclear
Medicine,
magnetic resonance (NMR) spectroscopy in the study
of body composition and metabolism. Her focus was
largely on how NMR has become a valuable tool for
the study of metabolism in vivo.-58---&dquo; Until the early 1970s,
New Haven,
beyond
scope of this article, and the reader is referred to recent
reviews concerning NMR applications in physiology
Dr Magnusson and her colleagues at Yale University
have combined NMR and MRI to study metabolic
questions that have proven difficult to solve w-ith other
techniques. For example, hepatic glycogenolysis and
gluconeogenesis are essential processes for maintaining
plasma glucose during fasting. The relative contribution
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100
of these processes to glucose production has been
difficult to quantify in humans. The advantage of 13C
NMR spectroscopy is that hepatic glycogen concentration
can be measured directly and noninvasively. Glycogenolysis is measured from the rate of decrease in the
liver glycogen concentration. The concentration of liver
glycogen is measured over time by l3C NMR. The l3C
NMR spectrum of liver glycogen is obtained by placing
a rigid receiving coil on the skin above the liver.
Sophisticated techniques are applied to obtain specifically the signal of liver 13C-labeled glycogen and not
surrounding tissue signals from the receiving coil. By
using a second measurement with an MRI instrument,6O--B2
liver volume is determined. Both liver volume and liver
glycogen concentration measurements are needed to
determine the rate of glycogen depletion with time.
Liver glucose production (the sum of the gluconeogenesis
and glycogenolysis processes) was determined by
measuring the dilution in blood glucose of a [6-3H]glucose
tracer infused intravenously at a known rate. Gluconeogenesis was calculated as the difference between the
liver glucose production and glycogenolysis measurements.
This technique was applied to study progressive fasting
and the relative contributions of gluconeogenesis vs
glycogenolysis to glucose production over time. Young,
healthy subjects were fasted for 68 hours .6’ During the
fasting period, liver volume was determined by MRI,
liver glycogen concentration was measured by NMR,
and liver glucose production was determined by the
3H-labeled glucose tracer infusion technique. For the
first 22 hours of the fast, liver glycogen concentration
decreased at an almost linear rate, showing a constant
rate of glycogenolysis. Liver volume decreased from 1.49
± 0.13 L (mean ± SEM) to 1.12 ± 0.08 L during the
68-hour fast. Gluconeogenesis accounted for 64 ± 5%
of body glucose production during the first 22 hours of
fasting; the contribution of gluconeogenesis increased
to 82 ± 6% and 96 ± 1% during the next 24-hour and
18-hour periods of the fast as glycogenolysis decreased.
Thus, gluconeogenesis contributed substantially to glucose production in humans both during the initial hours
of a fast and during starvation.
Hepatic glycogenolysis and gluconeogenesis were also
measured in patients with type II (non-insulin-dependent) diabetes mellitus and in age- and weight-matched
control subjects.’ Liver glycogen concentration 4 hours
after a standardized meal was lower in the diabetics
than in the controls (131 -!- 20 mmollL ~s 282 z- 60
mmol/L in liver). Net hepatic glycogenolysis was
decreased and whole-body glucose production was
increased in the diabetics compared with the control
subjects. Consequently, gluconeogenesis was increased
in the diabetic patients and accounted for 88 ± 2% of
glucose production compared witch 70 ± 6% in the
control subjects. It was concluded that increased
gluconeogenesis was responsible for the increased
glucose production in patients with type II diabetes
after the overnight fast.
Glycogen should be measurable in any area of the
body where a surface coil receive can be placed.
Unfortunately, the ability of NMR
to
measure
the
concentration of a substrate is limited, and 13C can only
be determined in compounds that are highly concentrated
in the body. For example, glycogen is concentrated in
the liver (> 100
mmol/L) but less plentiful elsewhere,
such as in leg or arm muscle. To enhance the &dquo;C signal
enough to be measurable in vivo., a labeled compound
such as [1-13C]glucose must be infused. Glycogen
synthesis (rather than breakdown) is then determined
in vivo in a leg with a surface coil from the rate of
increase in 13C signal derived from the [1-13C]glucose
infusion with time. 65 Glucose production can also
determined from the dilution of the 13C-labeled glucose
tracer in blood. Such a study has determined that when
glucose is infused into humans with insulin in large
amounts, the disposal of most of the infused glucose
is by muscle uptake for glycogen synthesis.65 This
approach has also been used to demonstrate that type
II diabetics, who are resistant to insulin, fail to synthesize
muscle glycogen at the same rate as normal subjects.
This result suggests that the mechanism for insulin
resistance in these diabetic subjects lies in a defect in
muscle glycogen synthesis.9
Application of Magnetic Resonance Spectroscopy to the
Study of Nutrition and Metabolism: A Comparison of
the Effects of Starvation and Sepsis on Skeletal Muscle
Danny O. Jacobs, MD, Harvard Medical School, Boston,
discussed how the major metabolic changes in skeletal
muscle that occur during starvation and sepsis might
be assessed in animal models in vivo. Dr Jacobs
emphasized the importance of measurement of the stores
of energy in muscle to the health of the cell. Although
the long-term stores of energy are the nutrient stores
of fat and protein, the short-term store of energy is the
&dquo;high-energy&dquo; phosphate bonds of ATP and phosphocreatine (PCr). The conversion of ATP to adenosine
diphosphate (ADP) is the standard unit of measure of
release of energy, just as the production of an ATP
molecule from an ADP molecule is the standard unit
of gain of energy in the cell. Living cells depend on
adequate ATP stores to maintain all the energy-requiring
processes in the body. ATP is produced as the result
of oxidation of fuel substrates. However, the cell is
limited in terms of the amount of ATP that can be
stored. In muscle, much of the high-energy phosphate
is transferred from ATP to creatine to form PCr. When
the muscle cell requires a burst of ATP energy, ATP is
produced from PCr. This approach allows ATP to be
maintained inside the cell at a constant level. When the
PCr stores are depleted, ATP levels quickly decrease
and cell death results.
31 P NMR can be used to measure the levels of the
high-energy phosphate bond-containing compounds,
such as PCr, ATP, ADP, and adenosine monophosphate,
as well as the levels of inorganic phosphate .51 The levels
of these compounds (in particular PCr and ATP) correlate
with the health of the cell and the degree of metabolic
stress imposed by a particular disease. By using surface
coils placed on rat hind limbs, Dr Jacobs has used NMR
to measure
the effect of sepsis and starvation
Downloaded from pen.sagepub.com at PENNSYLVANIA STATE UNIV on September 19, 2016
on
energy
101
metabolism in muscle. 66--67 Rats were fed ad libitum for
24 hours after cecal ligation and puncture with fluid
resuscitation to develop a septic model or after 24 or
96 hours of starvation. Because ATP levels are maintained
at a nearly constant level until all high-energy phosphate
stores have been depleted, the 31 P NMR signal from
ATP was used to normalize for differences among
animals, placement of the surface coil, etc. The energy
level of the muscle was expressed as the ratio of the
3lp NMR PCr signal to the ATP signal. Changes in the
3lp NMR position of the inorganic phosphate signal were
used to determine intracellular pH. In a separate set of
measurements, gastrocnemius muscles were excised
from rats and quickly frozen by the &dquo;freeze-clamp&dquo;
technique to determine by conventional biochemical
methods intracellular PCr, ATP levels, and pH. ATP
levels were similar among the control, septic, and starved
rat gastrocnemius muscles, as expected. There were no
differences in intracellular pH among groups. PCr levels
decreased less than 10% after 96 hours of starvation.
In normal animals, fuel (fat and protein) stores are
oxidized to keep the PCr and ATP levels stable. However,
in the septic rats, PCr levels decreased by more than
20% within the first 24 hours and ADP levels increased.
This type of study using in vivo 3lp NMR can demonstrate
metabolic changes induced by disease states such as
infection that clearly have significantly different metabolic results than simple starvation.
cell energetics. ~’6’e have observed Z-band degeneration
and calcium accumulation with hypocaloric feeding in
humans and have suggested that it is related to changes
in cell energetics. Cell energetics is also important for
muscle activity, and we shov4?ed that skeletal muscle
function including that of the diaphragm can be altered
by nutrient deprivation and restored by refeeding,
observations confirmed by others. Windsor and Hin7l
also showed that nutrition support improves muscle,
including diaphragmatic function, before there is any
increase in body protein or body mass. The investigators
demonstrated that the functional effects of nutrition are
more important than subnormal body protein as an
index of surgical risk.
The studies reported by Dr Jeejeebhoy39,68-í2 show that
malnutrition has profound effects at the membrane level,
changing the energetics of the sodium pump as well as
changing the calcium kinetics affecting muscle function.
The central problem seems to be limitation of aerobic
and anaerobic energy production. The energetic changes
are then responsible for altered function and changes
in cell composition. For example, the estimation of LBM
by total body potassium probably reflects an alteration
in the sodium-potassium pump energetics rather than
an actual change in lean tissue per se. Therefore, the
demonstration of the effects and treatment of malnutrition should be based on functional considerations.
ACKNOWLEDGMENTS
Body Composition, Cellular Function, and Outcome
Kersheed N. Jeejeebhoy, MD, PhD, University
Toronto, School of Medicine, described his studies
of
of
body composition, cellular function, and outcome.39.68-72
Lack of nutrient intake results in a loss of body fat
and lean tissue, and up to this time the effects of
nutrition have been judged by changes in body
composition, especially composition of lean tissue. Lean
tissue is composed of water, minerals, nitrogen, and
glycogen, and feeding wasted individuals results in a
gain of the multiple elements in lean tissue as well as
body fat. One of the elements responding to nutrient
intake is body potassium, which has been used as an
index of BCM, the metabolically active component of
lean tissue. We and others have shown that, in contrast
body nitrogen, body potassium responds rapidly to
feeding by both oral and intravenous routes. The early
restitution of body potassium indicates that cell ion
uptake occurs earlier than protein synthesis with
nutrition support. In support of this conclusion, it has
been shown, by using ion-selective electrodes, that
hypocaloric feeding results in a decrease in muscle
membrane potential and the concentration of intracellular ionic potassium. The changes were specifically
related to nutrient deprivation, inasmuch as they could
not be reversed by potassium supplementation per se.
That five molecules of ATP are required for the
incorporation of one molecule of amino acid into protein,
77% of the free-energy change of ATP hydrolysis is
used to maintain the sodium-potassium gradient across
the cell membrane, and energy intake limits nitrogen
to
retention all suggest that nutrition support
initially alters
The 1993 ASPEN Research Workshop was supported
in part by a grant from the National Institutes of Health
(National Institute of Diabetes and Digestive and Kidney
Diseases, National Institute of General Medical Sciences,
and National Cancer Institute).
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