Albumina sarcopenia

552 Aim, J Cliii Nuir 1996:64:552-8. Printed in USA. © 1996 American Society for Clinical Nutrition

Serum albumin is associated with skeletal muscle in elderlymen and women13

Richard N Bau�ngartner, Kathleen M Koehler, Linda Ro,nero, and Philip J Garrv

ABSTRACT Serum albumin concentrations decrease with

age and values < 38 g/L are associated with increased morbidity,

mortality, and disability in the elderly. It is not clear to what extent

the decreases are associated independently with changes in metab-

olism, dietary intake, physical activity, morbidity, or body com-

position. We examined associations of serum albumin with age.

protein and energy intakes, physical activity, morbidity, and mus-

cle mass in 275 men and women aged 60-95 y. Serum albumin

was measured with the bromcresol green procedure. Usual dietary

intake and physical activity were quantified through question-

naires. Morbidity was ascertained from medical history, question-

naire, and examination. Muscle mass was estimated from dual-

energy X-ray absorptiometry. In multivariate analyses, serum

albumin was associated significantly with muscle mass after age,

protein intake, physical activity, and comorbidity were controlled

for in men and women. This study suggests that decreases with age

in serum albumin concentrations are associated with muscle loss

(sarcopenia) in the elderly. This association is independent of other

factors that may affect muscle mass and albumin concentration.

We suggest that the increased risk of disability with low serum

albumin concentrations observed in the elderly may actually re-

fleet an association with sarcopenia. Am J Cliii NuirI 996:64:552-8.

KEY WORDS Muscle, serum albumin, aging

INTRODUCTION

Serum albumin has long been recognized as a crude indicator

of “health” and “nutritional” status. Several recent epidemio-

logic and clinical studies have described an apparent associa-

tion of low serum albumin concentrations with increased mor-

tality as well as morbidity, and have also described possible

protective effects of high concentrations (1-5). Functional im-

pairment and disability in elderly groups are also reported to be

associated with low serum albumin (4, 6).

Serum albumin is the main protein synthesized by the liver.

Acute changes may be produced by large reductions in protein

intake or by trauma and infectious diseases. Long-term changes

may be produced by chronic renal and liver diseases. Serum

albumin concentrations decrease with age. especially in the

elderly, although the magnitude of decrease varies consider-

ably among studies (3, 4, 7-9). It is not clear to what extent the

lower concentrations seen at older ages are associated indepen-

dently with age-related changes in metabolism, dietary intake,

physical activity, morbidity, or body composition (8). Age-

related changes in the absence of significant disease, trauma, or

reductions in protein intake may be due to alterations in the

balance between protein synthesis and degradation (10-12).

These changes in protein turnover may occur in peripheral

muscle tissues as well as in liver, and could explain, in part, the

observed decreases with age in muscle mass in the elderly, a

phenomenon now referred to as sarcopenia ( 13, 14). Taken

together, these observations suggest that changes in protein

metabolism in liver and muscle could be interrelated, resulting

in a correlation between serum albumin concentration and

muscle mass (13).

In some epidemiologic reports, low serum albumin concen-

trations have been reported to be associated with risk factors

related to muscle strength and function, such as impaired

mobility, balance, and gait, suggesting a link with sarcopenia

(4, 6). To date, however, there are few data for the possible

association of the sarcopenia of aging with morbidity, mortal-

ity, or disability. This may be due to the difficulty of accurately

measuring muscle mass in epidemiologic studies. The reported

association of low body mass index (BMI: in kg/rn2) with

increased morbidity, mortality, and disability suggests such an

association (15).

The purpose of the present study was to examine the joint

associations among age, serum albumin, dietary intakes of

protein and energy, morbidity, physical activity, and muscle

mass in a cohort of elderly men and women. A strength of this

study is the availability of accurate estimates of muscle mass

from dual-energy X-ray absorptiometry (DXA) in a relatively

large cohort of healthy elderly men and women.

SUBJECTS AND METHODS

The data analyzed in the present report were collected in

1993 for 275 participants in the New Mexico Aging Process

Study, an ongoing longitudinal study of nutrition and aging that

began in 1980 (14). These elderly volunteers are white, are of

above average income and education, and reside mostly in the

I From the Clinical Nutrition Program, School of Medicine. University

of New Mexico, Albuquerque.2 Supported by grants AG1O149 (to RNB). AG02049 (to PJG). and GCR

DRR, 5 MO1-00997-13-l3,l4 from the National Institutes of Health.

3 Address reprint requests to RN Baumgartner. Clinical Nutrition Program.

215 Surge Building. 2701 Frontier Place. University ofNew Mexico School of

Medicine, Albuquerque. NM. E-mail: [email protected].

Received February 15, 1996.

Accepted for publication June 26, 1996.

by guest on January 18, 2015ajcn.nutrition.org

Dow

nloaded from

http://ajcn.nutrition.org/

SERUM ALBUMIN AND MUSCLE IN THE ELDERLY 553

‘� ± SD.2 Significantly different from men. P < 0.02.

area of Albuquerque. NM. Ninety-six percent of the partici-

pants are non-Hispanic whites, whereas 4% claim Hispanic

origin: the cohort does not represent a population-based sample

of Albuquerque, which is 33% Hispanic. The entrance crite-

na for the study excluded persons with serious diseases, for

example, cancer (other than skin) within the past 5 y; recent,

acute myocardial infarction; or chronic obstructive pulmonary

disease, and persons taking a meaningful number of medica-

tions, such as those undergoing chemotherapy or taking car-

diac, respiratory, or antipsychotic medications. About 56% of

the participants in the present data set were recruited between

1980 and 1985: the remainder were recruited in 1992-1993.

Because the maintenance of good health is not required to

remain in the study, participants who developed chronic ill-

nesses before or during the 1993 study year are included in the

present analyses. All participants gave their informed consent

to participate in the study. The study protocol was approved by

the Human Subjects Research Review Committee of the Uni-

versity of New Mexico School of Medicine.

Serum albumin concentrations were determined with the

bromcresol green procedure on a 747 SMA (Hitachi, Tokyo) at

the New Mexico Medical Reference Laboratory (Albuquerque,

NM). Usual dietary intake was estimated through a modified,

standard food-frequency questionnaire administered in an in-

terview (Health Habits and History Questionnaire, version 2.2;

16). Physical activity was graded using a modification of the

self-administered instrument first described by Shapiro et al

( I 7) and later adapted by Cassel et al ( 1 8) to study the relation

of physical activity to coronary heart disease. The modifica-

tions were a substitution of questions on job-related activities

with a more extended set relating to leisure-time activities

appropriate to ambulatory, community-dwelling elderly peo-

pIe. The questionnaire results in a summary score (range: 0-65)

that grades individuals with regard to self-reported “usual”

physical activity, rather than in an estimate of energy expen-

diture. Past and current morbidity and medication use were

ascertained from medical histories and examinations. Prevalent

major chronic diseases were ascertained by physical examina-

tion and from medical records and grouped by International

Classification of Diseases codes ( I 9). An index of comorbidity

was defined as the sum of the current, chronic conditions

present at the time of the body-composition examinations.

Subjects with current, acute infectious illness or recent trauma

(eg, hip fractures) were excluded.

Body composition (fat, fat-free soft tissue, and bone mineral

content) was estimated using DXA (Lunar DPX, version 3.6z

software: Lunar Corp. Madison, WI), as described previously

(14). Fat-free mass (FFM) was defined as the sum of the

fat-free soft tissue and total-body bone mineral content from

whole-body scans. Medium-length scans (20 mm) were used

for all subjects except for those with > 27-cm anteroposterior

thicknesses, for whom the slow (40-mm) scan speed was used.

The technical errors of body-composition determinations by

DXA were estimated to be ± 0.77 kg for FFM or ± 1 .2% for

percentage body fat from two repeated scans taken on separate

days for five randomly selected subjects. Appendicular skeletal

muscle mass (ASM) was derived as the sum of the fat-free soft

tissue masses of the arms and the legs, as described by Heyms-

field et al (20). Anthropometric measurements were taken

using standardized methods (2 1). Weight was measured to the

nearest 0. 1 kg on a balance scale and stature was measured to

the nearest 0.1 cm with a wall-mounted stadiometer. Knee

height was measured with a sliding caliper as described previ-

ously (22). All anthropometric measurements were taken twice

and the reported values are the means of the repeated

measurements.

Data for men and women were analyzed separately. All

variables were regressed on age to describe age differences.

Regressions of muscle mass on age were adjusted additionally

for body weight, knee height, comorbidity, energy and protein

intakes, and physical activity score. Muscle was also expressed

as a percentage of lean soft tissue mass (FFM less bone) and

protein intake as a percentage of total energy intake. Univariate

associations of muscle mass, percentage muscle mass, protein

and energy intakes, and physical activity with serum albumin

were tested by linear regression. The association of serum

albumin with levels of comorbidity (0 to � 4 comorbid con-

ditions) was tested by analysis of variance. Differences in

age-adjusted mean serum albumin concentrations across levels

of comorbidity were tested using analysis of covariance. Mul-

tiple regression was used to test for the independent effects of

age, protein intake, comorbidity, physical activity, and muscle

mass on serum albumin. Estrogen replacement therapy (ERT)

was also entered as a variable in regression analyses for

women. Statistical significance was evaluated at a 0.05.

RESULTS

Descriptive statistics for the study variables are shown in

Table 1 . Twenty-six percent of the men and 3 1% of the women

had BMIs > 27. Percentage body fat ranged from 7% to 40%

in the men and from 17% to 53% in the women. ASM, as

quantified from DXA, was 41.3% of FFM in the men and

38.8% in the women. Dietary energy and protein intakes were

comparable with those reported elsewhere for healthy elderly

adults (23). Protein as a percentage of energy intake was

15.8 ± 2.6% and there was no significant difference between

the men and the women. Protein intake was 0.90 g/kg body wt

( I .46 glkg FFM) in the women and 0.89 gfkg body wt ( I .22

g/kg FFM) in the men.

Physical activity scores were significantly higher in the men

than in the women (P < 0.02). The scores were positively

TABLE I

Descriptive statistics for study variables’

Men

(ii - 108)

Women

(ii 167)

Age (y) 76.0 ± 5.4 75.7 ± 6.4

Weight (kg) 76.2 ± 10.8 63.1 ± 10.7

Stature (cm) 172.6 ± 6.9 158.3 ± 6.1

Knee height (cm) 53.6 ± 2.5 48.5 ± 2.5

BMI (kg/m2) 25.6 � 3.4 25.1 ± 3.8

Body fat(%) 27.0 ± 6.9 37.3 � 7.3

Fat-free mass (kg) 55.0 ± 6.1 38.1 ± 3.7

Appendicular skeletal muscle (kg) 22.7 ± 2.9 14.8 ± 1.8

Energy intake (kJ/d) 7065.9 ± 189.6 6010.0 ± 152.5

Protein intake (g/d) 66.3 � 20.9 55.5 ± 16.6

Serum albumin (gIL) 41.3 ± 2.9 40.9 ± 2.4

Physical activity score 18.5 ± 0.6 16.7 ± 0.52


Dow

nloaded from


554 BAUMGARTNER ET AL

correlated with ASM in the men (r 0.28, P < 0.003) and the

women (r = 0. 13, P < 0.09). Correlations with percentage

body fat, however, were negative, were about the same mag-

nitude in both sexes, and were also significant (r = -0.22, P <

0.04).

As shown in Table 2, only 2% and 2.5% of serum albumin

concentrations in the men and women, respectively, were < 35

g/L, the lower limit of the normal reference range (10). Ten

percent of serum albumin values were < 38 g/L in each sex,

the concentration below which risk has been reported to in-

crease (6). None of the men and only 3.6% of the women were

current smokers. There was no detectable difference in serum

albumin concentration between smoking and nonsmoking

women. Alcohol consumption (not shown) was light to mod-

erate. About 26% of the women were receiving ERT and mean

serum albumin concentrations were slightly but significantly

lower in these women (40.3 ± 0.4 gIL) than in those not

receiving ERT (4 1 . I ± 0.2 gIL, P < 0.03). None of the

participants was taking any other steroid hormones at the time

of data collection.

Table 2 also shows the prevalences of major chronic diseases

in the study population. Osteoarthritis was the most common

condition, occurring in more than one-half of all participants,

followed by hypertension. None of the men or women had

rheumatoid arthritis or other acute or chronic inflammatory

conditions known to affect serum albumin (24). About 10% of

the men and 3% of the women had diagnosed renal or liver

diseases. Although renal and liver disease may significantly

affect serum albumin, this group did not differ significantly for

mean age, protein intake, physical activity, body composition,

or serum albumin concentration from the group without these

diseases. The exclusion of participants with diagnosed renal or

liver disease did not materially affect the results of the analyses

except in terms of reduced statistical power, as would be

expected as a result of the somewhat smaller sample sizes. As

a result, the analyses reported were made with data for the

complete study population.

Results for the linear regressions of the variables on age are

shown in Table 3. Serum albumin, ASM, ASM as a percentage

of lean soft tissue mass, and physical activity score had signif-

TABLE 2Percentages of men and women with low serum albumin concentrations,

smoking habit, medication use, or chronic disease’

Men

(n 108)

Women

(n 167)

%

Serum albumin

�35g/L 2.0 2.5

� 38 g/L 10.0 10.0

Current smokers 0.0 3.6

Estrogen replacement therapy NA 26.3

CHD or CVD 19.4 16.8

Neoplasias2 14.8 9.0

Osteoarthritis 51.9 66.5

Hypertension 24.1 28.7

Renal or liver disease 10.2 3.0

‘ NA, not applicable; CHD, coronary heart disease; CVD, cardiovascu-

lar disease.2 Benign or in remission during 1993.

icant negative correlations with age in both sexes (P < 0.05),

whereas comorbidity had significant positive correlations. Pro-

tein and energy intakes were not associated significantly with

age in either sex. Albumin decreased with age in both men

(slope = -0.16 g � L_i . y_i) and women (slope = -0.08

g � L � y I) ASM (absolute as well as a percentage of lean

soft tissue mass) decreased significantly with age in the men

and women even after adjustment for weight, knee height,

comorbidity, energy and protein intakes, and physical activity.

There were no significant differences in age-adjusted mean

serum albumin concentrations across levels of comorbidity

(Table 4). In addition, there were no differences in age-ad-

justed mean serum albumin concentrations between those with

and without specific categories of morbidity. It is recognized,

however, that the statistical power to detect significant differ-

ences is low for some of these comparisons because of the

small numbers of cases.

Serum albumin concentrations were positively associated

with total muscle mass in the men (Figure 1), even after age,

protein intake, comorbidity, and physical activity were con-

trolled for, as shown in Table 5. Serum albumin concentrations

were positively associated with muscle as a percentage of lean

soft tissue mass in the women (Figure 2), even after age,

protein intake, comorbidity, ERT, and physical activity were

controlled for (Table 5). Age remained significantly associated

(P < 0.05) with serum albumin in both men and women after

adjustment for the other independent variables. Physical activ-

ity had a significant negative association with serum albumin in

the women but not in the men. Serum albumin also had a

significant negative association with ERT in the women after

adjustment for age, protein intake, comorbidity, physical ac-

tivity, and muscle. The inclusion of dietary energy intake in

these regression models had no meaningful effect on the

results.

DISCUSSION

This study suggests that low serum albumin concentrations

are associated with reduced muscle mass (sarcopenia) in rela-

tively healthy, well-nourished elderly men and women. In our

study population, serum albumin concentrations were generally

within the normal reference range (35-50 g/L), but decreased

significantly with age. The concentrations were not associated

significantly with either protein or energy intake and did not

differ among categories of chronic morbidity or across levels of

comorbidity. Serum albumin was associated significantly with

skeletal muscle mass independent of age, dietary protein and

energy intakes, physical activity, ERT in women, and morbid-

ity. This association suggests some connection between serum

albumin and muscle mass such that losses of somatic (muscle)

protein stores either covary with or affect decreases in serum

albumin concentrations. This association is independent of

factors known to affect protein metabolism, such as dietary

intake and physical activity. The mechanism or mechanism

connecting serum albumin and skeletal muscle is not known

but could involve changes in either I) the extravascular distri-

bution of albumin in muscle or 2) protein synthesis and deg-

radation in both muscle and liver.

Rall Ct al (10) recently reviewed current knowledge about

serum albumin as an indicator of nutritional and health status.


Dow

nloaded from



TABLE 3

Correlation and regression of study variables with age (y)’

Men (n = 108) Women (n = 167)

r Slope2 r Slope2

Serum albumin (gIL) -0.29” -0.158 ± 0.050 -0.077 � 0.028

ASM (g) -0.34� - 1 83.45 ± 50.08 -0.34� -94.97 ± 20.�1

ASM/LSTM (Ck) �0.341 -0.1 17 ± 0.032 -0.32” -0.1 16 � 0.026

Protein intake

(g/d) -0.06 -0.254 ± 0.377 -0.1 1 -0.295 ± 0.199

(‘7c of energy) -0.09 -0.036 ± 0.040 -0.1 1 -0.049 � 0.034

Energy (kJ/d) -0.02 -9.28 ± 39.94 -0.05 - 15.49 ± 21.73

Comorbidity 0.34” 0.061 ± 0.017 0.40” 0.060 ± 0.01 1

Physical activity score -0.38� -0.448 ± 0.105 -0.23” -0.212 ± 0.684

‘ ASM, appendicular skeletal muscle mass; LSTM, lean soft tissue mass.2 � SE.

“P < 0.05.

In brief summary, albumin is the main protein synthesized by acute reduction in albumin production and serum albumin

the liver. Serum concentrations depend on liver synthesis, concentrations are often low in patients with alcoholic cirrhosis

degradation in peripheral tissue, and intra- and extravascular (1 1 ). The effects of chronic diseases, other than renal and liver

distribution in extracellular fluids. The functions of serum disease, are unclear. Heavy smoking is reported to be inversely

albumin are 1) to maintain osmotic pressure, 2) to act as a associated with serum albumin and may confound associations

transport vehicle for amino acids and other substances to pe- with chronic morbidity and mortality in some studies (4). There

ripheral tissues, and 3) to serve as a temporary amino acid is little evidence that hepatic synthesis of albumin is impaired

storage site. About 1 20-220 mg albumin/kg body wt is syn- with age independent of disease ( 1 1).

thesized daily and its half-life is = 17-20 d. About one-third of Protein distribution and turnover in the visceral and muscle

the amino acids in daily dietary intake are used in the synthesis compartments were not measured in the present study. As a

of albumin and other plasma proteins. Hepatic synthesis of result, we can only speculate as to the underlying nature of the

albumin increases after a meal in response to the increased association observed between serum albumin and muscle mass,

availability of amino acids and decreases during fasting in which could be direct or indirect. Sixty percent of total body

association with the reduction of the amino acid pool (1 1). albumin is extravascular in muscle and skin, and serum albu-

These changes in albumin synthesis, however, do not result in mm exchanges with this pool (10, 1 1). It is not clear, however,

large changes in serum concentrations, so serum albumin is how an alteration in the extravascular muscle pool would affect

often regarded as an insensitive indicator of dietary intake serum albumin concentrations unless exchange between the

status ( 10). intra- and extravascular pools is somehow altered ( 1 1 ). It

Serum albumin synthesis appears to be spared in starvation seems more likely that the connection is indirect; covariation

because amino acids are drawn from skeletal muscle. Long- between serum albumin and muscle mass may reflect shared

term protein deficiency with adequate energy intake (protein- effects of changes with age in protein metabolism.

energy malnutrition), however, results in skeletal muscle up- It is generally believed that rates of protein synthesis and

take of carbohydrate, fatty acids, and amino acids at the degradation decrease with age (25). Some recent studies mdi-

expense of hepatic protein synthesis and leads to hypoalbumin- cate, however, that whole-body protein synthesis rates are

emia. Injury and inflammation cause acute declines in serum actually slightly higher and that rates of degradation are the

albumin concentrations ( I 0, 24). Alcohol intake causes an same in elderly compared with young adults when expressed in

TABLE 4

Analysis of variance of serum albumin concentrations by number of comorbid conditions present (0 to � 4)!

0 1 2 3

Men

ml 25 39 35 6 3

Crude value (gIL) 41.1 41.3 41.7 41.0 39.7

Age-adjusted value, (gIL) 40.6 41.4 41.8 41.6 39.7

Women

ii 23 82 41 15 6

Crude value (gIL) 41.0 40.8 41.1 40.2 41.3

Age-adjusted value. (gIL) 40.8 40.8 41.1 40.8 41.9

, Crude values are mean serum albumin concentrations; age-adjusted values are mean concentrations adjusted by analysis of covariance for differences

in age across levels of comorbidity. Comorbidity was defined as the sum of International Classification of Disease-coded prevalent chronic conditions,

including coronary heart disease and cardiovascular disease, neoplasias (benign or in remission), osteoarthritis and arthrosis, hypertension, and renal and

liver diseases.


Dow

nloaded from


..1..(

50

45

40

35

-I

C)

C

E.0

Co

E5-a)Cl)

U. .

U

UU

UU U U_U U UU #{149}U U

U #{149}#{149}UU

U F�

#{149}UU #{149}- U U

U UU

U

r = 0.29U

10 35

-j

C)

C

E.0Co

E5-a)

Cl)

45

40

35

30

S #{149}

.

.. _.... .

. S S � #{149}

. �__.

.� S #{149}#{149}#{149}

__... . .

... _._.

- ..� ... .

. . .

. a

.

r = 0.25

‘ ASM, appendicular skeletal muscle mass: NS, not significant: LSTM.

lean soft tissue mass.

2 � SE.

4 Total R2 (ek) = 14.06 for men and 20.23 for women.

Muscle (% of lean soft tissue mass)


FIGURE 2. Correlation of seruiii alhuniin concentration with muscle

mass as a percentage of lean soft tissue mass in elderly women. ii = 167.

3015 20 25 30

Muscle mass (kg)

FIGURE 1. Correlation of serum albumin concentration with muscle

mass in elderly men. n = 108.

relation to body cell mass or creatinine excretion (26). Young

(26) and associates have suggested that these results reflect the

decreased contribution of skeletal muscle to whole-body pro-

tein turnover. They estimate that muscle contributes 20% to

whole-body protein turnover in the elderly compared with 30%

in younger adults. The decreased reserve of skeletal muscle

protein in the elderly limits the supply of amino acids from

peripheral tissues for protein synthesis by vital organs during

acute physiologic stresses such as disease, injury, and starva-

tion. The elderly, therefore, should have an increased likeli-

hood of low serum albumin concentrations compared with

younger adults under these stressful conditions. It is not clear,

TABLE SMultiple-regression results for serum albumin on independent variables’

.Independent variable

Regression.

coefficienrP <

Partial�

R

%

Men (n = 108)

Intercept 48.702 ± 5.694 - -

Age (y) -0.154 ± 0.059 0.0008 8.56

Protein intake (g/d) -0.002 ± 0.013 NS 0.05

Comorbidity 0.254 ± 0.294 NS 1.05

ASM (g) 0.219 ± 0.098 0.039 3.69

Physical activity score -0.043 ± 0.047 NS 0.71

Women (‘i = 167)

Intercept 40.539 ± 4.476 - -

Age (y) -0.108 ± 0.032 0.0008 4.34

Protein intake (g/d) 0.005 ± 0.010 NS 0.10

Comorbidity 0.098 ± 0.197 NS 0.13

Estrogen replacement

therapy (0, 1 ) - I .524 ± 0.404 0.0002 6.21

Physical activity -0.098 ± 0.031 0.002 4.30

ASM/LSTM (C/c) 0.250 ± 0.078 0.()02 5.16

however, how a decreased availability of muscle amino acids

could result in low serum albumin in relatively ‘unstressed”

elderly people with “adequate” dietary protein intake. Thus. it

seems that we are forced to return to the hypothesis that

decreased rates of protein turnover do occur with age in both

liver and muscle and underlie covarying changes in serum

albumin concentrations and muscle mass.

With regard to the effects of dietary intake, acute and chronic

disease, alcohol intake, and smoking, it is important to empha-

size several facts in the present study. Both serum albumin and

body composition were measured after an overnight fast. The

participants were not malnourished. Those with acute illness.

recent trauma, or serious chronic disease were excluded from

the study. Only a handful of subjects smoked, and none were

known to be alcoholic. Nonetheless, a possible limitation of

this study could be the ascertainment of chronic morbidity and

the quantification of the effects of comorbidity in the analyses.

As noted, the presence of chronic illnesses in the study partic-

ipants was ascertained from a combination of self-report, med-

ical history, and examination, which should reduce the likeli-

hood of missed or misclassified illnesses. Nonetheless, we

cannot rule out the possibility of the influence of undiagnosed,

subclinical chronic illnesses. The severity of the chronic ill-

nesses present was not graded. Also, the comorbidity index

could have obscured the associations of specific illnesses with

serum albumin. Significant differences in serum albumin con-

centrations were not observed, however, among the different

classes of morbidity, but these analyses lacked statistical power

because of small numbers.

Roubenoff et al (24) observed that serum albumin, as well as

body cell mass, is reduced in patients with rheumatoid arthritis.

They hypothesized that other chronic inflammatory conditions

alter protein metabolism also, and could underlie the decreases

seen in both serum albumin and muscle mass with aging.

Inflammatory illnesses and illnesses that cause the acute-phase

response reduce albumin gene expression, alter the intra- and

extravascular distribution of albumin, and increase the rate of

degradation ( 1 1 ). We did not measure C-reactive protein or

30 35 40 45 50


Dow

nloaded from



cytokines that could serve as markers or mediators for inflam-

mation-based alterations in protein metabolism in both liver

and muscle (24). It is therefore possible that the association

between serum albumin and muscle mass observed in the

present study reflects the effects in some of our subjects of

underlying chronic inflammatory conditions that were not ac-

counted for in our ascertainment of morbidity.

Serum albumin was reduced significantly in the women

receiving ERT. This could be due to increased plasma volume

in these women but we cannot test this hypothesis with the

current data. In any event, the associations of serum albumin

with age and muscle mass in the women were independent of

this effect of ERT. None of the men was currently using any

steroid medications. As a result, the associations of serum

albumin with age and muscle cannot be readily explained by

confounding effects of medications in either sex. In addition,

we have noted elsewhere that decreases with age in muscle

mass, as well as in body cell mass, in women may be masked

somewhat by increases in the fraction of FFM that is extracel-

lular fluid (14). This could explain why in the women ASM as

a percentage of lean soft tissue mass was a better predictor of

serum albumin than absolute ASM.

Finally, the association between serum albumin and muscle

mass was independent of physical activity. Physical activity, as

graded in the present study, was associated significantly with

age and body composition in both sexes and with serum albu-

mm concentrations in the women. The physical activity assess-

ment instrument used captures a broad range of activities from

relatively sedentary (eg, gardening and fishing) to high-energy-

expenditure activities (eg, jogging and cross-country skiing).

We believe that the significant correlations of the physical

activity scores with body composition support the general

validity of our questionnaire for grading physical activity in

this study population. Recent studies suggest that high-inten-

sity, weight-bearing exercise stimulates muscle protein metab-

olism in older men and may elevate the need for dietary protein

(27). Although participants in the Aging Process Study may be

generally characterized as healthy, active elderly adults, few

are known to engage regularly in high-intensity weight lifting

or resistive exercise.

Controversy exists for the effects on protein metabolism of

low-intensity or aerobic exercise, which is more typical of

relatively healthy, community-dwelling elderly people. Carraro

et al (28) reported no effects on the fractional rates or concen-

trations of serum albumin in men after 4 h of aerobic exercise

at 40% maximal oxygen consumption while dietary protein

intake was held constant. In the present analyses, the associa-

tion of physical activity with serum albumin in the women was

negative. This might suggest that higher levels of physical

activity in the elderly women were associated with increased

protein degradation without a corresponding stimulation of

protein synthesis. This interpretation is highly speculative,

however, in the absence of data for protein turnover. Some

investigators have reported a transient decrease in serum albu-

mm after moderate-intensity exercise that lasts 4-10 d (29). It

is important to keep in mind that the instrument used in the

present study was designed to measure habitual or usual phys-

ical activity and therefore would be expected to reflect chronic

rather than transient effects on protein metabolism. Also, there

is no obvious explanation for why an association between

serum albumin and physical activity was found in the women

but not in the men. In sum, although the decrease with age in

muscle mass, or sarcopenia, can be attributed in part to a

progressive decline in physical activity with age (30), it is

difficult to explain either the age-related decrease in serum

albumin or the association between albumin and muscle in

terms of physical activity.

An important strength of the current study was the estimation

of muscle mass by DXA. Previous studies have not reported

significant associations between serum albumin and indexes of

body composition, such as the BMI (3 1 ). BMI, however, cor-

relates more strongly with body fat than with lean body mass

and may not be a very sensitive index of muscle or body

protein stores, except in emaciation. In elderly people, muscle

loss can be masked by increased body fat. The elderly also tend

to have less muscle and more fat at any BMI than younger

adults ( 14). There are inconsistent reports of associations of

serum albumin with more specific components of fat-free body

composition, such as body cell mass and FFM (24, 32). Both of

these components include inert subcomponents, such as water

and bone mineral, and do not separate skeletal muscle from

organ tissue. DXA is not affected in any known way by

age-related changes in anatomy. physiology. or metabolism.

which may bias anthropometric and creatinine excretion meth-

ods of estimating muscle mass (33). Estimates of muscle mass

from DXA compare favorably with those from computerized

tomography, which is considered to be the most accurate in

vivo means of quantitating major soft tissue components such

as muscle and adipose tissue (33).

Serum albumin concentrations < 38 g/L have been shown to

be associated with increased risk of disability in elderly adults

(6). Low BMI has also been shown to be associated with

reduced functional capabilities in community-dwelling elderly

( 15). Most elderly people with low BMIs have reduced muscle

mass, which may be worsened by weight loss (14). Regardless

of the nature of the mechanisms underlying the relation be-

tween serum albumin and somatic protein reserves in healthy

elderly persons, the present study suggests that serum albumin

does reflect muscle mass to some extent. It is not possible to

establish any causal direction to this relation from the present

cross-sectional analyses. It seems reasonable, however, to hy-

pothesize that the reported risk of disability with low serum

albumin concentrations in the elderly is more likely to be

attributable to sarcopenia. Further research is needed to clarify

the joint associations between serum albumin, sarcopenia, mor-

bidity, and disability in elderly populations. It is possible that

low serum albumin concentrations and sarcopenia are corre-

lated, early warning signs ofdeleterious underlying, subclinical

conditions and impending disease and disability. Future studies

should include more precise estimates of skeletal muscle mass

from DXA as a risk factor for functional disability as well as

for chronic diseases. A

REFERENCES

I . Phillips A, Shaper AG. Whincup PH. Association between serum

albumin and mortality from cardiovascular disease. cancer. and other

causes. Lancet 1989:2:1434-6.

2. Kuller LH, Eichner JE, Orcahrd Ti. The relationship between serum

albumin levels and risk of coronary heart disease in the Multiple Risk

Factor Intervention Trial. Am J Epidemiol l99l:l34:l266-77.

3. Klonoff-Cohen H. Barrett-Conor EL. Edelstein SL. Albumin levels as


Dow

nloaded from



a predictor of mortality in the healthy elderly. J Clin Epidemiol

1992:4�:207-12.

4. Salive ME, Cornoni-Huntley J, Phillips CL, et al. Serum albumin in

older persons: relationship with age and health status. J Clin Epidemiol

1992:4�:213-21.

5. Gillum RF, Ingram DD. Makuc DM. Relationship between serum

albumin concentration and stroke incidence and death: the NHANESI Epidemiologic Follow-up Study. Am J Epidemiol 1994;140:876-88.

6. Corti M-C, Guralnik JM, Salive ME, Sorkin JD. Serum albumin leveland physical disability as predictors of mortality in older persons.

JAMA l994;272: 1036-42.7. Campion EW, deLabry LO, Glynn Ri. The effect of age on serum

albumin in healthy males: report from the Normative Aging Study. J

Gerontol l988;43:M I 8-20.8. Shibata H, Haga H. Ueno M, Nagai H, Yasumura S. Koyano W.

Longitudinal changes of serum albumin in elderly people living in the

community. Age Ageing l991;20:417-20.

9. Romero L, Hunt WC, Garry PJ. Serum albumin results from a longi-tudinal study of community-dwelling healthy elderly in the New

Mexico Aging Process Study. In: Rosenberg IH, ed. Nutritional as-

sessment of elderly populations. Bristol-Myers SquibblMead Johnson

nutrition symposia. Vol 13. New York: Raven Press, 1995:40-9.

10. RaIl LC, Roubenoff R, Harris TB. Albumin as a marker of nutritionaland health status. In: Rosenberg IH, ed. Nutritional assessment of

elderly populations. Bristol-Myers SquibblMead Johnson nutritionsymposia. Vol 13. New York: Raven Press, 1995:1-17.

1 1. Rothschild MA, Oratz M, Schrieber SS. Serum albumin. Hepatology

1988:8:385-410.12. Gersovitz M, Munro HN, Udall J, Young yR. Albumin synthesis in

young and elderly subjects using a new stable isotope methodology:response to level of protein intake. Metabolism 1980;29: 1075-85.

13. Young VR, Sanchez M. Albumin, skeletal muscle, and lean body massas functional predictors in the elderly: brief comment and analysis. In:

Rosenberg IH, ed. Nutritional assessment of elderly populations.Bristol-Myers SquibbfMead Johnson nutrition symposia. Vol 13.

New York: Raven Press, 1995:63-73.

14. Baumgartner RN. Stauber PM, McHugh D, Koehler K. Garry PJ.Cross-sectional age-differences in body compostion in persons 60+

years of age. I Gerontol l995:50A:M307-l6.

I 5. Galanos AN, Pieper CF. Coroni-Huntley JC, Bales CW, FillenbaumGO. Nutrition and function: is there a relationship between body mass

index and the functional capabilities of community-dwelling elderly?

J Am Geriatr Soc 1994;42:368-73.

I 6. National Cancer Institute. Health habits and history questionnaire: diet

history and other risk factors. Personal computer system packet, ver-

sion 2.2. Bethesda, MD: National Cancer Institute, 1989.

17. Shapiro 5, Weinblatt E, Frank CW, Sager RV. The HIP. study of

incidence and prognosis of coronary heart disease: preliminary find-

ings on incidence of myocardial infarction and angina. J Chronic Dis

1965; 18:527-58.

18. Cassel J, Heyden 5, Bartel AG, et al. Occupation and physical activity

and coronary heart disease. Arch Intern Med 197 1:128:920-8.

19. Commission on Professional and Hospital Activities. The international

classification of diseases. 9th revision. Ann Arbor, MI: Edwards

Brothers, 1987.

20. Heymsfield SB. Smith R. Aulet M. et al. Appendicular skeletal muscle

mass: measurement by dual photon absorptiometry. Am J Clin Nutr

l990;52:2l4-8.

21. Lohman TG, Roche AF, Martorell R, eds. Anthropometric standard-

ization reference manual. Champaign, IL: Human Kinetics, 1988.22. Cockram DB, Baumgartner RN. Evaluation of accuracy and reliability

of calipers for measuring recumbent knee height in elderly people.Am J Clin Nutr l990;52:397-400.

23. Mares-Perlman IA, Klein BEK, Klein R, Ritter LL, Fisher MR.

Freudenheim JL. A diet history questionnaire ranks nutrient intakes in

middle-age and older men and women similarly to multiple food

records.J Nutr 1993;l23:489-S0l.

24. Roubenoff R, Grimm LW, Roubenoff RA. Albumin, body composi-

tion, and dietary intake in chronic inflammation. In: Rosenberg IH. ed.

Nutritional assessment of elderly populations. Bristol-Myers Squibb/

Mead Johnson nutrition symposia. Vol 13. New York: Raven Press.

1995:30-9.25. Richardson A, Ward WF. Changes in protein turnover as a function of

age and nutritional status. In: Watson RR, ed. Handbook of nutrition in

the aged. Boca Raton, FL: CRC Press, 1994:309-16.26. Young yR. Amino acids and proteins in relation to the nutrition of

elderly people. Age Ageing l990;l9:S10-24.

27. Evans Wi. Exercise, nutrition and aging. J Nutr 1992:122:796-801.28. Carraro F, Hartl WH, Stuart CA, Layman DK, Jahoor F, Wolfe RR.

Whole body and plasma protein synthesis in exercise and recovery in

human subjects. Am J Physiol 1990;258:E82 1-31.29. Butterfield 0. Whole body protein utilization in humans. Med Sci

Sports Exerc 1987;19:S157-65.30. Bortz WM. Disuse and aging. JAMA 1982;248: 1203-8.

3 1 . Lemonnier D, Acher S. Boukaiba N. et al. Discrepancy between

anthropometry and biochemistry in the assessment of the nutritional

status of the elderly. Eur J Clin Nutr l99l;45:28l-6.

32. Forse RA, Shizgal HM. Serum albumin and nutritional status. JPEN J

Parenter Enteral Nutr 1908:4:450-4.

33. Wang Z, Visser M, Ma R, et a!. Skeletal muscle mass: validation of

neutron activation and dual energy X-ray absorptiometry methods by

computed tomography. J AppI Physiol I 996;80:824-3 I.


Dow

nloaded from


Documents

Albumina sarcopenia