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Maturitas 81 (2015) 1727

Contents lists available at ScienceDirect

Maturitas
journal homepage: www.elsevier.com/locate/maturitas

Review

Serum albumin and health in older people: Review and meta analysis

Sonia Cabrerizo a , Daniel Cuadras b , Fernando Gomez-Busto c , Inaki


Artaza-Artabe d ,
e
e,
Fernando Martn Ciancas , Vincenzo Malafarina
a

Nutrition Service, Clinica Los Manzanos, Grupo Viamed, Calle Hermanos Maristas, 26140 Lardero, Spain
Servei dAssessorament Metodolgic i Estadstic a la RecercaUnitat de Recerca i Desenvolupament, Parc Sanitari Sant Joan de Du Fundaci Sant Joan de
Du, Dr. Antoni Pujades 42, 08830 Sant Boi de Llobregat (Barcelona), Spain
c
Geriatric Department, Residencia San Prudencia, Calle Francia 35, 01002 Vitoria-Gasteiz, Spain
d
Geriatric Department, Orue Centro Socio Sanitario, Grupo Igurco, B San Miguel Dudea s/n, 48340 Amorebieta, Spain
e
Geriatric Department, Clinica Los Manzanos, Grupo Viamed, Calle Hermanos Maristas, 26140 Lardero, Spain
b

a r t i c l e

i n f o

Article history:
Received 18 February 2015
Received in revised form 20 February 2015
Accepted 21 February 2015
Keywords:
Hypoalbuminemia
Undernutrition
Ageing
Protein energy malnutrition
Nutritional screening
Body composition

a b s t r a c t
Albumin is the most abundant plasmatic protein. It is only produced by the liver and the full extent of its
metabolic functions is not known in detail. One of the main roles assigned to albumin is as an indicator of
malnutrition. There are many factors, in addition to nutrition, that inuence levels of albumin in plasma.
The main aim of this review is to assess the clinical signicance of albumin in elderly people in the
community, in hospital and in care homes. Following the review, it can be stated that age is not a cause of
hypoalbuminemia. Albumin is a good marker of nutritional status in clinically stable people. Signicant
loss of muscle mass has been observed in elderly people with low albumin levels. Hypoalbuminemia
is a mortality prognostic factor in elderly people, whether they live in the community or they are in
hospital or institutionalized. Low levels of albumin are associated to worse recovery following acute
pathologies. Inammatory state and, particularly, high concentrations of IL-6 and TNF-alpha, are two of
the main inuencing factors of hypoalbuminemia. In elderly patients with a hip fracture, albumin levels
below 38 g/L are associated to a higher risk of post-surgery complications, especially infections. Further
research is needed on the impact of nutritional intervention upon albumin levels and on the outcomes
in elderly people in the community, in hospital and in care.
2015 Elsevier Ireland Ltd. All rights reserved.

Contents
1.
2.
3.

4.

5.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Search strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2.1.
Statistical methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Albumin as an index of nutritional status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.1.
In the community . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.2.
In hospitalized elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3.3.
Meta-analysis results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
The association of serum albumin with function and health status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.1.
In community dwelling and in nursing home . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.2.
In hospitalized elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
4.3.
In hip fracture patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Albumin as predictor of mortality . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.1.
In community-dwelling elderly and in nursing-home residents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
5.2.
In hospitalized elderly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Corresponding author at: Geriatric Department, Clinica los Manzanos, Calle Hermanos Maristas, 26140 Lardero (La Rioja), Spain. Tel.: +34 941 499 490;
fax: +34 941 499 491.
E-mail address: vmalafarina@gmail.com (V. Malafarina).
http://dx.doi.org/10.1016/j.maturitas.2015.02.009
0378-5122/ 2015 Elsevier Ireland Ltd. All rights reserved.

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S. Cabrerizo et al. / Maturitas 81 (2015) 1727

Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Competing interests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Provenance and peer review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. Introduction
Ongoing population ageing will lead to a doubling of the number
of people over 65, in the coming ve decades. There is increasing
evidence that caloricproteic malnutrition is a widespread problem in this section of the population [1]. Nutritional assessment
and treatment of malnutrition are imperative in order to attempt
to minimize the risk of illness or complications associated to old
age. Elderly people living in the community present the lowest incidence of malnutrition, whereas institutionalized elderly people are
the most malnourished [2].
Malnutrition in the elderly can be multi-factorial, with negative
consequences on most organs and systems [3].
Despite increasing scientic evidence that hepatic protein levels depend on other factors in addition to intake, these proteins
continue being used to assess nutritional state and to diagnose malnutrition [4,5] (Fig. 1). The biological functions of albumin have not
been comprehensively dened, but its inverse relation to mortality,
to the development of complications and to mean length of stay in
hospital for acute patients, is clear [68]. Procedures for measuring
concentration of albumin in serum can be affected by the higher
volume of distribution observed in patients in an acute phase [9].
For all these reasons, the main aim of this review is to assess published articles on the subject of albumin in elderly people in order to
attempt to understand its relationship with age, its importance as a
nutritional index and as a prognostic factor in the various geriatric
clinical settings (the community, hospitals and care homes).
2. Search strategy
We searched PubMed for articles published until July 2014, in
English, Italian and Spanish. We completed our search by revising

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the bibliographies of the articles included in our review. We used


the following search terms and associations: albumin, hypoalb*,
protein, elderly/older, nutr*, malnutri*, undernutri*, hospital*, hip
fracture, community dwelling, nursing home/residen*/home care,
function* outcome, complica*, mortality. We included research on
people above 65 in which serum concentration of albumin was
measured. The authors (SC and VM) solved doubts about inclusion
criteria for the papers assessed were solved by analyzing the entire
text of the papers and discussing their characteristics. Following
assessment of papers that could potentially be included, a total of
8 papers were discarded for the following reasons: three studies
were carried out exclusively on people below the age of 65, one
because the research was carried out by the same authors on the
same population used for another included article and did not add
any new results compared to the former, and another four papers
were discarded because they did not state albumin values.
33 papers were nally included, with a total population of
91,160 people (82,066 elderly people in the community, 662 in care
homes, 8432 in hospital). The mean age of patients in the included
papers was between 71.5 and 84.
2.1. Statistical methods
Meta-analysis of the albumin mean value was performed on
the studies where it was reported, with both xed and random
effects models, using the inverse variance method and the DerSimonianLaird estimator for tau2 . Homogeneity among studies
was tested by the Q statistic (p-values <0.05 were considered
signicant) and tau2 , H, I2 statistics. Statistical analyses were
performed with R version 3.0.3 (R Foundation for Statistical Computing, Vienna, Austria) with package meta version 4.0-3 (Guido
Schwarzer, meta: Meta-Analysis with R).

Fig. 1. Graphic representation of physiopathology and mechanisms that determine hypoalbuminemia. The result is accumulative, so the more factors occur in the same
person the greater the impact is on the risk of developing hypoalbuminemia. The dashed line represents factors whose importance in determining hypoalbuminemia depends
on the presence of other cofactors. The dotted line represents factors that increase the prevalence of other associated factors.

Table 1
Albumin as a nutritional index in hospitalized elderly.
Author
Year
Origin

Aim

Design
Population characteristics

n (menwomen)
Age mean SD (y)
BMI mean SD (kg/m2 )

Exclusion

Albumin
Mean value (g/L)

Results

Tamas [42]
1991
Switzerland

Alb correlation with LOS


and mortality

552 (197335)
80.3 7.5
NA

NA

35 5.6

Lumbers [54]
2001
UK

Dietary intake and


nutritional status

Retrospective
Hospitalized:
197 cancer
335 other disorders
Cross sectional
Hospitalized (HF)
Day centres (DC)

75 (075)
80.5 8.2
24.1 4.7

Mental Function Test <7

36.5 4.7

Alb not correlated with LOS


Signicant correlation:
Between cancer and alb
Death and nutritional values
Signicant differences between HF and DC in: weight, BMI,
MUAMC, alb, CRP, protein and E intake.
In both groups:
E intakes < EAR
Alb CRP (r = 0.45)
In HF group: protein intake <EAR

42.5 3.3

38.3 3.7

311 (111200)
79.9 11.3
NA

ICU
LOS <3 days

NA

Retrospective
Hip fracture patients

214 (43171)
84 18.2
NA

NA

NA

- Albas malnutrition
marker
- ADL association with Alb

Cross sectional
Outpatient clinic, nursing
home, geriatric hospitals

262 (86176)
81.8 7.5
19.7 3.9

Infection, liver and kidney


disorders, cancer, CRP
1 mg/dL

36 5.7

Admission alb and


functional outcome

Retrospective
Hip fracture patients
Retrospective (1y)
Hip fracture patients

Osteoarthritis fracture,
Rehabilitation <7days, Acute
disabilities
Pathologic fractures and
non-ambulatory before
fracture

36 4

Correlation of Alb and TLC


with clinical outcome

Compare MNA, NRS and


serum proteins

Cross-sectional
Acute geriatric ward

Correlation of Alb with


clinical outcome

Retrospective (1y)
Hip fracture patients

449 (90359)
82.1 6.9
NA
74 (2252)
M 76.86 8.85
W 78.29 8.05
NA
104 (2381)
84 (7889)
23.1 (2027.3)
200 (39161)
81
NA

Alb as a measure of
nutritional status

Prospective
Ischaemic stroke patients

Covinsky [30]
2002
USA

Alb concordance with


nutritional status

Cross sectional General


medicine ward

Symeonidis
[57]
2006
UK

Correlation of Alb and TLC


with clinical outcome

Kuzuya [31]
2007
Japan

Mizrahi [51]
2007
Israel
ztrk [53]
2009
Turkey

32.9(1743)

NA

Median (IQR)
31 (2833)

NA

NA

Alb deteriorated steadily during four weeks of


hospitalization.
Ranking Score, MUAC, and transferrin explained variance in
alb at week four.
The variance at admission and two weeks is explained also
by age and serum iron.
Alb 40 g/L:
60% well nourished
38% Moderately malnourished
Alb <30 g/L:
35% severely malnourished
28% well nourished
30 g/L is a positive predictive value for malnutrition
1 year mortality:
Alb <35 g/L+ TLC <1500 cell/mL OR = 3.02 (1.118.27)
Alb <35 g/L+ TLC 1500 cell/mL OR = 5.59 (1.5719.97)
Waiting time to operation greater than 48 h:
Alb <35 g/L+ TLC <1500 cell/mL OR = 3.97 (1.1513.72)
Alb 35 g/L 76% are wellnourished
Alb <35 g/L 69% have some degree of malnutrition
Low ADL + alb <35 g/L 74% some degree of malnutrition
High ADL + alb 35 g/L 81% BMI 18.5; 90% well
nourished;
Well-nourished 23% alb <35 g/L
alb <35 g/L FIM
MMSE admission, pre-fracture function and female gender
predictors of discharge FIM
Alb <35 g/L LOS and 2 comorbidities
Alb >35 g/L + TLC >1500 cell/mL FS
Alb <35 g/L + TLC <1500 cell/mL mortality
Alb not independent predictor of 1y mortality
Alb were similar in the different groups of MNA or NRS
After adjusted for CRP and GFR: alb MNA
calf circumference alb; MNA; NRS
3-month mortality:
Alb <35 g/L TLC <1500 cell/mL OR 4 (IQR 1.312.2)
12-month mortality:
Alb <35 g/L + TLC <1500 cell/mL OR 4.6 (IQR 1.021.3)
Alb and age independent prognostic factors

S. Cabrerizo et al. / Maturitas 81 (2015) 1727

Malabsorption, gastrectomy,
hepatic and renal impairment,
heart failure, sepsis and
malignancy

Gariballa [27]
2001
UK

Drescher [29]
2010
Switzerland

ODaly
[56]
2010
Ireland

50 (050)
79.8 7.5
27.5 4.9
201 (81120)
77.9 9.1
NA

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33.8 4.5
Osteoporotic fractures, vehicle
accidents

ADL = activities of daily living; Alb = albumin; ASMM = Appendicular skeletal muscle mass; BI = Barthel Index; BMI = body mass index; BCM = body cell mass; COPD = chronic obstructive pulmonary disease; CRP = C-reactive
protein; E = energy; EAR = estimated average requirement; EMS = Elderly Mobility Score; FIM = functional independence measurement; FS = functional status; GFR = glomerular ltration rate; HF = Hip fracture; ICU: Intensive care
unit; IQR = interquartile ranges; LOS = length of hospital stay; LM = lean mass; M = men; MMSE = mini-mental state examination; MNA = mini nutritional assessment; MUAC = mid-upper arm circumference; NA = not available;
NRS = nutritional risk screening; r = Spearmans rank correlation; TLC = total lymphocyte count; TST = triceps skinfold thickness; W = women; = correlation; = increase.

38.5 5
Hypo or hypernatremia,
hepatic or renal insufciency

125 (3491)
83.8 7.7
23.2 4.7
583 (167416)
82.4 7.3
NA
Alb relationship with LM,
BCM, morbidity and
mortality
Association of alb and
in-hospital mortality and
complications
Bouillanne [28]
2011
France
Pimlott [47]
2011
Canada

Cross sectional
Geriatric rehabilitation
care unit
Prospective
Hip fracture patients

Admission alb: not signicant independent predictors for


EMS and BI outcomes on discharge.
Multivariate analysis: age and urinary incontinence on
admission were signicant negative predictors for BI
outcome, while female gender MMSE, admission EMS and BI
were signicant positive predictors for satisfactory BI
outcome
Alb not correlated to LM, ASMM, or BCM
Alb infections and pressure ulcers (r = 0.22)
BMI LM, ASMM, or BCM
Alb <35 g/L:
- Hospital death OR 2.44(IQR 1.175.12)
- Post-operative complications OR 1.96(IQR 1.362.83)
32.1 6.7
NA
1604 (693991)
82.4 7.2
21.4 4.5
Alb and functional recovery
Luk [36]
2011
Hong Kong

Retrospective
Acute geriatrics ward

Results
Exclusion
Design
Population characteristics
Aim
Author
Year
Origin

n (menwomen)
Age mean SD (y)
BMI mean SD (kg/m2 )

Albumin
Mean value (g/L)

S. Cabrerizo et al. / Maturitas 81 (2015) 1727

Table 1 (Continued)

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3. Albumin as an index of nutritional status


3.1. In the community
The physiology of ageing raises many doubts and has gaps in the
knowledge of what should and should not be normally considered
to be associated to ageing. Alterations in analytical indices are often
wrongly interpreted as secondary to ageing itself, but there is no
evidence that a reduction in albumin values to pathological values
happens with age. We found ve papers that assessed the way in
which the serum concentration of albumin changes with age (three
cross-sectional, a prospective one and one divided into a cross sectional part and a second, prospective, phase) (total elderly people
included = 67,948) [1013].
Various studies demonstrated a progressive reduction of albumin serum concentration between 0.08 and 0.17 g/L per year,
associated to ageing; with greater reductions in men than in women
[1014]. Despite these secondary-to-age changes, albumin values
in healthy elderly people in the community stay above 38 g/L until
after the age of 90 [15]. Therefore, in a situation of clinical stability,
in elderly people in the community albumin can be a good marker
of nutritional status.
Despite the difculties in diagnosing malnutrition in the elderly,
one of its most-feared consequences is the change in body composition. Weight loss, reductions in Body Mass Index (BMI) and a
decrease in muscle mass are indirect markers of malnutrition [16].
The BMI is an indirect estimation of body composition with different values for elderly people, due to their typical structural changes
(loss of height of the vertebral body, decrease in height due to
degenerative skeleton malformations, different distribution of fat
and muscles). Despite this, various studies showed that BMI values
22 kg/m2 are associated to an increase in mortality, number of
admissions to hospital, functional dependency, risk of fracture and
healthcare costs. The authors agree that BMI <20 kg/m2 is a criterion for malnutrition, but higher scores may not sufce to discard
the presence of malnutrition [17,18].
Three of the papers included, two cross-sectional studies and a
prospective one, researched the association between body composition and albumin (total n = 2270 people). Two transversal studies
(on 275 and 113 elderly people in the community) showed an association between low serum concentrations of albumin and reduced
appendicular skeletal muscle mass (ASMM) values [14,18]. These
results coincide with the observations of a population prospective
study (on 1882 elderly people), which demonstrated the association between hypoalbuminemia and loss of ASMM [19].
Loss of strength occurs more quickly than loss of muscle mass
and maintaining or increasing muscle mass does not prevent the
decrease in strength associated to age [20]. An inadequate protein
intake, together with a reduction in the ability to use proteins may
be two important causes of sarcopenia [21]. A protein-poor diet for
a long time determines a compensatory response characterized by
a reduction in lean mass. Nevertheless, there is no evidence that
protein and energy intake is associated to either albumin serum
levels or body composition [14,19].
3.2. In hospitalized elderly
The design of the various studies, the characteristics of the
included patients and their main results are summarized in Table 1.
Symptoms of malnutrition in the elderly (tiredness, apathy, loss
of strength, among others) are often incorrectly interpreted as signs
associated to ageing itself, which in many cases delays realization
of the presence of malnutrition and, therefore, its diagnosis [22].
An increase of certain cytokines, such as IL-1, IL-6 and TNF-alpha,
determines a delay in gastric emptying, inhibits appetite reduces
motility in the intestine [23]. These mechanisms could explain the

S. Cabrerizo et al. / Maturitas 81 (2015) 1727

high prevalence of malnutrition and the increase in the risk of


developing malnutrition observed in the hospitalized elderly [24].
The difculty in diagnosing malnutrition during hospitalization
also stems from the fact that one same illness or syndrome can
present itself in different ways. Therefore, the various tools for diagnosing malnutrition should be based on a range of anthropometric,
biochemical and clinical parameters [1,25]. It is not always possible to observe a simultaneous alteration of all the indicators of the
illness and not all alterations have one single cause [18].
Among the most common causes of hypoalbuminemia are illnesses that increase protein catabolism or alterations of the hepatic
metabolism that cause a reduction in their synthesis. Albumin
serum concentration is also affected by kidney illnesses and by
alterations in patients state of hydration [26].
A prospective study on elderly patients with a stroke observed
how serum concentration of albumin is a negative prognostic
index, for mortality and for the development of complications
and lack of recovery [27]. Similarly, in elderly patients admitted
to a rehabilitation unit, albumin concentration was associated to

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the development of complications [28]. This latter study observed


that serum albumin concentration was not linked to body composition measured with DXA. However, correlations were found
between albumin and mid-upper arm circumference (MUAC) in
elderly people with a cerebrovascular accident [27] and with calf
circumference in elderly patients with an acute pathology [29].
Albumin serum concentration is highly sensitive in the diagnosis
of malnutrition in the hospitalized elderly, but it has low specicity
[30].
Thus, in elderly people with functional disability and albumin
<35 g/L it was found that malnutrition prevalence was 70%, whilst in
autonomous elderly people with albumin concentrations >35 g/L,
the prevalence of malnutrition was only 13% [3136].
3.3. Meta-analysis results
The studies were divided into two groups, Hospitalized and
Community-Dwelling, and a meta-analysis on the albumin mean
value was performed in each one of them (Gom 2007 was not

Fig. 2. Forest Plots for hospitalized and community-dwelling meta-analyses on albumin mean level, with a results summary on both Fixed and Random effects models.
Squares represent mean albumin level for each study, and the horizontal bars represent 95% CIs. Sizes of the squares is inversely proportional to the standard error of the
mean of the study. Diamond shapes represent the mean estimators for both xed and random effects models with their 95% CIs, with vertical lines helping to compare them
with the individual studies.

22

S. Cabrerizo et al. / Maturitas 81 (2015) 1727

included due to its sample size exceeding all other studies combined). In the Hospitalized studies, the random effects model
estimation of the albumin mean value was 36.04 g/L, 95% CI (34.81
and 37.28 g/L). In the Community-Dwelling studies, the random
effects model estimation of the albumin mean value was 41.13 g/L,
95% CI (40.26 and 42.00 g/L). In both cases, the heterogeneity among
studies was very high (I2 > 99%) and the Q statistic was signicant
(p < 0.0001), therefore we can consider that there are differences
in the albumin mean values among them. The xed effects models provided similar results, but the random effects one provides a
more conservative estimate and therefore is preferred.
Fig. 2 shows a forest plot for each group of studies (Hospitalized
and Community-Dwelling), and the results of the meta-analysis for
both xed and random effects models with the weight of each study
on both models.

4. The association of serum albumin with function and


health status
4.1. In community dwelling and in nursing home
The main aspects of the papers reviewed for this section can
be found in Table 2. The association between muscle mass and
strength is not linear; it varies depending on the quality of the
muscle, intramuscular fat inltration and neurological control of
contraction. In elderly people, an increase of the fat content in
muscle groups (intermuscular fat tissue) and between the fascicule
of the muscle (intramuscular fat tissue) can be observed [37,38].
Fat tissue contributes to excessive secretion of proinammatory
cytokines, which are associated to a progressive increase in glucocorticoid and catecholamine levels, together with a decrease in
growth hormone (GH) and sexual hormone levels [39]. These traits
are similar to those of a state of chronic stress. In addition, IL-6
and TNF-alpha are directly associated to lower levels of albumin, to
muscle mass loss and to a decrease in muscle strength in the elderly
[21].
Albumin concentration is associated to muscle strength measured by handgrip in transversal studies [34,40,41]. For some
authors there is a direct link between albumin concentration and
strength loss over two years [40], whilst in other studies this association presented no statistical signicance [34,41].
The association between autonomy in the activities of daily living (ADL) and albumin levels is more evident. Both transversal
[3234] and longitudinal studies [12,35] have demonstrated that
lower albumin values are associated to greater disability in the
ADL. Similarly, progressive reduction of albuminemia is associated
to the development of greater inability than in those elderly people who maintain a stable level of albumin [32]. This correlation
is stronger when reduced cholesterol levels are associated, which
could lead to a greater importance of peoples nutritional status in
the development of some level of disability in the ADL [33].

must be said that this study included a large number of subjects


with cancer, which could result in selection bias.

4.3. In hip fracture patients


Numerous papers assessed the relationship between albumin and various consequences, in a hospital environment, in hip
fracture patients (Table 2). Hip fractures are a highly prevalent complication in the elderly, and are a syndrome with a high rate of
complications and risk of developing disability [43,44]. Nutritional
status was shown to be a negative prognostic factor for the development of complications, especially infection [45,46]. Thus, elderly
patients with lower albumin levels (<38 g/L) had a higher probability of suffering post-surgery complications (cardiac, pulmonary,
infections, haemorrhage, thromboembolic) [47]. One of the aims of
orthogeriatrics units is to identify prognostic markers for evolution
that allow early identication of the elderly patients that have the
highest risk of developing complications and to determine which
patients may benet from more intensive treatment [4850].
Immobilization and connement to bed following admission
due to a hip fracture are associated to loss of muscle mass, strength
and function [51,52], and could be one of the causes of non-recovery
of patients functional status prior to fracture [51].
Albumin concentration on admission is associated to a better functional status upon discharge and an increase of albumin
concentration during patients stay in hospital is an independent
prognostic factor for improvement of functional status upon discharge [51,53].
In elderly women, energy intake is usually below recommended
levels, especially as regards protein intake in women with hip fractures compared to women living at home [54]. Almost all women
admitted to hospital with a hip fracture presented malnutrition
anthropometric indices [54,55] such as mid upper arm muscle circumference (MUAMC) below the 10 percentile, compared to a fth
of women in the community with such scores [54]. This could indicate that these women suffered malnutrition prior to the fracture.
Albumin levels are clearly associated to higher hospital mortality, 3 months and one year after discharge [47,53,56,57].
As mentioned above, use of a single parameter to identify
patients at risk of malnutrition can lead to a weak and unreliable diagnosis. Therefore, several authors used total lymphocyte
count (TLC) in addition to albumin as a prognostic factor for mortality in patients with hip fractures. In one study hypoalbuminemia
associated to a reduction in TLC is a negative prognostic factor for
mortality [56]. However, other studies show that albumin values
<35 g/L, can increase mortality to almost fourfold that of subjects
with normal albumin, regardless of the number of lymphocytes
[53,57].

5. Albumin as predictor of mortality

4.2. In hospitalized elderly

5.1. In community-dwelling elderly and in nursing-home


residents

We found few papers on research into the association between


albumin and outcomes in hospitalized elderly patients. Higher levels of albumin are not associated to a signicant improvement
of functional capacity measured with the Elderly Mobility Score
(EMS) and with the Barthel Index (BI) [36]. However, a relationship
between higher albumin levels and a shorter mean stay in hospital
was found, which could mean that patients with higher levels of
albumin achieve the same improvement of functional status in a
shorter period of rehabilitation [36]. Tamas et al. [42] did not nd
an association between albumin and length of stay (LOS), but it

In the elderly living in the community there is a clear association between albumin levels and long-term mortality (between 3
and 12 years) [13,33,5861]. However, in the elderly living in care
homes albumin was associated to short-term mortality (1 year)
but not to long-term mortality [13]. Chronic inammatory state
is an independent prognostic factor for mortality in 4 years [61].
In the presence of low concentrations of IL-6, mortality in 4 years
increases from albumin levels lower than or equal to 44 g/dL.
If we add disability in the ADL to hypoalbuminemia and walking
anomalies the risk of mortality may be as high as 7.5 (men) and

Table 2
Albumin as a nutritional index and its correlation with outcomes in community-dwelling elderly people.
Aim

Design
Population
characteristics

n (Men-Women)
Age mean SD (years)
BMI mean SD (kg/m2 )

Exclusion

Albumin mean value


(g/L)

Results

Cooper [10]
1989
USA
Salive [12]
1992
USA

Alb correlation with age

Cross-sectional
Community dwelling

Serious illness

35.742.8 (range of
the mean)

Alb per decade 1.7 g/L (4% for every 10 years)


Mean albumin in group> 91y (n16) = 35.7 g/L

Alb correlation with age


and health status

Cross sectional
250 NH
3865 HL

241 (NA)
55101 (range)
NA
4115 (14862629)
> 71
NA

NA

40.5 3.1
NH
40.7 HL

Baumgartner
[14]
1996
New Mexico

Alb correlation with age


and muscle mass

Cross-sectional
Community dwelling

275 (108167)
M = 76.0 5.4
25.6 3.4
W = 75.7 6.4
25.1 3.8

Cancer, myocardial infarct or


COPD

M = 41.3 2.9
W = 40.9 2.4

Schalk [32]
2005
Netherlands

Alb correlation and HS

Longitudinal (3 and 6y)

NA

M 45.2 3.2
W 45.0 3.3

Schalk [40]
2005
Netherlands

Alb and FS decline

Longitudinal (3y)

NA

NA

Sergi [18]
2006
Italy

Alb correlation with FFM


and ASMM

Cross-Sectional
Outpatients

1320 (644676)
M 75.6 6.6
W 75.4 6.6
NA
588 (NA)
5585 (range)
26.727.8 (range of the
means)
113
BMI > 20 n = 69 (3336)
80.7 7.9 y
BMI < 20 n = 44 (1628)
79.3 7.8 y

Alb per decade 1.2 g/L


Healthy group: 0.83 g/L
Sick group: 1.09 g/L
Predictors of <35 g/L: OR (95% CI)
Age: 1.56 (1.142.13)
Living at NH 2.54 (1.44.6)
2 ADL limitations 4.81 (2.59.2)
Alb = 0.16 g/L/y in men
Alb = 0.08 g/L/y in women
Alb< 3.5 g/L: 2% (M), 2.5% (W)
Alb with total muscle mass in the men
Alb negative association with physical activities and ERT in
women
Per 1 g/L alb HS (3y):
(M) 0.53 kg; (W) 0.30 kg (p < 0.05) (after adjusted for IL-6 and
CRP)
Alb HS (at baseline and 3y)
3y alb <43 g/L FS (compared with stable alb >43 g/L)
Chronic low alb (<43 g/L) not correlated with FS

Acute illnesses, severe liver,


heart or renal failure,
endocrinopathies, neoplasms,
inammatory states, diuretics,
steroid hormones, body weight
variation
Dependency in ADL

39.5 5.5
33.2 5.9

42.5 2.5

Gom [11]
2007
Japan

Alb correlation with age

Cross-sectional
Longitudinal (5y)

62,854 (22,705 40,149)


74.5 6.0
NA

Okamura [33]
2008
Japan

Alb correlation with


mortality and ADL (Katz)

Cohort Prospective
(12.4y)

1844 (7971047)
NA
NA

CHD or Stroke

M 42.3 2.6
W 42.9 2.3

Onem [35]
2010
Turkey

Alb correlation with


MMSE and ADL (Katz)

Cross sectional
NH

180 (68112)
71.5 5.1
21.7 7.4

Transfusion, MMSE <10

40.1 4.4

Snyder [41]
2012
USA
Kitamura [34]
2012
Japan

Alb correlation with


change in ASMM and HS

Prospective cohort (2y)

Walk with assistance, 2 hip


prosthesis

41.7 3.1

Alb and ADL (BI)

Cohort (2y)
Frail elderly

1267 (12670)
72.8 5.4
27.4 4.0
116 (3482)
83 8.3
20.6 (3.8)

Acute illness

Baseline
40 3
2y
39 4

FFM and ASMM signicantly lower in underweight patients.


Alb < 35 g/L:
17% in BMI 20 Kg/m2
55% in BMI < 20

Cross-sectional:
alb with age
incidence of alb < 35 g/L with age
Longitudinal:
alb 2% with age
Risk of mortality for 1 g/L alb:
(M) HR = 0.93 (0.880.97)
(W) HR = 0.92 (0.870.97)
OR of ADL:
(M) 0.93(0.811.06)
(W) 0.86 (0.770.96)
For Alb 40 g/L:
OR of ADL or mortality:
(W) 3.06 (1.894.95)
if added CH < 200 OR = 4.50 (2.259.02)
ADL MMSE: r = 0.66
ADL alb: r = 0.33
ADL BMI: r = 0.36
No signicant correlation of alb with MMSE and age
Baseline Alb baseline grip strength and leg power
Baseline and Alb inconsistent correlation with loss of ASMM,
HS, and LP
Alb and BI: r = 0.29
Alb and HS: r = 0.40
 alb and BI: r = 0.23
HS and HS: r = 0.55

23

ADL = activities of daily living; Alb = albumin; ASMM = appendicular skeletal muscle mass; BI = Barthel index; BMI = body mass index; CH = cholesterol; CHD = coronary heart disease; CRP = C-reactive protein; = difference from the
two time points; ERT = oestrogen replacement therapy; FFM = free fatty mass; FS = functional status; HL = home Living; HR = hazard ratio; HS = handgrip strength; LP = leg power; M = men; MMSE = mini mental state examination;
NH = nursing home; OR = odds ratio; r = Spearmans rank correlation; y = years; W = women; = correlation; = increase; = decrease; = marked decrease.

S. Cabrerizo et al. / Maturitas 81 (2015) 1727

Author
Year
Origin

24

Table 3
Association between albumin and mortality.
Aim

Design
Population characteristics

n (MW)
Age mean SD (years)
BMI mean SD (kg/m2 )

Exclusion

Albumin
mean value (g/L)

Results

Klonoff-Cohen
[60]
1992
USA
Corti [59]
1994
USA

1. alb and age and


health status
2. alb correlation with
mortality
Alb correlation with
disability and mortality

Prospective (3y)
Community-dwelling

2342 (10451297)
NA
NA

NA

M 43.1 2.7
W 42.8 2.8

Alb age (independent of disease)


r = 0.46 (M); r = 0.35 (W)
Alb mortality; r = 0.77

Cohort prospective (3, 7y)


Community-dwelling

NA

M 40.6 3.1
W 40.5 3.1

Sahyoun [13]
1996
USA

Alb correlation with


age and mortality

Cohort (912y)
Non institutionalized

4116 (14862630)
M 78.1 5.5
W 79.1 5.7
M 25.9 4.1
W 25.3 5
287 (101186)
74.6
NA
176 (64112)
80.7
NA

Terminal, wasting
diseases and severe
metabolic disorder

M 41.8 2.4
W 41.3 2.4

Alb <35 g/L and disability independent predictors of


mortality
The simultaneously presence of alb and disability the risk of
mortality increase 12 times (W) and 7 times (M) when compare
with alb 43 g/L and no disability
Dietary intake and anthropometric measures not associated with
alb
alb 0.9 g/L per decade
With alb the risk of mortality
alb 1.3 g/L per decade
Alb associated with mortality:
10 g/L alb RR = 0.43(0.210.87)
0.1 mg alb RR = 0.31
Alb <40 g/L RR = 2.18(1.263.79)
Among those without inammation (3.20 pg/mL), there was a
protective effect of high alb level (44 g/L).
3 m after discharge alb or = 83%
3 m after discharge alb 17%
3-month Alb associated with mortality
The % of change in alb between discharge and 3-month not
associated with mortality
Alb and CRP independent association with mortality
Combined effects alb < 35 g/L RR independent of levels of CRP

Institutionalized

M 37.8 3
W 37 3.7

Reuben [61]
2000
USA

Alb correlation with


mortality and its
relationship to IL-6

Longitudinal (4y)
Community-dwelling

632 (262370)
77.5 4.9
27.6 4.5

Disability in ADL

NA

Sullivan [65]
2005
USA

alb 3 month after


discharge and
mortality

Prospective (5y)
Geriatric rehabilitation unit
Hospitalized

282 (2802)
75.4 8.6
23.9 4.3

Cancer and
terminal conditions

At discharge:
36.4 4.6.
At 3-month:
36.7 4.9

Iwata [63]
2006
Japan
Kitamura [58]
2010
Japan

Alb and CRP with


in-hospital mortality

Retrospective
Hospitalized

1638 (870768)
77.5 7.7

NA

38 6

Risk factors for 2y


mortality

Cohort (2y)
Community-dwelling

205 (63142)
83.6 8
19.7 3.8

Acute illness

NA

Tal [64]
2011
Israel

Predictors of
in-hospital mortality

Prospective
Hospitalized

1509 (573936)
81.5 7.1
NA

36 5

Hannan [62]
2012
USA

In-hospital mortality
with alb < 20 g/L

Retrospective
Hospitalized

543 (290253)
75.4
NA

B12 supplement,
liver, small bowel,
gastric and colon
disorders,
malignancy
Age <60y, Alb
>20 g/L, Admission
<24 h.

NA

Alb risk factor for 2y mortality.


BMI (<17) OR = 3.96(1.798.79)
AGE (90) OR = 3.3(1.497.32)
Alb (1 g/L) OR = 0.86 (0.770.96)
1% alb 8.1% mortality
1% B12 0.53% mortality
1% CCI 0.19% mortality (not signicant)

Signicant (p < 0.001)but low correlation between alb and LOS,


mortality and discharge at home
Mortality rates:
Alb 1014 g/L 41%
Alb 1519 g/L 21%

ADL = activities of daily living; Alb = albumin; ASMM = appendicular skeletal muscle mass; BI = Barthel index; BMI = body mass index; CCI = Charlson co-morbidity index; CH = cholesterol; CHD = coronary heart disease; CRP = Creactive protein;  = difference from the two time points; FFM = free fatty mass; FS = functional status; HL = home living; HR = hazard ratio; HS = handgrip strength; LOS = length of hospital stay; LP = leg power; M = men; MMSE = mini
mental state examination; NH = nursing home; OR = odds ratio; r = Spearmans rank correlation; RR = relative risk; W = women; = correlation; = increase; = decrease; = marked decrease.

S. Cabrerizo et al. / Maturitas 81 (2015) 1727

Author
Year
Origin

S. Cabrerizo et al. / Maturitas 81 (2015) 1727

12.5 (women) times higher than in the elderly with albumin values
higher than 43 g/L and without disability [59].
5.2. In hospitalized elderly
Low levels of albumin are associated to higher mortality during
hospital stay [6264] (Table 3).
Sullivan et al. studied the change in albumin levels 3 months
after discharge from hospital and observed these levels were more
closely associated to long-term mortality than albumin levels at the
time of discharge [65].
6. Discussion
From our literature review, we can conclude that there is agreement that the healthy elderly have normal albumin values, which
indicates that age in itself is not a physiopathological mechanism
of hypoalbuminemia.
Albumin values are a sensitive index for nutritional screening
that indicates the need for a more complete and detailed nutritional assessment. In the elderly, whether in the community, or
in care or hospital, hypoalbuminemia is a prognostic indicator for
complications, for the onset of disability and for mortality. Despite
hypoalbuminemia often also depending on non-nutritional factors,
serum concentration of albumin is strongly correlated to the Mini
Nutritional Assessment both in hospitalized elderly people and
those in nursing homes [29,66].
Intake reduction is one of the main causes of chronic malnutrition in the elderly [8,67]. Among the most important causes of
what is known as geriatric anorexia (a para-physiologic process
associated to age) are alterations in taste and smell, changes in the
hormones that regulate gastric and intestinal motility, and mood
alterations (depression, loneliness and dementia, among others)
[68].
Proteins are the macronutrients most lacking in elderly peoples diets, with intake well below recommended quantities for this
population group [69,70].
The lack of a universally accepted denition of malnutrition in
elderly people is one of the causes of it being under diagnosed
and hinders a standardized ltering process and, therefore, a correct intervention and nutritional follow-up [71]. Various methods
for nutritional assessment based on the combination of several
parameters have been developed and then validated in elderly
populations [72,73].
Despite the higher or lower sensitivity of the various ltering
and diagnostic tests for malnutrition, weight is the fundamental
basis of nutritional assessment, which should not be missing in
any complete geriatric assessment. Anthropometric indices (BMI,
skin folds, muscular diameters, etc.), despite their important limitations as indirect markers of body composition in the elderly,
enhance nutritional assessment and aid in diagnosing malnutrition.
Elderly patients with a hip fracture are of special interest in geriatrics, due to their having undergone an acute episode, which often
unmasks a slowly evolving chronic process and which in many
cases triggers serious complications and disability. The prevalence
of malnutrition in these patients varies widely among the papers
reviewed, reaching 50% in several of them [26,54,74,75]. Two of
the long term consequences of an insufcient calorie and protein
intake are loss of strength and osteoporosis, which leads to fractures due to increase in falls and a reduction of bone resistance to
impact [74].
Hip fracture patients are often malnourished to start with. These
patients suffer a hypercatabolic state secondary to two factors. One
is inammation, which increases muscle loss and the second factor

25

is insulin resistance, which causes hyperinsulinemia. The latter


causes and stimulates muscle protein depletion [26]. This hypercatabolic state is perpetuated after discharge from hospital and
often together with a decient intake contributes to weight loss,
mainly at the expense of muscle tissue, with fat tissue remaining
stable [76].
The association between hypoalbuminemia and mortality is
cause for concern, which we must assess with caution and
remember that clinical decisions should not be based on a single
parameter. In addition, despite the association found both short
and long term between mortality, hypoalbuminemia and functional status in hospitalized elderly people and elderly people
living at home, it remains to be proven whether adequate nutritional intervention can correct the lack of albumin and reduce
mortality.
This review has a number of limitations. The rst is that despite
the fact that most of the papers reviewed dene hypoalbuminemia
as serum concentration <35 g/L, most of the included studies had
albumin levels >35 g/L. The second limitation is that only a few of
the studies assessed and measured other factors that could cause
hypoalbuminemia, such as an increase of inammatory cytokines.
Finally, there are aspects that we did not analyze due to space constraints, such as the association between albumin and cognitive
status or the clinical signicance of albumin serum concentrations
in haemodialysis patients; we should like to return to these issues
in a future paper.
Despite these limitations, one of the strengths of this review
is the fact it approaches the signicance of hypoalbuminemia in
elderly people in various settings (the community, care homes, hospital), something on which we have not found any specic reviews
in the literature. Another strength of this review is that, despite our
using one single database and having discarded the papers that did
not present albumin level data, we did manage to include a relatively large number of papers, which makes the conclusions of this
revision more solid.
7. Conclusions
Hypoalbuminemia is not a physiological process secondary to
ageing. Therefore, in elderly people with hypoalbuminemia it is
necessary to implement a ltering and assessment process in order
to nd out the cause of this alteration. Nutritional status is one of
the main factors, but it is not the only one inuencing changes in
albumin concentration.
Hypoalbuminemia, regardless of its cause, is a negative prognostic index in the elderly, which should not go unnoticed.
As a general conclusion, we believe more research is required,
investigating the physiopathological mechanisms of hypoalbuminemia and its possible treatment.
Contributors
SC is the principal investigator, she wrote the rst draft. VM
designed the study, collaborate in the drafting of the article, and
supervised and coordinate the editing of manuscript. DC revised
statistical aspects of the manuscript and carried out the metaanalysis. IAA, FGB and FMC collaborated actively with the scientic
basis of the review and collaborated in drafting and editing the
manuscript. All of the authors approved the nal version of the
manuscript.
Competing interests
None.

26

S. Cabrerizo et al. / Maturitas 81 (2015) 1727

Funding
None.
Provenance and peer review
Not commissioned; externally peer reviewed.
References
[1] Agarwal E, Miller M, Yaxley A, Isenring E. Malnutrition in the elderly: a narrative
review. Maturitas 2013;76(4):296302.
[2] Kergoat MJ, Leclerc BS, PetitClerc C, Imbach A. Discriminant biochemical markers for evaluating the nutritional status of elderly patients in long-term care.
Am J Clin Nutr 1987;46(5):84961.
[3] Ballmer PE. Causes and mechanisms of hypoalbuminaemia. Clin Nutr (Edinburgh, Scotland) 2001;20(3):2713.
[4] Fuhrman MP, Charney P, Mueller CM. Hepatic proteins and nutrition assessment. J Am Diet Assoc 2004;104(8):125864.
[5] Moshage HJ, Janssen JA, Franssen JH, Hafkenscheid JC, Yap SH. Study of the
molecular mechanism of decreased liver synthesis of albumin in inammation.
J Clin Invest 1987;79(6):163541.
[6] Vincent JL, Dubois MJ, Navickis RJ, Wilkes MM. Hypoalbuminemia in acute illness: Is there a rationale for intervention? A meta-analysis of cohort studies
and controlled trials. Ann Surg 2003;237(3):31934.
[7] Sullivan DH, Sun S, Walls RC. Protein-energy undernutrition among elderly
hospitalized patients: a prospective study. JAMA 1999;281(21):20139.
[8] Seiler WO. Clinical pictures of malnutrition in ill elderly subjects. Nutrition
(Burbank, Los Angeles County, Calif) 2001;17(6):4968.
[9] Franch-Arcas G. The meaning of hypoalbuminaemia in clinical practice. Clin
Nutr (Edinburgh, Scotland) 2001;20(3):2659.
[10] Cooper JK, Gardner C. Effect of aging on serum albumin. J Am Geriatr Soc
1989;37(11):103942.
[11] Gom I, Fukushima H, Shiraki M, et al. Relationship between serum albumin level
and aging in community-dwelling self-supported elderly population. J Nutr Sci
Vitaminol 2007;53(1):3742.
[12] Salive ME, Cornoni-Huntley J, Phillips CL, et al. Serum albumin in older persons:
relationship with age and health status. J Clin Epidemiol 1992;45(3):21321.
[13] Sahyoun NR, Jacques PF, Dallal G, Russell RM. Use of albumin as a predictor of
mortality in community dwelling and institutionalized elderly populations. J
Clin Epidemiol 1996;49(9):9818.
[14] Baumgartner RN, Koehler KM, Romero L, Garry PJ. Serum albumin is associated with skeletal muscle in elderly men and women. Am J Clin Nutr
1996;64(4):5528.
[15] Campion EW, deLabry LO, Glynn RJ. The effect of age on serum albumin in healthy males: report from the normative aging study. J Gerontol
1988;43(1):M1820.
[16] Flood A, Chung A, Parker H, Kearns V, OSullivan TA. The use of hand grip
strength as a predictor of nutrition status in hospital patients. Clin Nutr (Edinburgh, Scotland) 2014;33(1):10614.
[17] Miller MD, Thomas JM, Cameron ID, et al. BMI: A simple, rapid and clinically meaningful index of under-nutrition in the oldest old? Br J Nutr
2009;101(9):13005.
[18] Sergi G, Coin A, Enzi G, et al. Role of visceral proteins in detecting malnutrition
in the elderly. Eur J Clin Nutr 2006;60(2):2039.
[19] Visser M, Kritchevsky SB, Newman AB, et al. Lower serum albumin concentration and change in muscle mass: the health, aging and body composition study.
Am J Clin Nutr 2005;82(3):5317.
[20] Clark BC, Manini TM. Functional consequences of sarcopenia and dynapenia in
the elderly. Curr Opin Clin Nutr Metab Care 2010;13(3):2716.
[21] Malafarina V, Uriz-Otano F, Iniesta R, Gil-Guerrero L. Sarcopenia in the elderly:
diagnosis, physiopathology and treatment. Maturitas 2012;71(2):10914.
[22] Keller HH. Use of serum albumin for diagnosing nutritional status in the
elderlyis it worth it? Clin Biochem 1993;26(6):4357.
[23] Morley JE, Thomas DR, Wilson MM. Cachexia: pathophysiology and clinical
relevance. Am J Clin Nutr 2006;83(4):73543.
[24] Neumann SA, Miller MD, Daniels L, Crotty M. Nutritional status and clinical outcomes of older patients in rehabilitation. J Hum Nutr Diet 2005;18(2):
12936.
[25] Kyle UG, Genton L, Pichard C. Hospital length of stay and nutritional status. Curr
Opin Clin Nutr Metab Care 2005;8(4):397402.
[26] Hedstrom M, Ljungqvist O, Cederholm T. Metabolism and catabolism in hip
fracture patients: Nutritional and anabolic interventiona review. Acta Orthop
2006;77(5):7417.
[27] Gariballa SE. Malnutrition in hospitalized elderly patients: when does it matter? Clin Nutr (Edinburgh, Scotland) 2001;20(6):48791.
[28] Bouillanne O, Hay P, Liabaud B, Duche C, Cynober L, Aussel C. Evidence
that albumin is not a suitable marker of body composition-related nutritional status in elderly patients. Nutrition (Burbank, Los Angeles County, Calif)
2011;27(2):1659.
[29] Drescher T, Singler K, Ulrich A, et al. Comparison of two malnutrition risk
screening methods (MNA and NRS 2002) and their association with markers

[30]

[31]

[32]

[33]

[34]

[35]

[36]

[37]
[38]

[39]

[40]

[41]

[42]

[43]

[44]

[45]

[46]

[47]

[48]
[49]

[50]

[51]

[52]

[53]

[54]

[55]

of protein malnutrition in geriatric hospitalized patients. Eur J Clin Nutr


2010;64(8):88793.
Covinsky KE, Covinsky MH, Palmer RM, Sehgal AR. Serum albumin concentration and clinical assessments of nutritional status in hospitalized older
people: Different sides of different coins? J Am Geriatr Soc 2002;50(4):
6317.
Kuzuya M, Izawa S, Enoki H, Okada K, Iguchi A. Is serum albumin a good marker
for malnutrition in the physically impaired elderly? Clin Nutr (Edinburgh, Scotland) 2007;26(1):8490.
Schalk BW, Deeg DJ, Penninx BW, Bouter LM, Visser M. Serum albumin and
muscle strength: a longitudinal study in older men and women. J Am Geriatr
Soc 2005;53(8):13318.
Okamura T, Hayakawa T, Hozawa A, et al. Lower levels of serum albumin
and total cholesterol associated with decline in activities of daily living and
excess mortality in a 12-year cohort study of elderly Japanese. J Am Geriatr Soc
2008;56(3):52935.
Kitamura K, Nakamura K, Nishiwaki T, Ueno K, Nakazawa A, Hasegawa M.
Determination of whether the association between serum albumin and activities of daily living in frail elderly people is causal. Environ Health Prev Med
2012;17(2):1648.
Onem Y, Terekeci H, Kucukardali Y, et al. Albumin, hemoglobin, body mass
index, cognitive and functional performance in elderly persons living in nursing
homes. Arch Gerontol Geriatr 2010;50(1):569.
Luk JK, Chiu PK, Tam S, Chu LW. Relationship between admission albumin
levels and rehabilitation outcomes in older patients. Arch Gerontol Geriatr
2011;53(1):849.
Parr EB, Coffey VG, Hawley JA. Sarcobesity: a metabolic conundrum. Maturitas
2013;74(2):10913.
Baumgartner RN, Wayne SJ, Waters DL, Janssen I, Gallagher D, Morley JE. Sarcopenic obesity predicts instrumental activities of daily living disability in the
elderly. Obes Res 2004;12(12):19952004.
Paddon-Jones D, Shefeld-Moore M, Urban RJ, Aarsland A, Wolfe RR, Ferrando
AA. The catabolic effects of prolonged inactivity and acute hypercortisolemia are offset by dietary supplementation. J Clin Endocrinol Metab
2005;90(3):14539.
Schalk BW, Visser M, Penninx BW, Baadenhuijsen H, Bouter LM, Deeg DJ. Change
in serum albumin and subsequent decline in functional status in older persons.
Aging Clin Exp Res 2005;17(4):297305.
Snyder CK, Lapidus JA, Cawthon PM, et al. Serum albumin in relation to change
in muscle mass, muscle strength, and muscle power in older men. J Am Geriatr
Soc 2012;60(9):166372.
Tamas Jr F, Herrmann F, Rapin CH. Prognostic role of serum albumin and prealbumin levels in elderly patients at admission to a geriatric hospital. Arch
Gerontol Geriatr 1991;12(1):319.
Lee HP, Chang YY, Jean YH, Wang HC. Importance of serum albumin level in
the preoperative tests conducted in elderly patients with hip fracture. Injury
2009;40(7):7569.
Uriz-Otano F, Uriz-Otano JI, Malafarina V. Factors associated with short-term
functional recovery in elderly people with a hip fracture. Inuence of cognitive
impairment. J Am Med Dir Assoc 2014.
Wouters-Wesseling W, Wouters AE, Kleijer CN, Bindels JG, de Groot CP, van
Staveren WA. Study of the effect of a liquid nutrition supplement on the
nutritional status of psycho-geriatric nursing home patients. Eur J Clin Nutr
2002;56(3):24551.
Stange I, Bartram M, Liao Y, et al. Effects of a low-volume, nutrient- and
energy-dense oral nutritional supplement on nutritional and functional status: a randomized, controlled trial in nursing home residents. J Am Med Dir
Assoc 2013;14(8):628.e18.
Pimlott BJ, Jones CA, Beaupre LA, Johnston DW, Majumdar SR. Prognostic
impact of pre-operative albumin on short-term mortality and complications
in patients with hip fracture. Arch Gerontol Geriatr 2011;53(1):904.
Perez Durillo FT, Ruiz Lopez MD, Bouzas PR, Martin-Lagos A. Nutritional status
in elderly patients with a hip fracture. Nutr Hosp 2010;25(4):67681.
Galvard H, Elmstahl S, Elmstahl B, Samuelsson SM, Robertsson E. Differences in
body composition between female geriatric hip fracture patients and healthy
controls: body fat is more important as explanatory factor for the fracture than
body weight and lean body mass. Aging Clin Exp Res 1996;8(4):2826.
Koren-Hakim T, Weiss A, Hershkovitz A, et al. The relationship between
nutritional status of hip fracture operated elderly patients and their functioning, comorbidity and outcome. Clin Nutr (Edinburgh, Scotland) 2012;31(6):
91721.
Mizrahi EH, Fleissig Y, Arad M, Blumstein T, Adunsky A. Admission albumin levels and functional outcome of elderly hip fracture patients: is it that important?
Aging Clin Exp Res 2007;19(4):2849.
Mansell PI, Rawlings J, Allison SP, et al. Low anthropometric indices in
elderly females with fractured neck of femur. Clin Nutr (Edinburgh, Scotland)
1990;9(4):1904.
Ozturk A, Ozkan Y, Akgoz S, Yalcin N, Aykut S, Ozdemir MR. The effect of blood
albumin and total lymphocyte count on short-term results in elderly patients
with hip fractures. Ulus Travma Acil Cerrahi Derg 2009;15(6):54652.
Lumbers M, New SA, Gibson S, Murphy MC. Nutritional status in elderly female
hip fracture patients: Comparison with an age-matched home living group
attending day centres. Br J Nutr 2001;85(6):73340.
Bastow MD, Rawlings J, Allison SP. Benets of supplementary tube feeding after
fractured neck of femur: a randomised controlled trial. Br Med J (Clin Res Ed)
1983;287(6405):158992.

S. Cabrerizo et al. / Maturitas 81 (2015) 1727


[56] ODaly BJ, Walsh JC, Quinlan JF, et al. Serum albumin and total lymphocyte
count as predictors of outcome in hip fractures. Clin Nutr (Edinburgh, Scotland)
2010;29(1):8993.
[57] Symeonidis PD, Clark D. Assessment of malnutrition in hip fracture patients:
effects on surgical delay, hospital stay and mortality. Acta Orthop Belg
2006;72(4):4207.
[58] Kitamura K, Nakamura K, Nishiwaki T, Ueno K, Hasegawa M. Low body mass
index and low serum albumin are predictive factors for short-term mortality in
elderly Japanese requiring home care. Tohoku J Exp Med 2010;221(1):2934.
[59] Corti MC, Guralnik JM, Salive ME, Sorkin JD. Serum albumin level and
physical disability as predictors of mortality in older persons. JAMA
1994;272(13):103642.
[60] Klonoff-Cohen H, Barrett-Connor EL, Edelstein SL. Albumin levels as a predictor
of mortality in the healthy elderly. J Clin Epidemiol 1992;45(3):20712.
[61] Reuben DB, Ferrucci L, Wallace R, et al. The prognostic value of serum albumin
in healthy older persons with low and high serum interleukin-6 (IL-6) levels. J
Am Geriatr Soc 2000;48(11):14047.
[62] Hannan JL, Radwany SM, Albanese T. In-hospital mortality in patients older
than 60 years with very low albumin levels. J Pain Symptom Manage
2012;43(3):6317.
[63] Iwata M, Kuzuya M, Kitagawa Y, Iguchi A. Prognostic value of serum albumin combined with serum C-reactive protein levels in older hospitalized
patients: continuing importance of serum albumin. Aging Clin Exp Res
2006;18(4):30711.
[64] Tal S, Guller V, Shavit Y, Stern F, Malnick S. Mortality predictors in hospitalized
elderly patients. QJM 2011;104(11):9338.
[65] Sullivan DH, Roberson PK, Bopp MM. Hypoalbuminemia 3 months after
hospital discharge: signicance for long-term survival. J Am Geriatr Soc
2005;53(7):12226.

27

[66] Malara A, Sgro G, Caruso C, et al. Relationship between cognitive impairment


and nutritional assessment on functional status in calabrian long-term-care.
Clin Intervent Aging 2014;9:10510.
[67] Volkert D, Berner YN, Berry E, et al. ESPEN guidelines on enteral nutrition:
geriatrics. Clin Nutr (Edinburgh, Scotland) 2006;25(2):33060.
[68] Malafarina V, Uriz-Otano F, Gil-Guerrero L, Iniesta R. The anorexia of ageing:
physiopathology, prevalence, associated comorbidity and mortality. A systematic review. Maturitas 2013;74(4):293302.
[69] Evans WJ. What is sarcopenia? J Gerontol A Biol Sci Med Sci 1995;50(Spec
No):58.
[70] Valenzuela RE, Ponce JA, Morales-Figueroa GG, Muro KA, Carreon VR, AlemanMateo H. Insufcient amounts and inadequate distribution of dietary protein
intake in apparently healthy older adults in a developing country: Implications
for dietary strategies to prevent sarcopenia. Clin Interv Aging 2013;8:11438.
[71] Meijers JM, van Bokhorst-de van der Schueren MA, Schols JM, Soeters PB,
Halfens RJ. Dening malnutrition: Mission or mission impossible? Nutrition
(Burbank, Los Angeles County, Calif) 2010;26(4):43240.
[72] Omran ML, Morley JE. Assessment of protein energy malnutrition in older
persons, Part I: History, examination, body composition, and screening tools.
Nutrition (Burbank, Los Angeles County, Calif) 2000;16(1):5063.
[73] Omran ML, Morley JE. Assessment of protein energy malnutrition in older persons, Part II: Laboratory evaluation. Nutrition (Burbank, Los Angeles County,
Calif) 2000;16(2):13140.
[74] Akner G, Cederholm T. Treatment of protein-energy malnutrition in chronic
nonmalignant disorders. Am J Clin Nutr 2001;74(1):624.
[75] Mila Villarroel R, Formiga F, Duran Alert P, Abellana Sangra R. Prevalence of malnutrition in Spanish elders: systematic review. Med Clin 2012;139(11):5028.
[76] DAdamo CR, Hawkes WG, Miller RR, et al. Short-term changes in body composition after surgical repair of hip fracture. Age Ageing 2014;43(2):27580.