The Impact of Dairy Protein Intake on Muscle Mass, Muscle Strength, and Physical Performance in Middle-Aged to Older Adults with or without Existing Sarcopenia: A Systematic Review and Meta-Analysis

Abstract

Sarcopenia is an age-related condition associated with a progressive loss of muscle mass and strength. Insufficient protein intake is a risk factor for sarcopenia. Protein supplementation is suggested to improve muscle anabolism and function in younger and older adults. Dairy products are a good source of high-quality proteins. This review evaluates the effectiveness of dairy proteins on functions associated with sarcopenia in middle-aged and older adults. Randomized controlled trials were identified using PubMed, CINAHL/EBSCO, and Web of Science databases (last search: 10 May 2017) and were quality assessed. The results of appendicular muscle mass and muscle strength of handgrip and leg press were pooled using a random-effects model. The analysis of the Short Physical Performance Battery is presented in narrative form. Adverse events and tolerability of dairy protein supplementation were considered as secondary outcomes. Fourteen studies involving 1424 participants aged between 61 and 81 y met the inclusion criteria. Dairy protein significantly increased appendicular muscle mass (0.13 kg; 95% CI: 0.01, 0.26 kg; P = 0.04); however, it had no effect on improvement in handgrip (0.84 kg; 95% CI: -0.24, 1.93 kg; P = 0.13) or leg press (0.37 kg; 95% CI: -4.79, 5.53 kg; P = 0.89). The effect of dairy protein on the Short Physical Performance Battery was inconclusive. Nine studies reported the dairy protein to be well tolerated with no serious adverse events. Although future high-quality research is required to establish the optimal type of dairy protein, the present systematic review provides evidence of the beneficial effect of dairy protein as a potential nutrition strategy to improve appendicular muscle mass in middle-aged and older adults.

Full text

REVIEW
The Impact of Dairy Protein Intake on Muscle Mass,
Muscle Strength, and Physical Performance in
Middle-Aged to Older Adults with or without
Existing Sarcopenia: A Systematic Review and
Meta-Analysis
Nivine I Hanach, Fiona McCullough, and Amanda Avery
Division of Nutritional Sciences, University of Nottingham, Leicestershire, United Kingdom
ABSTRACT
Sarcopenia is an age-related condition associated with a progressive loss of muscle mass and strength. Insufficient protein intake is a risk factor for
sarcopenia. Protein supplementation is suggested to improve muscle anabolism and function in younger and older adults. Dairy products are a
good source of high-quality proteins. This review evaluates the effectiveness of dairy proteins on functions associated with sarcopenia in middle-
aged and older adults. Randomized controlled trials were identified using PubMed, CINAHL/EBSCO, and Web of Science databases (last search:
10 May 2017) and were quality assessed. The results of appendicular muscle mass and muscle strength of handgrip and leg press were pooled
using a random-effects model. The analysis of the Short Physical Performance Battery is presented in narrative form. Adverse events and tolerability
of dairy protein supplementation were considered as secondary outcomes. Fourteen studies involving 1424 participants aged between 61 and 81
y met the inclusion criteria. Dairy protein significantly increased appendicular muscle mass (0.13 kg; 95% CI: 0.01, 0.26 kg; P=0.04); however, it had
no effect on improvement in handgrip (0.84 kg; 95% CI: −0.24, 1.93 kg; P=0.13) or leg press (0.37 kg; 95% CI: −4.79, 5.53 kg; P=0.89). The effect
of dairy protein on the Short Physical Performance Battery was inconclusive. Nine studies reported the dairy protein to be well tolerated with no
serious adverse events. Although future high-quality research is required to establish the optimal type of dairy protein, the present systematic review
provides evidence of the beneficial effect of dairy protein as a potential nutrition strategy to improve appendicular muscle mass in middle-aged
and older adults. Adv Nutr 2018;0:1–11.
Keywords: sarcopenia, muscle mass, muscle strength, physical performance, dairy protein, systematic review, meta-analysis, middle-age and older
adults
Introduction
Sarcopenia, the term used to dene age-related progressive
decline in muscle mass and muscle strength, was rst
reported by Rosenberg in 1989 (1). This condition can occur
with or without a reduction in fat mass (1). There is not a
specic age at which muscle mass and strength begin to di-
minish because of various contributing factors, including diet
and physical activity levels. However, the sarcopenic process
starts as early as the fourth or fth decade of life (2). Sarcope-
nia is recognized as an increasing public health problem (3),
The authors declared no nancial support received for this work.
Author disclosures: NIH, FM, and AA, no conicts of interest.
Address correspondence to AA (e-mail: amanda.avery@nottingham.ac.uk).
Abbreviations used: AMM, appendicular muscle mass; CG, control group; IG, intervention
group; SPPB, Short Physical Performance Battery.
with the number of people aected by sarcopenia worldwide
projected to increase from >50 million in 2010 to >200
million in 2050 (4). Sarcopenia is associated with increased
risk of adverse outcomes such as a poor quality of life, physi-
cal disability, depression, injurious falls, hospital admissions,
and death (3). As a consequence, high health care expendi-
tures of $900/person per year are attributed to sarcopenia (5).
The etiology of sarcopenia is multifactorial; it includes
increased inammatory mediators (e.g., cytokines), bed rest
or low physical activity levels, hormonal disorders (6), and
poor nutrition, particularly an inadequate energy and/or
protein intake (4,7). Nutrition is a modiable risk factor
for sarcopenia (8). For example, dietary protein enhances
the anabolic activity in skeletal muscle and provides the
© 2018 American Society for Nutrition. All rights reserved. Adv Nutr 2018;0:1–11; doi: https://doi.org/10.1093/advances/nmy065. 1

necessary amino acids to stimulate postprandial muscle pro-
tein synthesis (9). Insucient protein consumption has been
associated with muscle mass depletion and poor physical
function in older adults (8). A number of studies have been
carried out to evaluate the potential eect of protein or
amino acid supplementation on reducing the decline in func-
tions associated with sarcopenia (i.e., muscle mass, muscle
strength, and physical performance) in younger and older
adults. In a meta-analysis of 22 randomized controlled trials
(10), protein supplementation after prolonged resistance
training was shown to increase lean muscle mass by 0.69 kg
(P<0.00001) and leg press strength by 13.5 kg (P<0.005)
compared with a placebo group in both younger and older
adults. The majority of the included trials supplemented with
whey protein from dairy, alone or in combination with amino
acids or another type of dairy protein. In a recent meta-
analysis of 10 trials, Hidayat et al. (12)foundapositive
eect of milk-based protein supplementation and resistance
training on fat-free mass (0.74 kg; 95% CI: 0.30, 1.17 kg) in
older adults, suggesting a potential role of dairy protein in
promoting muscle anabolism.
Dairy products are good sources of high-quality protein,
primarily in the form of either whey or casein (11). They
are aordable and readily available throughout the world
(12). Dairy products, including milk-protein supplements,
do not require cooking or require only minimal preparation
compared with other protein-rich foods such as lean meat,
poultry, sh, and eggs (12). This makes dairy sources a
practical option for older adults to consume adequate protein
(12). Further research is required to determine if dairy
proteins could be used as a dietary strategy to reduce the
health risks associated with sarcopenia by improving muscle
mass and muscle function.
Although previous meta-analyses have evaluated the ef-
fect of protein supplementation on muscle mass and strength,
the potential dietary role of dairy protein in improving the
primary outcome parameters of sarcopenia has not been
specically investigated to our knowledge. Therefore, this
systematic review and meta-analysis aimed to evaluate the
impact of dairy protein intake on muscle mass, muscle
strength, and physical performance in middle-aged to older
adults with or without existing sarcopenia.
Methods
The current systematic review was conducted according to
the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) statement (13).
Eligibility criteria
The selection of the studies was restricted to full-text articles
and the English language. The relevant studies had to meet
the following criteria:
Participants: Studies conducted in humans only. Middle-
aged to older adults [middle age dened as between 45 and
65 y old (14)] with or without sarcopenia.
Types of study: Randomized controlled trials in which
the recruited subjects were randomly assigned to ≥1
TAB LE 1 Cutos of SPPB scores in older adults1
SPPB score Performance level
4–6 Low
7–9 Intermediate
10–12 High
1Data from referen ce 17. SPPB, Short Physical Performance Battery.
intervention group (IG) compared with a control group
(CG).
Types of intervention: The IG received dairy protein
supplementation (e.g., whey protein, milk-protein con-
centrate, casein) or a protein-based dairy product (e.g.,
ricotta cheese). The duration of the intervention was
≥12 wk. This period of time was decided on the basis
of the available evidence that muscle hypertrophy occurs
within 12 wk in response to dietary modications and
protein supplementations during resistance training (15,
16). Inclusion of resistance training as part of the study
intervention was optional.
Types of outcome measures: Primary outcomes were
changes in muscle strength (kilograms) of handgrip and
leg press measured by hydraulic hand dynamometer and
1-repetition-maximum strength test, respectively, and
changes in appendicular skeletal muscle mass (kilograms)
measured by DXA. Physical performance was assessed us-
ing the Short Physical Performance Battery (SPPB) score.
The SPPB is a standard measure of physical performance,
itassessestheindividual’sbalance,strength,gait,anden-
durance (4). The score is calculated by summing the scores of
3 equally weighted tests: balance, gait speed, and chair stand
(4). Table 1 denes the cuto points of SPPB score in older
adults (17).
These variables have been suggested as primary outcome
domains to dene sarcopenia by the European Work Group
on Sarcopenia in Older People (4), with the proposed
measuring tools conrmed to be reliable and valid. Adverse
events and intervention adherence were reported as the
secondary outcomes. Exclusion criteria are presented in
Table 2.
Search strategy
PubMed (https://www.ncbi.nlm.nih.gov/pubmed/), CINAHL
(EBSCO) (https://www.ebsco.com/products/research-data
bases/cinahl-database), and Web of Science (https://
clarivate.com/products/web-of-science/databases/)databas-
es were used for electronic searches. References of the
retrieved studies and existing meta-analyses were also
hand-searched. The search covered the period up to 10 May
2017. There were no publication date or publication type
restrictions in this review. Key terms included in the search
engines were as follows—study design: #1 randomized
controlled trial OR controlled trial OR clinical trial;
population: #2 adult OR older adults OR middle-aged adults;
exposure: #3 milk OR milk protein OR dairy protein OR
whey OR whey protein OR whey protein supplementation
OR casein OR protein supplementation; outcome: #4 muscle
2 Hanach et al.

TAB LE 2 Exclusion criteria
Exclusion criteria
Study design Observational studies, meta-analyses, systematic reviews
Population Animals; children; subjects diagnosed with liver disease, kidney disease, or cancer; allergic/intolerant to milk protein or
lactose; taking medications that might interfere with the intervention; with low cognitive function; taking protein
supplementation other than the intervention dairy protein of study of interest
Outcome Postprandial protein synthesis, muscle protein synthesis, muscle fibers, muscle biopsy
mass OR skeletal muscle mass OR appendicular muscle mass
#5 muscle strength #6 physical performance OR physical
function OR functionality #7 (#4 OR #5 OR #6) #8 (#1 AND
#2 AND #3 AND #7).
Data extraction
The following data were extracted and tabulated: author(s),
year of publication, country of publication, study design,
duration of intervention, participants’ characteristics (e.g.,
sample size, baseline characteristics, inclusions), description
ofthestudyarms,measuredoutcomes,andvaluesofthe
outcomes of interests pre- and postintervention.
Quality assessment
The quality of the included studies was assessed according
totheCochraneCollaboration’stoolforassessingrisk
of bias (18). It addresses 6 specic domains: sequence
generation, allocation concealment, blinding of participants,
personnel and outcome assessors, incomplete outcome data,
and selection reporting. In this review, as suggested by the
Cochrane Handbook for systematic reviews of interventions
(18),aqualityscaletoassesstheoverallriskofbiaswas
not used. The use of quality scales to appraise the included
randomized trials tends to combine the assessments of
aspects of the quality reporting with those of trial conduct
(19). Instead, the judgments of overall risk of bias are made
explicit by separating the assessment of internal and external
validity (19). The study selection, data extraction, and quality
assessment were primarily performed by NIH with oversight
by 2 experienced researchers (AA and FM). Dierences were
resolved by consensus.
Statistical analysis
RevMan software (Review Manager, version 5.3.5; The
Nordic Cochrane Centre, The Cochrane Collaboration, 2014;
http://community.cochrane.org/tools/review-production-
tools/revman-5/revman-5-download)wasusedtoperform
the meta-analysis. The mean change (meannal –mean
baseline)
of handgrip strength and appendicular muscle mass (AMM)
andmeanoutcomevalue(nalvalue)oflegpressstrength
were retrieved for analysis. When only the baseline and
nal SDs were reported, the change SD was computed
using the Cochrane Handbook proposed equation (18), as
follows:
SD change =√(SDbaseline)2+(SDfinal )2
−(2×corr ×SDbaseline ×SDfinal)(1)
where the imputed correlation coecient is 0.80. Eect sizes
are presented as mean dierences (95% CIs) for the contin-
uous outcomes. The results were pooled using the inverse
variance random-eects model (DerSimonian and Laird). I2
statistics were used to assess heterogeneity between studies.
The I2indicates the percentage of the variability in eect
estimates across studies due to heterogeneity rather than
sampling error (I2>50%: substantial heterogeneity) (19).
The xed-eects model was used when no heterogeneity was
identied. A Pvalue <0.05 was considered to be signicant.
To investigate whether the changes in primary outcomes
were aected by the subjects’ characteristics and individual
intervention, a subgroup analysis was conducted adjusting
for subjects’ mean age, subjects’ health status, and amount
of protein supplementation. In addition, a sensitivity analysis
was performed by excluding a single study, in turn, to
investigate its eect on the results of the meta-analysis.
Results
Literature search
Figure 1 shows the ow of the studies through the review
process. A total of 202 articles were identied after the
electronic search of PubMed, CINAHL/EBSCO, and Web
of Science databases. Four articles were retrieved after the
manual search of references of key articles and existing
reviews. The abstract screening resulted in the exclusion
of 191 articles not meeting inclusion criteria: 8 studies
evaluated the increase in the muscle fractional synthesis
rate, 5 studies were not randomized controlled trials, 1
study was animal-based, and the remaining studies contained
irrelevant content. After the full-text screening for eligibility,
one article was excluded for not providing the exposure of
interest. A total of 14 studies were therefore included in this
systematic review, and 11 were then included in the meta-
analysis. The publication dates ranged from 2009 to 2016.
The included studies were conducted in Mexico (2), United
States (3), Netherlands (3), Iceland (1), Finland (1), Germany
(1), Canada (1), Australia (1), and Ireland (1).
Study characteristics
Table 3 presents a summary of the characteristics of the
included studies. The eligible randomized controlled trials
included a total of 1424 participants with a mean ±SD age
range between 61 ±5yand81±1 y. Participants’ character-
istics varied between studies. Individuals with sarcopenia and
polymyalgia rheumatism were recruited in 3 trials (20–22)
and 1 trial (23), respectively, whereas the remaining studies
Dairy protein intake and sarcopenia: a review 3

Records identified through PubMed,
CINAHL/EBSCO, and Web of Science databases
searching
(n= 202)
Additional records identified through other
sources
(n=4)
Records after duplicates removed
(n=206)
Full-text articles excluded, with reasons
(n=1)
the exposure of interest is not a protein- based
supplement or dairy product
Records screened
(n=206)
Full-texts screening for eligibility
(n=15)
Records excluded
(n=191)
8 the outcome of interest was the muscle
fractional synthesis rate
2 cross-sectional studies
3 animal-based interventions
1 cohort studies
177 irrelevant studies
Studies included in qualitative synthesis
(n= 14)
Studies included in quantitative synthesis (meta-
analysis)
(n= 11)
FIGURE 1 PRISMA flow diagram of the selection of the studies. PRISMA, Preferred Reporting Items for Systematic Reviews and
Meta-Analyses.
enrolled healthy individuals. The subjects were nonfrail and
fully mobile in all studies with the exception of 3 in which
theyhadalimitedmobility(21,24,25).
Intervention
The duration of the intervention varied from 12 to
24 wk. The dairy protein supplement used in the IG varied
between studies. Two studies provided ricotta cheese with
the habitual diet (20,26). Five studies supplemented whey
protein either alone (23,25) or in combination with leucine
and vitamin D (21,22,28). Two studies supplemented
leucine- (23) and cysteine- (29) enriched whey protein. One
study supplemented skimmed milk–based high protein with
whey (28). Milk-protein concentrate was given in 2 studies
(24,31), and a milk-based matrix and casein hydrolysate were
used in 2 studies as a supplement (32,33). Only in one study
(33) was the amount of protein supplementation reported
according to body weight (0.33 g/kg), whereas the remaining
studies reported the extra protein intake according to daily
amounts ranging from 14 to 40 g/d. In all but 2 trials
the protein supplement was given daily; in the 2 studies
(27,32) it was consumed on “training” days only. The
frequency of protein supplementation varied among the
studies from 1 time/d (22,27–32), 2 times/d (21,23–25,29,
33), or 3 times/d (20,26). Seven of the included trials (22,
25,27–29,31,32) integrated resistance training as part of the
intervention, which ranged from 3 to 5 times/wk.
Comparison
In 2 studies (20,26),thesubjectsintheCGwereaskedto
follow their habitual diet. In 6 studies, an isocaloric product
wasprovidedasasupplementtotheCG(21,22,25,27,
28,33). Three studies used a placebo supplement (24,31,
32). A regular dairy product, casein, and skim milk–based
supplement were given to the CG in Björkman et al. (23),
Karelis et al. (29), and Zhu et al. (30), respectively.
Quality assessment
Figure 2 shows the risk-of-bias graph of the included
randomized controlled trials. According to the Cochrane
Collaboration tool for risk of bias (18), 64% of the tri-
als reported adequate random sequence generation and
allocation concealment, 86% had blinded participants and
personnel, 79% had blinded outcome assessors, 93% of the
4 Hanach et al.

TAB LE 3 Characteristics of the randomized controlled trials on dairy protein and the outcome variables of sarcopenia in middle-aged to older adults1
Study (ref) Region
Study
duration
Age,
y
Subjects,
nSex Health status
Type o f
protein
Total
amount
of protein2Comparator
RT
frequency Measured outcomes
Alemán-Maeto et al. (20)Mexico 3mo ≥60 40 F, M Sarcopenic Ricotta cheese 15.7 g/d Habitual diet NA AMM; MS of handgrip; AEs
Bauer et al. (21)Germany13wk≥65 380 F, M Sarcopenic,
limited
mobility
Whey protein 40 g/d Isocaloric drink NA AMM, MS of handgrip, SPPB
Rondanelli et al. (22) United States 12 wk ≥65 130 F, M Sarcopenic Whey protein 22 g/d Isocaloric
maltodextrin
drink
5 d/wk MS of handgrip
Björkman et al. (23) Finland 20 wk >50 46 F, M Polymyalgia
rheumatic
Whey protein 14 g/d Casein-based
dairy product
NA AMM, MS of handgrip
Tieland et al. (24) Netherlands 24 wk ≥65 65 F, M Frail MPC 30 g/d Placebo,
carbohydrate
drink
NA AMM; MS of handgrip; MS of leg
press; SPPB
Chalé et al. (25) United States 6 mo 70–85 67 F, M Limited
mobility
Whey protein 40 g/d Isocaloric
maltodextrin
drink
3 d/wk MS of leg press; SPPB
Alemán-Maeto et al. (26)Mexico 3mo ≥60 90 F, M Healthy Ricotta cheese 15.7 g/d Habitual diet NA AMM; MS of handgrip; SPPB, AEs
Arnarsonetal.(27) Iceland 12 wk 65–91 141 F, M Healthy Whey protein 20 g/d Isocaloric drink 3 d/wk AMM
Verreijen et a l. (28) Netherlands 13 wk >55 65 F, M Obese Whey protein 20–40 g/d4Isocaloric drink 3 d/wk AMM; MS of handgrip
Karelis et al. (29) Canada 135 d 65–88 80 F, M Healthy Cysteine-rich
whey
protein
20 g/d Casein 3 d/wk MS of leg press
Zhu et al. (30) Australia 2 y 70–80 181 F Healthy Skim
milk–based
high protein
30 g/d Skim milk–based
supplement
NA AMM; MS of handgrip
Leenders et al. (31) Netherlands 24 wk 70 ±1 57 F, M Healthy MPC 15 g/d Placebo, isocaloric
drink
3 d/wk MS of leg press
Verdijk et al. (32) United States 12 wk 72 ±2 28 F, M Healthy Casein
hydrolysate
20 g/d Placebo, flavored
drink
3 d/wk MS of leg press
Norton et al. (33) Ireland 24 wk 45–60 60 F, M Healthy Milk-based
protein
matrix3
0.33 g/kg Isocaloric drink NA AMM
1AE, adverse event; AMM, appendicular muscle mass; MPC, milk-protein concentrate; MS, muscle strength; NA, not available; RT, resistance training; SPPB, Short Physical Performance Battery.
2The amount of extra protein provided by the test supplement.
3The milk protein matrix is composed of a 9:2:1 ratio of milk-protein concentrate, whey-protein concentrate, and whey-protein isolate, respectively.
4The 40 g of protein was given on the training days only.
Dairy protein intake and sarcopenia: a review 5

FIGURE 2 Risk-of-bias graph. Review authors’judgments about each risk-of-bias item presented as percentages across all included
studies using the Cochrane risk-of-bias tool (18).
trials addressed adequately the incomplete outcome data,
and 100% of the trials were free of selective reporting. The
high risk of bias was mainly attributed to performance and
detection bias (20,26,28)andtoattritionbias(28). There
was insucient information to assess the degree of selection
bias in 6 trials (20,23,25,26,29,31)(Figure 3).
Primary outcomes
Muscle strength of handgrip. The meta-analysis of the
mean dierences in mean change in muscle strength of
handgrip included 7 studies with 435 participants in each
oftheIGsandCGs.Thedairyproteinhadnoeectonthe
improvement in handgrip strength (mean dierence: 0.84 kg;
95% CI: −0.24, 1.93 kg; P=0.13) (Figure 4). A signicant
substantial heterogeneity was shown between the studies
(I2=82%, P<0.00001). When a sensitivity analysis was
performed, the exclusion of Rondanelli et al. (22)ledtothe
absence of between-study heterogeneity (I2=0%), without
altering the overall results (mean dierence: 0.17 kg; 95%
CI: −0.25, 1.59 kg; P=0.43). Therefore, the results must
be interpreted with caution. In Björkman et al. (23), the
measurement of handgrip strength of both hands showed a
signicant decrease in the right handgrip strength (−5.2%;
P<0.001) but did not aect the left handgrip strength (3.7%;
P=0.659) after the consumption of milk protein (IG). The
ndingsofthistrialwerenotincludedintheanalysisdueto
dierences in the way the data was reported.
Muscle strength of leg press. The meta-analysis of the
mean dierence in mean endpoint values of muscle strength
of leg press included 4 studies with 114 participants in
the IG and 109 participants in the CG. The dairy protein
supplementation had no eect on leg press strength, with
a mean dierence of 0.37 kg (95% CI: −4.79, 5.53 kg;
P=0.89) (Figure 5). Similar ndings were obtained when a
sensitivity analysis was performed. In Leenders et al. (31), the
data were reported as percentage change from the baseline,
whichwasnotconvenienttobeincludedintheanalysis.A
signicant improvement in leg press strength was found in
both women and men after the 24-wk intervention (31% and
26%, respectively; P<0.001), with no dierence between the
study arms (P=0.37)
AMM. AMM was assessed in 9 trials, of which 8 were
included in the meta-analysis. The meta-analysis of the mean
dierence in mean change of appendicular muscle mass
included a total of 444 and 457 participants in the IGs and
CGs,respectively.IncomparisontotheCG,dairyprotein
supplementation resulted in a signicant increase in AMM
(mean dierence: 0.13 kg; 95% CI: 0.01, 0.26 kg; P=0.04)
(Figure 6). No changes in the results were detected after a
sensitivity analysis was done. Björkman et al. (23)reported
no dierence in AMM improvement between the groups (IG
compared with CG: 0.9% compared with 0.2%; P=0.510).
SPPB. Four out of the 14 included studies evaluated the
SPPB (21,24–26). Tieland et al. (24)andChaléetal.(25)
reported a signicant increase in SPPB score from baseline
to postintervention compared with the CG [8.9 ±0.6 to
10 ±0.6 (P=0.02) and 8.5 ±1.1 to 10.3 ±1.5 (P<0.0001),
respectively], although Alemán-Mateo et al. (26)andBauer
et al. (21) found no eect of dairy protein on the SPPB at the
end of the study [10.7 ±1.7 to 10.8 ±1.5 (P=0.55) and 7.5
to 8.36 (P=0.51), respectively].
Subgroup analyses. A stratied analysis was conducted
accordingtosubjects’healthstatus(withorwithoutsarcope-
nia), mean age, and amount of extra protein supplemen-
tation. The subgroup analysis by sex and type of protein
supplement was dicult to be perform due to only 3 out of
the14includedtrials(20,27,31) reporting sex dierences
in the main outcomes and to the marked dissimilarity in
the given type of protein among the studies. Similarly, the
subgroup analysis stratied by the integration of resistance
training was not possible to be performed due to dierences
in the length and type of workout program among the studies.
There was no signicant change in handgrip strength and
AMM across the subgroups (Tab l e 4 ).
6 Hanach et al.

FIGURE 3 Risk-of-bias summary. Review authors’judgments
about each risk-of-bias item for each included study using the
Cochrane risk-of-bias tool (18).
Secondary outcomes
Nine of the included studies included adverse events in
their reporting. The assessment of safety and tolerability of
the study supplements varied between studies. For instance,
Alemán-Mateo et al. (20,26) measured the relative change
of lipid prole, glomerular ltration rate, kidney function
markers, and microalbuminuria. In the 7 remaining trials,
the gastrointestinal tolerance of the supplement was assessed.
None of the included trials found a signicant dierence in
the incidence of serious adverse events between study arms.
Alemàn-Mateo et al. (20) found that the consumption of
ricotta cheese was associated with early satiety among 25%
of the female participants, and Björkman et al. (23)found
that some gastrointestinal side eects (e.g., early satiety,
diarrhea, atulence, and nausea) were reported by 44.7%
in the IG compared with 32.6% participants in the CG
(P=0.180).
The intervention product was generally well tolerated, and
the compliance rate ranged from 72.1% to 100% among the
studies. In Zhu et al. (30), the adherence to the intervention
was signicantly higher in the IG compared with the CG
(87.1% compared with 80.8%, respectively; P=0.03).
Discussion
The aim of this review was to determine if dairy proteins
couldbeusedtoreducethehealthrisksassociatedwith
sarcopenia by improving muscle mass, muscle function,
and physical performance in middle-aged to older adults.
A meta-analysis was performed to assess the improvement
in muscle strength of handgrip and leg press and AMM.
The results showed a signicant favorable eect of dairy
protein, at amounts of 14–40 g/d, on AMM without having an
eect on muscle strength of handgrip and leg press. Overall,
compliance and acceptability of the protein supplementation
were reported to be good across the studies. Dierences in
the amount of protein supplementation and subjects’ mean
age and baseline health status between the studies did not
signicantly inuence the ndings.
Previous studies have reported a direct relation between
muscle mass and strength in middle-aged to older adults.
Hayashida et al. (34) conducted a cross-sectional study in 318
individuals with the aim to evaluate the correlation between
muscle mass and muscle strength on the basis of sex and
age groups. The obtained results conrmed a signicant
association between muscle strength and AMM in men aged
≥65 y and women aged ≥75 y; however, Goodpaster et al.
(35) suggested in a prospective study in 1880 older adults
with a mean age of 73.5 ±2.8 y that the loss of muscle
strength is more rapid than the loss of muscle mass and
that the decline in the age-dependent strength cannot be
explained by the loss of muscle mass alone.
It was previously argued that older adults tend to develop
a phenomenon called anabolic resistance, an impaired
response of skeletal muscle to an anabolic stimulus with
normal muscle protein synthesis (36). Nevertheless, Burd
et al. (36) observed that, although many factors contribute
to the anabolic resistance of muscle protein synthesis in
older adults, minimal dierences could be seen in muscle
protein synthesis rates between young and older adults after
protein ingestion (36). Hence, the diversity of age groups
in this review probably has little impact on the signicant
improvement of AMM reported (P=0.04).
With regard to physical performance, the analyzed data
do not allow us to make any conclusions about the potential
Dairy protein intake and sarcopenia: a review 7

FIGURE 4 Forest plot showing results for the meta-analysis of difference in mean change from baseline in muscle strength (kilograms)
for handgrip after the intervention in middle-aged to older adults. IV, inverse variance.
eect of dairy protein on SPPB score in middle-aged to
older adults. Two of the included trials reported a signicant
increase in SPPB score (24,25).InBaueretal.(21), although
the results showed no dierence in SPPB score between
the groups (P=0.51), a signicant improvement in chair-
rise time was reported in the IG compared with the CG
(P=0.018). A better chair-stand performance has been
shown to be related to a better leg extensor power in middle-
aged and older adults (37). Cesari et al. (38) claimed that the
chair-stand test has the highest prognostic value compared
with the other SPPB subtasks. Because the chair stand has
been suggested as a useful measure of physical function, this
could partially explain the potential benets of dairy protein
on physical performance.
There are limited scientic data on dairy protein and
sarcopenia available. To the best of our knowledge, this is
the rst review to determine the impact of dairy protein
intake on muscle mass, muscle strength, and physical
performance in middle-aged to older adults with or without
existing sarcopenia. However, the ndings of the review
are limited and the following factors must be considered
when interpreting the results. First, there were dierences
in health status (sarcopenic compared with healthy subjects)
and physical functionality (e.g., frailty and mobility) of the
participants in the included trials at baseline. According to
Alemán-Mateo et al. (26), the responsiveness to the anabolic
stimulus of protein supplementation is likely to be more
eective in healthy subjects than in those with sarcopenia.
Second, the amount, regimen, form of administration (food
compared with supplements), and types of dairy protein used
(e.g., whey, milk-protein concentrate, casein) varied between
the studies (Tab l e 3), which makes it challenging to interpret
the ndings. Third, the baseline dietary protein intake, an
important confounding factor, was only measured in 7 of the
included trials (21,24,25,31–33). Campbell and Leidy (39)
armed that protein supplementation induces a signicant
enhancement in muscle mass and strength in individuals
with a habitual dietary protein intake below the RDA (<0.8
gkg−1d−1), and this was consistent with the results of
Verdjik e t a l . ( 32)andTielandetal.(24). Only Bauer et al.
(21) adjusted for baseline dietary protein intake. This might
have inuenced the precision of the ndings and created bias.
Dairy protein was not the only supplement in all the
trials. Bauer et al. (21), Verreijen et al. (28), and Rondanelli
et al. (22) enriched the dairy protein supplement with
leucineandvitaminD.Dairyprotein,suchasnativewhey,
is naturally a good source of the essential amino acid leucine,
which has been reported to stimulate protein synthesis and
enhance muscle mass and function (40,41). In addition,
vitamin D has been shown to induce a signicant positive
impact on muscle strength in the elderly (42). Therefore,
the absence of adjustment of the postintervention serum 25-
hydroxyvitamin D in addition to the anabolic eect of leucine
could have created an overestimation of the positive eect
of dairy protein in these trials and thus have limited the
accuracy of the ndings.
A further confounding factor is the incorporation of
physical activity in some of the included studies. In Verdjik
FIGURE 5 Forest plot showing results for the meta-analysis of difference in the mean endpoint value of muscle strength for leg press
(kilograms) after the intervention in middle-aged to older adults. IV, inverse variance.
8 Hanach et al.

FIGURE 6 Forest plot showing results for the meta-analysis of difference in mean change from baseline in appendicular muscle mass
(kilograms) after the intervention in middle-aged to older adults. IV, inverse variance.
et al. (32)andChaléetal.(25), the study arms were involved
in resistance training 3 times/wk. The authors reported a
signicant improvement in muscle strength in both groups,
regardless of the consumption of protein supplementation,
which underlines the possible eect of physical activity on
the outcomes.
Overall, 6 trials were of a high quality and had all the key
domains at low risk of bias. The high risk of bias in certain
trials was attributable to the lack of blinding of participants
and/or outcome assessors (20,26,32)andtomissingdataof
the primary outcome (28). Thus, the accuracy of the ndings
of these trials might be limited and should be interpreted with
caution. Although in some studies the allocation was stated to
be randomly generated and concealed, a detailed description
of the methods used was not clearly reported. This has
raised some uncertainty about the results and rendered the
judgment of risk of bias as unclear.
This systematic review has several limitations: 1)broad
inclusion criteria with minimal restrictions on the type
of intervention; 2) the presence of a high degree of het-
erogeneity in the data reporting among the studies; 3)
lack of adjustment for baseline protein intake; 4) lack of
publication bias assessment; 5) lack of postintervention
follow-up to evaluate the long-term eect of dairy protein
supplementation; 6) the relatively small sample sizes, which
inuences the external validity of the trials and restricts
the ndings to be generalized to the entire population; 7)
lack of blinding of participants and outcome assessors and
incomplete data reporting increased the risk of bias in certain
trials (Figure 3) and thus aected the results of the meta-
analysis; 8) only 6 of the included studies were of high
quality; 9) lack of subgroup analysis stratied by gender,
type of protein, and the integration of resistance training;
10) the methodologic diversity between the studies; and 11)
the assessment of muscle mass does not predict the physical
functioning (4).
However,thesystematicreviewandmeta-analysisalsohas
the following strengths: 1) this is the rst systematic review
and meta-analysis to highlight the possible eect of dairy
protein consumption on the outcome variables of sarcopenia,
which could be clinically meaningful for the general popula-
tion; 2) the review was conducted according to the PRISMA
statement (13); 3)allthemeasuringtoolsthatwereused
to assess the outcomes of interest were proved to be valid
and reliable and thus can be applied in clinical and research
settings; 4) the inclusion of a considerable number of studies
in the meta-analysis; 5) despite the diversity in the provided
type of dairy protein, all of the included trials reported a high
adherence and tolerance to the exposure, which conrmed
the safety of protein supplementation; and 6)theassessment
TAB LE 4 Subgroup analyses of mean changes in muscle strength for handgrip and AMM according to subjects’health status, mean age,
and amount of protein consumed1
Changes in handgrip strength, kg Changes in AMM, kg
nEffect (95% CI) PI
2,% nEffect (95% CI) PI
2,%
Health status
With sarcopenia 3 1.62 (−0.94, 4.18) 2 0.17 (0.00, 0.33)
0.26 21.9 0.79 0
Without sarcopenia 4 0.11 (−0.40, 0.62) 6 0.13 (−0.07, 0.33)
Amount of protein
<20 g/d 3 0.74 (−0.95, 2.44) 3 0.30 (−0.57, 0.96)
0.91 0 0.87 0
≥20 g/d 4 0.86 (−0.44, 2.17) 5 0.14 (−0.02, 0.29)
Mean age
>65 y NA 6 0.45 (−0.09, 0.98) 0.20 40.4
≤65 y 2 0.08 (−0.03, 0.20)
1AMM, appendicular muscle mass; NA, not available.
Dairy protein intake and sarcopenia: a review 9

ofhandgripstrength,whichisagoodindicatorofphysical
capability (4).
In conclusion, the ndings of this systematic review and
meta-analysis suggest that dairy proteins, at an amount of 14–
40 g/d, can signicantly increase the AMM in middle-aged
and older adults without a signicant clinical eect on muscle
strength of handgrip and leg press. The eect of dairy protein
on the SPPB was inconclusive due to insucient reported
data. This review highlights the need for larger-scale and
high-quality randomized controlled trials with longer follow-
ups using standardized primary outcomes (muscle mass,
muscle strength, and physical performance) when investigat-
ing the role of dairy protein in the prevention and treatment
ofsarcopenia;toestablishtheoptimaltype,amount,timing,
and frequency of dairy protein supplementation in middle-
aged to older adults; and subsequently, to examine its clinical
eectiveness in the improvement of the primary outcomes of
sarcopenia in middle-aged to older adults.
Acknowledgments
All authors read and approved the nal manuscript.
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