Nutrition and physical activity in the prevention and ... · 37. Nutrition.tw 38. Exp nutrition...
Transcript of Nutrition and physical activity in the prevention and ... · 37. Nutrition.tw 38. Exp nutrition...
REVIEW
Nutrition and physical activity in the prevention and treatmentof sarcopenia: systematic review
C. Beaudart1,2 & A. Dawson1& S. C. Shaw1
& N. C. Harvey1 & J. A. Kanis3,4 & N. Binkley5 &
J. Y. Reginster6 & R. Chapurlat7 & D. C. Chan8,9,10& O. Bruyère6 & R. Rizzoli11 &
C. Cooper1,12 & E. M. Dennison1& the IOF-ESCEO Sarcopenia Working Group
Received: 9 January 2017 /Accepted: 31 January 2017# The Author(s) 2017. This article is published with open access at Springerlink.com
AbstractSummary This systematic review summarizes the effect ofcombined exercise and nutrition intervention on muscle massand muscle function. A total of 37 RCTs were identified.Results indicate that physical exercise has a positive impacton muscle mass and muscle function in subjects aged 65 yearsand older. However, any interactive effect of dietary supple-mentation appears to be limited.Introduction In 2013, Denison et al. conducted a system-atic review including 17 randomized controlled trials(RCTs) to explore the effect of combined exercise andnutrition intervention to improve muscle mass, musclestrength, or physical performance in older people.They concluded that further studies were needed to pro-
vide evidence upon which public health and clinicalrecommendations could be based. The purpose of thepresent work was to update the prior systematic reviewand include studies published up to October 2015.Methods Using the electronic databases MEDLINE andEMBASE, we identified RCTs which assessed the combinedeffect of exercise training and nutritional supplementation onmuscle strength, muscle mass, or physical performance insubjects aged 60 years and over. Study selection and dataextraction were performed by two independent reviewers.Results The search strategy identified 21 additional RCTs giv-ing a total of 37 RCTs. Studies were heterogeneous in terms ofprotocols for physical exercise and dietary supplementation(proteins, essential amino acids, creatine, β-hydroxy-β-
This paper has been endorsed by the Committee of Scientific Advisors ofthe IOF.
* C. [email protected]
1 MRC Lifecourse Epidemiology Unit, University of Southampton,Southampton General Hospital, Southampton SO16 6YD, UK
2 Department of Public Health, Epidemiology and Health Economics,University of Liège, Liège, Belgium
3 Centre for Metabolic Bone Disease, Medical School, University ofSheffield, Sheffield, UK
4 Institute for Health and Aging, Catholic University of Australia,Melbourne, Australia
5 University of Wisconsin Osteoporosis Clinical Center and ResearchProgram, Madison, WI, USA
6 Department of Public Health, Epidemiology and Health Economics,University of Liège, Liège, Belgium
7 INSERM UMR 1033, Université de Lyon, Hôpital E Herriot,Lyon, France
8 Department of Geriatrics and Gerontology, National TaiwanUniversity Hospital, Taipei, Taiwan
9 Department of Internal Medicine, National Taiwan UniversityHospital, Taipei, Taiwan
10 Superintendent’s Office, National Taiwan University HospitalChu-Tong Branch, Hsinchu City, Taiwan
11 Service of Bone Diseases, Geneva University Hospitals and Facultyof Medicine, Geneva, Switzerland
12 NIHR Musculoskeletal Biomedical Research Unit, Institute ofMusculoskeletal Sciences, University of Oxford, Oxford, UK
Osteoporos IntDOI 10.1007/s00198-017-3980-9
methylbuthyrate, vitamin D, multi-nutrients, or other). In 79%of the studies (27/34 RCTs), muscle mass increased with ex-ercise but an additional effect of nutrition was only found in 8RCTs (23.5%). Muscle strength increased in 82.8% of thestudies (29/35 RCTs) following exercise intervention, and di-etary supplementation showed additional benefits in only asmall number of studies (8/35 RCTS, 22.8%). Finally, themajority of studies showed an increase of physical perfor-mance following exercise intervention (26/28 RCTs, 92.8%)but interaction with nutrition supplementation was only foundin 14.3% of these studies (4/28 RCTs).Conclusion Physical exercise has a positive impact on musclemass and muscle function in healthy subjects aged 60 yearsand older. The biggest effect of exercise intervention, of anytype, has been seen on physical performance (gait speed, chairrising test, balance, SPPB test, etc.). We observed huge vari-ations in regard to the dietary supplementation protocols.Based on the included studies, mainly performed on well-nourished subjects, the interactive effect of dietary supple-mentation on muscle function appears limited.
Keywords Dietary . Intervention . Physical activity .
Sarcopenia
Introduction
Sarcopenia has been defined by the European Working Groupon Sarcopenia in Older People as a progressive and general lossof muscle mass and muscle function (defined either by a lowmuscle strength or a low physical performance) with advancingage [1]. Even though the loss of both is a natural part of theaging process, sarcopenia is defined when muscle mass andfunction falls below defined thresholds. Diagnosis of sarcopeniarequires, therefore, the measurement of muscle mass, musclestrength, and physical performance [2]. Sarcopenia is recog-nized as a major public health problem [3, 4] due to significantclinical, economic, and social consequences. The implementa-tion of preventive and therapeutic interventions has become achallenge due to the growing number of older persons affectedby sarcopenia and its disabling complications.
Physical activity and nutritional supplementation havebeen investigated in several interventional studies. Recently,Cruz-Jentoft et al. [5] published a systematic review summa-rizing studies assessing the effect of physical activity and/ordietary supplementation on sarcopenia. Results indicated thatmost exercise trials showed an improvement of musclestrength and physical performance with physical activity, pre-dominantly resistance training interventions. Results wereconsistent regarding the effect of dietary supplementation onmuscle mass. Some studies have suggested a role of proteins,β-hydroxy β-methylbutyric acid, or amino acid on musclefunction. However, the effects of these exercise and dietary
interventions were assessed separately in this particular re-view; little is known about the combined effects of these twointerventions. For this reason, Denison et al. [6] conducted asystematic review in 2013 to determine the effect of combinedexercise and nutrition interventions on muscle mass, strength,and function in older people. That systematic review com-prised 17 studies involving older (≥ 65 years) adults publishedup to April 2013. The authors concluded that further studieswere required to provide adequate evidence on which to basepublic health and clinical recommendations. The purpose ofthe present work was to provide an update to that systematicreview by including studies published up to October 2015,and to focus on whether additional benefits arose if dietarysupplementation was combined with exercise training.
Methods
Literature search
The literature search was performed in accordance with thePreferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Using MEDLINE/Ovid andEMBASE/Ovid, we identified randomized controlled studies(RCTs) which assessed the combined effect of exercise trainingand nutritional supplementation on muscle strength, musclemass, or physical performance. We updated the paper byDenison et al. [6] which limited the search strategy toFebruary 2013. Therefore, we searched for any additional stud-ies published betweenApril 2013 andOctober 2015. The searchstrategy and search terms that were used for this research aredetailed in Table 1. Additional studies were identified by a man-ual search of bibliographic references of relevant articles andexisting reviews. Conference abstracts were not included.
Study selection
In the initial screening stage, two investigators independentlyreviewed the title and abstract for each of these references toexclude articles irrelevant to the systematic review. Rigorousinclusion criteria were adhered to (Table 2). In the second step,the two investigators independently read full texts of the arti-cles not excluded in the initial stage, then selected the studiesmeeting the inclusion criteria (Table 2). All differences ofopinion regarding selection of articles were resolved throughdiscussion and consensus.
In order to maintain consistency between this update andthe previous systematic review, the same inclusion criteriawere used [6]. No age restriction was included in the searchstrategy but this review focused only on subjects aged 60 yearsand older. Studies performed on children, adolescents, andyoung adults were therefore excluded. Studies in which thenutritional intervention was energy restriction to promote
Osteoporos Int
weight loss were also excluded. Finally, studies were alsoexcluded if they included populations with a specific healthcondition (e.g., cirrhosis, cancer, diabetes, chronic kidney dis-ease, etc.).
Data extraction
Data were extracted according to a standardized form to in-clude authors, journal name, year of publication, country, ob-jective of the study, length of intervention, type of population,gender ratio, mean age, age range, detailed groups with sam-ple size, adherence to the treatment, % of participants whocompleted the study, adverse events, protocol of exercise in-tervention, protocol of nutritional intervention, muscle massoutcomes, muscle strength outcomes, and physical perfor-mance outcomes.
Methodology quality assessment
The quality of each study was independently assessed by twoauthors using the Jadad Score [7] system. The Jadad score
Table 1 Search strategy (application to MEDLINE Ovid andEMBASE)
1. Sarcopenia/2. Sarcopeni$.tw3. Muscle atrophy/4. Muscle weakness/5. Fat free mass.tw6. Lean body mass.tw7. Muscle mass.tw8. Exp hand strength/9. Grip strength.tw10. Anthropometry/11. Body composition/12. Lean mass.tw13. Or/1-1214. Exp exercise/15. Exp Movement/16. Muscle contraction/17. Muscle Development/18. Physical exertion/19. Exp Physical endurance/20. Exp muscle strength/21. Physical fitness/22. Exp Exercise test/23. Exercise therapy.tw24. Exp Exercise movement techniques/25. Exp Psychomotor performance/26. Muscle contraction/27. Resistance exercise.tw28. Aerobic exercice.tw29. Endurance.tw30. Physical exercise.tw31. Physical performance.tw32. Physical training.tw33. Exercise programme.tw34. Exercise technique.tw35. Muscle mass.tw36. Or/14-3537. Nutrition.tw38. Exp nutrition therapy/39. Exp Nutritional physiological phenomena/40. Exp Diet/41. Exp Diet therapy/42. Exp Dietary fats/43. Exp Dietary proteins/44. Exp Food/45. Exp Food, fortified/46. Exp Micronutrients/47. Exp Dietary supplements/48. Energy intake/49. Nutrition.tw50. Nutrition trial.tw51. Dietary lipids.tw52. Or/37-5153. Randomized controlled trials/54. Randomised controlled trial.tw55. Randomized controlled trial.tw56. Controlled clinical trial/57. Controlled study.tw58. Random allocation/59. Random$.tw60. Randomly allocated.tw61. Double blind method/62. Single blind method/63. Clinical trials.tw64. Clinical trial/65. Trial$.tw66. Intervention studies/
Table 1 (continued)
67. Intervention study.tw68. Interventional study.tw69. Placebo.tw70. Placebo$.tw71. Or/53-7072. And/36,5273. And/13, 71, 7274. (73 and humans/) or (73 not (humans/ or animals/))75. Limit 74 to English language76. Limit 75 to yr. = B2013-Current^ (344 results on PubMed (308 afterdeleting duplicates)– 859 with Embase (819 after remove duplicates)) –total 992 after remove duplicates between the 2 databases
Table 2 Inclusion criteria
Design Randomized controlled trials
Participants Human, men, and women aged 60 years and older
Exposure Studies which include at least two groups ofcomparison: a control group with only exerciseintervention and a treated group with combinedexercise intervention and nutritional intervention.Exercise intervention can be resistance exercise,aerobic exercise, or other. Nutrition interventioninvolves the provision of nutrients supplied witheither a supplement or food
Outcome Outcomes on muscle mass, on muscle strength,or on physical performance
Language English only
Date Studies published between April 2013 andend of October 2015
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ranges from 0 to 5 points. Studies were considered to be ofexcellent quality if the score was 5, good quality if the scorewas 3 or 4, and poor quality if otherwise.
Presentation of results
The findings were evaluated in a descriptive manner based onthe information provided by each of the included studies.Because of the huge heterogeneity observed in the protocolsof exercise and dietary supplementation, nometa-analysis wasundertaken.
Results
Included studies
A total of 993 references were identified through the databasesearch. A manual search of the bibliography of 10 relevantsystematic reviews and meta-analyses did not generate anyfurther studies for inclusion. After reading all titles and ab-stracts, 36 RCTs were selected for full-text review, followingwhich 21 were included in this systematic review update.These 21 studies, added to the previous 17 considered byDenison et al. [6], gave a total of 37 RCTs included in thecurrent systematic review (Fig. 1).
Characteristics of the studies are shown in Table 3. Twelvestudies were performed in Europe, 11 in the USA/Canada, 7 inAsia, 4 in South America, and 3 in Australia. The number ofparticipants ranged from 17 [35] to 222 [26] and study dura-tion ranged from 4 weeks [27] to 18 months [42, 43]. Themajority of studies included both male and female participantsbut 10 studies were confined to women only and 5 includedonly men. The mean age of participants varied from59.5 ± 4.5 years [9, 10] to 87.1 ± 0.6 years [39, 40]. TwelveRCTs were graded on the Jadad Scale as having an excellentquality, 15 a good quality, and 10 a poor quality.
Twenty-two studies used a two-group comparison method-ology: one group receiving exercise + nutrition and the othergroup receiving exercise only (with placebo or no interven-tion). Eleven other studies used a four-group comparisonmodel with one control group with no intervention, one groupwith exercise only, one group with nutrition only and finally,one group with combined exercise and nutrition interventions.Three other studies chose to randomize their population intothree groups comprising a control group with no intervention,a group with exercise only, and a group with exercise com-binedwith nutrition. Finally, one study used a five-group com-parison model that included two groups with exercise andnutrition interventions, but used a different nutritional supple-ment in each of these two groups. For this systematic review,we used only results from two groups, one receiving exercise +
nutrition and one receiving exercise only. It has to be notedthat only half of the studies were double blinded.
Regarding nutritional interventions, 10 of the 37 studiesused proteins. One further study used protein combined withessential amino acids, a second used protein combined withvitamin D, and a third used protein combined with creatine.Three studies used essential amino acids alone, five studiesused creatine alone, three studies used β-hydroxy-β-methylbutyrate alone, and two used vitamin D alone. Of theremaining 12 studies, five used multi-nutrient supplementsand six used other products (vitamin and mineral-enhanceddairy and fruit products, green tea, magnesium oxide, milkfat globule membrane, soy isoflavones, and tea catechin).For exercise, the majority of studies used resistance trainingwith the remainder using multicomponent training involvingboth resistance and additional exercises such as walking, fit-ness, aerobics, balance, etc.
Types of nutritional intervention
Results of the interventions are summarized in Table 4.
Fig. 1 Flow chart of literature search
Osteoporos Int
Protein supplementation
Thirteen individual studies assessed the impact of a combinedprotein supplement and exercise intervention on the musclefunction of elderly people. Most of these studies were of goodquality but four were of poor quality [12, 24, 26, 29]. Inthree of the 13 studies, protein was combined with creatine[12], essential amino acids [24], or vitamin D [26].Supplementation protocols were heterogeneous in terms ofstudied population, duration of study, and supplementationdose, which varied from 7.4 to 45 g of protein per day.Twelve studies assessed the effect of the interventions onmus-cle mass and/or muscle strength but only nine reported resultson physical performance.
Muscle mass: Muscle mass increased significantly withexercise in 11 of the 12 included RCTs. An interactive effectof protein supplementation and exercise was reported in onlythree of these studies: one looked at frail individuals [33], asecond has been performed in elderly sarcopenic men [25],and the third enrolled female retirement village residentswhose protein supplementation was lean red meat [22]. Oneother study [8] reported an increase of fat-free mass and ap-pendicular lean mass only in the group supplemented withprotein and exercise but the difference between the groupswas not described.Muscle strength: All studies showed a sig-nificant improvement of leg muscle strength with exercise. Noadditional effect of protein was seen in the majority of thesestudies with the exception of three studies, each one of excel-lent quality: Daly et al. [22] showed significant improvementin leg extension in the group receiving lean red meat (45 g ofprotein/day) and exercise compared to an exercise-only groupand Chalé et al. [17], who showed greater improvement inknee extensor peak power after a supplementation of 40 g ofprotein/day and, finally, Zdzieblik et al. [25] reported thatquadriceps strength of the right leg (effect on the left leg wasnot assessed) increased more in the group taking 15 g of col-lagen peptide as supplement/day. Improvement in handgripstrength was seen in one study [33] but was absent in threeothers [20, 24, 29]. Finally, one study [8] reported an increaseof the 1 repetitionmaximum (1RM) knee extensors only in thegroup with protein combined with exercise; however, the dif-ference between the two groups was not reported. Physicalperformance: All studies showed a significant improvementof at least one physical performance test with exercise. Nostudies showed a significant difference between the groupsreceiving exercise only compared to the group receiving ex-ercise combined with protein.
Summary: Muscle mass increased with exercises in 11/12RCTs but an additional effect of protein was found in only 3/12 RCTs; Muscle strength increased with exercises in 12/12RCTs but an additional effect of protein was found in only 3/12 RCTs; Physical performance increased with exercise, for at
least one outcome, in 9/9 RCTs with no additional effect ofprotein.
Essential amino acids supplementation
Three studies used essential amino acids (EAA) supplemen-tation, 6 g/day for 3 months in sarcopenic community-dwelling older women [36], 10 g/day for 4 weeks in olderadults recruited from nursing homes and adult day-carecenters [27], and 12 g/day for 12 weeks in older men[35]. One study was of poor quality [35]. All three assessedthe effect of intervention on muscle mass and musclestrength and two also measured the effect on physical per-formance [27, 36].
Muscle mass: Two studies reported an increase of musclemass with exercise but did not report any difference betweenthe group receiving EAA supplements and the group who didnot [35, 36]. The third study did not report any increase ofmuscle mass, neither for subjects receiving exercises only, norin the groups of subjects receiving a combination of exerciseand EAA supplements [27].Muscle strength: Knee extensionincreased with exercise in two studies but no interaction wasfound with EAA supplementation. In the third study, no effecton isometric leg strength was observed [27]. Physicalperformance: Walking speed [36] and timed up and go [27]tests improved with exercise with no additional effect of EAAsupplements. Standing balance and chair-stand test did notimprove with treatment [27].
Summary: Muscle mass and muscle strength increasedwith exercise in 2/3 RCTs with no additional effect of EAA;Physical performance (walking speed and SPPB test only)increased with exercise in 2/2 RCTs with no additional effectof EAA.
β-hydroxy-β-methylbutyrate (HMB) supplementation
Three studies of good quality used Ca-HMB [13, 16, 37] asa dietary supplement. In all studies, the treated group re-ceived 3 g of Ca-HMB per day. The study duration varied:24 weeks [13], 12 weeks [37], and 8 weeks [16].Participants were healthy ambulatory older adults in thefirst two studies [13, 37] and healthy adults confined tocomplete bed rest for 10 days for the latter [16]. All studiesassessed the effect on muscle mass and muscle strength butonly two assessed the effect of treatment on physical per-formance [13, 16].
Muscle mass: Effects of Ca-HMB supplementation on mus-cle mass were not consistent across the three studies. Fat-freemass significantly increased with exercise in one study but nodifference was evident between the group with combined exer-cise + Ca-HMB and the group with exercise only [13].Moreover, a significantly greater increase in fat-free mass was
Osteoporos Int
Tab
le3
Characteristicsof
included
studies
Reference
Settin
gs,study
participants,
meanage±SD
Studydesign
Exercisetraining
interventio
nNutritio
nalsupplem
ent
Outcomemeasures
Qualityscore
(Jadad
scale)
Grysonet
al.2014[8]
France.35
healthysedentarymen
60.7
±0.4years
16-w
eekintervention.
Participants
random
ized
in5groups:(i)no
exercise
+placebo,(ii)exercise
+placebo,(iii)
exercise
+fortified
milk,(iv)no
exercise
+fortified
leucine,(v)exercise
+fortified
leucine.Treatmentswere
administrated
doubleblind
Resistanceandaerobicexercises.3
sessions
perweek,non-consecutive
days,45–60
min
foreach
session
Protein.M
ilk-based
supplement
drinks
containing,proteins(total
milk
proteins
10g/dayor
fast
digested
solublemilk
proteins
10g/day),carbohydrates,and
fat.
Placebo
drinks
contains
4gof
totalm
ilkprotein
MM:appendicularmusclemassand
fat-free
massin
thedominant
legM
S:isom
etricstrength
ofthe
knee
extensors
4
Lebon
etal.2014,[9]
Choquetteet
al.2013
[10]
Canada.34
postmenopausal
wom
en59.5
±4.5years
6-month
intervention.Participants
random
ized
intwogroups:(i)
exercise
andisoflavone,(ii)
exercise
andplacebo.Treatmentswere
administereddoubleblind
Com
binedaerobicandresistance
training,3
sessions
perweek(1
h,30
min
ofaerobic,30
min
ofresistance)
Other
(soy
isoflavones).4
capsules
daily
with
either
soyisoflavones
orplacebo.The
70-m
gdaily
dose
ofisoflavonescontained44
mgof
daidzein,16mgof
glycitein,and
10mgof
genisteinextractedfrom
naturalsoy.P
laceboscontained
cellu
lose
MM:w
aistandhipcircum
ference,
musclemassindexM
S:grip
strength,1RM
(leg
press,bench
press,latp
ulldow
n)PP
:chair
standtest
5
Gualano
etal.2014[11]
Brazil.60
vulnerableolder
wom
en.T
reated
67.1
±5.6years/control
63.6
±3.6years
24-w
eekintervention.Participantswere
random
ized
infour
groups:(i)
placebo,(ii)creatin
e,(iii)
placebo+
exercise,(iv)creatine+exercise.
Treatmentswereadministereddouble
blind
Supervised
resistance
training.T
wo
sessions
perweek
Creatine.Su
pplementspackages
20g/dayof
creatinemonohydrate
for5days
dividedinto
four
equal
doses,followed
bysingledaily
dosesof
5gforthenext
23weeks.P
lacebo
was
dextrose
MM:appendicularleanmassMS:leg
press,benchpressPP:
timed-standstests.,T
imed
upand
gotest
4
Villanueva
etal.2014
[12]
USA.22healthymen,
recreationally
active
68.1
±6.1years
12-w
eekintervention.Participantswere
random
ized
inthreegroups:(i)exer-
cise
+creatineandprotein
supplementation,(ii)exercise
only,
(iii)
control.Treatmentadm
inistration
was
notd
oubleblinded
Resistancetraining.3
sessions
perweek
Protein
+creatine.Su
pplemented
group(encapsulatedpowder)
consum
ed0.3g/kg/day
ofcreatin
efor5days
followed
by0.07
g/kg/day
until
completionof
thestudy.The
supplemented
groupalso
consum
edone35-g
liquidproteinready-to-drink
daily
MM:leanbody
massM
S:leg
press,
chestp
ress,strengthendurance.
PP:stairclim
bing
power,
dynamicpower,400-m
walk
2
Stoutetal.2013[13]
USA.48am
bulatory
participants
(22men
and26
wom
en)
73±1years
24-w
eekintervention.Participantswere
random
ized
intwogroups:(i)
exercise
+placebo,(ii)exercise
+HMB.T
reatmentswereadministered
doubleblind
Supervised
resistance
training.T
hree
sessions
perweek
β-hydroxy-β-m
ethylbuthyrate.CaH
-MB(H
MB,1,5
gCaH
MB+4g
carbohydrate)twicedaily.
Placebo
(200
mgcalcium
+4g
carbohydrates)twice
daily.Participantswereaskedto
mixtheirp
roductinnon-alcoholic
beveragesanddrinkit
MM:totallean
mass,reginalleg
lean
mass,regionalarm
lean
massM
S:handgrip
strength,leg
extension,
benchpress,legpress,leg
extensionstrength.PP:G
etup
and
Go
5
Okazaki
etal.2013[14]
Japan.35
healthymiddle-aged
andolderwom
en.T
reated
60±3years/control
61±3years
5-month
intervention.Participantswere
random
ized
intwogroups:(i)
exercise
only,(ii)
exercise
+post-exercisemacronutrient.
Treatmentadm
inistrationwas
not
doubleblinded
Hom
e-basedintervalwalking
training.4
ormoredays
perweek
Multi-nutrient
(macrunutrient
mixture).215gof
amacronutrient
mixture
within
30min
aftereach
training
session
(com
position200kcal;7
,6g
protein;3
2,5gCHO;4
,4gfat)
MM:totalmuscletissueareaMS:
isom
etricknee
extension,
isom
etricknee
flexion,isokinetic
knee
extension,isokineticknee
flexion
2
Narotzkietal.2013[15]
Israel.13elderlymen
and9
elderlywom
en.
71.1
±1.2years
12-w
eekintervention.Participantswere
random
ized
intwogroups:(i)
exercise
+greenteaandvitamin
E,
(ii)exercise
+vitamin
Eonly.
Treatmentadm
inistrationwas
not
doubleblinded
Fitness-guided
exercises.6tim
esaweek.
30min
ofdaily
walks
Other
(green
tea).P
articipantswere
askedtobrew
teasachets3tim
esa
dayin240mlofb
oilingwaterfor
3min.O
nevitamin
Ecapsule
composedof
400IU
ofd-alpha-tocopheroladay.Placebo
groupdidnotd
rink
teaand
consum
edacapsuleof
vitamin
Eplaceboaday
MM:w
aistandhipcircum
ference
2
Osteoporos Int
Tab
le3
(contin
ued)
Reference
Settin
gs,study
participants,
meanage±SD
Studydesign
Exercisetraining
interventio
nNutritio
nalsupplem
ent
Outcomemeasures
Qualityscore
(Jadad
scale)
Deutzet
al.2013[16]
USA.24olderadultsconfined
tocompletebedrestfor10
days.
Treated
67.4
±1.4years/control
67.1
±1.7years
8-weekinterventio
n.Participantswere
random
ized
intwogroups:(i)
exercise
+HMB,(ii)
exercise
+placebo.Treatmentswere
administereddoubleblind.Testswere
performed
beforebedrest,afterbed
rest,and
afterthe8weeks
ofrehabilitation
Resistanceexercise
training
rehabilitation.3days
perweek.
Strength
training
during
1h
β-hydroxy-β-m
ethylbuthyrate.2
sachetsof
Ca-HMBperd
ay.E
ach
sachetcontained1.5gof
Ca-HMB,4
gmaltodextrin,and
200mgcalcium.T
hecompositionof
placebowas
identicalwith
theexclusionof
Ca-HMB
MM:leanbody
massM
S:knee
extension,flexor
force,legpress,
standing
plantarflexor
force,and
stairascent
anddescentp
ower.
PP:SPPB
test,G
etup
andGotest,
5-item
SPPB
5
Chaléet
al.2013[17]
USA.80mobility-lim
itedwom
enaged
70–85years.Treated
78.0
±4.0years/control
77.3
±3.9years
6-month
intervention.Participants
random
ized
intwogroups:(i)
exerciseandproteins,(ii)
exerciseand
isocaloriccontrol.Treatmentswere
administereddoubleblind
Supervised
progressiveprogram.3
times
perweekwhich
entailedlegpress,
seated
row,leg
extension,chestp
ress
andlegcurl
Protein(w
heyprotein).W
heyprotein
inpowderform
40g/day(one
servingcontains
20gprotein,
25gmaltodextrin,1gfat,
189kcal)Isocaloriccontrolin
powderform
(45gmaltodextrin,
1gfat,189kcal)
MM:leanmass,totalm
uscle
CSA
MS:
Leg
press,knee
extensionstrength,peakpower
PP:S
tairclim
bing,chairrise
performance,S
PPBtest,400
mwalktim
e
5
Kim
etal.2013[18]
Japan.128community-dwelling
elderlysarcopenicwom
enTreated
81.1
±3.7years
/control
79.6
±4.2years
3-month
intervention.Participantswere
random
ized
infour
groups:(i)
exercise
andteacatechin,(ii)
exercise
only,(iii)tea
catechinonly,(iv)h
ealth
education,control.Treatmentswere
administereddoubleblind
Stretching,m
usclestrengthening,
balanceandgaittraining.T
wo
sessions
perweek.Eachsession
60mins
Other
(tea
catechin).One
bottleper
daycontaining
350mLof
tea
fortifiedwith
540mgof
catechin
MM:leanbody
mass,appendicular
lean
massandlegmusclemass
MS:gripstrength,kneeextension
strength
PP:u
sualandmaxim
umwalking
speed,TUG,balance
ability
4
Aguiaret
al.2013[19]
Brazil.18
healthywom
en64.9
±5.0years
12-w
eekintervention.Participantswere
random
ized
intwogroups:(i)
exercise
+creatin
e,(ii)exercise
+placebo.Treatmentswere
administereddoubleblind
Resistancetraining.T
hree
sessions
per
week.The
training
volumewas
progressivethroughout
thetraining
program
Creatine.One
capsule(5.0
g/day).
The
placebogroupingested
anidentical-looking
equivalent
amount
ofplacebo,maltodextrin
MM:appendicularmusclemassMS:
benchpress,knee
extension,
biceps
curlstrengthPP:
30-schair
standandarm
curltestandatest
ofgetting
upfrom
lyingon
the
floor
4
Leenderset
al.2014[20]
The
Netherlands.29healthy
e lderlymen
and24
healthy
elderlywom
en70
±1years
24-w
eekintervention.Participantswere
random
ized
intwogroups:(i)
exercise
+placebo,(ii)exercise
+protein.Treatmentswere
administereddoubleblind
Supervised
resistance
training.T
hree
sessions
perweek
Protein.250
mlb
everages
perday.
Protein
beveragescontains
15g
ofprotein,0.5gfat,7.13
glactose,0.42
gcalcium.P
lacebo
beveragescontainno
proteinor
fat,7.13
glactose,0.42
gcalcium
MM:totalbody
lean
mass,leglean
mass,quadriceps
CSA
MS:
leg
press,legextension,
handgrip
testPP
:sit-to-stand
test
3
Veroneseet
al.2014[21]
Italy.139healthyelderlywom
en.
71.5
±5.2years
12-w
eekintervention.Participantswere
random
ized
intwogroups:(i)
exercise
+magnesium
oxide,(ii)
exercise
only.T
reatment
administrationwas
notd
ouble
blinded
Mild
fitnessprogram.T
wosessions
per
week
Other
(magnesium
oxide)sachets.
900mg/dof
oralmagnesium
oxidecorrespondingto
300mg
bioavailablemagnesium
MM:appendicularskeletalmuscle
massindexM
S:isom
etricknee
extension,handgrip
strength
PP:
SPPB
test
3
Dalyet
al.2014[22]
Australia.100
wom
enresiding
inretirem
entv
illages.T
reated
72.1
±6.4years/control
73.6
±7.7years
4-month
intervention.Participantswere
random
ized
intwogroups:(i)
exercise
+meat,(ii)exercise
only.
Treatmentadm
inistrationwas
not
doubleblinded
Supervised
progressiveresistance
and
balance-agility
training
program.2
sessions
perweek
Protein
(leanredmeat).220
glean
redmeattobe
consum
ed6days/week=160gcooked
meat/day
(45gprotein).C
ontrol
75gcooked
rice
and/or
pasta/day
(thatp
rovides25–35
carbohydrates/day)
MM:leantissuemassMS:
leg
extensionP
P:4-squarestep
test,
Tim
edUpandGo,30-s
sit-to-stand
test
5
Cooke
etal.2014[23]
Australia.20middleto
older
males
Treated
61.4
±5.0years/control
60.7
±5.4years
12-w
eekintervention.Participantswere
random
ized
intwogroups:(i)
exercise
+CHO,(ii)
exercise
only.
Treatmentswereadministereddouble
blind
High-intensity
resistance
training
program.3
days
perweek
Creatine
monohydrate-carbohydrates.
Treated
group20
gof
CrM
combinedwith
5gof
glucosefor
7days
follo
wed
by0.1gkg
−1
(average
dosage
of∼8
.8g)
ofCrM
with
5gof
glucoseon
MM:fat-freemassMS:leg
press,
benchpress
4
Osteoporos Int
Tab
le3
(contin
ued)
Reference
Settin
gs,study
participants,
meanage±SD
Studydesign
Exercisetraining
interventio
nNutritio
nalsupplem
ent
Outcomemeasures
Qualityscore
(Jadad
scale)
training
days.P
lacebo
20gof
glucoseonly
for7days
followed
by5gof
glucoseon
training
days
Oesen
etal.2015[24]
Italy.82
olderadultsliv
ingin
retirem
entcarefacilities
82.8
±6.0years
6-month
intervention.Participantswere
random
ized
inthreegroups:(i)
exercise
only,(ii)
exercise
+nutrient
supplementation,
(iii)
cognitive
training
group.Treatment
administrationwas
notd
ouble
blinded
Supervised
resistance
exercise
with
elastic
band.T
wosessions
perweeks
onnon-consecutivedays
(separately
min
48h)
Protein
andessentialaminoacids.
Twonutrient
supplementd
rink
perday.Eachdrinkhadacaloric
valueof
150kcal,20.7gprotein
(3gleucine,>10
gessential
aminoacids),9.3
gcarbohydrates,3gfat,vitamins
andminerals
MS:kneeextensor
peak
torque,knee
flexor
peak
torque,handgrip
strengthPP
:chairstandtest,gait
speed,six-minutewalking
test,
functio
nalreach
test,arm
liftin
gtest
2
Zdzieblik
etal.2015[25]
Germany.53
elderlymen
with
sarcopenia.72.2±4.68
12-w
eekintervention.Participantswere
random
ized
intwogroups:(i)
exercise
+collagenpeptide,(ii)
exercise
+placebo.Treatmentswere
administereddoubleblind
Guidedtraining
program
onfitness
devices.Three
sessions
aweekovera
period
of60
min
Protein
(collagenpeptide).Treated
groupreceived
15gof
collagen
peptides
each
day.Placebo
group
received
silicon
dioxideas
placebo.Bothweregivenin
powderto
dissolve
in250mlo
fwater.
MM:fat-freemassMS:isokinetic
quadriceps
strength
oftheright
leg
5
Yam
adaet
al.2015[26]
Japan.222community-dwelling
olderadults(142
wom
enand
80men).Treated
76.3
±5.9years/control
75.8
±5.2years
6-month
intervention.Participantswere
random
ized
inthreegroups:(i)
walking
andnutrition,(ii)
walking
only,(iii)control.Treatment
administrationwas
notd
ouble
blinded
Walking
program.U
seof
pedometer-based
walking
programs.
Participantswereinstructed
toincrease
thenumberof
daily
stepsby
10%
each
month
Protein
andvitamin
D.D
aily
supplementscomposedof
200kcal,10.0gof
proteinwith
branched
chainam
inoacids
12.5
mgof
vitamin
D,and
300mgof
calcium
MM:skeletalm
uscleindex
2
Trabaletal.2015[27]
Spain.24olderadultsin
nursing
homes
andadultd
aycare
centers(16wom
enand8
men).Treated
85±8years/control
84±4years
4-weekinterventio
n.Participantswere
random
ized
intwogroups:(i)
exercise
andleucine,(ii)exercise
only.T
reatmentswereadministered
doubleblind
Resistancetraining.T
hree
sessions
ofprogressiveresistance
training
adaptedforolderadultsandone
sessionof
balanceexercise
perweek
Essentialaminoacid
(leucine).
Leucine
10g/dayor
thesame
amount
ofmaltodextrinas
placebo.Bothsupplementsand
placebowereaccompanied
with
alemon
andlim
eflavor
todisguise
thecharacteristictasteof
leucine
MM:calfcircum
ference,waist
circum
ference.MS:
maxim
alisom
etriclegstrength.P
P:
standing
balance,4m
walk,chair
stands
testandTUGtest
5
Ki m
etal.2015[28]
Japan.130community-dwelling
frailw
omen.T
reated
81.0
±2.6years/control
81.1
±2.8years
3-month
intervention.Participantswere
random
ized
infour
groups:(i)
exercise
andmilk
fatg
lobule
mem
brane,(ii)exercise
only,(iii)
milk
fatg
lobulemem
braneonly,(iv)
health
education,control.Treatments
wereadministereddoubleblind
Physicalcomprehensive
training
program
ofmoderateintensity.E
ach
classwas
60min,twiceperweek
Other
(milk
fatg
lobulemem
brane).
The
compositionwas
21.5%
protein,44%
fat,26.5%
carbohydrate,33.3%
phospholipids,6.4%
ash,and
1.6%
moisture.Six
pills
(1gof
MFG
M)ingested
daily.T
heplaceboconsistedof
pills
ofsimilarshape,taste,andtexture
andincluded
milk
powderinstead
ofMFG
M.M
ilkpowderwas
composedof
26.3%
protein,
25.2%fat,39.5%
carbohydrate,
0.286phospholipids,5.7%
ash,
and3,3%
moisture
MM:appendicularmusclemass,leg
musclemassMS:g
ripstrength,
knee
extensionPP
:usualwalking
speed,tim
edup
andgo
5
Shahar
etal.2013[29]
Malaysia.65
elderlieswith
sarcopenia(18wom
enand47
men).67.1
±5.3years
12-w
eekintervention.Participantswere
random
ized
infour
groups:(i)control
group,(ii)exercise
group,(iii)
protein
supplementation,(iv)
exercise
+proteinsupplementation.Treatment
administrationwas
notd
ouble
blinded
Moderatelyintensive,well-roundedac-
tivities
infacilitated
groupsessions.
During60
min,twosessions
per
week
Protein
(soy
protein).20g/dayand
40g/dayof
high
protein
supplementationinapowderform
tomen
andwom
en,respectively.
Control
groupdidnotreceived
placebobuta
relaxatio
nexercise
MM:totalmusclemassandfat-free
massMS:h
andgripstrength,arm
curltestPP
:chairstandtest,chair
sitand
reach,back
scratch,8-ft
andgo,6-m
inwalk
1
Osteoporos Int
Tab
le3
(contin
ued)
Reference
Settin
gs,study
participants,
meanage±SD
Studydesign
Exercisetraining
interventio
nNutritio
nalsupplem
ent
Outcomemeasures
Qualityscore
(Jadad
scale)
program
tomaintaininteraction
andincrease
motivation
Arnarsonet
al.2013[30]
Iceland.161healthy
community-dwellingmen
and
wom
en.(94
wom
enand67
men)Treated
73.3
±6.0/control:
74.6
±5.5,8
12-w
eekintervention.Participantswere
random
ized
intwogroups:(i)
exercise
+wheyproteinsupplement
or(ii)exercise
only.T
reatment
administrationwas
notd
ouble
blinded
Resistanceexercise
program.
Participantsexercisedthreetim
esper
week
Protein
(wheyprotein).D
rink
(250
mL)providing20
gprotein,
20gcarbohydrate,1
gfat
(169
kcal)(intervention)
oriso-
caloricdrinkcontaining
40g
carbohydrate,1
gfat(control)
consum
edim
mediately
afterex-
ercise
MM:leanbody
mass,appendicular
lean
massMS:
quadriceps
muscle
strength
PP:tim
edup
andgo;
6-min
walkfordistance
5
Rosendahl
etal.[31]
2006,C
arlssonet
al.
2011
[32]
Sweden.191
oldermen
and
wom
enin
residentialcare.
(139
wom
enand52
men)
84.7
±6.5years
3-month
intervention.Participants
random
ized
tofour
groups:(i)
protein-enriched
drink,control
activ
ity,(ii)
exercise
training
+placebodrink,(iii)
protein-enriched
drink
+exercise
training,or(iv)
neith
er(control
activity,placebo
drink).T
reatmentadm
inistrationwas
notd
oubleblinded
High-intensity
multicom
ponent
exercise
program,including
resistance
exercise
training
andbalance
exercises.Participantsexercisedfive
times
perfortnight
Protein
(milk
-based
protein-enriched
drink).D
rink
(200
mL),provid-
ing7.4gprotein,15.7
gcarbohydrate,408
kJper100g.
Placebo
drink(200
mL)
contained0.2gprotein,10.8
gcarbohydrate,191
kJper100g.
Drinksofferedwithin
5min
ofexercise
session
MM:totallean
massM
S:lower-lim
bmusclestrengthPP
:balance
(Berg
Balance
Scale),gaitability(2.4
mtim
edtest)
3
Tieland
etal.2012[33]
The
Netherlands.20frailo
lder
men
and41
frailolderwom
enTreated
78±9years/control:
79±6years
24-w
eekintervention.
Participants
random
ized
intwogroups:(i)
exercise
+proteinsupplementation
or(ii)exercise
+placebodrink.
Treatmentswereadministereddouble
blind
Resistance-type
exercise
training.
Participantsexercisedtwiceperweek
Protein.P
rotein-supplem
enteddrink
(250
mL),(15gprotein,7.1g
lactose,0.4gcalcium)and
placebodrink(noprotein,7.1g
lactose,0.4gcalcium)consum
edtwiceperday
MM:leanmassMS:
legpress,leg
extension,handgripPP
:SPP
Btest
5
Verdijk
etal.2009[34]
The
Netherlands.28healthy
oldermen,living
independently
72±2years
12-w
eekintervention.Participantswere
random
ized
intwogroups:(i)
exercise
+proteinor
(ii)exercise
+water.T
reatmentswereadministered
doubleblind
Resistance-type
exercise
training.
Participantsexercisedthreetim
esper
weekin
themorning,atsam
etim
eof
day
Protein.P
rotein
drink(10gcasein
hydrolysate,250mL)or
placebo
drink(250
mLwater)given
immediatelybeforeandfollo
wing
exercise
sessions
MM:leanmass,leglean
mass,
cross-sectionalareaof
quadriceps
MS:leg
press,legextension
3
Godardet
al.2002[35]
USA.17oldermen
Treated
70.8
±1.5/control7
2.1±1.9
12-w
eekintervention.Participantswere
random
ized
intwogroups:(i)
exercise
+EAAor
(ii)exercise
with
nodietarysupplementation(control).
Treatmentadm
inistrationwas
not
doubleblinded
Progressiveknee
extensor
resistance
training
program.P
articipants
exercisedthreetim
esperweek
Essentialaminoacids.Amino
acid-containingdrink(400
mL)
providing12
gessentialamino
acids,72
gfructose
anddextrose;
consum
edim
mediately
after
training
oratsametim
eeach
day
MM:w
holemusclecross-sectional
area
ofrightthigh
MS:knee
extension
1
Kim
etal.2012[36]
Japan.155sarcopenic,
community-dwellingolder
wom
enTreated
79.5
±2.9years/control
79,2
±2,8
3-month
intervention.Participants
random
ized
tofour
groups:(i)EAA,
(ii)exercise
training,(iii)
supplementation+exercise
oriv)
health
education(oncepermonth).
Treatmentadm
inistrationwas
not
doubleblinded
Multicom
ponent
exercise
program
includingresistance
exercise
training.
Participantsexercisedtwiceperweek
Essentialaminoacids.Pow
dered
aminoacid
supplementsprovided
tobe
takentwicedaily
with
water
ormilk,supplying
6gessential
aminoacidsperday
MM:totalmusclemassMS:
knee
extension.PP
:usualand
maxim
umwalking
speed
3
Vukovichet
al.2001[37]
USA.15healthyoldermen
and16healthyolderwom
en70
±1years
8-weekinterventio
n.Participantswere
random
ized
intwogroups:(i)
HMB+exercise
or(ii)aplacebo
supplement+exercise.T
reatments
wereadministereddouble-blind
Multicom
ponent
exercise
training
includingresistance
exercises.
Participantsexercised5days
per
week(2
days
strength
training,
3days
walking
andstretching)
β-hydroxy-β-m
ethylbuthyrate.
Supplem
entcapsulescontained
250mgCa-HMB;p
articipants
consum
edfour
capsules,three
times
perday(3
g/day).P
lacebo
capsules
wereidenticalin
appearance,providing
3g/day
rice
flour
MM:fat-freemass,musclearea.M
S:upperandlower
body
strength
4
Bonnefoyet
al.2003[38]
9-month
intervention.Participants
random
ized
tofour
groups:(i)
Multicom
ponent
exercise
training
includingresistance
exercises.
Multi-nutrient.N
utritionald
rinks
(200
mL)(providing
200kcal,
MM:fat-freemassMS:explosive
leg
extension(pow
er).PP
:gaitspeed,
3
Osteoporos Int
Tab
le3
(contin
ued)
Reference
Settin
gs,study
participants,
meanage±SD
Studydesign
Exercisetraining
interventio
nNutritio
nalsupplem
ent
Outcomemeasures
Qualityscore
(Jadad
scale)
France.57
frailresidentin
retirem
enth
omes
(50wom
enand7men)83
years
nutritionaldrink+controlactivity
(mem
ory),(ii)
exercise
training
+placebodrink,(iii)
nutritional
drink+exercise
training,or(iv)
controlactivity
+placebodrink.
Treatmentadm
inistrationwas
not
doubleblinded
Participantsexercisedthreetim
esper
week.Three
weeklymem
orysessions
served
ascontrolsforexercise
15gprotein,vitaminsand
minerals)or
placebo(providing
nonutrients)giventwicedaily
six-step
stairclim
b,chairrise,
balanceabnorm
alities
Fiataroneet
al.1994,[39]
Fiataroneet
al.1993
[40]
USA.100
frailn
ursing
home
residents,37
men
and63
wom
en87.1
±0.6years
10-w
eekintervention.
Participants
random
ized
tofour
groups:(i)
multi-nutrient
supplementation,(ii)
exercise
training,(iii)
supplementation+exercise
oriv)
neith
er(control).Treatment
administrationwas
notd
ouble
blinded
Progressiveresistance
exercise
training
ofhipandknee
extensors.
Participantsexercised3days
per
week.Other
participantsoffered
alternativerecreationalactivities
Multi-nutrient.N
utritional
supplementp
rovidedas
adaily
drink(240
mL),supplying
360kcal,15gproteinand
vitaminsandminerals.
Participantswho
werenot
supplementedweregivena
minim
allynutritive
drinkof
equal
volume(4
kcal)
MM:thigh
musclearea,fat-freemass
MS:g
ripstrength,hip
andknee
extensorsPP:
gaitspeed,stair
clim
b,balance
2
Miller
etal.2006[41]
Australia.79olderwom
enand
21oldermen
hospitalized
followingafall-related
lower-lim
bfracture
83.5
(82.3–84.7)years
12-w
eekintervention.
Participants
random
ized
tofour
groups:(i)
nutritionalsupplementation,(ii)
exercise
training,(iii)
supplementation+exercise
oriv)
attentioncontrol(homevisitsonly,
generalnutritio
nandexerciseadvice).
Treatmentadm
inistrationwas
not
doubleblinded
Progressiveresistance
exercise
training
program.P
articipantsexercisedthree
times
perweek
Multi-nutrient.C
ompleteoral
nutritionalsupplementp
rescribed
toprovide45%
ofindividually
estim
ated
energy
requirem
ent,
administeredin
four
daily
doses
whilehospitalized
ortwodoses
afterdischargehome
MS:q
uadricepsstrength
PP:g
ait
speed
3
Bunoutetal.2
001,[42]
Bunoutetal.2004
[43]
Chile.108
community-dwelling
poorolderpeople(42men
and
66wom
en).Treated
73.7
±3.0/control7
4.4±3.3
18-m
onth
intervention.Evaluationat12
and18
months.Participantswere
random
ized
intwogroups:(i)
exercise
+nutritional
supplementationor
(ii)exercise
but
nodietarysupplementation.
Treatmentadm
inistrationwas
not
doubleblinded
Resistanceexercise.P
articipants
exercisedtwiceperweek
Multi-nutrient.N
utritionalp
roduct
(preparedas
asoup
orporridge,
givenas
twodaily
snacks),to
provide400kcal,13gprotein,
∼25%
daily
requirem
entsfor
micronutrients
MM:fat-freemassMS:h
andgrip,
quadriceps,bicepsstrength
PP:
walking
capacity
(m)
1
ChinAPawet
al.2001
[44],D
eJong
etal.
2000
[45]
The
Netherlands.217
frail
community-dwellingolder
men
andwom
en(45men
and
172wom
en).Treated
78.9
±6.0/control7
6.2±4.5
17-w
eekintervention.
Participants
random
ized
tofour
groups:(i)
supplementation,(ii)exercise
training,(iii)supplementation+
exercise
oriv)neither
(control).The
nutritionalinterventionwas
double-blin
ded
Multicom
ponent
exercise
training
(gradually
increasing
intensity).
Participantsexercisedtwiceperweek
Other
(vitaminsandminerals).
Supplem
entedgroupaskedto
consum
eonefruitand
onedairy
productenrichedwith
vitamins
andmineralsperday.Other
participantsreceived
same
productsthatwerenotenriched
MM:leanbody
mass,waist
circum
ference,hipcircum
ference
MS:h
andgrip,quadriceps
strengthPP:
gaitspeed,chairrise,
balance,flexibility
4
Binderet
al.1995[46]
USA.25nursinghomeresidents
with
dementia
(16men
and9
wom
en).Treated
87±4.4years/control
88.7
±6.9years
8-weekinterventio
n.Participantswere
random
ized
intwogroups:(i)
exercise
+calcium
carbonate+
vitamin
Dsupplementation,or
(ii)
exercise
+calcium
carbonateonly.
Treatmentadm
inistrationwas
not
doubleblinded
Multicom
ponent
butm
ainly
resistance-typeexercise.P
articipants
exercisedthreetim
esperweek
Vitamin
D.Interventiongroupgiven
bolusdose
(orally)of
100,000U
vitamin
D3atstarto
fstudy,then
weeklysupplements50,000
U
MS:k
neeextensor,low
erextrem
ityPP
:gaitspeed,balance
2
Bunoutetal.2006[47]
Chile.96community-dwelling
oldermen
andwom
en,w
ithlowvitamin
Dstatus
(86
wom
en,10men)76±4years
9-month
intervention.Participants
random
ized
toreceiveexercise
training
orno
training,and
further
random
ized
toreceive
supplementation(doubleblind)
with
vitamin
D/calcium
orcalcium
alone.
Resistanceexercise
training;p
articipants
exercisedtwiceperweek
Vitamin
D.C
ombinedoralvitamin
D/calcium
supplement
(400
IU/800
mg)
orcalcium-only
supplement(800mg)
provided,
tobe
takenin
theevening
MM:leanmassMS:
handgrip,
quadriceps
strength
PP:
TUG,
SPPB
5
Osteoporos Int
found in men from the placebo group. One study did not showany effect of the treatment on fat-free mass but did show anincrease in thigh muscle area with exercise; no inter-group dif-ference was seen [37]. Finally, the third study showed a signif-icantly greater effect of exercise + Ca-HMB in preventing thedecline of lean bodymass over a period of bed rest compared toexercise only [16].Muscle strength: Muscle strength increasedin two studies with exercise but no additional effect of Ca-HMB was found. In the third study [37], no improvement inupper or lower body strength was found. Physicalperformance: The two studies showed an improvement in theperformance of the Timed Up and Go test with exercise but didnot show any added effect of nutritional supplementation andexercise. In a single study, no effect on the Short PhysicalPerformance Battery (SPPB) test was found [16].
Summary: Muscle mass increased with exercise in 3/3RCTs and an interactive effect of HMB was found in 1/3RCTs; Muscle strength increased with exercises in 2/3 RCTswith no additional effect of HMB; Physical performance in-creased with exercise (TUG only) in 2/2 RCTs with no addi-tional effect of HMB.
Multi-nutrient intervention
Five studies reported results of treatment combining multi-nutrients and exercise on muscle strength; four of the fivestudies also looked at muscle mass and physical performance.Studies were performed on community-dwelling participants[14, 42, 43], frail retirement community residents [38], ornursing home residents [39, 40]. The majority of studies wereof poor quality [14, 39, 40, 42, 43].
Muscle mass: Two out of four studies did not report anyimprovement in fat-free mass with exercise or with exercisecombined with multi-nutrient supplementation [38, 42, 43].Two studies reported an increase in muscle mass with exercise[14, 39, 40] but only in the cross-sectional area for the study ofFiatarone et al. [39, 40]. One of these failed to show anyadditional effect of nutritional supplementation [14] and theother did not describe the additional effect of multi-nutrientsupplementation [39, 40]. Muscle strength: Results were het-erogeneous for the five studies that assessed the combinedeffect of exercise and multi-nutrient supplementation on mus-cle strength. Two studies [14, 42] showed a significant im-provement in muscle strength with exercise, one [42] did notreport any additional effect of nutrition whereas the otherstudy [14], reported greater improvement in isometric kneeflexion in the group receiving combined exercise and multi-nutrient supplementation versus only exercise. Fiatarone et al.[39, 40] also reported an increase of muscle strength withexercise but did not describe the difference between the exer-cise only and combined multi-nutrient and exercise group.Finally, two other studies [38, 41] did not report any increaseof muscle strength with treatment. Physical performance:T
able3
(contin
ued)
Reference
Settin
gs,study
participants,
meanage±SD
Studydesign
Exercisetraining
interventio
nNutritio
nalsupplem
ent
Outcomemeasures
Qualityscore
(Jadad
scale)
Treatmentswereadministereddouble
blind
Brose
etal.2003[48]
Canada.30
healthy-community-dwelling
oldermen
andwom
en(15
wom
enand15
men)65+
years.
14-w
eekintervention.Participantswere
random
ized
intwogroups:(i)
exercise
+creatinesupplementor(ii)
exercise
+placebo.Treatmentswere
administereddoubleblind
Resistanceexercise
training.P
articipants
exercisedthreetim
esperweek
Creatine.Dailycreatinemonohydrate
supplement(5g+2gdextrose)
(intervention)
orplacebo(7
gdextrose)(control)
MM:fat-freemassMS:h
andgrip,
ankledorsiflexion,knee
extension,dynamic1R
MPP
:chairrise,stairclim
b,walking
speed
4
Tarnopolskyet
al.2012
[49]
Canada.39
community-dwelling
oldermen
andwom
en(10
wom
en,19men)65+years
6-month
intervention.Participantswere
random
ized
intwogroups:(i)
exercise
+supplementationwith
creatinemonohydrateandconjugated
linoleicacid,(ii)
exercise
+placebo.
Treatmentswereadministereddouble
blind
Resistanceexercise
training
program;
participantsexercisedtwiceperweek
Creatine.Dailysupplementationwith
creatinemonohydrate(5
g)+
conjugated
linoleicacid
(6g)
+2gdextrose
orplacebo(7
gdextrose
+6gsafflower
oil)
MM:fat-freemassMS:h
andgrip,
ankledorsiflexion,kneeextension
strength,endurance
PP:chairrise,
stairclim
b,walking
speed,
balance
5
MM
musclemass,MSmusclestrength,P
Pphysicalperformance,1-RM
onerepetitionmaxim
umtest,IUinternationalunit,HMBβ-hydroxy-β-m
ethylbuthyrate,SPPBshortphysicalperform
ance
battery,
TUGTim
edUpandGo,CSA
cross-sectionalarea,CHOcarbohydrate
Osteoporos Int
Three studies described a significant improvement in physicalperformance with exercise. No additional effect of nutritionwas seen in two studies [38, 42, 43]; one further study did notreport whether there were any additional effect of nutrition[39, 40]. Finally, a fifth study did not show any effect oftreatment on gait speed [41].
Summary: Muscle mass increased with exercises in 2/4RCTs with no additional effect of multi-nutrient; Musclestrength increased with exercises in 3/5 RCTs and an addi-tional effect of multi-nutrient was found in 1/5 RCTs; Physicalperformance increased with exercise in 3/4 RCTs with no ad-ditional effect of multi-nutrient.
Creatine supplementation
Five good-quality studies have reported results of the effects ofcreatine supplementation on muscle mass and muscle strength;four of these also reported effects on physical performance. Theprotocols of supplementation were heterogeneous with threestudies using 5 g/day of creatine while the two other studiesused a higher dose of creatine for the first week followed by5 g/day in one of the study and 0.1 g/kg/day in the second study.The study duration varied from 12 weeks to 6 months.
Muscle mass: four out of the 5 studies showed greater im-provement of muscle mass in the group treated with the com-bination of exercise and creatine compared to the controlgroup with exercise only. The other study showed a significantincrease in muscle mass with exercise but without any addi-tional effect of creatine supplementation. Muscle strength:Muscle strength improved with exercise in all studies, withthe exception of handgrip strength, which remained un-changed in one study [48]. Several studies found additionaleffects of creatine supplementation in addition to exercise on:bench press [11, 19, 23], knee extension [19, 48, 49], bicepscurl performance [19], leg press [19], ankle dorsiflexion [48],isokinetic muscle strength [49], and, finally, endurance ofknee extension [49]. Physical performance: Results were lessconsistent regarding physical performance. Two studies [48,49] reported an improvement in physical performance withexercise but did not report any additional effects of creatinesupplementation. One study reported no improvement inphysical performance with either exercise or exercise pluscreatine [11]. The final study found a greater improvementin the 30-s chair stand test and in an exercise where partici-pants raised themselves from the floor, in the group receivingcombined exercise and creatine [19].
Summary: Muscle mass increased with exercises in 5/5RCTs and an additional effect of creatine was found in 4/5RCTs; Muscle strength increased with exercises in 5/5 RCTsand an additive effect of creatine was found, for some of themuscle strength outcomes, in 4/5 RCTs; Physical performanceincreased with exercises in 3/4 RCTs and an interactive effectof creatine was found in 1/4 RCTs.
Vitamin D supplementation
Two studies [46, 47] reported effects of combined exerciseand vitamin D3 supplementation onmuscle strength and phys-ical performance. One of those studies also reported effect onarm, waist and hip circumferences as well as lean mass [47].The vitamin D3 dose was 400 IU/day for 9 months in the studyof Bunout et al. [47] and 50,000 IU/week (after an initialinjection of 100,000 IU at study entry) for 8 weeks for thestudy of Binder et al. [46]. This last study was graded ashaving a poor quality [46] whereas the study of Bunoutet al. [47] was a good-quality study.
Muscle mass: Only one study reported results on musclemass [47]. No effects of exercise alone or of exercise com-bined with vitamin D supplementation were observed. Indeed,no significant changes in weight, circumferences, or bodycomposition measured by DXA were observed in any of thegroups.Muscle strength: Both studies reported significant im-provement in muscle strength with exercise but did not reportany difference between the exercise-only group and the groupwith combined exercise and vitamin D supplementation.Physical performance: Binder et al. [46] reported improvedbalance with exercise in a population of elderly nursing homeresidents with dementia. No additional effect of vitamin Dsupplementation was found and no improvement in gait speedwas evident in either group. Bunout et al. [47] reported asignificant improvement in the Timed Up and Go test for thegroup with combined vitamin D and exercise but no differ-ence for the SPPB test between groups.
Summary: Muscle mass did not improve with exercise andno additional effect of vitamin D was found; Muscle strengthincreased with exercise in 2/2 RCTs with no additional effectof vitamin D; Physical performance increased, for some of thephysical performance outcomes, in 2/2 RCTs with no addi-tional effect of vitamin D, except for TUG in 1/2 RCTs.
Other supplementation
Our systematic review identified six studies of good quality thatused other types of nutritional supplements: green tea in elderlymen and women [15], magnesium oxide in healthy elderly sub-jects [21], milk fat globule membrane in frail women [28], soyisoflavones in frail older women [9, 10], vitamin and mineral-enhanced dairy and fruit products in frail community-dwellingolder people [44, 45] and finally, tea catechin in sarcopenicwomen [18]. Four studies were 12 weeks in length [15, 18,21, 28], one was 6-months in length [9, 10], and the last onewas 17 weeks in length [44, 45].
Muscle mass: A significant effect of exercise alone onmus-cle mass was seen in various studies: in waist and hip circum-ference in men in the green tea [15] study, hip circumferencein the soy isoflavones [9, 10]study participants, lean mass inthe vitamin and mineral-enhanced dairy and fruit products
Osteoporos Int
[44, 45]study, and leg lean mass in tea catechin [18]. No ad-ditional effects of nutritional supplements were observedacross studies. Muscle strength: Exercise increased benchpress and 1RM leg press without an additional effect of soyisoflavones [9, 10] and knee extension without additional ef-fects of tea catechin [18]. A small increase of quadricepsstrength was also shown in one study but the difference be-tween groups was not described [44, 45]. No effect of treat-ment was found on knee extension and handgrip strength inthe other studies [9, 10, 21, 28]. Physical performance:Exercise combined with magnesium oxide significantly im-proved performance in the SPPB test, the chair stand test, andin the 4-m walking speed in the study of Veronese et al. [21].TUG, usual gait speed, and maximum walking speed signifi-cantly improved in the exercise + tea catechin group comparedto exercise group only in another study of Kim et al. [18]Walking speed and TUG test performance also improved withexercise in the study of Kim et al. [28] but no additional effectof milk fat globule membrane was described. In the study byChin A Paw et al., improvements in physical performancewere described but the additional effect of vitamin- andmineral-enhanced dairy and fruit products was not described[44, 45]. Finally, the chair stand test did not improve withtreatment in two other studies [9, 10, 18].
Summary: Muscle mass increased with exercise in 4/6RCTs and no additional effect of nutrition was found;Muscle strength increased with exercise in 3/5 RCTs and nointeractive effect of nutrition was found; Physical perfor-mance increased with exercise in 4/5 RCTs and an additionaleffect of nutrition was found in 2/5 RCTs.
Discussion
This systematic review aimed to summarize results of RCTsassessing the effect of an intervention combining physicalactivity and dietary supplement on muscle mass and musclefunction of subjects aged 60 years and older. Following asystematic review previously performed in 2013 by Denisonet al. including 17 RCTs, we performed an update of thiscomprehensive systematic review and identified 21 RCTspublished between April 2013 and October 2015. Thus, 37RCTSs assessing the impact of a therapeutic intervention con-taining both physical activity and a nutritional supplement onmuscle parameters were included in the present work. Thestudy protocols were quite heterogeneous. Different types ofphysical activities have been studied in different populationsthat varied in sex, settings, and health status. Moreover, withineach category of dietary supplements, the supplement doseand the length of study differed across RCTs.
Among the 37 RCTs included in the systematic review,34 RCTs assessed the impact of intervention on musclemass in elderly subjects. In almost 80% of the RCTs (27/T
able4
Generalsummaryof
thesystem
aticreview
Musclemass
Musclestrength
Physicalperformance
Significantincrease
with
exercises
Significantadded
effectwith
nutrition
Significant
increase
with
exercises
Significantadded
effectwith
nutrition
Significantincrease
with
exercises
Significantadded
effectwith
nutrition
Protein
11/12RCTs
3/12
RCTs
12/12RCTs
3/12
RCTs
9/9RCTs
0/9RCTs
EAA
2/3RCTs
0/3RCTs
2/3RCTs
0/3RCTs
2/2RCTs
(onlyforSPP
BandTUG)
0/2RCTs
HMB
3/3RCTs
1/3RCTs
2/3RCTs
0/3RCTs
2/2RCTs
(onlyforTUG)
0/2RCTs
Multi-nutrient
2/4RCTs
0/4RCTs
3/5RCTs
1/5RCTs
3/4RCTs
0/4RCTs
Creatine
5/5RCTs
4/5RCTs
5/5RCTs
4/5RCTs
(for
someof
musclestrength
outcom
es)
3/4RCTs
1/4RCTs
Vitamin
D0/1RCTs
0/1RCTs
2/2RCTs
0/2RCTs
2/2RCTs
(for
someof
physicalperformance
outcom
es)
1/2RCTs
(onlyforTUG)
Other
4/6RCTs
0/6RCTs
3/5RCTs
0/5RCTs
4/5RCTs
2/5RCTs
RCTs
random
ized
controlledtrials,SPPBshortp
hysicalp
erform
ance
battery,T
UGtim
edup
andgo
Osteoporos Int
34 RCTs), muscle mass increased with exercise training.In the majority of studies where no effect of exercise wasobserved, these were undertaken in frail subjects, residingin a nursing home, or, subjects with limited mobility. Ahypothesis could be that the physical condition of thesesubjects did not allow them to perform the protocol forthe physical activity intervention correctly. The majorityof studies proposed three sessions per week. Fewer ses-sions may compromise efficacy of the physical activityintervention. An additional effect of nutritional interven-tion on muscle mass was only found in 8 RCTs (23.5%),which were all of high quality (4 or 5 points in the JadadScale), 4 using creatine, 3 using proteins, and 1 usingHMB as dietary supplement. The majority (75%) of stud-ies using creatine as a dietary supplement showed a highereffect on muscle mass once exercise intervention wascombine with creatine. The combination of creatine sup-plementation and resistance training therefore seems to actsynergistically. Only 3 of the 12 RCTs using protein as adietary supplement reported an additional effect of proteinwhen combined with physical activity. These three studiesvaried in type and dose of protein with no specific simi-larity between them that could explain their positive re-sults as distinct from the other nine studies that did notreport an effect on mass muscle with protein. Because ofblunted response in muscle protein synthesis in olderadults and reduced post-prandial inhibition of muscle pro-tein breakdown, some authors recommended increasingprotein intake to 1.2 g/kg body weight/day in older adultsand even more in frail older adults or elderly with acute orchronic disease [50, 51]. Based on these recommenda-tions, we hypothesized a beneficial effect of protein sup-plementation in muscle function in older people.However, it should be discussed that the baseline dietaryintake of protein has not been reported in the differentstudies. Therefore, we do not know if the target of1.2 g/kg/day has been reached or if differences could havebeen observed between populations who reached this tar-get and those who did not. A meta-analysis published in2012 [52] showed a positive effect of protein supplemen-tation on muscle mass gains during prolonged resistance-type exercise training in older subjects. This probablymeans that the type of exercise training could have anon-negligible impact on results. Indeed, in this system-atic review, inclusion criteria were not limited to one par-ticular type of physical exercise. Finally, one out of thethree studies using HMB as a dietary supplement alsoshowed an intergroup difference between subjects under-going exercise intervention and subjects undergoing acombination of exercise and dietary intervention. Of note,this study comprised subjects confined to bedrest.Subjects receiving a combination of exercise and HMBsupplementation were more prevented for decline of lean
body mass over bed rest compared to subjects undergoingexercises only. In this study, HMB supplementation didnot increase muscle mass but prevented its decline.
Muscle strength increased in 82.8% of the studies (29/35RCTs) following an exercise intervention and, once again,dietary supplementation showed additional benefits in only asmall number of studies (8/35 RCTS, 22.8%) principally forcreatine but only at specific muscle sites. In 4 out of the 5RCTs using creatine as a dietary supplement (dose range 5–20 g/day), the group treated with the combination of exerciseand dietary intervention showed greater improvement of mus-cle strength compared to exercise only. Three good-qualityRCTs using protein as a dietary supplement also showed agreater effect on muscle strength when compared to the exer-cise group. These three studies were providing a high amountof protein with, respectively, 45, 40, and 15 g (collagen pep-tide) daily whereas the mean dose of supplementation in otherstudies was approximately 20 g/day. The dose of supplemen-tation is likely to contribute to the inconsistent findings be-tween studies. Handgrip strength, a component of sarcopeniadefinitions, was an outcome in 13 RCTs assessing the effect ofa combined exercise and dietary intervention. Approximatelyhalf of the studies (6/13 RCTs) showed an improvement ingrip strength with exercise. However, none of these RCTsshowed an additional effect of dietary supplementation.Highlighted by these last results, it should be noted that, evenif this systematic review revealed an increase of musclestrength following exercise in the majority of the studies, thisseems particularly true for leg muscle strength.
A total of 29 RCTs also assessed the impact of combinedphysical activity and dietary supplementation on physical per-formance. We observed, in the majority of studies, an im-provement in physical performance outcomes following anexercise intervention (26/28 RCTs, 92.8%). In the two studiesthat did not report an improvement on physical performance,one was performed on frail people and the other one on hos-pitalized people. Physical performance was assessed using avariety of measures in the reported studies. The most com-monly used measures were gait speed (used in 17 RCTs),followed by chair stand test (used in 13 RCTs), Timed Upand Go test (used in 8 RCTs), and SPPB test (used in 6RCTs). The heterogeneity of both the type of exercise inter-vention and physical performance outcomes impedes generalstatements of findings on the association between exercisetraining and improvements in physical performance.Interaction of exercise and nutrition was found in only17.8% of these studies (5/28 RCTs): one study when amulti-nutrient was used as a dietary supplement, another withcreatine, a third study with vitamin D, another with tea cate-chin, and finally, one with magnesium oxide.
This study is an update of an existing systematic reviewand it followed the same rigorous methodology as the previ-ous one. We searched multiple electronic databases to identify
Osteoporos Int
as many studies as possible that would meet our inclusioncriteria. Nevertheless, this review is limited by the disparitybetween the studies. The exercise interventions described inthe RCTs varied in regards of the types of exercises, doses,intensity, and duration. Moreover, adherence to these proto-cols were not reported, which impacts the assessment of thereal effect of exercise on muscle features. Supplementationsprovided also varied, not merely for the dosage, but also forthe duration, the way, and the frequency of administration. Itmust also be noted that half of these studies were not doubleblinded. These parameters are likely to be key factors in mod-ulating the outcomes of studies investigating the potentialbenefit of dietary supplementation to further augment gainsin muscle mass and strength during exercise training.Moreover, the majority of individual RCTs did not take intoaccount the baseline nutritional status of the population. Itmakes perfect sense that elders, close to undernutrition insome of the dietary supplements presented, failed to respondproperly to exercise training meant to increase their musclemass and strength. Even a reasonable dose of the supplementmay be insufficient if participants are very sick, frail, and/ormalnourished at baseline. In the same vein, even if exercisecould have a positive effect, nutritional supplement may notbe effective in very healthy, fit, and/or vigorous elderly.Nutrition supplementation is likely to be more efficient if mal-nutrition is present. The specific elderly subpopulation shouldbe regarded when evaluating the need for nutritional supportduring exercise training. Finally, even if our purpose was toassess combined effects of exercise training and dietary sup-plementation on muscle outcomes in sarcopenic subjects, avery limited number of included studies have been performedspecifically on subjects affected by sarcopenia. Because of thecondition of sarcopenic patients, it is likely that the effectsobserved in this systematic review would have been lesser insolely sarcopenic patients. It was however difficult for thisstudy to focus only on sarcopenic subjects. Indeed, there areno universally accepted criteria for the diagnosis of sarcopeniain an operational sense. Therefore, we chose to focus on el-derly subjects in a broader sense instead of focusing on one ormore restricted definitions of sarcopenia.
In conclusion, physical exercise has a beneficial impact onmuscle mass, muscle strength, or physical performance inhealthy subjects aged 60 years and older. However, the addi-tional effect of dietary supplementation has only been reportedin a limited number of studies. For the majority of studiesincluded in this systematic review, the population was com-posed of healthy older subjects. Studies assessing the impactof a combined exercise intervention and dietary interventionare still lacking in frail and sarcopenic populations, popula-tions suffering from nutritional deficiency, or populations atrisk of malnutrition. Further well-designed and well-conducted studies performed on these types of populationsshould be implemented. It seems likely that nutritional
interventions in populations who are presenting nutritionalor physical deficiencies would be more beneficial than inter-ventions in well-nourished and replete populations. There is aneed of a rigorous documentation of subject’s baseline exer-cise level and nutritional status prior to implement interven-tion regimens in those future studies.
Compliance with ethical standards
Conflict of interest N Binkley received research support from Amgen,GEHealthcare, and Lilly, Merck and consultant/advisory board fees fromAmgen, Astellas, Lilly, Merck, Nestle, and Radius. J-Y Reginster re-ceived consulting fees or paid advisory boards from Servier, Novartis,Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle,Nycomed-Takeda, NPS, IBSA-Genevrier, Theramex, UCB, AsahiKasei, Endocyte, and Radius Health; lecture fees from Merck Sharpand Dohme, Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier,Roche, GlaxoSmithKline, Merckle, Teijin, Teva, Analis, Theramex,Nycomed, NovoNordisk, Ebewee Pharma, Zodiac, Danone, WillPharma, Amgen, and PharmEvo; and grant support from Bristol MyersSquibb, Merck Sharp & Dohme, Rottapharm, Teva, Roche, Amgen,Lilly, Novartis, GlaxoSmithKline, Servier, Pfizer, Theramex, Danone,Organon, Therabel, Boehringer, Chiltern, and Galapagos. ML Brandi isa consultant and grant recipient from Alexion, Abiogen, Amgen, BrunoFarmaceutici, Eli Lilly, MSD, NPS, Shire, SPA, and Servier. C Beaudart,A Dawson, S Shaw, N Harvey, JA Kanis, R Chapurlat, D Chan, OBruyère, R Rizzoli, C Cooper, EM Dennison, G Adib, T Chevalley, PClark, B Dawson-Hughes, A El Maghraoui, K Engelke, R Fielding, JFoldes, G Guglielmi, JM Kaufman, B Larijani, W Lems, L van Loon,G Lyritis, S Maggi, L Masi, E McCloskey, ODMessina, A Papaioannou,P Szulc, and N Veronese have nothing to declare.
Appendix
the IOF-ESCEO Sarcopenia Working GroupG. AdibM. L. BrandiT. ChevalleyP. ClarkB. Dawson-HughesA. El MaghraouiK. EngelkeR. FieldingA. J. FoldesG. GugliemiJ. M. KaufmanB. LarijaniW. LemsL. J. C. van LoonG. P. LyritisS. MaggiL. MasiE. McCloskeyO. D. MessinaA. PapaioannouP. SzulcN. Veronese
Osteoporos Int
Open Access This article is distributed under the terms of the CreativeCommons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncom-mercial use, distribution, and reproduction in any medium, providedyou give appropriate credit to the original author(s) and the source, pro-vide a link to the Creative Commons license, and indicate if changes weremade.
References
1. Cruz-Jentoft AJ, Baeyens JP, Bauer JM et al (2010) Sarcopenia:European consensus on definition and diagnosis: report of theEuropean Working Group on Sarcopenia in Older People. AgeAgeing 39:412–423. doi:10.1093/ageing/afq034
2. Cooper C, Fielding R, VisserM et al (2013) Tools in the assessment ofsarcopenia. Calcif Tissue Int 93:201–210. doi:10.1007/s00223-013-9757-z
3. Beaudart C, Rizzoli R, Bruyère O et al (2014) Sarcopenia: burdenand challenges for public health. Arch Public Heal 72:45. doi:10.1186/2049-3258-72-45
4. Bruyère O, Beaudart C, Locquet M et al (2016) Sarcopenia as apublic health problem. Eur Geriatr Med 7:272–275. doi:10.1016/j.eurger.2015.12.002
5. Cruz-Jentoft AJ, Landi F, Schneider SM, et al. (2014) Prevalence ofand interventions for sarcopenia in ageing adults: a systematic re-view. Report of the International Sarcopenia Initiative (EWGSOPand IWGS). Age Ageing. doi: 10.1093/ageing/afu115
6. Denison HJ, Cooper C, Sayer AA, Robinson SM (2015) Preventionand optimalmanagement of sarcopenia: a review of combined exerciseand nutrition interventions to improve muscle outcomes in older peo-ple. Clin Interv Aging 10:859–869. doi:10.2147/CIA.S55842
7. Jadad AR, Moore RA, Carroll D et al (1996) Assessing the qualityof reports of randomized clinical trials: is blinding necessary?Control Clin Trials 17:1–12
8. Gryson C, Ratel S, Rance M et al (2014) Four-month course ofsoluble milk proteins interacts with exercise to improve musclestrength and delay fatigue in elderly participants. J Am Med DirAssoc 15(958):e1–e9. doi:10.1016/j.jamda.2014.09.011
9. Lebon J, Riesco E, Tessier D, Dionne IJ (2014) Additive effects ofisoflavones and exercise training on inflammatory cytokines andbody composition in overweight and obese postmenopausal wom-en: a randomized controlled trial. Menopause 21:869–875. doi:10.1097/GME.0000000000000177
10. Choquette S, Dion T, Brochu M, Dionne IJ (2013) Soy isoflavonesand exercise to improve physical capacity in postmenopausal wom-en. Climacteric 16:70–77. doi:10.3109/13697137.2011.643515
11. Gualano B, Macedo AR, Alves CRR et al (2014) Creatine supple-mentation and resistance training in vulnerable older women: arandomized double-blind placebo-controlled clinical trial. ExpGerontol 53:7–15. doi:10.1016/j.exger.2014.02.003
12. Villanueva MG, He J, Schroeder ET (2014) Periodized resistancetraining with and without supplementation improve body composi-tion and performance in older men. Eur J Appl Physiol 114:891–905. doi:10.1007/s00421-014-2821-1
13. Stout JR, Smith-Ryan AE, Fukuda DH et al (2013) Effect of calciumβ-hydroxy-β-methylbutyrate (CaHMB) with and without resistancetraining in men andwomen 65 + yrs: a randomized, double-blind pilottrial. Exp Gerontol 48:1303–1310. doi:10.1016/j.exger.2013.08.007
14. Okazaki K, Yazawa D, Goto M et al (2013) Effects of macronutri-ent intake on thigh muscle mass during home-based walking train-ing in middle-aged and older women. Scand J Med Sci Sports 23:e286–e292. doi:10.1111/sms.12076
15. Narotzki B, Reznick AZ, Navot-Mintzer D et al (2013) Green tea andvitamin E enhance exercise-induced benefits in body composition,glucose homeostasis, and antioxidant status in elderlymen andwomen.J Am Coll Nutr 32:31–40. doi:10.1080/07315724.2013.767661
16. Deutz NEP, Pereira SL, Hays NP et al (2013) Effect of β-hydroxy-β-methylbutyrate (HMB) on lean body mass during 10 days of bed restin older adults. Clin Nutr 32:704–712. doi:10.1016/j.clnu.2013.02.011
17. Chalé A, Cloutier GJ, Hau C et al (2013) Efficacy of whey proteinsupplementation on resistance exercise-induced changes in leanmass, muscle strength, and physical function in mobility-limitedolder adults. J Gerontol A Biol Sci Med Sci 68:682–690. doi:10.1093/gerona/gls221
18. Kim H, Suzuki T, Saito K et al (2013) Effects of exercise and teacatechins on muscle mass, strength and walking ability incommunity-dwelling elderly Japanese sarcopenic women: a ran-domized controlled trial. Geriatr Gerontol Int 13:458–465. doi:10.1111/j.1447-0594.2012.00923.x
19. Aguiar AF, Januário RSB, Junior RP et al (2013) Long-term crea-tine supplementation improves muscular performance during resis-tance training in older women. Eur J Appl Physiol 113:987–996.doi:10.1007/s00421-012-2514-6
20. Leenders M, Verdijk LB, Van der Hoeven L et al (2013) Proteinsupplementation during resistance-type exercise training in the el-derly. Med Sci Sports Exerc 45:542–552. doi:10.1249/MSS.0b013e318272fcdb
21. Veronese N, Berton L, Carraro S et al (2014) Effect of oral magne-sium supplementation on physical performance in healthy elderlywomen involved in a weekly exercise program: a randomized con-trolled trial. Am J Clin Nutr 100:974–981. doi:10.3945/ajcn.113.080168
22. Daly RM, O’Connell SL, Mundell NL et al (2014) Protein-enricheddiet, with the use of lean red meat, combined with progressiveresistance training enhances lean tissue mass and muscle strengthand reduces circulating IL-6 concentrations in elderly women: acluster randomized controlled trial. Am J Clin Nutr 99:899–910.doi:10.3945/ajcn.113.064154
23. Cooke MB, Brabham B, Buford TW et al (2014) Creatine supple-mentation post-exercise does not enhance training-induced adapta-tions in middle to older aged males. Eur J Appl Physiol 114:1321–1332. doi:10.1007/s00421-014-2866-1
24. Oesen S, Halper B, Hofmann M et al (2015) Effects of elastic bandresistance training and nutritional supplementation on physical per-formance of institutionalised elderly—a randomized controlled tri-al. Exp Gerontol 72:99–108. doi:10.1016/j.exger.2015.08.013
25. Zdzieblik D, Oesser S, Baumstark MWet al (2015) Collagen pep-tide supplementation in combination with resistance training im-proves body composition and increases muscle strength in elderlysarcopenic men: a randomised controlled trial. Br J Nutr 114:1–9.doi:10.1017/S0007114515002810
26. Yamada M, Nishiguchi S, Fukutani N et al (2015) Mail-based in-tervention for sarcopenia prevention increased anabolic hormoneand skeletal muscle mass in community-dwelling Japanese olderadults: the INE (Intervention by Nutrition and Exercise) Study. JAmMed Dir Assoc 16:654–660. doi:10.1016/j.jamda.2015.02.017
27. Trabal J, Forga M, Leyes P et al (2015) Effects of free leucinesupplementation and resistance training on muscle strength andfunctional status in older adults: a randomized controlled trial.Clin Interv Aging 10:713–723. doi:10.2147/CIA.S75271
28. Kim H, Suzuki T, Kim M et al (2015) Effects of exercise and milkfat globule membrane (MFGM) supplementation on body compo-sition, physical function, and hematological parameters incommunity-dwelling frail Japanese women: a randomized doubleblind, placebo-controlled, follow-up trial. PLoS One 10:e0116256.doi:10.1371/journal.pone.0116256
29. Shahar S, Kamaruddin NS, Badrasawi M et al (2013) Effectivenessof exercise and protein supplementation intervention on body
Osteoporos Int
composition, functional fitness, and oxidative stress among elderlyMalays with sarcopenia. Clin Interv Aging 8:1365–1375. doi:10.2147/CIA.S46826
30. Arnarson A, Gudny Geirsdottir O, Ramel A et al (2013) Effects ofwhey proteins and carbohydrates on the efficacy of resistance train-ing in elderly people: double blind, randomised controlled trial. EurJ Clin Nutr 67:821–826. doi:10.1038/ejcn.2013.40
31. Rosendahl E, Lindelöf N, Littbrand H et al (2006) High-intensityfunctional exercise program and protein-enriched energy supple-ment for older persons dependent in activities of daily living: arandomised controlled trial. Aust J Physiother 52:105–113
32. Carlsson M, Littbrand H, Gustafson Y et al (2011) Effects of high-intensity exercise and protein supplement on muscle mass in ADLdependent older people with and without malnutrition: a random-ized controlled trial. J Nutr Health Aging 15:554–560
33. Tieland M, Dirks ML, van der Zwaluw N et al (2012) Proteinsupplementation increases muscle mass gain during prolongedresistance-type exercise training in frail elderly people: a random-ized, double-blind, placebo-controlled trial. J Am Med Dir Assoc13:713–719. doi:10.1016/j.jamda.2012.05.020
34. Verdijk LB, Jonkers RAM, Gleeson BG et al (2009) Protein sup-plementation before and after exercise does not further augmentskeletal muscle hypertrophy after resistance training in elderlymen. Am J Clin Nutr 89:608–616. doi:10.3945/ajcn.2008.26626
35. Godard MP, Williamson DL, Trappe SW (2002) Oral amino-acidprovision does not affect muscle strength or size gains in older men.Med Sci Sports Exerc 34:1126–1131
36. Kim HK, Suzuki T, Saito K et al (2012) Effects of exercise andamino acid supplementation on body composition and physicalfunction in community-dwelling elderly Japanese sarcopenic wom-en: a randomized controlled trial. J Am Geriatr Soc 60:16–23. doi:10.1111/j.1532-5415.2011.03776.x
37. VukovichMD, Stubbs NB, Bohlken RM (2001) Body compositionin 70-year-old adults responds to dietary beta-hydroxy-beta-methylbutyrate similarly to that of young adults. J Nutr 131:2049–2052
38. Bonnefoy M, Cornu C, Normand S et al (2003) The effects ofexercise and protein-energy supplements on body compositionand muscle function in frail elderly individuals: a long-term con-trolled randomised study. Br J Nutr 89:731–739. doi:10.1079/BJN2003836
39. Fiatarone MA, O’Neill EF, Ryan ND et al (1994) Exercise trainingand nutritional supplementation for physical frailty in very elderlypeople. N Engl J Med 330:1769–1775. doi:10.1056/NEJM199406233302501
40. Fiatarone MA, O’Neill EF, Doyle N et al (1993) The BostonFICSIT study: the effects of resistance training and nutritional
supplementation on physical frailty in the oldest old. J AmGeriatr Soc 41:333–337
41. Miller MD, Crotty M, Whitehead C et al (2006) Nutritional supple-mentation and resistance training in nutritionally at risk older adultsfollowing lower limb fracture: a randomized controlled trial. ClinRehabil 20:311–323
42. Bunout D, Barrera G, de la Maza P et al (2001) The impact ofnutritional supplementation and resistance training on the healthfunctioning of free-living Chilean elders: results of 18 months offollow-up. J Nutr 131:2441S–2446S
43. Bunout B, Barrera G, de la Maza P et al (2004) Effects of nutritionalsupplementation and resistance training on muscle strength in freeliving elders. Results of one year follow. J Nutr Health Aging 8:68–75
44. Chin A, Paw MJ, de Jong N, Schouten EG et al (2001) Physicalexercise and/or enriched foods for functional improvement in frail,independently living elderly: a randomized controlled trial. ArchPhys Med Rehabil 82:811–817. doi:10.1053/apmr.2001.23278
45. de Jong N, Chin A, Paw MJ, de Groot LC et al (2000) Dietarysupplements and physical exercise affecting bone and body com-position in frail elderly persons. Am J Public Health 90:947–954
46. Binder, E.F. (1996) Implementing a structured exercice program forfrail nursing home residents with dementia: issues and challenge.JAPA, vol 3(issue 4).
47. Bunout D, Barrera G, Leiva L et al (2006) Effects of vitamin Dsupplementation and exercise training on physical performance inChilean vitamin D deficient elderly subjects. Exp Gerontol 41:746–752. doi:10.1016/j.exger.2006.05.001
48. Brose A, Parise G, Tarnopolsky MA (2003) Creatine supplementa-tion enhances isometric strength and body composition improve-ments following strength exercise training in older adults. JGerontol A Biol Sci Med Sci 58:11–19
49. Tarnopolsky M, Zimmer A, Paikin J et al (2007) Creatinemonohydrate and conjugated linoleic acid improve strength andbody composition following resistance exercise in older adults.PLoS One 2:e991. doi:10.1371/journal.pone.0000991
50. Nowson C, O’Connell S (2015) Protein requirements and recom-mendations for older people: a review. Nutrients 7:6874–6899. doi:10.3390/nu7085311
51. Bauer J, Biolo G, Cederholm Tet al (2013) Evidence-based recom-mendations for optimal dietary protein intake in older people: aposition paper from the PROT-AGE Study Group. J Am Med DirAssoc 14:542–559. doi:10.1016/j.jamda.2013.05.021
52. Cermak NM, Res PT, de Groot LCPGM et al (2012) Protein sup-plementation augments the adaptive response of skeletal muscle toresistance-type exercise training: a meta-analysis. Am J Clin Nutr96:1454–1464. doi:10.3945/ajcn.112.037556
Osteoporos Int