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Lead Article
Nutritional interventions to improve muscle mass, muscle
strength, and physical performance in older people: an
5 umbrella review of systematic reviews and meta-analyses
Evelien Gielen *, David Beckwee*, Andreas Delaere, Sandra De Breucker, Maurits Vandewoude, and
Ivan Bautmans; on behalf of the Sarcopenia Guidelines Development Group of the Belgian Society of
Gerontology and Geriatrics (BSGG)†
10 Context: Sarcopenia is a progressive and generalized skeletal muscle disorder asso-
ciated with an increased risk of adverse outcomes such as falls, disability, and
death. The Belgian Society of Gerontology and Geriatrics has developed evidence-
based guidelines for the prevention and treatment of sarcopenia. This umbrella re-
view presents the results of the Working Group on Nutritional Interventions.
15 Objective: The aim of this umbrella review was to provide an evidence-based over-
view of nutritional interventions targeting sarcopenia or at least 1 of the 3 sarcope-
nia criteria (ie, muscle mass, muscle strength, or physical performance) in persons
aged 65 years. Data sources: Following the Preferred Reporting Items for
Systematic Reviews and Meta-Analyses guidelines, the PubMed and Web of Science
20 databases were searched for systematic reviews and meta-analyses reporting the
effect of nutritional supplementation on sarcopenia or muscle mass, strength, or
physical performance. Data extraction: Two authors extracted data on the key
characteristics of the reviews, including participants, treatment, and outcomes.
Methodological quality of the reviews was assessed using the product A
25 Measurement Tool to Assess Systematic Reviews. Three authors synthesized the
extracted data and generated recommendations on the basis of an overall synthe-
sis of the effects of each intervention. Quality of evidence was rated with the
Grading of Recommendations Assessment, Development and Evaluation approach.
Data analysis: A total of 15 systematic reviews were included. The following
30 supplements were examined: proteins, essential amino acids, leucine,
Affiliation: E. Gielen is with the Department of Geriatrics, UZ Leuven, Leuven, Belgium; Department of Public Health and Primary Care, KU
Leuven, Leuven, Belgium. D. Beckwee is with the Rehabilitation Sciences Research Department, Vrije Universiteit Brussel, Brussels, Belgium;
Frailty in Ageing Research Department, Vrije Universiteit Brussel, Brussels, Belgium; Department of Gerontology, Vrije Universiteit Brussel,
Brussels, Belgium; Department of Rehabilitation Sciences and Physiotherapy, University of Antwerp, Antwerp, Belgium; Department of
Geriatric Physiotherapy, SOMT University of Physiotherapy, Amersfoort, The Netherlands. A. Delaere is with the Frailty in Ageing Research
Department, Vrije Universiteit Brussel, Brussels, Belgium; Department of Gerontology, Vrije Universiteit Brussel, Brussels, Belgium. S. De
Breucker is with the Department of Geriatrics, Erasme Hospital, Brussels, Belgium. M. Vandewoude is with the Department of Geriatrics,
University of Antwerp, Antwerp, Belgium. I. Bautmans is with the Frailty in Ageing Research Department, Vrije Universiteit Brussel,
Brussels, Belgium; Department of Gerontology, Vrije Universiteit Brussel, Brussels, Belgium; Department of Geriatric Physiotherapy, SOMT
University of Physiotherapy, Amersfoort, The Netherlands.
Correspondence: E. Gielen, Department of Geriatrics, UZ Leuven, Herestraat 49, B3000 Leuven, Belgium. E-mail: evelien.gielen@uzleuven.be.
*These authors contributed equally to this review.
†
The members of the Sarcopenia Guidelines Development Group of the Belgian Society of Gerontology and Geriatrics are listed in the
Acknowledgments section.
Key words: diet, exercise, intervention, sarcopenia.
C The Author(s) 2020. Published by Oxford University Press on behalf of the International Life Sciences Institute.
V
All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
doi: 10.1093/nutrit/nuaa011
Nutrition ReviewsV Vol. 00(0):1–27
R
1b-hydroxy-b-methylbutyrate, creatine, and multinutrient supplementation (with or
without physical exercise). Because of both the low amount and the low to moder-
ate quality of the reviews, the level of evidence supporting most recommendations
was low to moderate. Conclusions: Best evidence is available to recommend
5 leucine, because it has a significant effect on muscle mass in elderly people with
sarcopenia. Protein supplementation on top of resistance training is recommended
to increase muscle mass and strength, in particular for obese persons and for
24 weeks. Effects on sarcopenia as a construct were not reported in the included
reviews.
10 INTRODUCTION and feasible interventions for sarcopenia. The afore-
mentioned variation in the age-related decline of mus-
Aging is associated with a progressive and general loss cle mass and strength indicates a potential role, not
of muscle mass and muscle strength.1 Loss of muscle only for sex, height, weight, and genetic heritability but
mass is estimated at approximately 35%–40% between also for physical exercise and nutritional intake over the 55
the ages of 20 and 80 years.2 The difference in muscle lifetime as determinants of sarcopenia, and thus as po-
15 strength between young persons and healthy elderly tential leads for intervention.4
persons ages 60 to 80 years is 20%–40%, and this differ- The role of physical exercise and nutritional inter-
ence increases to 50% when compared with those ventions has been examined in several randomized con-
older than 80 years.3 There is, however, wide interindi- trolled trials (RCTs). The Belgian Society of 60
vidual variation in the peak muscle mass and strength Gerontology and Geriatrics has developed evidence-
20 achieved during early life as well as in the rate of decline based guidelines for the prevention and therapy of sar-
of muscle mass and strength in adult and older life. copenia for use in broad clinical practice,12 and recently
This explains the differences in the remaining amount the results of the Working Groups on Pharmacology
of muscle mass and muscle strength between older indi- and on Exercise Interventions have been published.13,14 65
viduals.4 When a threshold of low muscle mass and This review presents the results of the Working Group
25 strength is reached, sarcopenia is defined, predisposing on Nutritional Interventions. The aim is to provide an
elderly persons to physical disability, mobility limita- overview of nutritional interventions targeting sarcope-
tions, falls, institutionalization, and death.1 nia or at least 1 of the sarcopenia criteria (ie, muscle
Since 2009, several expert groups, such as the mass, muscle strength, or physical performance), with a 70
European Working Group on Sarcopenia in Older focus on interventions studied in systematic reviews or
30 People (EWGSOP), have tried to incorporate the con- meta-analyses. Therefore, a systematic umbrella review
cept of sarcopenia into an operational definition, but so was performed and specific recommendations for clini-
far, no consensus definition has been reached.1,5–9 cal practice were proposed according to the levels of ev-
Common to these definitions of sarcopenia is that they idence. The Preferred Reporting Items for Systematic 75
contain a component of low muscle mass and a compo- Reviews and Meta-Analyses guidelines were followed
35 nent of low muscle function, which may be low physical for this review (Appendix S1 in the Supporting
performance or low muscle strength. Recently, the Information online).15
EWGSOP updated its definition of sarcopenia, which
now focuses on low muscle strength as the key clinical METHODS
characteristic of sarcopenia and considers low muscle
40 mass and/or quality to confirm the diagnosis and poor Search strategy and selection criteria 80
physical performance to determine its severity.10 On
October 1, 2016, sarcopenia received an International Two databases (PubMed, Web of Science) were system-
Statistical Classification of Diseases and Related Health atically searched from the earliest date available (1950s
Problems code (M62.84), which is necessary to diagnose for PubMed, 1900 for Web of Science) until November
45 it as a disease. This recognition urges the need to diag- 8, 2017. Keywords corresponded to the PICOS design,
nose sarcopenia in clinical practice and to develop as follows: population: older adults; intervention: nutri- 85
guidelines to effectively prevent or counter this tion; comparison: no nutrition; outcomes: sarcopenia;
condition.11 study design: systematic review and meta-analysis)
Because of the major clinical and economic bur- (Table 1; see Appendix S2 in the Supporting Information
50 dens of sarcopenia, it is, indeed, critical to find efficient online for full search strategies).
2 Nutrition ReviewsV Vol. 00(0):1–27
RTable 1 PICOS criteria for inclusion of studies
Parameter Criteria Description
Study design 1. Is the study a systematic review? • Only systematic reviews are considered
• No narrative reviews are considered
Participants 2. Does the study involve older people? Adults aged 65 years are considered
Groups that may be covered:
A. Healthy older people who remain above the cutoff values of the
EWGSOP diagnostic criteria
B. Older people with muscle mass below the cutoff values of the
EWGSOP diagnostic criteria but without impact on muscle strength or
physical performance (EWGSOP pre-sarcopenia)
C. Older people with low muscle mass plus low muscle strength and/or
low physical performance (EWGSOP sarcopenia)
Intervention 3. Does the study evaluate caloric Caloric and protein supplementation including:
interventions? A. Studies in which the effect of caloric/protein supplementation is com-
4. Are these interventions aimed at pre- pared with no supplementation
vention or treatment of sarcopenia? B. Studies in which caloric/protein supplementation is added to an exer-
cise program and compared with a control group of exercise without
supplementation
C. Barriers and motivators to initiate, adhere, and change related lifestyle
Outcomes 6. Does the study report effects on sarco- Relevant outcomes include:
penia-related outcomes? A. muscle mass
B. muscle strength
C. muscle endurance
D. flexibility
E. morbidity
F. disability
G. death
H. quality of life
I. function and participation
J. adverse events
Abbreviation: EWGSOP, European Working Group on Sarcopenia in Older People.
Study selection Data extraction and methodological quality
assessment
Systematic reviews in English reporting the effect of ca-
loric or nutritional supplementation (with or without Data extraction was completed by 1 author (A.D.) and
an exercise program) on 1 or more of the 3 criteria of verified by a second author (D.B.) using a data extrac- 25
5 sarcopenia in older adults 65 years (ie, muscle mass, tion form based on a template provided by the
muscle strength, or physical performance) were consid- Cochrane Collaboration.17 The authors extracted data
ered eligible for inclusion in this umbrella review. regarding the key characteristics of the reviews, includ-
Original studies, editorials, letters to the editor, and ing participants, treatment, and outcomes. No assump-
narrative reviews were excluded. Animal studies and tions were made on missing or unclear data. 30
10 studies in patients with ongoing diseases were also ex- Two authors (D.B., A.D.) assessed the methodolog-
cluded (Table 1). Reviews reporting on the effects of ical quality of the systematic reviews using the A
vitamin D supplementation were not taken into consid- Measurement Tool to Assess Systematic Reviews
eration, because these were investigated and recently (AMSTAR) (Appendix S3 in the Supporting Information
published by the Working Group on Pharmacology.13 online).18,19 This 11-item tool assesses the degree to 35
15 Four authors (D.B., E.G., S.D.B., M.V.), blinded to each which review methods avoided bias. The methodologi-
other’s results, screened the titles and abstracts for du- cal quality was rated as high (score 8–11), moderate
plicate studies and for eligibility using the Rayyan web (score 4–7) or low (score 0–3). A quality assessment of
application for systematic reviews.16 Subsequently, full- the studies included in the systematic reviews was not
text articles were screened by the same authors. performed. 40
20 Disagreements were resolved by discussion until con- To organize the evidence, 3 authors (D.B., A.D.,
sensus was reached. E.G.) systematically synthesized the extracted data of
Nutrition ReviewsV Vol. 00(0):1–27
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3Inial Quality of Body of Evidence AMSTAR
1. High (4) if meta-analysis 1. -1 if review of moderate quality
(AMSTAR score of 4–7)
2. Moderate (3) of no meta-analysis 2. -2 if review of low quality
(AMSTAR score of 0–3)
Figure 1 Method used to rate the quality of the evidence supporting each bottom-line statement. Abbreviation: AMSTAR, A
Measurement Tool to Assess Systematic Reviews.18
each review. This resulted in standardized effectiveness exercise,28,29,31,33 EAA supplementation plus (various
statements (ie, sufficient evidence, some evidence, in- types of) physical exercise,28,29,33 HMB supplementation
sufficient evidence, insufficient evidence to determine) plus (various types of) physical exercise,29,33 and multi-
about the treatment effect of the intervention(s) in the nutrient supplementation plus (various types of) physi- 45
5 individual systematic reviews (Appendix S4 in the cal exercise.31,33 “Various types of physical exercise”
Supporting Information online). In addition, 2 authors indicates that, in those reviews, the exercise program
(D.B., E.G.) developed an overall synthesis, beyond a was not specified or consisted of a multimodal exercise
simple summary of the main results of each review. program (eg, the combination of progressive resistance
These are the “bottom-line statements” about the main training with balance training or a walking program). 50
10 effects of each intervention category. The quality of the The following sections start with an evaluation of
evidence (QoE) supporting each bottom-line statement the effect of different nutritional interventions on mus-
was rated by using a method based on the Grading of cle mass, muscle strength, and physical performance,
Recommendations Assessment, Development and leading to bottom-line statements and recommenda-
Evaluation (GRADE) approach for primary evidence tions within each intervention category. Importantly, 55
15 (1 ¼ very low; 2 ¼ low; 3 ¼ moderate; 4 ¼ high) for most of the nutritional interventions, this umbrella
(Figure 118).20 This method takes into account study de- review could not distinguish the effect in sarcopenic
sign (meta-analysis: yes or no) and AMSTAR rating of individuals from the effect in healthy subjects, because
the included systematic reviews. most of the reviews did not specify the sarcopenia status
of the participants. 60
Table 222–35 presents an overview of the included
RESULTS
systematic reviews together with the standardized effec-
tiveness statements and AMSTAR score of the individ-
20 Included studies
ual reviews. The bottom-line statements about the main
effects of each intervention together with the QoE sup- 65
A total of 516 studies were screened for eligibility
porting each bottom-line statement are presented in
(Figure 215). After removal of duplicates and screening
Tables 2 and 3. Table 4 gives an overview of the recom-
of titles and abstracts, 448 records were excluded and
mendations for each intervention category.
53 additional records were removed after assessment of
25 the full texts. Eventually, 15 systematic reviews were in-
cluded,21–35 of which a meta-analysis had been con- Protein supplementation
ducted in 6.21–24,30,34 In 1 of these, the meta-analysis
was performed for body composition but not for muscle Five systematic reviews provided data on protein 70
strength and physical performance.24 AMSTAR scores supplementation only,23,26–29 of which 1 included a
30 varied between 328,31 and 922 (Figure 318). meta-analysis.23 Four systematic reviews (1 with a
The included reviews examined the effects of nutri- meta-analysis34) evaluated the combination of protein
tional interventions on muscle mass, muscle strength, supplementation and resistance training27,32,34,35 and 4
and/or physical performance. Effects on sarcopenia as a (without meta-analyses) evaluated the combination 75
construct were reported in none of the included with various types of physical exercise.28,29,31,33
35 reviews. The following interventions were examined: Most systematic reviews with, in general, low to
supplementation with protein,23,26–29 essential amino moderate AMSTAR scores indicated either insufficient
acids (EAAs),21,25,29 leucine,22,25,29,30 and b-hydroxy-b- evidence or were unable to determine whether protein
methylbutyrate (HMB)24,29; and protein supplementa- supplementation alone is effective to improve muscle 80
tion plus resistance training,27,32,34,35 creatine supple- mass, strength, and/or physical performance.26,28,29 One
40 mentation plus resistance training,28,31,33 protein meta-analysis of moderate quality showed, in a small
supplementation plus (various types of) physical number of participants, some evidence in favor of no
4 Nutrition ReviewsV Vol. 00(0):1–27
RFigure 2 PRISMA flowchart of study selection process. Abbreviation: PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-
Analyses.15
difference between protein supplementation and pla- moderate quality, sufficient evidence in favor of the
cebo on muscle mass and muscle strength.23 In con- combined intervention on muscle mass and strength,
trast, a large systematic review of moderate quality, but only in persons with a body mass index 30 kg/m2
including 2940 individuals, showed some evidence in and, for muscle mass, also when the duration of the in- 30
5 favor of protein supplementation on muscle mass.27 tervention was longer than 24 weeks.34 Together, the
According to this review, a recommended dietary allow- data in this umbrella review show a significant additive
ance of 0.83 g of good-quality protein per kilogram effect of protein supplementation on top of resistance
body weight per day represents the minimum dietary training on muscle mass and muscle strength in persons
protein need of virtually all healthy elderly with obesity and, for muscle mass, also in persons with 35
10 persons.27Together, the data in this umbrella review a duration of intervention of 24 weeks, but no clear
suggest a positive effect of protein supplementation on additive effect on physical performance. In conclusion,
muscle mass, whereas no clear effect has been reported to achieve optimal effects on muscle mass and strength
on muscle strength and physical performance. On the in older adults, particularly those who are obese, protein
basis of the current evidence, proteins may be consid- supplementation is recommended in combination with 40
15 ered an intervention to increase muscle mass (QoE resistance training, with a minimum duration of
level, 2). 24 weeks to increase muscle mass (QoE level, 3).
When combined with resistance training, 2 system- When combined with a multimodal exercise pro-
atic reviews of moderate to high quality were unable to gram, 2 systematic reviews of moderate to low quality
determine whether this combined intervention is more found insufficient evidence to determine whether the 45
20 effective to improve muscle mass than resistance train- combination of protein supplementation with physical
ing alone.27,32 There was some evidence from 2 system- exercise is more effective than no treatment or than the
atic reviews of moderate quality in favor of no multimodal exercise program alone to improve muscle
difference between the combined intervention vs resis- mass or muscle strength.28,29 Most of the reviews
tance training alone on body composition, muscle showed some evidence in favor of no difference on 50
25 strength, or physical performance.34,35 However, 1 of muscle mass, muscle strength, and/or physical perfor-
these systematic reviews showed, in a meta-analysis of mance.29,31,33 The quality of these reviews was low to
Nutrition ReviewsV Vol. 00(0):1–27
R
5Figure 3 A Measurement Tool to Assess Systematic Reviews scores. 2 indicates “no”; ? indicates “cannot answer/not applicable”; 1 indi-
cates “yes.”
moderate. There was 1 systematic review of low quality whey proteins were consumed directly after resistance
that showed some evidence in favor of the combined in- training.36 However, due to the low number of partici-
tervention on muscle mass when compared with an ex- pants in these reviews, the evidence was considered in-
ercise program alone.28 In the individual trials in these sufficient to determine the adverse effect of protein 25
5 4 reviews, the exercise intervention varied widely but supplementation.
generally consisted of progressive resistance training
with or without additional exercises such as balance Essential amino acid supplementation
training, aerobic exercises, or a walking program,28,31,33
or was not specified.29 Together, these data suggest a The reviews included in this section did not specify the
10 positive effect of protein supplementation on top of content of the EAA supplement. Reviews specifically
physical exercise on muscle mass, but not on muscle assessing the effect of leucine, a branched-chain amino 30
strength or physical performance. In conclusion, pro- acid (AA), are discussed in the next section. Three sys-
teins on top of physical exercise may be considered to tematic reviews provided data on supplementation with
increase muscle mass, but not for improving muscle EAA.21,25,29 In 1, a meta-analysis was performed.21
15 strength and physical performance (QoE level, 2). Three systematic reviews (all without meta-analysis)
Two systematic reviews examined the adverse evaluated the combination of EAA supplementation 35
effects of proteins alone28 or combined with resistance with various types of physical exercise.28,29,33
training.32 The intake of 1.0 to 1.4 g of proteins per kilo- Two systematic reviews of moderate quality
gram body weight per day was not associated with ad- showed either insufficient evidence or were unable to
20 verse events.28 In particular, renal function was not determine whether EAA supplementation alone is effec-
affected by a 12-week intervention in which 20 g of tive to improve muscle mass, muscle strength, and/or 40
6 Nutrition ReviewsV Vol. 00(0):1–27
RTable 2 Results of the individual systematic reviews
Reference S BC MS PP AE No. of studies MA Results/findingsa Standardized ef- AMSTAR Bottom-line statement about QoE
(no. of fectiveness the main effects of interven-
participants) statement tions and recommendation
R
within each intervention
category
Protein supplementation Data suggest a positive effect
Malafarina et al v 2 (311) N FFM: “Could not find significant differen- Insufficient 5 of protein supplementation 2
(2013)29 ces due to treatment in FFM.” evidence on muscle mass. No clear ef-
Nutrition ReviewsV Vol. 00(0):1–27
FFM: “No change” fect has been reported on
Naseeb et al v 3 (828) N aLM: “Protein intake was a positive pre- Insufficient 3 muscle strength and physical
(2017)28 dictor of change in aLM over 2.6 y evidence performance.
(P ¼ 0.003) after adjustment for energy
intake. Protein intake was a significant In conclusion, based on the
independent positive predictor of conflicting evidence, protein
change in aLM (P ¼ 0.007). In addition, supplementation may be
protein intake was negatively associ- considered an intervention
ated with the rate of muscle loss and to increase muscle mass.
positively associated with muscle mass,
but not muscle strength. Consequently,
protein reduced the progression of
sarcopenia.”
Muscle mass: “No significant changes in
muscle mass”
Muscle cross-sectional area: “Protein sup-
plementation (20 g twice daily) did
not decrease muscle loss (muscle cross
sectional area).”
Pedersen et al v 3 (2940) N 3/3 studies in favor of intervention Some evidence 6
(2014)27 The evidence is assessed as suggestive in favor of
regarding a positive relation between intervention
muscle mass and total protein intake in
the range of 13–20 E%.
The evidence is assessed as probable for
an EAR of 0.66 g good-quality protein/
kg BW/day based on nitrogen-balance
studies and the subsequent RDA of
0.83 g good-quality protein/kg BW/day
representing the minimum dietary pro-
tein needs of virtually all healthy elderly
persons.
Theodorakopo- v 1 (40) N Body composition: “No significant Insufficient evi- 8
ulos et al changes were seen in body dence to
(2017)26 determine
(continued)
7Table 2 Continued
Reference S BC MS PP AE No. of studies MA Results/findingsa Standardized ef- AMSTAR Bottom-line statement about QoE
(no. of fectiveness the main effects of interven-
8
participants) statement tions and recommendation
within each intervention
category
composition, in either experimental or
control groups.”
Xu et al v 6 (394) Y LBM: “Overall difference in mean change Some evidence 7
(2014)23 in LBM between treatment interven- in favor of no
tion and placebo was 0.34 kg, which difference
was not significant (95%CI, 0.42 to
1.10 kg, P ¼ 0.386).”
Malafarina et al v 2 (311) N Handgrip strength: “Improvement in the Insufficient 5
(2013)29 supplemented group compared with evidence
the control group.
Handgrip strength: “No change”
Naseeb et al v 3 (828) N Muscle strength: “No significant associa- Insufficient 3
(2017)28 tion between nutrient intake and mus- evidence
cle strength”
Muscle strength: “No significant changes
in muscle mass or muscle strength”
Muscle strength: “Protein supplementa-
tion (20 g twice daily) did not de-
crease muscle loss (muscle strength)”
Theodorakopo- v 1 (40) N Muscle strength: “The group receiving Insufficient evi- 8
ulos et al the extra protein noted a non-signifi- dence to
(2017)26 cant trend towards an increase in determine
strength (þ0.9% relative increase).
Although the control group experi-
enced a drop in strength (3.5%), the
difference between the two groups did
not achieve statistical significance
(P ¼ 0.06).”
Xu et al v 4 (354) Y Leg press: “Overall difference between Some evidence 7
(2014)23 treatment group and placebo in mean in favor of no
change from baseline to end of study difference
¼ 2.14 kg (95%CI, 10.92 to 15.20 kg,
P ¼ 0.748) (3 studies)”
Leg extension: “Overall difference be-
tween treatment group and placebo in
mean change from baseline to end of
study ¼ 2.28 kg (95%CI, 1.73 to 6.29
kg, P ¼ 0.265) (4 studies)”
Naseeb et al v 1 (65) N Physical performance: “Protein supple- Insufficient evi- 3
R
(2017)28 mentation significantly improved phys- dence to
ical performance after achieving a daily determine
protein intake from 1.0 to 1.4 g/kg
BW/day (P ¼ 0.02).”
Malafarina et al v 1 (210) N Reduction of functional limitations: 5
Nutrition ReviewsV Vol. 00(0):1–27
(2013)29 “There was a tendency to reduce
(continued)Table 2 Continued
Reference S BC MS PP AE No. of studies MA Results/findingsa Standardized ef- AMSTAR Bottom-line statement about QoE
(no. of fectiveness the main effects of interven-
participants) statement tions and recommendation
within each intervention
category
R
functional limitations, although this Insufficient evi-
outcome was not statistically dence to
significant.” determine
Naseeb et al v 1 (117) N Adverse events: “Consumption of 1.0 to Insufficient evi- 3
(2017)28 1.4 g of protein/kg BW/day was not as- dence to
sociated with any adverse events.” determine
Nutrition ReviewsV Vol. 00(0):1–27
EAA supplementation No clear effect has been
Malafarina et al v 1 (32) N FFM: “Dal Negro et al proved a significant Insufficient evi- 5 reported of EAA supplemen- 4
(2013)29 increase (P ¼ 0.05) of FFM in the group dence to tation on muscle mass, mus-
supplemented with EAA but the differ- determine cle strength and physical
ence was not significant compared to performance.
the control group.”
Yoshimura et al v 5 (501) Y ASM: WMD ¼ 0.34 kg (95%CI, 0.78 to Some evidence 8 In conclusion, EAA supplemen-
(2017)21 0.10, P ¼ 0.13) (3 articles) in favor of no tation should not be consid-
ASMI: WMD ¼ 0.15 kg/m2 (95%CI, 0.66 difference ered an intervention to
to 0.96, P ¼ 0.72) (1 article) increase muscle mass, muscle
FFM: WMD ¼ 3.3 kg (95%CI, 0.56 to strength, and physical
7.16, P ¼ 0.09) (1 article) performance.
Wandrag et al v 2 (26) N LBM: “Significantly higher after 3 months Insufficient evi- 6
(2015)25 of EAA compared to placebo” dence to
LBM: “Improvement (P ¼ 0.038)” determine
Yoshimura et al v 4 (475) Y Grip strength: WMD ¼ 0.36 kg (95%CI, Some evidence 8
(2017)21 1.40 to 0.67, P ¼ 0.49) (2 articles) in favor of no
Knee extension strength: WMD ¼ 0.11 difference
Nm/kg (95%CI, 0.03–0.20, P ¼ 0.008) (1
article)
Knee extension strength: WMD ¼ 1.61
Nm (95%CI, 5.43 to 2.20, P ¼ 0.41) (2
articles)
Knee extension strength: WMD ¼ 2.07 N
(95%CI, 18.77 to 22.91, P ¼ 0.85) (1
article)
Wandrag et al v 1 (12) N Leg strength: “Leg strength improvement Insufficient evi- 6
(2015)25 (P < 0.001)” dence to
determine
Malafarina et al v 1 (32) N Climbed steps: “In the trials by Dal Negro Insufficient evi- 5
(2013)29 et al a statistically significant increase dence to
of the functional state of the supple- determine
mented group, expressed as an in-
crease of steps climbed (P ¼ 0.01), was
observed.”
(continued)
910
Table 2 Continued
Reference S BC MS PP AE No. of studies MA Results/findingsa Standardized ef- AMSTAR Bottom-line statement about QoE
(no. of fectiveness the main effects of interven-
participants) statement tions and recommendation
within each intervention
category
Yoshimura et al v 3 (422) Y Usual walking speed: WMD ¼ 0.01 m/s Some evidence 8
(2017)21 (95%CI 0.06 to 0.04, P ¼ 0.66) (3 in favor of no
articles) difference
Wandrag et al v 2 (53) N Physical performance: “The results Insufficient 6
(2015)25 showed that the EAA mixture signifi- evidence
cantly improved nutritional status,
physical performance, muscle function
and levels of depression.”
Walking speed and functional assess-
ment: “Improvement in walking speed
(P ¼ 0.002) and functional assessment
(P ¼ .007)”
Leucine supplementation A significant effect of leucine
Komar et al v 10 (LBM) (426) Y LBM:MD ¼ 0.99 kg (95%CI, 0.43–1.55, Sufficient evi- 7 supplementation on muscle 3
(2015)30 P ¼ 0.0005) dence in favor mass is shown in persons
Healthy seniors: MD ¼ 0.05 kg of intervention with sarcopenia but not in
(95%CI, 1.55 to 1.46, P ¼ 0.95) (only sarco- healthy subjects. No clear ef-
Sarcopenic seniors: MD ¼ 1.14 kg penic seniors) fect has been reported on
(95%CI, 0.55–1.74, P ¼ 0.0002) muscle strength and physical
No effect on fat mass or percent body fat performance.
Xu et al v 4 (121) Y LBM: Pooled standardized difference in Some evidence 9
(2015)22 mean changes ¼ 0.18 (95%CI, 0.18 to in favor of no In conclusion, leucine supple-
0.54, P ¼ 0.318 (4 studies) difference mentation is recommended
Leg lean mass: Pooled standardized dif- for sarcopenic older people
ference in mean changes ¼ 0.006 to increase muscle mass.
(95%CI, 0.32 to 0.44, P ¼ 0.756 (3
studies)
Wandrag et al v 1 (29) N Muscle mass: “No differences after 3 Insufficient evi- 9
(2015)25 months of supplementation” dence to
determine
Malafarina et al v 2 (90) N Fat-free mass and fat mass: “In the trials Insufficient 5
(2013)29 conducted by Leenders et al and evidence
Verhoeven et al, the effect of leucine
supplementation was assessed, with
no change in fat free mass and fat
R
mass (measured with DXA) observed in
the supplemented groups over those
using a placebo.”
(continued)
Nutrition ReviewsV Vol. 00(0):1–27Table 2 Continued
Reference S BC MS PP AE No. of studies MA Results/findingsa Standardized ef- AMSTAR Bottom-line statement about QoE
R
(no. of fectiveness the main effects of interven-
participants) statement tions and recommendation
within each intervention
category
Komar et al v 5 (hand grip) Y No effect on handgrip strength or knee Some evidence 7
Nutrition ReviewsV Vol. 00(0):1–27
(2015)30 6 (knee extension strength in favor of no
extension difference
strength)
(578)
Wandrag et al v 1 (29) N Muscle strength: “No difference after 3 Insufficient evi- 9
(2015)25 months of supplementation” dence to
determine
Malafarina et al v 2 (90) N Thigh strength: “Leenders et al found a Insufficient 5
(2013)29 statistically significant (P < 0.001) in- evidence
crease of thigh strength after a 6-
month follow-up in both the supple-
mented and the control group, but the
difference between them was not sig-
nificant. The same outcome was ob-
served by Verhoeven et al.”
HMB supplementation Data suggest a positive effect
Malafarina et al v 1 (104) N FFM: “Baier et al demonstrated a signifi- Insufficient evi- 5 of HMB supplementation on 4
(2013)29 cant increase of FFM in the group sup- dence to muscle mass. No clear effect
plemented with HMB compared with determine has been reported on muscle
the control group. 1/1 article in favour strength and physical
of intervention.” performance.
Wu et al v 7 (287) Y FM: SMD ¼ 0.08 kg (95%CI, 0.32 to Sufficient evi- 8
(2015)24 0.159, P ¼ 0.511) dence in favor In conclusion, based on the
Muscle mass: SMD ¼ 0.352 kg (95%CI, of intervention conflicting evidence, HMB
0.11–0.594, P ¼ 0.004) supplementation may be
Malafarina et al v 2 (161) N Handgrip strength: “Baier et al found a Insufficient evi- 5 considered an intervention
(2013)29 decrease of handgrip strength in both dence to to increase muscle mass.
the supplemented and control groups, determine
whereas Flakoll et al observed a statis-
tically significant improvement
(P ¼ 0.04) of this parameter in the sup-
plemented group.”
(continued)
11Table 2 Continued
Reference S BC MS PP AE No. of studies MA Results/findingsa Standardized ef- AMSTAR Bottom-line statement about QoE
(no. of fectiveness the main effects of interven-
participants) statement tions and recommendation
12
within each intervention
category
Wu et al v 5 (238) N 2/5 studies in favor of intervention Some evidence 8
(2015)24 in favor of no
difference
Wu et al v 4 (214) N 2/4 studies in favor of intervention Insufficient 8
(2015)24 evidence
Protein supplementation 1 progressive resistance training (PRT) A significant additive effect of
Colonetti et al v 1 (80) N LBM ¼ 0.26 (95%CI, 0.43 to 0.95) (aver- Insufficient evi- 8 protein supplementation on 3
(2017)32 age difference between supplementa- dence to top of resistance training on
tion þ PRT vs control þ PRT) determine muscle mass and muscle
Fat mass: 0.12 (95%CI, 0.87–0.64) strength is shown in persons
(P ¼ 0.41) (supplementation vs control) with obesity (BMI 30) and,
Liao et al v 16 (LBM) (802) Y LBM: SMD ¼ 0.58 (95%CI, 0.32–0.84, Sufficient evi- 7 for muscle mass, also in per-
(2017)34 8 (aLM) (566) P < 0.0001; I2 ¼ 66%; P < 0.0001) dence in favor sons with a duration of inter-
11 (AFM) (633) Subgroup duration 24 wk: of intervention vention of 24 wk. No clear
15 (BF%) (752) SMD ¼ 0.66 (95%CI, 0.35–0.97; for obese (BMI additive effect has been
6 (muscle P < 0001; I2 ¼ 41%; P ¼ 0.13) 30) or dura- reported on physical
volume) (242) Subgroup BMI 30 kg/m2: tion of inter- performance.
SMD ¼ 0.53 (95%CI, 0.19–0.87, vention 24
P ¼ 0.002; I2 ¼ 35%; P ¼ 0.19) weeks In conclusion, to achieve opti-
aLM: SMD ¼ 0.33 (95%CI, 0.07–0.60, mal effects on muscle mass
P ¼ 0.01; I2 ¼ 51%, P ¼ 0.04) and muscle strength in older
Absolute FM: SMD ¼ 0.61 (95%CI, adults, particularly those who
0.93 to 0.29, P ¼ 0.0002; I2 ¼ 72%, are obese, protein supple-
P ¼ 0.0001) mentation in combination
BF%: SMD ¼ 1.14 (95%CI 1.67 to with resistance training is
0.60, P < 0.0001; I2 ¼ 90%, recommended (with a mini-
P ¼ 0.00001) mum duration of 24 wk to in-
Muscle volume: SMD ¼ 1.23 (95%CI, crease muscle mass).
0.50–1.96, P ¼ 0.001; I2 ¼ 83%,
P ¼ 0.00001)
Pedersen et al v 2 (55) N Body composition: “The evidence is Insufficient evi- 6
(2014)27 assessed as inconclusive regarding the dence to
relation of total protein intake and determine
sources of protein (animal versus vege-
table protein) to muscle mass and
body composition in combination with
resistance training.”
Thomas et al v 9 (615) N LBM/FM/FM%/total MM/FFM/muscle Some evidence 6
(2016)35 size: “Five measurements from 2 studies in favor of no
R
(out of 9 studies) indicated significant difference
differences between groups, with
greater increases in LBM, leg LTM, ap-
pendicular LTM and FM in the supple-
mented groups compared with the
Nutrition ReviewsV Vol. 00(0):1–27
exercise-only controls.”
(continued)Table 2 Continued
Reference S BC MS PP AE No. of studies MA Results/findingsa Standardized ef- AMSTAR Bottom-line statement about QoE
(no. of fectiveness the main effects of interven-
participants) statement tions and recommendation
within each intervention
R
category
Muscle size: “7/8 studies reported signifi-
cant increases in supplemented (þPRT)
and non-supplemented (PRT only)
Nutrition ReviewsV Vol. 00(0):1–27
groups, but with no significant differen-
ces between the groups.”
Thomas et al v 15 (917) N Knee extension and hand grip strength: Some evidence 6
(2016)35 “3/15 reported significant differences in favor of no
between control (PRT only) and sup- difference
plemented (protein þ PRT) groups,
with greater improvements in the sup-
plemented groups in measures of knee
extension strength and hand grip
strength.”
Liao et al v 6 (handgrip Y Handgrip strength: “No significant differ- Sufficient evi- 7
(2017)34 strength) (357) ence in the increase in handgrip dence in favor
13 (leg strength) strength” of intervention
(668) Leg strength: SMD ¼ 0.69 (95%CI, 0.39– for leg
0.98, P < 0.00001; I2 ¼ 67%, P ¼ 0.0001) strength in
Subgroup men: SMD ¼ 0.87 (95%CI, people with
0.43–1.31, P< 0.001; I2 ¼ 51%, obesity (BMI
P ¼ 0.06) 30)
Subgroup BMI 30 kg/m2: SMD ¼ 0.88
(95%CI, 0.42–1.34; P ¼ 0.0004;
I2 ¼ 26%, P ¼ 0.26)
Liao et al v 10 (654) Y Gait speed, 6-min, or 400-m walk test, Some evidence 7
(2017)34 chair rise time, stair climbing test, in favor of no
physical activity test, functional reach difference
test, SPPB: “Non-significant treatment
effects on gait speed, physical activity,
timed up-and go and chair rise time in
favour of protein supplementation”
Colonetti et al v 1 (144) N Renal function: “Not negatively affected Insufficient evi- 8
(2017)32 after 20 g of whey protein dence to
supplementation” determine
Creatine supplementation 1 PRT Data suggest a positive effect
Beaudart et al v 5 (167) N Muscle mass: 4/5 studies in favor of an Some evidence 7 of creatine supplementation 2
(2017)33 additional effect of creatine supple- in favor of on top of progressive resis-
mentation on top of exercises intervention tance training on muscle
Denison et al v 2 (69) N FFM: 2/2 studies showed greater gains 3 mass and muscle strength.
(2015)31 among supplemented participants
13
(continued)14
Table 2 Continued
Reference S BC MS PP AE No. of studies MA Results/findingsa Standardized ef- AMSTAR Bottom-line statement about QoE
(no. of fectiveness the main effects of interven-
participants) statement tions and recommendation
within each intervention
category
who received exercise training, com- Some evidence No clear effect has been
pared with the placebo groups that in favor of reported on physical
only received exercise training. intervention performance.
Creatine supplementation on
top of progressive resistance
training may be considered
an intervention to increase
muscle mass and muscle
strength.
Naseeb et al v 2 (78) N Muscle mass and FFM: “Creatine supple- Some evidence 3
(2017)28 mentation with resistance training in- in favor of
creased muscle mass (D% ¼ þ2.8%) intervention
and FFM (D% ¼ þ3.2%). The increase
was greater than in the exercise only
group (P < 0.05).”
aLM: “Creatine supplementation with re-
sistance training improved aLM. The in-
crease was greater than in the exercise
only group.”
Beaudart et al v 5 (167) N Muscle strength: 4/5 studies in favor of Some evidence 7
(2017)33 an additional effect of creatine for in favor of
some strength outcomes intervention
Denison et al v 2 (69) N Muscle strength: 2/2 studies showed Some evidence 3
(2015)31 greater improvements in participants in favor of
supplemented with creatine, compared intervention
with the placebo groups. All groups
also received exercise training.
Naseeb et al v 1 (18) N 1 RM strength: “Creatine supplementa- Insufficient evi- 3
(2017)28 tion with resistance training increased dence to
1RM strength (D ¼ þ5.1%). The determine
R
(continued)
Nutrition ReviewsV Vol. 00(0):1–27Table 2 Continued
Reference S BC MS PP AE No. of studies MA Results/findingsa Standardized ef- AMSTAR Bottom-line statement about QoE
(no. of fectiveness the main effects of interven-
participants) statement tions and recommendation
R
within each intervention
category
increase was greater than in the exer-
cise only group (P < 0.05).”
Beaudart et al v 4 (147) N Physical performance: 1/4 studies in favor Some evidence 7
Nutrition ReviewsV Vol. 00(0):1–27
(2017)33 of an interactive effect of creatine in favor of no
difference
Denison et al v 2 (69) N Physical performance: 0/2 studies Some evidence 3
(2015)31 showed evidence of additional benefits in favor of no
arising from supplementation on top difference
of exercise training.
Nutritional supplementation 1 physical exercise program
Protein (or: protein or EAA) supplementation þ physical exercise program Data suggest a positive effect
Beaudart et al v 12 (1049) N Muscle mass: 3/12 studies showed addi- Some evidence 7 of protein supplementation 2
(2017)33 tional effect of protein supplementa- in favor of no on top of physical exercise
tion on top of exercises difference on muscle mass but not on
Denison et al v 7 (646) N Muscle size: 5/7 studies showed no inter- Some evidence 3 muscle strength and physical
(2015)31 action between exercise training and in favor of no performance.
protein/EAA supplementation on mus- difference
cle mass, cross-sectional area, or lean In conclusion, protein supple-
body mass. mentation on top of physical
Lean mass: 1/7 studies showed evidence exercise may be considered
of increase in lean mass after HMB sup- to increase muscle mass, but
plementation (HMB þ PRT vs placebo not for muscle strength and
þPRT, P ¼ 0.08). physical performance.
Lean body mass: 1/7 studies showed in-
teractive effects when following a resis-
tance exercise training program and
consuming protein-supplemented
drinks.
Malafarina et al v 1 (149) N FFM: “No changes following physical ex- Insufficient evi- 5
(2013)29 ercise and supplementation, compared dence to
with the group with no treatment (no determine
exercise and no supplementation)”
Naseeb et al v 2 (162) N Lean body mass: “Lean body mass in- Some evidence 3
(2017)28 creased in protein supplemented group in favor of
compared with the placebo group intervention
(P ¼ 0.006). Both groups performed
PRT.”
(continued)
1516
Table 2 Continued
Reference S BC MS PP AE No. of studies MA Results/findingsa Standardized ef- AMSTAR Bottom-line statement about QoE
(no. of fectiveness the main effects of interven-
participants) statement tions and recommendation
within each intervention
category
Lean tissue mass and fat mass: “Protein
intake of 1.3 g/kg BW/day enhanced
PRT effects on lean tissue mass
(P < 0.05) and decreased fat mass
(P < 0.05) and percent of body fat
(P < 0.01).”
Beaudart et al v 12 (909) N Muscle strength: 3/12 studies showed ad- Some evidence 7
(2017)33 ditional effect of protein on top of in favor of no
exercises difference
Denison et al v 7 (646) N Muscle strength: Some evidence 3
(2015)31 6/7 studies: No interaction between in favor of no
protein/EAA supplementation and difference
exercise training
1/7 study: Additional gains from EAA
supplementation combined with a
multicomponent exercise training
program in sarcopenic community-
dwelling women older than 75 y
Naseeb et al v 1 (100) N Muscle strength: “Protein intake of 1.3 g/Insufficient evi- 3
(2017)28 kg BW/day enhanced PRT effects on dence to
muscle strength (P < 0.05).” determine
Beaudart et al v 9 (793) N Physical performance: “No additional ef- Some evidence 7
(2017)33 fect of protein on top of exercises” in favor of no
difference
Denison et al v 4 (569) N Physical performance: 0/4 studies Some evidence 3
(2015)31 showed additional improvement of the in favor of no
combination of exercise training and difference
protein/EAA supplementation
Malafarina et al v 2 (326) N Berg Balance Scale: “Improvement in Some evidence 5
(2013)29 measurements with the Berg Balance in favor of no
Scale for exercise with and without sup- difference
plementation, but not specified
R
whether this improvement was
significant.”
(continued)
Nutrition ReviewsV Vol. 00(0):1–27Table 2 Continued
Reference S BC MS PP AE No. of studies MA Results/findingsa Standardized ef- AMSTAR Bottom-line statement about QoE
(no. of fectiveness the main effects of interven-
participants) statement tions and recommendation
within each intervention
R
category
Walking speed: “Walking ability de-
creased in a significant way in the con-
trol group (no exercise and no
supplementation) compared with the
Nutrition ReviewsV Vol. 00(0):1–27
supplemented group. Walking capacity
remained constant in trained subjects
whereas it declined significantly in non-
trained groups, regardless of
supplementation.”
EAA supplementation þ physical exercise program No clear additive effect of EAA
Beaudart et al v 3 (196) N Muscle mass: “No additional effect of EAA Some evidence 7 supplementation on top of 2
(2017)33 on top of exercises” in favor of no physical exercise has been
difference reported on muscle mass,
Malafarina et al v 2 (183) N Leg muscle mass: “Significant increase in Some evidence 5 muscle strength and physical
(2013)29 the group treated with physical exer- in favor of performance.
cise and supplementation compared intervention
with the group without treatment (only In conclusion, EAA supplemen-
health education) (P ¼ 0.007)” tation on top of physical ex-
FFM: “Significant increase (P ¼ 0.05) in ercise should not be
the group supplemented with EAA, but considered an intervention
not significantly different compared to to increase muscle mass,
the control group. Both groups fol- muscle strength, and physi-
lowed an exercise program.” cal performance.
Naseeb et al v 1 (155) N Muscle mass: “Exercise with EAA supple- Insufficient evi- 3
(2017)28 mentation improved muscle mass in dence to
women with sarcopenia > 75y. determine
Exercise only did also improve muscle
mass, but EAA only did not.”
Beaudart et a. v 3 (196) N Muscle strength: “No additional effect of Some evidence 7
(2017)33 EAA on top of exercises” in favor of no
difference
Naseeb et al v 1 (155) N Muscle strength: “Exercise with EAA sup- Insufficient evi- 3
(2017)28 plementation improved muscle dence to
strength in women with sarcopenia determine
> 75y. EAA only and exercise only did
not improve muscle strength.”
Beaudart et al v 2 (179) N Walking speed and SPPB: “No additional Some evidence 7
(2017)33 effect of EAA on top of exercises” in favor of no
difference
(continued)
17Table 2 Continued
Reference S BC MS PP AE No. of studies MA Results/findingsa Standardized ef- AMSTAR Bottom-line statement about QoE
18
(no. of fectiveness the main effects of interven-
participants) statement tions and recommendation
within each intervention
category
Malafarina et al v 1 (155) N Walking speed: “Significant increase in Insufficient evi- 5
(2013)29 the groups treated with physical exer- dence to
cise (with or without EAA), compared determine
with the group with no treatment
(P ¼ 0.007)”
Naseeb et al v 1 (155) N Walking speed: “Exercise with EAA sup- Insufficient evi- 3
(2017)28 plementation improved walking speed dence to
in women with sarcopenia > 75y. EAA determine
only and exercise only did also im-
prove walking speed”
HMB supplementation þ physical exercise program No clear additive effect of HMB
Beaudart et al v 3 (103) N Muscle mass: 1/3 articles in favor of HMB Some evidence 7 on top of physical exercise 2
(2017)33 supplementation on top of exercises in favor of no has been reported on muscle
difference mass, muscle strength, and
Beaudart et al v 3 (103) N Muscle strength: “No additional effect of Some evidence 7 physical performance.
(2017)33 HMB supplementation on top of in favor of no
exercises” difference In conclusion, HMB supple-
Malafarina et al v 1 (31) N Leg curl strength: “Vukovich et al showed Insufficient evi- 5 mentation on top of physical
(2013)29 a significant improvement of leg curl dence to exercise should not be con-
in the HMB supplemented group com- determine sidered an intervention to in-
pared to the control group. Both crease muscle mass, strength
groups followed an exercise program.” and physical performance.
Beaudart et al v 2 (72) N Timed up-and-go test: “No additional ef- Some evidence 7
(2017)33 fect of HMB supplementation on top of in favor of no
exercises” difference
Multinutrient supplementation þ physical exercise program No clear additive effect of mul-
Beaudart et al v 4 (300) N Muscle mass: 0/4 studies showed an ad- Insufficient 7 tinutrient supplementation 2
(2017)33 ditional effect of multinutrient supple- evidence on top of physical exercise
mentation on top of exercises has been reported on muscle
Denison et al v 5 (?) N Muscle size: 0/6 studies showed evidence Insufficient 3 mass, muscle strength, and
(2015)31 of interactive effects of multinutrient evidence physical performance.
supplementation with exercise training
Beaudart et al v 5 (379) N Muscle strength: 1/5 studies showed an Insufficient 7 In conclusion, multinutrient
(2017)33 additional effect of multinutrient sup- evidence supplementation on top of
plementation on top of exercises physical exercise should not
Denison et al v 6 (659) N Muscle strength: 0/6 studies showed evi- Insufficient 3 be considered an interven-
(2015)31 dence of interactive effects of multinu- evidence tion to increase muscle mass,
R
trient supplementation with exercise muscle strength, and physi-
training cal performance.
Beaudart (et v 4 (304) N Physical performance: 0/4 studies Insufficient 7
al). 201733 showed an additional effect of multi- evidence
nutrient intervention on top of
Nutrition ReviewsV Vol. 00(0):1–27
exercises
(continued)physical performance.25,29 There was some evidence
QoE
analysis; MD, mean difference; MM, muscle mass; MMI, muscle mass index; MS, muscle strength; PP, physical performance; PRT, progressive resistance training; QoE, quality of evidence; RDA,
ASMI, appendicular muscle mass index; BC, body composition; BMI, body mass index (calculated as kg/m2); BW, body weight; CI, confidence interval; DXA, dual-energy X-ray absorptiometry;
event; aLM, appendicular lean mass; ASM, appendicular skeletal muscle mass;
from 1 meta-analysis of high quality in favor of no dif-
the construct that is addressed: sarcopenia (as a construct) or the sarcopenia subdimensions (muscle mass, muscle strength, physical performance) or adverse events; WMD, weighted mean
recommended dietary allowance; RM, repetition maximum; S, sarcopenia; SMD, standardized mean difference; SPPB, short physical performance battery; SR, systematic review; v, indicates
E%, energy percent; EAA, essential amino acid; EAR, estimated average requirement; FFM, fat-free mass; FM, fat mass; HMB, b-hydroxy-b-methylbutyrate; LBM, lean body mass; MA, meta-
Bottom-line statement about ference between EAA supplementation and placebo.21
the main effects of interven-
tions and recommendation
within each intervention
Together, no clear effect has been reported of EAA sup-
plementation only on muscle mass, muscle strength, 45
category and physical performance. In conclusion, EAA supple-
mentation should not be considered to increase muscle
mass, strength, and physical performance (QoE level,
4).
Regarding the effects of EAA supplementation with 50
physical exercise, 2 systematic reviews of low to moder-
Standardized ef- AMSTAR
ate quality showed insufficient evidence to determine
3
the effect of the combined intervention on muscle mass,
muscle strength, or physical performance compared
with the effect of the exercise intervention alone, EAA 55
fectiveness
statement
supplementation alone, or no intervention.28,29 One
evidence
Insufficient
systematic review of moderate quality showed some evi-
dence in favor of no difference between EAA supple-
mentation and EAA supplementation on top of
of multinutrient supplementation with
showed evidence of interactive effects
exercise, either on muscle mass, muscle strength, or 60
physical performance.33 In contrast, another systematic
Physical performance: 0/6 studies
review of moderate quality showed some evidence in fa-
vor of the combined intervention when compared with
Results/findingsa
Abbreviations: ?, the number of studies was not mentioned in the systematic review/meta-analysis; AE, adverse
no treatment or with exercise alone.29 In the individual
trials in these reviews assessing the combined effect of 65
EAA supplementation and physical exercise, the exer-
exercise training
cise program was not specified29 or consisted of pro-
gressive resistance training combined with or without
balance, gait, or other exercises.28,33 Together, no clear
additive effect of EAA supplementation on top of physi- 70
cal exercise has been reported on muscle mass, muscle
strength, and physical performance. In conclusion,
MA
N
EAA supplementation on top of physical exercise
should not be considered an intervention to increase
No. of studies
participants)
muscle mass, muscle strength, and physical perfor- 75
(no. of
mance (QoE level, 2).
6 (659)
Leucine supplementation
AE
Four systematic reviews examined the effect of leucine
supplementation only.22,25,29,30 Of these, a meta-analysis
was performed in 2.22,30 In 1 of these reviews, a sub-
PP
v
80
group analysis was performed to differentiate between
healthy and sarcopenic persons.30
MS
One systematic review of high quality was unable
to determine whether leucine supplementation alone is
BC
Outcomes are underlined.
effective to improve muscle mass or strength.25 One 85
systematic review of moderate quality showed insuffi-
S
Table 2 Continued
cient evidence that leucine supplementation is more ef-
fective to improve muscle mass and muscle strength
Denison et al
compared with the nonsupplemented group,29 whereas
difference.
(2015)31
Reference
2 systematic reviews of moderate to high quality showed 90
some evidence in favor of no difference between leucine
a
and placebo.22,30 However, there was sufficient evidence
Nutrition ReviewsV Vol. 00(0):1–27 R
19Table 3 Bottom-line statements with quality of evidence about the main effects of interventions within each intervention
category
Intervention Bottom-line statement about the main effects of interventions within each interven- QoEa
tion category
Nutritional supplementation only
Protein supplementation Data suggest a positive effect of protein supplementation on muscle mass. No clear ef- 2
fect has been reported on muscle strength and physical performance.
EAA supplementation No clear effect has been reported of EAA supplementation on muscle mass, muscle 4
strength, and physical performance.
Leucine supplementation A significant effect of leucine supplementation on muscle mass is shown in persons 3
with sarcopenia but not in healthy subjects. No clear effect has been reported on
muscle strength and physical performance.
HMB supplementation Data suggest a positive effect of HMB supplementation on muscle mass. No clear ef- 4
fect has been reported on muscle strength and physical performance.
Nutritional supplementation 1 progressive resistance training
Protein supplementation þ A significant additive effect of protein supplementation on top of resistance training 3
progressive resistance on muscle mass and muscle strength is shown in persons with obesity (BMI 30)
training and, for muscle mass, also in persons with a duration of intervention of 24 wk. No
clear additive effect has been reported on physical performance.
Creatine supplementation þ Data suggest a positive effect of creatine supplementation on top of progressive resis- 2
progressive resistance tance training on muscle mass and muscle strength. No clear effect has been
training reported on physical performance.
Nutritional supplementation 1 (various types of) physical exercise
Protein supplementation þ Data suggest a positive effect of protein supplementation on top of physical exercise 2
physical exercise on muscle mass, but not on muscle strength and physical performance.
EAA supplementation þ No clear additive effect of EAA supplementation on top of physical exercise has been 2
physical exercise reported on muscle mass, muscle strength, and physical performance.
HMB supplementation þ No clear additive effect of HMB supplementation on top of physical exercise has been 2
physical exercise reported on muscle mass, muscle strength, and physical performance.
Multinutrient supplementa- No clear additive effect of multinutrient supplementation on top of physical exercise 2
tion þ physical exercise has been reported on muscle mass, muscle strength, and physical performance.
a
QoE supporting each bottom-line statement is based on the Grading of Recommendations Assessment, Development and Evaluation
approach for primary evidence: 1, very low; 2, low; 3, moderate; 4, high.
Abbreviations: BMI, body mass index (calculated as kg/m2); BW, body weight; EAA, essential amino acid; HMB, b-hydroxy-b-methylbuty-
rate; QoE, quality of evidence.
Table 4 Recommendations with quality of evidence for each intervention category
Protein supplementation
• Protein supplementation alone may be considered as an intervention to increase muscle mass (low QoE).
• Protein supplementation in combination with progressive resistance training (with a minimum duration of 24 wk to increase
muscle mass) is recommended to achieve optimal effects on muscle mass and muscle strength in older adults, particularly those who
are obese (moderate QoE).
• Protein supplementation on top of physical exercise may be considered to increase muscle mass, but not muscle strength and
physical performance (low QoE).
EAA supplementation
• EAA supplementation alone should not be considered an intervention to increase muscle mass, muscle strength, and physical perfor-
mance (high QoE).
• EAA supplementation on top of physical exercise should not be considered an intervention to increase muscle mass, muscle
strength, and physical performance (low QoE).
Leucine supplementation is recommended for sarcopenic older people to increase muscle mass (moderate QoE).
HMB supplementation
• HMB supplementation alone may be considered an intervention to increase muscle mass (high QoE).
• HMB supplementation on top of physical exercise should not be considered an intervention to increase muscle mass, strength and
physical performance (low QoE).
Creatine supplementation on top of progressive resistance training may be considered an intervention to increase muscle mass
and muscle strength (low QoE).
Multinutrient supplementation on top of physical exercise should not be considered an intervention to increase muscle mass, mus-
cle strength, and physical performance (low QoE).
Abbreviations: EAA, essential amino acid; HMB, b-hydroxy-b-methylbutyrate; QoE, quality of evidence.
from 1 meta-analysis in favor of leucine supplementa- muscle mass is shown in persons with sarcopenia but
tion on muscle mass, but only in sarcopenic older per- not in healthy subjects. No clear effect has been 5
sons.30 Together, a significant effect of leucine on reported on muscle strength and physical performance.
20 Nutrition ReviewsV Vol. 00(0):1–27
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