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nutrients
Review
Is Branched-Chain Amino Acids Supplementation an
Efficient Nutritional Strategy to Alleviate Skeletal
Muscle Damage? A Systematic Review
Alexandre Fouré* and David Bendahan
Aix Marseille University, CNRS, Centre de Résonance Magnétique Biologique et Médicale (CRMBM), UMR 7339,
Facultéde Médecine la Timone, 27 Boulevard Jean Moulin, 13385 Marseille, France;
david.bendahan@univ-amu.fr
*Correspondence: alexandre.foure@hotmail.fr; Tel.: +33-(0)4-9132-4803; Fax: +33-(0)4-9125-6539
Received: 22 August 2017; Accepted: 19 September 2017; Published: 21 September 2017
Abstract:
Amino acids and more precisely, branched-chain amino acids (BCAAs), are usually
consumed as nutritional supplements by many athletes and people involved in regular and moderate
physical activities regardless of their practice level. BCAAs have been initially shown to increase
muscle mass and have also been implicated in the limitation of structural and metabolic alterations
associated with exercise damage. This systematic review provides a comprehensive analysis of
the literature regarding the beneficial effects of BCAAs supplementation within the context of
exercise-induced muscle damage or muscle injury. The potential benefit of a BCAAs supplementation
was also analyzed according to the supplementation strategy—amount of BCAAs, frequency and
duration of the supplementation—and the extent of muscle damage. The review protocol was
registered prospectively with Prospective Register for Systematic Reviews (registration number
CRD42017073006) and followed Preferred Reporting Items for Systematic reviews and Meta-Analyses
guidelines. Literature search was performed from the date of commencement until August 2017 using
four online databases (Medline, Cochrane library, Web of science and ScienceDirect). Original research
articles: (i) written in English; (ii) describing experiments performed in Humans who received at
least one oral BCAAs supplementation composed of leucine, isoleucine and valine mixture only as a
nutritional strategy and (iii) reporting a follow-up of at least one day after exercise-induced muscle
damage, were included in the systematic review analysis. Quality assessment was undertaken
independently using the Quality Criteria Checklist for Primary Research. Changes in indirect
markers of muscle damage were considered as primary outcome measures. Secondary outcome
measures were the extent of change in indirect markers of muscle damage. In total, 11 studies were
included in the analysis. A high heterogeneity was found regarding the different outcomes of these
studies. The risk of bias was moderate considering the quality ratings were positive for six and
neutral for three. Although a small number of studies were included, BCAAs supplementation
can be efficacious on outcomes of exercise-induced muscle damage, as long as the extent of muscle
damage was low-to-moderate, the supplementation strategy combined a high daily BCAAs intake
(>200 mg kg
−1
day
−1
) for a long period of time (>10 days); it was especially effective if taken prior to
the damaging exercise.
Keywords:
branched-chain amino acids (BCAAs); exercise-induced muscle damage; skeletal muscle;
nutritional strategy
1. Introduction
In a recent report entitled “Protein Ingredients Market by Source (Animal and Plant), Application
(Food & Beverage, Animal Feed, Cosmetics & Personal Care and Pharmaceuticals), and Region—
Nutrients 2017,9, 1047; doi:10.3390/nu9101047 www.mdpi.com/journal/nutrients
Nutrients 2017,9, 1047 2 of 15
Forecast to 2022”, the market for protein ingredients was projected to reach 58.49 billion dollars by 2022
(i.e., compound annual growth rate of 6.0% from 2017). Indeed, Olympic as well as college athletes
and many people exercising in gyms regularly use supplements with amino acids representing 10–20%
of these nutritional strategies [
1
–
4
]. Branched chain amino acids (BCAAs)—i.e., leucine, isoleucine and
valine—account for almost 50% of the essential amino acids in food and 35% of the total content of
essential amino acids in muscle proteins [5,6].
BCAAs are important precursors of tricarboxylic acid (TCA) cycle intermediates via acetyl-CoA
and Succinyl-CoA [
7
] and can be involved in energy production through the modulation of
exercise-induced serum BCAAs oxidation [
8
]. In addition to their involvement as constitutive
elements of the structural and contractile proteins synthesis [
9
], BCAAs are also considered signaling
molecules [
10
]. Indeed, BCAAs and especially leucine have been reported to activate the mammalian
target of rapamycin signaling pathway [
11
,
12
], thereby promoting muscle-protein synthesis [
13
–
15
].
It has also been suggested that they could enhance mitochondrial biogenesis and reactive oxygen
species scavenging [7,16] leading to potential benefits in skeletal muscle energy metabolism [17–19].
Taking into account all the physiological mechanisms linked to BCAAs intake and that BCAAs
are mainly metabolized in skeletal muscle [
5
], whereas other essential amino acids are catabolized in
liver [
20
]; BCAAs supplementation has been considered as a potential nutritional strategy to avoid or at
least alleviate exercise-induced muscle damage or its consequences. Exercise-induced muscle damage
(EIMD) has been primarily associated with mechanical strain [
21
,
22
] and the subsequent inflammation
processes [
23
]. On that basis, it has been considered that diminished muscle-protein breakdown during
exercise [
24
] and the scavenging of reactive oxygen species [
7
] could alleviate structural and metabolic
alterations observed after EIMD [
25
,
26
]. In addition, the anabolic effect associated with BCAAs
consumption and especially leucine [
9
,
27
] has been considered a potential promoter of the repair
process of altered muscle tissues in part composed of proteins. However, so far, no imaging study has
ever reported direct evidence supporting these assumptions (e.g., [
28
]). Therefore, the occurrence of
muscle damage in all studies considered in this systematic review was assessed on the basis of EIMD
outcomes, including muscle function alteration (i.e., force loss), increased blood markers of muscle
damage (i.e., creatine kinase (CK), lactate dehydrogenase (LDH) and myoglobin) and delayed onset
muscle soreness.
The aim of this systematic review was to objectively describe the effects of BCAAs
supplementation on indirect markers of muscle damage considering studies reporting clinical trials
(cross-over design and randomized clinical trials with a control group) involving healthy subjects
supplemented with BCAAs only. Potential confounding factors were determined relating to the extent
of muscle damage (i.e., low, moderate and high) and the supplementation strategy (i.e., duration,
frequency and amount).
This systematic review provides a comprehensive analysis of the literature regarding the
assumption that BCAAs supplementation can alleviate alterations of skeletal muscle function acting on
exercise-induced muscle damage or muscle injury. Recommendations on the most efficient nutritional
strategy to minimize consequences of damage induced by exercise on muscle function are highlighted.
2. Methods
The pre-defined review protocol was registered prospectively with Prospective Register for
Systematic Reviews (PROSPERO—registration number: CRD42017073006). This systematic review was
completed in accordance with the recommendations of the Preferred Reporting Items for Systematic
reviews and Meta-Analyses (PRISMA) guidelines [29].
2.1. Eligibility Criteria
Criteria for study inclusion were chosen using the Population-Intervention-Comparator-Outcomes-
Study design (PICOS) format [
29
]. Articles and studies were included if they met all the following
criteria: (1) experiments performed in humans; (2) healthy subjects received at least one oral BCAAs
Nutrients 2017,9, 1047 3 of 15
supplementation as a nutritional strategy in the context of skeletal muscle damage (i.e., decrease
in muscle performance and/or increase in plasma/serum intracellular component concentration);
(3) supplementation only composed of leucine, isoleucine and valine; (4) follow up performed at
least one day after exercise-induced muscle damage or muscle injury; (5) original research articles;
and (6) written in English. Studies were excluded if the experimental group(s) undertook any
other practice that could be perceived as a strategy to alleviate muscle damage (e.g., massage,
cryotherapy). Outcome measures were changes in indirect markers of muscle damage, i.e., muscle
function performance (isometric force, jump height) and plasma/serum concentration of intracellular
components (creatine kinase, lactate dehydrogenase, myoglobin). Clinical trials using a control group
or a cross over design were included in the systematic review.
2.2. Search Strategy
The computerized literature search was performed from date of commencement until August 2017
using four online databases: Medline (PubMed), Cochrane library, Web of Science and ScienceDirect;
a supplementary Google Scholar search was also undertaken. The key words used to find relevant
papers were: (“muscle damage” OR “muscle injury” OR “exercise-induced muscle damage” OR
EIMD) AND (“nutritional strategy” OR “branched-chain amino acid” OR BCAA OR supplementation).
The reference sections of all identified articles were also examined.
2.3. Data Extraction and Quality Assessment
Data related to participants (sex, sample size, age), experimental design (randomization, blinding,
wash-out period in case of cross-over design, dietary control), exercise (intensity, volume and type of
exercise), outcome measures (muscle performance and blood analyses) and supplementation strategy
(duration, frequency, daily intake of BCAAs, relative concentration of leucine/isoleucine/valine) were
extracted. The quality of selected studies (i.e., corresponding to all eligibility criteria) were rated
using the Quality Criteria Checklist for Primary Research [
30
] to limit the risk of bias. Significant
and non-significant results were also exhaustively reported to objectively assess effects of each
supplementation strategy (combining duration, frequency and amount of daily BCAAs intake) on the
extent of muscle damage.
3. Analysis
A greater emphasis was placed on findings from studies achieving high-quality ratings. Significant
effects described in the included studies were extracted to quantify outcomes associated with the
damaging exercise and the BCAAs supplementation. Rating criteria were created according to the
supplementation strategy and the extent of muscle damage (Table 1). Due to the heterogeneity of the
study designs, interventions and outcomes, a meta-analysis was not undertaken.
Table 1.
Rating criteria concerning the supplementation strategy (i.e., duration, frequency and amount
of daily BCAAs intake) and the extent of muscle damage assessed from changes in indirect markers of
muscular alterations in the control group.
Category Rating Criteria
Supplementation
Strategy
Duration
Short The supplementation was performed on 3 days or less
Moderate The supplementation was performed between 4 and 10 days
Long The supplementation was performed for more than 10 days
Frequency Low Less than 2 intakes per day during the supplementation period
High 2 or more intakes per day during the supplementation period
Amount Low Less than 200 mg kg−1day−1of BCAAs intake
High 200 mg kg−1day−1or more of BCAAs intake
Nutrients 2017,9, 1047 4 of 15
Table 1. Cont.
Category Rating Criteria
Extent of Muscle Damage
Low
Low peak decrease in force (≤10% of baseline) and significant
peak change in CK/LDH/myoglobin at D1 (with no significant
difference in the following days)
Moderate
Moderate peak decrease in force (≥10% and ≤15% of baseline)
and significant peak change in CK/LDH/myoglobin at D1
(with significant difference in the following days)
High High peak decrease in force (>15% of baseline) and significant
peak change in CK/LDH/myoglobin after D2
4. Results
We initially identified two thousand one hundred and thirty-three papers from databases and
internet searches and included 11 studies in the present systematic review according to the 4-phase
flow diagram described in Figure 1.
The included studies were trials with numbers of subjects ranging from 9 to 30 and were conducted
in the last 20 years (Table 2). We identified large heterogeneity regarding supplementation strategies
and damaging exercise modalities leading to a large variability in the damage extents.
Nutrients 2017, 9, 1047 4 of 15
Amount Low Less than 200 mg kg−1 day−1 of BCAAs intake
High 200 mg kg−1 day−1 or more of BCAAs intake
Extent of Muscle Damage
Low
Low peak decrease in force (≤10% of baseline) and significant
peak change in CK/LDH/myoglobin at D1 (with no significant
difference in the following days)
Moderate
Moderate peak decrease in force (≥10% and ≤15% of baseline)
and significant peak change in CK/LDH/myoglobin at D1
(with significant difference in the following days)
High High peak decrease in force (>15% of baseline) and significant
peak change in CK/LDH/myoglobin after D2
4. Results
We initially identified two thousand one hundred and thirty-three papers from databases and
internet searches and included 11 studies in the present systematic review according to the 4-phase flow
diagram described in Figure 1.
The included studies were trials with numbers of subjects ranging from 9 to 30 and were conducted
in the last 20 years (Table 2). We identified large heterogeneity regarding supplementation strategies
and damaging exercise modalities leading to a large variability in the damage extents.
Figure 1. Study selection and flow diagram of articles included in the systematic review.
Figure 1. Study selection and flow diagram of articles included in the systematic review.
Nutrients 2017,9, 1047 5 of 15
Table 2. Studies included in the systematic review.
Study Population Study Design Damaging Exercise Supplementation Strategy
Outcomes
Soreness Blood Analysis
(Myoglobin/LDH/CK)
Muscle
Performance
Coombes &
McNaughton
(2000) [31]
16 healthy males
age: 21 ±1 years
˙
V
O
2max
: 52
±
4 mL min
−1
kg
−1
training status: regular
physical activity
CG (n= 8)
Dietary control
Cycling ergometer
exercise at 70%
˙
VO2max for 120 min
14 days of supplementation (7 days
before and 6 days after exercise).
2×6 g every day + 20 g before and
after the exercise
Amount of BCAA: 208 g (14 days)
LEU/ISO/VAL (1:1:1)
Placebo: no supplementation
-
CG > SG at H4, D1, D3
and D5 for CK
and LDH
-
Fouréet al.
(2016) [32]
26 healthy males
age: 22 ±2 years
training status:
recreationally active
RCT, DB
CG (n= 13)
Dietary control
Neuromuscular
Electrostimulation—40
isometric
knee extensions
5 days of supplementation (2 supp
before, 1 supp after exercise and 1
supp every day for 4 days)
Amount of BCAA: 48.3 g (5 days)
LEU/ISO/VAL (2:1:1)
Placebo: microcrystalline cellulose
CG = SG SG > CG at D4 for CK CG = SG for
the MVC
Gee & Deniel
(2016) [33]
11 healthy males
age: 25 ±6 years
training status:
resistance-trained
RCT, SB
Cross-over
(washout: 7 days)
Strength exercises
(back squat, press
exercises, deadlift and
barbell row)
Single day supplementation (1 supp
before and 1 supp after exercise)
Amount of BCAA: 20 g (1 day)
LEU/ISO/VAL (2:1:1)
Placebo: apple and blackcurrant juice
CG = SG -
SG > CG at D1
for the CMJ and
the SSPT
Greer et al.
(2007) [34]
9 healthy males
age: 22 ±3 years
˙
V
O
2max
: 36
±
2 mL min
−1
kg
−1
training status: untrained
Cross-over
(washout: 8 days)
Dietary control
Cycling ergometer
exercise at 55%
˙
VO2max for 90 min
Single day supplementation (1 supp
before and 1 supp at 60 min during
the exercise)
Amount of BCAA: 5 g (1 day)
LEU/ISO/VAL (2.5:1:1.5)
Placebo: water, lemon flavor, salts
and artificial sweeteners.
CG > SG at D1
CG > SG at H4, D1
and D2 for CK
CG > SG at H4
for LDH
SG > CG at D2
for leg flexion
torque (180◦/s)
Nutrients 2017,9, 1047 6 of 15
Table 2. Cont.
Study Population Study Design Damaging Exercise Supplementation Strategy
Outcomes
Soreness Blood Analysis
(Myoglobin/LDH/CK)
Muscle
Performance
Howatson et al.
(2012) [35]
12 healthy males
age: 23 ±2 years
training status: trained in
collective sports
(twice per week)
RCT, DB
CG (n= 6)
Drop jumps (5 ×20,
height: 60 cm)
12 days of supplementation (7 days
before and 4 days after exercise).
2×10 g every day + 20 g before and
after the exercise Amount of BCAA:
280 g (12 days)
LEU/ISO/VAL (2:1:1)
Placebo: aspartame based
artificial sweeteners.
CG > SG at D1
and D2
CG > SG for CK
(group effect
considering the time
range from D0 to D4)
SG > CG
(group effect
considering the
time range from
D0 to D4) for
the MVC
Jackman et al.
(2010) [36]
24 healthy males
age: n/a
training status: n/a
SB
CG (n= 12)
Dietary control
Eccentric exercise
(12 ×10 knee
extensions, 120% of
1 RM)
3 days of supplementation (1 supp
before, 3 supp after exercise and
4 supp every day for 2 days)
Amount of BCAA: 87.6g (3 days)
LEU/ISO/VAL (2.1:1.2:1)
Placebo: Artificially sweetened and
flavored water
CG > SG with
knee flexed at
D2 and D3
CG = SG for CK and
myoglobin CG = SG
Kephart et al.
(2016) [37]
30 healthy males
age: 22 ±1 years
training status:
resistance-trained
RCT
CG (n= 15)
Dietary control
3 back squat exercises
on three consecutive
days (10 ×5 at 80% of
1 RM)
4 days of supplementation (1 supp
after the exercise on the first 3 days
and 1 supp on day 4)
Amount of BCAA: 24g (4 days)
LEU/ISO/VAL (3:1:2) and CHO
Placebo: CHO
CG = SG CG = SG for
myoglobin CG = SG
Matsumoto et al.
(2007) [38]
12 healthy subjects (males: n= 6
and female: n= 6)
age: 20 ±1 years
training status: trained in long
distance running
RCT DB
Cross-over
(washout: 3 weeks)
Dietary control
7 sessions on 3 days of
long distance runs
3 days of supplementation (20g/day)
Amount of BCAA: 60g (3 days)
LEU/ISO/VAL (2:1:1)
Placebo: n/a
CG > SG at D1 CG > SG at D1 for CK,
LDH and myoglobin -
Ra et al.
(2013) [39]
18 healthy male subjects
age: 23 ±1 years
training status: n/a
RCT, DB
CG (n= 9)
Eccentric exercise
(6 ×5 elbow flexions,
90% of MVC)
18 days of supplementation (14 days
before and 4 days after exercise).
3×3.2 g every day
Amount of BCAA: 172.8g (18 days)
LEU/ISO/VAL (2:1:1)
Placebo: starch
CG = SG CG = SG for CK and
LDH -
Nutrients 2017,9, 1047 7 of 15
Table 2. Cont.
Study Population Study Design Damaging Exercise Supplementation Strategy
Outcomes
Soreness Blood Analysis
(Myoglobin/LDH/CK)
Muscle
Performance
Shimomura et al.
(2010) [40]
12 healthy female subjects
age: 22 ±2 years
training status: untrained
Cross-over
(washout:
11 weeks)
Resistance exercise
(7 ×20 squat with
body weight)
Single day supplementation (1 supp
before the exercise)
Amount of BCAA: 5.5g (1 day)
LEU/ISO/VAL (2.3:1:1.2)
Placebo: dextrin
CG > SG at D2
and D3
CG = SG for CK and
myoglobin
SG > CG at D3
for MVC
Waldron et al.
(2017) [41]
16 healthy subjects (males:
n= 14 and female: n= 2)
age: 22 ±2 years
training status: trained in
resistance exercise
RCT
CG (n= 8)
Dietary control
Strength exercise
(10 ×6 back squats at
70% of 1 RM)
3 days of supplementation (1 supp
before, 1 supp after exercise and
2 supp every day for 2 days)
Amount of BCAA: 48g (3 days)
LEU/ISO/VAL (2:1:1) and dextrose
Placebo: dextrose
CG = SG
SG > CG at D1 and D2
for CK
CG = SG for
MVC and CMJ
LDH: lactate dehydrogenase; CK: creatine kinase;
˙
V
O
2max
: maximal oxygen consumption; CG: control group; SG: supplemented group; RM: maximal repetition; H: hour (e.g., H4: four hours
after the end of the damaging exercise); D: day (e.g., D4: four days after the damaging exercise); supp: supplementation; LEU: leucine; ISO: isoleucine; VAL: valine; CHO: carbohydrates;
RCT: randomized clinical trial; DB: double blind; SB: single blind; MVC: maximal voluntary contraction force; CMJ: counter movement jump; SSPT: seated shot-put throw; n/a: not available.
Nutrients 2017,9, 1047 8 of 15
4.1. Study Quality
The majority of studies included in the systematic review were rated as positive (55%). Neutral
(27%) and negative (18%) qualities were reported for the other studies (Table 3) for multiple reasons
including a cross-over design without a control group [
33
,
34
,
38
,
40
], the lack of efficient randomization
and blinding [
31
,
33
,
34
,
36
,
37
,
40
] and the absence of statements on funding and sponsorship [
31
,
34
,
38
,
40
].
In addition, short follow-up of exercise-induced muscle damage outcomes (<2 days) was also observed
in studies rated as negative [33,38].
Table 3. Quality assessment of included studies.
References Validity Rating Overall
Rating
12345678910
Coombes & McNaughton (2000) [31] Y Y Y N N Y Y Y Y N ø
Fouréet al. (2016) [32] YYYYYYYYYY +
Gee & Deniel (2016) [33] Y Y N N N N Y Y Y Y ø
Greer et al. (2007) [34] Y Y N N N N Y N Y N –
Howatson et al. (2012) [35] YYYYYYYNYY +
Jackman et al. (2010) [36] Y Y Y N N Y Y Y Y Y +
Kephart et al. (2016) [37] Y Y Y N N Y Y Y Y Y +
Matsumoto et al. (2007) [38] Y N N N Y Y Y Y Y N ø
Ra et al. (2013) [39] Y Y Y N Y Y Y Y Y Y +
Shimomura et al. (2010) [40] Y Y N N N N Y N Y N –
Waldron et al. (2017) [41] Y Y Y N Y Y Y N Y Y +
Total 11 10 6 2 5 8 11 7 11 7
Validity items: 1 research question stated; 2 subject selection free from bias; 3 comparable study groups; 4 method
for withdrawals described; 5 blinding used; 6 interventions described; 7 outcomes stated, measurements valid
and reliable; 8 appropriate statistical analysis; 9 appropriate conclusions, limitations described; 10 funding and
sponsorship free from bias. Validity items 2, 3, 6, 7 must be satisfied for a positive quality rating. Y: yes, N: no,
+: positive, ø: neutral, –: negative.
Moreover, the supplementation strategy and the extent of EIMD were considered as cofounding
parameters to objectively assess the effects of BCAAs on muscle damage outcomes.
4.2. Supplementation Strategy and Muscle Damage Extent
Duration, frequency and daily amount of BCAAs was rated (Table 4). More than half of the
studies reported a short (
≤
3 days) duration of supplementation whereas the frequency and the daily
amount of BCAAs intakes (from low to high) was similarly distributed among the included studies.
Table 4. Rating of supplementation strategy and extent of muscle damage.
References Extent of Muscle
Damage
Supplementation Strategy
Duration Frequency Amount
Fouréet al. (2016) [32] High Moderate Low Low
Ra et al. (2013) [39] High Long High Low
Jackman et al. (2010) [36] Moderate Short High High
Coombes & McNaughton (2000) [31] Moderate Long High High
Howatson et al. (2012) [35] Moderate Long High High
Greer et al. (2007) [34] Low Short Low Low
Shimomura et al. (2010) [40] Low Short Low Low
Gee & Deniel (2016) [33] Low Short Low High
Matsumoto et al. (2007) [38] Low Short High High
Waldron et al. (2017) [41] Low Short High High
Kephart et al. (2016) [37] Low Moderate Low Low
Nutrients 2017,9, 1047 9 of 15
The damage extent was generally low in the included studies. It is noteworthy that a few studies
reported discordant changes in muscle performance and CK/LDH measurements [
36
,
40
] as a result of
EIMD (i.e., large decrease in force and no/small change in plasma CK).
4.3. Outcomes
The positive effects of BCAAs supplementation on EIMD outcomes are reported in Table 5.
The number of studies demonstrating a positive effect was equivalent to the number of studies which
showed no effect. It should be noted that a positive effect was clearly reported by the lower quality
studies whereas positive quality studies described no significant effect except for the results from
Howatson et al. [35].
Table 5. Muscle damage exercise outcomes of included studies.
References Effects in the Control Group Positive Effect of
Supplementation
Muscle performance
Fouréet al. (2016) [32] Significant decrease in MVC from POST to D4 -
Gee & Deniel (2016) [33] Significant decrease in CMJ and SSPT performances at D1 Yes
Greer et al. (2007) [34]Significant decrease in torque (leg flexion and extension)
from POST to D2 Yes
Howatson et al. (2012) [35] Significant decrease in MVC from D1 to D3 Yes
Jackman et al. (2010) [36] Significant decrease in maximal force from H1 to D3 -
Kephart et al. (2016) [37] Significant decrease in isokinetic peak torque -
Shimomura et al. (2010) [40] Significant decrease in MVC at D3 Yes
Waldron et al. (2017) [41] Decrease in MVC and CMJ performance from POST to D1 -
Blood analyses
Coombes & McNaughton (2000) [31] Significant increase in CK and LDH (from POST to D5) Yes
Fouréet al. (2016) [32] Significant increase in plasma CK activity at D3 and D4 -
Greer et al. (2007) [34] Significant increase in CK (from H4 to D2) and LDH (at H4) Yes
Howatson et al. (2012) [35] Significant increase in CK from D1 to D3 Yes
Jackman et al. (2010) [36]Significant increase in CK (from H8 to D3) and myoglobin
(at H1, H8 and D3) -
Kephart et al. (2016) [37] Significant increase in myoglobin -
Matsumoto et al. (2007) [38] Significant increase in CK and LDH at POST Yes
Ra et al. (2013) [39] Significant increase in CK and LDH at D3 and D4 -
Shimomura et al. (2010) [40]No significant change in CK and LDH on the three days
post-exercise -
Waldron et al. (2017) [41] No change in CK on the two days post-exercise -
LDH: lactate dehydrogenase, CK: creatine kinase, POST: immediately after the damaging exercise, H: hour
(e.g., H4: four hours after the end of the damaging exercise), D: day (e.g., D4: four days after the damaging
exercise), MVC: maximal voluntary contraction force, CMJ: counter movement jump, SSPT: seated shot-put throw.
Considering the studies with positive and neutral quality rating, the benefits of BCAAs
supplementation was mostly observed when the supplementation strategy included a high amount of
BCAAs intake (>200 mg kg
−1
day
−1
) in a context of low-to-moderate muscle damage extent [
31
,
33
,
35
,
38
].
In addition, a high frequency of BCAAs intake (2 or more daily intakes) and a long duration of
supplementation (>10 days) and even more on several days before the damaging exercise (at least
7 days prior to the damaging exercise in the two studies showing a positive effect of BCAAs
supplementation) appears to alleviate outcomes of EIMD [31,35].
5. Discussion
In the last few years, nutritional strategy has been considered crucial for the optimization of
muscle performance. More particularly, BCAAs supplementation has been used in the field of sports
Nutrients 2017,9, 1047 10 of 15
with the aims of limiting the outcomes (e.g., force loss) of EIMD. Throughout this systematic review,
we identified that BCAAs can alleviate outcomes of EIMD for specific conditions regarding the extent
of muscle damage and the supplementation strategy. Potential benefits of BCAAs supplementation can
actually be obtained for low-to-moderate extent of muscle damage and considering a supplementation
strategy that includes high daily BCAAs intake over a long period of time (i.e., several days) and
especially before the damaging exercise period.
Previous systematic reviews have reported positive chronic effects of protein supplementation on
muscle mass, strength and power [
42
]. The corresponding physiological mechanisms—i.e., a decreased
muscle-protein breakdown [
24
] and a reactive oxygen species scavenging [
7
]—could also lead to
improved muscle performance and be beneficial in alleviating muscle damage. However, the efficiency
of the latter mechanisms could require time thereby explaining the potential need for long-lasting
supplementation prior to EIMD in order to obtain potential benefits.
5.1. Extent of Exercise-Induced Muscle Damage
A first confounding factor for the assessment of BCAAs supplementation was the extent of muscle
tissue alteration reported in the included studies. These alterations and the corresponding extent
were estimated and rated from changes in indirect markers of muscle damage including decreased
muscle performance and increased amount of blood markers (i.e., plasma/serum CK, LDH and/or
myoglobin). As reported previously, the maximal voluntary contraction (MVC) loss is currently
considered as the most reliable indicator of muscle injury [
43
] as compared to CK measurements.
Indeed, a high inter-subject variability was found in plasma/serum CK level changes resulting from
EIMD [
25
,
36
]. In “high-responder” subjects—i.e., those with the higher CK levels—the increased
plasma/serum CK levels were then uncorrelated to the extent of muscle damage [
21
,
44
]. However,
despite the variability of this outcome, it remains moderately correlated to muscle alterations assessed
with MRI [
45
]. Therefore, we considered in the present systematic review that the combination of
changes in force and blood markers both led to an objective assessment of muscle damage extent.
Muscle soreness is a subjective outcome of EIMD [
46
,
47
] given that it is strongly related
to the subject’s previous experience with muscle damage. In the papers selected in the present
systematic review, soreness was quantified as an outcome of EIMD in order to detect onset of muscle
damage [
21
] but was not taken into account to estimate the extent of the corresponding alterations [
48
].
A methodological limitation can also be addressed regarding the assessment of muscle damage on the
basis of MVC measurements. Indeed, MVC could not be considered a reliable marker to assess muscle
damage extent taking into account the peripheral and central nervous alterations demonstrated in the
first days after the damaging exercise [
45
,
49
–
52
]. Ideally, imaging methods such as electron microscopy,
MRI or ultrasound elastography could be used to visualize the extent and assess the severity of muscle
damage [
28
,
53
,
54
]. Most of the studies included in this review did not use these imaging methods in
order to assess muscle damage and it has been sometimes difficult to assess muscle damage extent
from changes in blood markers and muscle performance.
Putting aside these methodological considerations, positive effects of BCAAs supplementation
have been mainly reported for low-to-moderate muscle damage induced by exercise. For larger
muscle alterations, which have been reported in two studies [
32
,
35
], no significant effect of BCAAs
supplementation has been disclosed. In these latter studies, the physiological benefits commonly
linked to BCAAs supplementation—i.e., promotion of muscle-protein synthesis, reduction of
protein oxidation, mitochondrial biogenesis and scavenging of reactive oxygen species—could
not overcome the large alterations of muscle structural organization and/or muscle metabolism
previously described [
25
,
26
,
28
,
55
,
56
]. However, muscle energetics impairment [
57
] and structural
alterations [
58
–
60
] associated with low-to-moderate extent of muscle damage could be alleviated by
a specific BCAAs supplementation strategy.
Nutrients 2017,9, 1047 11 of 15
5.2. The Supplementation Strategy
In the present review, we considered three criteria (frequency, amount, duration) in order to
more accurately assess the BCAAs supplementation strategies reported in the selected studies. A high
frequency of BCAAs intake (i.e., two or more daily intakes per day) was used over the whole set of
studies demonstrating benefits regarding EIMD. In addition, the daily amount of BCAAs and the
supplementation duration seem to be important factors. Positive effects of BCAAs supplementation
were mainly obtained for a high daily amount of BCAAs intake (>200 mg kg
−1
day
−1
) over a long
period of time [
31
,
35
]. However, the combination of these three criteria (i.e., frequency, amount
and duration) appears critical to potentially trigger beneficial effects from BCAAs supplementation.
For instance, considering low-to-moderate EIMD, a low frequency (i.e., less than 2 intakes per day)
and a low daily amount of BCAAs intake (i.e., less than 200 mg kg
−1
day
−1
) during a moderate
supplementation duration (i.e., between 4 and 10 days) was not enough to produce benefits on
EIMD indirect markers [
37
]. Moreover, no significant positive effects on outcomes has been found
when supplementation combined a high frequency and a high daily amount over a short period of
time [
36
,
41
]. A long BCAAs supplementation period (>10 days) appears necessary if one is expecting
beneficial effects. Previous studies investigating the damaging effect of marathon on skeletal muscle
used this rationale to assess the potential beneficial effects of BCAAs supplementation [
61
]. The authors
reported no effect but did not investigate the delayed outcomes of EIMD and the study was thus
excluded from the present systematic review. The inclusion/exclusion criteria we chose were relatively
restrictive. In that way, several studies of interest were excluded to avoid additional confounding
effects mainly associated with the composition of the supplementation mixture. A recent systematic
review reported the global effects of protein supplementation [62].
Chronic BCAAs supplementation has been shown to produce positive effects in both animals
and humans [
7
,
16
]. Increased skeletal muscle mitochondrial biogenesis and prevention of oxidative
damage were described as potential mechanisms contributing to the increased lifespan in animals [
16
].
Therefore, BCAAs supplementation taken prior (days/weeks) to damaging exercise could prevent
skeletal muscle tissues alterations through the enhanced mitochondrial biogenesis and reactive oxygen
species scavenging [
7
]. This would occur via an upregulation of peroxisome proliferator-activated
receptor-γcoactivator 1αexpression [7,16].
6. Conclusions
In summary, the efficacy of a nutritional strategy based on BCAAs supplementation and aimed
at reducing/preventing muscle damage resulting from high-intensity exercise seems to be poor.
Among the studies selected in the present review, only one rated as positive regarding the quality
of reported beneficial effects [
35
]. However, these beneficial effects should be considered with
caution given the small sample size (n= 6) of both the control and supplemented groups. Overall,
this systematic review suggests that a BCAAs supplementation strategy with daily intake larger than
200 mg kg
−1
day
−1
, duration longer than 10 days starting at least 7 days before the damaging exercise
would be effective to limit muscle damage resulting from exercise. On that basis, one can expect a peak
force loss of less than 15% and/or an increase in plasma/serum CK peaking at one day following the
damaging exercise. However, further placebo-controlled randomized clinical trials would be needed
to support the beneficial effects of this strategy. In addition, it might be of interest to assay the effects
of other nutritional strategies for which BCAAs could be combined with taurine [
39
] or other essential
amino acids [63] and for which potentiator effects of BCAAs have been suggested.
As a take home message, there is no direct evidence of positive effects of BCAAs on muscle
damage. However, in specific conditions, BCAAs supplementation seems to diminish the outcomes of
EIMD. It would be of interest to further support these findings on the basis of imaging investigations.
Acknowledgments:
This study was supported by Centre National de la Recherche Scientifique (CNRS UMR 7339).
Nutrients 2017,9, 1047 12 of 15
Author Contributions:
A.F. conducted the literature search, collated, selected studies for inclusion, analyzed
and interpreted the data. Both authors contributed to the conception of the review, wrote the manuscript and
approved the final version submitted for publication.
Conflicts of Interest: The authors declare no conflict of interest.
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