Effect of branched-Chain Amino Acid Supplementation on Muscle Soreness following Exercise: A Meta-Analysis

Abstract

Abstract. Delayed onset muscle soreness (DOMS) is a symptom of exercise-induced muscle damage that occurs following exercise. Previous research has indicated that branched-chain amino acid (BCAA) supplementation may attenuate exercise-induced muscle damage that causes delayed onset muscle soreness, however the results are inconsistent. The primary aim of this study was to examine the previous literature assessing the effect of BCAA supplementation on DOMS following an acute bout of exercise in adults. This review was conducted in accordance with PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-analyses), and identified peer-reviewed articles comparing a BCAA supplement to a placebo non-BCAA supplement following an acute bout of exercise. An electronic search of three databases (EbscoHost, Web of Science, and SPORTDiscus) yielded 42 articles after duplicates were removed. All studies included in the current analyis were: 1) peer-reviewed publications; 2) available in English; 3) utilized a random control design that compared a BCAA group to a placebo control group following exercise; 4) and assessed soreness of muscle tissue during recovery. DOMS was assessed in 61 participants following ingestion of a BCAA supplement over the course of these interventions. The cumulative results of 37 effects gathered from 8 studies published between 2007 and 2017 indicated that BCAA supplementation reduced DOMS following exercise training (ES = 0.7286, 95% CI: 0.5017 to 0.9555, p < 0.001). A large decrease in DOMS occurs following BCAA supplementation after exercise compared to a placebo supplement.

Full text

Branched-chain amino acids and muscle soreness
EFFECT OF BRANCHED-CHAIN AMINO ACID SUPPLEMENTATION ON MUSCLE
SORENESS FOLLOWING EXERCISE: A META-ANALYSIS
Michael V. Fedewa Ph.D.,1 Steven O. Spencer, M.A.,1 Tyler D. Williams Ph.D.,1,2 Zachery E.
Becker, M.A.,1 Collin A. Fuqua.1
Institutional Affiliations:
1Department of Kinesiology, The University of Alabama, Tuscaloosa, Alabama, United States.
2Department of Kinesiology, Samford University, Birmingham, Alabama, United States.
Address correspondence to: Michael V. Fedewa, The University of Alabama, Department of
Kinesiology, 2003 Moore Hall, Box 870312, Tuscaloosa, AL 35487-0231. Telephone: 205-348-
9779. Fax 205-348-0867. E-mail: mvfedewa@ua.edu.
Key Words: delayed onset muscle soreness, branched-chain amino acid, exercise training, meta-
analysis, systematic review
Total word count (text only): 2,666
Number of pages: 15
Tables: 2
Figures: 3
Running Title: BCAA supplementation and muscle soreness
Competing Interest: The authors have no potential, perceived, or real conflicts of interest to
disclose. None of the authors declare competing financial interests.
Michael V. Fedewa (mvfedewa@ua.edu)
Steven O. Spencer (sospencer515@gmail.com)
Tyler D. Williams (twilli11@samford.edu)
Zachery E. Becker (zebecker@crimson.ua.edu)
Collin A. Fuqua (cafuqua@crimson.ua.edu)
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ABSTRACT
Delayed onset muscle soreness (DOMS) is a symptom of exercise-induced muscle
damage that occurs following exercise. Previous research has indicated that branched-chain
amino acid (BCAA) supplementation may attenuate exercise-induced muscle damage that causes
delayed onset muscle soreness, however the results are inconsistent. The primary aim of this
study was to examine the previous literature assessing the effect of BCAA supplementation on
DOMS after exercise, and to provide a quantitative estimate of effect on recovery status. This
review was conducted in accordance with PRISMA guidelines (Preferred Reporting Items for
Systematic Reviews and Meta-analyses), and identified peer-reviewed articles comparing a
BCAA supplement to a placebo non-BCAA supplement following an acute bout of exercise. An
electronic search of three databases (EbscoHost, Web of Science, and SPORTDiscus) yielded 39
articles after duplicates were removed. All studies included in the current analysis were: 1) peer-
reviewed publications; 2) available in English; 3) utilized a random control design that compared
a BCAA group to a placebo control group following exercise; 4) and assessed soreness of muscle
tissue during recovery. Data from 93 participants (22.3±2.7 yrs, 87% male, 18.6±2.3 per study)
were included in the analysis. The cumulative results of 26 effects gathered from 5 studies
published between 2007 and 2013 indicated that DOMS decreased following BCAA
supplementation (ES=0.8956, 95% CI: 0.6822 to 1.1090, p<0.001). A large decrease in DOMS
occurs following BCAA supplementation after exercise compared to a placebo supplement.
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INTRODUCTION
Delayed onset muscle soreness (DOMS) is a type of subclinical muscular injury which
occurs following exercise and can present symptoms that vary from slight tenderness and
stiffness to severe debilitating pain which restricts movement.[1] Typically, symptoms of DOMS
peak 24-48 hours after exercise, and subside within 7 days.[2] Although a number of possible
treatments are available, cryotherapy, stretching, anti-inflammatory drugs, electrical stimulation,
and dietary supplements are most commonly used to alleviate the increased muscle soreness
following exercise.[3] Specifically, branched-chain amino acid (BCAA) supplementation is used
to reduce DOMS, promote protein metabolism, and inhibit muscle damage following exercise
training, resulting in an anabolic effect on the muscles.[4] Although these amino acid
supplements appear to be safe when consumed in recommended dosages, current research does
not support an ergogenic effect of BCAA supplementation when consumed before or during
exercise.[5] BCAA supplementation has the potential to aid in the recovery of both athletes and
individuals who adhere to a strict workout regimen. DOMS that is associated with the events
these individuals engage in can severely restrict progress in their respective activities. BCAA
supplementation may be able to aid in the post-activity soreness and recovery, thus aiding in the
reduction of downtime between activities and training sessions.[6] This would allow for quicker
recovery and participation, thus allowing the individual to progress in their respective interests.
Additional research has emerged related to the potential benefits of BCAA supplementation
following exercise training to enhance recovery, however the effect of BCAA supplementation
on DOMS has yet to be completely characterized.[7] Should BCAA supplementation reduce
symptoms of DOMS, it is possible that exercise adherence may increase among sedentary
populations, and improve performance among athletes and non-athletes alike. As such, the
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primary aim of this analysis is to examine the effect of BCAA supplementation on DOMS
following an acute bout of exercise in adults.
METHODS
This study was conducted in accordance with PRISMA (Preferred Reporting Items for
Systematic Reviews and Meta-analyses) statement guidelines.[8] Articles published by February
20, 2016, were located by searching three electronic online databases, EBSCOhost,
SPORTDiscus, and Web of Science, using combinations of the terms branched-chain amino
acids, BCAA, delayed onset muscle soreness, DOMS, muscle, recovery, soreness, randomized
trial, and randomized controlled trial. Duplicate publications were removed, and the reference
lists from retrieved articles were manually reviewed for additional publications not discovered
during the database search.
Study Selection
The inclusion criteria for this analysis were as follows: (1) peer-reviewed publication; (2)
available in English; (3) involving human subjects; (4) randomized crossover and randomized
controlled trials including a BCAA and placebo supplement; (5) assessed muscle soreness
following a single bout of exercise training. Excluded studies had the following characteristics:
(1) were non-peer reviewed; (2) provided a review, meta-analysis, position statement, or
proposed study design; (3) used a cross-sectional or prospective study design; (4) included
BCAA intake as part of a multicomponent treatment (eg, BCAA + caffeine, BCAA +
preworkout), from which an ES for BCAA supplementation alone could not be calculated; or (5)
compared BCAA supplementation only with an active treatment (eg, nutritional intervention or
alternative supplementation). A total of 18 articles were identified during the initial search
process. A flowchart of the study selection method is provided in Fig 1. No additional
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publications were identified by manually searching references of relevant publications. Study
characteristics (age, percent of the study sample comprised of female participants, total mass,
height, BMI, and relative adiposity (%Fat)) were extracted by two independent reviewers
(Authors 1 and 2). Discrepancies were resolved by consensus, with a third reviewer (Author 3)
available, if needed. Study methodological quality was assessed using the Jadad scale (Table 1).
[9] Randomization methods, blinding, and description of withdrawals were evaluated by
reviewers, and scored out of 5 total points. Higher scores indicate a greater number of key
criteria having been reported, and trials with scores ≥3 were considered of high methodological
quality.
Effect Size Calculation
ES values were calculated by subtracting the mean (M) change in the placebo condition
from the mean change in the BCAA condition and dividing the difference by the pooled standard
deviation (SD) of the baseline scores, and adjusted for small sample bias.[10] An improvement in
perceived pain/discomfort resulted in a positive ES. All authors independently calculated ES
from each study, with inconsistencies resolved prior to analyses.
Statistical Analysis
Random effects models were used to calculate a mean ES and 95% confidence interval
(CI) for the effect of BCAA supplementation on DOMS using macros (MeanES) in IBM SPSS
version 23.0 (IBM SPSS Statistics, IBM Corporation, Armonk, NY). Missing values not
obtained from the literature were imputed using the mean of the available values.[11] Multi-level
linear regression with maximum likelihood estimation was used according to standard
procedures to adjust for between-study variance and the correlation between effects nested
within studies.[12, 13] The data analysis for the multilevel model was performed using SAS 9.4
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(SAS Institute Inc., Cary, North Carolina). Data available for study and participant characteristics
are presented as M±SD. Data available for study and subject characteristics are demonstrated as
M±SD.
RESULTS
DOMS was assessed in 93 participants over the course of these interventions. Study
samples ranged from 9 to 36 (27.4±9.4) participants per treatment effect, with 2 to 8 (5.2±2.7)
effects gathered from each study. A single bout of resistance training was the most commonly
used stimulus, occurring in 20 of the 26 effects (76.9%), with plyometrics (k=4, 15.4%), and
aerobic exercise (k=2, 7.7%). Characteristics of experimental designs are outlined in Table 1.
The cumulative results of 26 effects gathered from 5 studies published between 2007 and
2013 indicated that BCAA supplementation reduced DOMS following exercise training
(ES=0.8956, 95% CI: 0.6822 to 1.1090, p<0.001). The mean ES remained significant after
accounting for the nesting of multiple effects nested within a single study (ES=0.9490, 95%CI
0.4793 to 1.4187, p=0.0050). Although the effect of BCAA supplementation on DOMS did not
vary significantly from day to day, the magnitude of the effect appeared largest 48 hours
following exercise (Table 2). BCAA supplementation reduced DOMS consistently across 100%
of the effects analyzed in the current study.
Participant age ranged from 21.6 to 23.0 yrs (22.5±0.3 yrs). Only a small portion of
effects (k=4, 15.4%) of treatment effects consisted of trained individuals, whom would likely see
a minimal effect from BCAA supplementation. In contrast, 22 effects (84.6%) from untrained or
previously inactive participants whom would likely experience an exponentially greater benefit
from treatment. Despite discrepancies in training status, all participants were healthy with no
history of any medical conditions that could impede in performance or unintentionally influence
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results. All 26 effects were obtained from sex-specific samples (k=22, 84.6% male only, k=4,
15.4% female only). Average BMI and %Fat across all effects were 22.4±1.3 kg/m2 and 18.2±1.8
%Fat, respectively.
Homogeneity of Results
Heterogeneity was indicated if Q total reached a significance level of P<.05 and the
sampling error accounted for >75% of the observed variance.[10] Heterogeneity was also
assessed by examination of the I2 statistic.[14] An I2 value was categorized as low, moderate, or
high based on calculations equal to 25%, 50%, or 75%, respectively. The effect of BCAA
supplementation on exercise-induced DOMS demonstrated low heterogeneity (Q=33.18,
I2=24.66, p=0.1266). Sampling error accounted for 95.6% of the variation observed in the
effects. Due to the low heterogeneity, the variability among ES was not different than what
would have occurred naturally as a result of study sample error. As a result, no further moderator
analysis was performed.
Assessment of Bias
Sixteen effects (61.5%) were obtained from high-quality studies, with overall quality of
scores for effects in the current analysis ranging from one to three (1.8±1.5). Sixteen effects
(61.5%) were randomized, however none of the effects were gathered from studies that provided
a description of the randomization process used (i.e. computer generated group allocation). A
placebo supplement was used in all of the effects included in the current analysis to blind
participants to the supplement being administered, however double-blinding procedures were
described in only 16 of the 26 effects (61.5%). None of the included studies described screening
procedures, enrollment of participants, or how the research team reached the final sample of
participants with complete data. Furthermore, these studies should have also included a
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description of participants whom did not complete the observation period or who were not
included in the analysis, and reasons for their exclusion. The study quality assessment is also
presented as part of Table 1.
The number of unpublished or unretrieved null effects that would diminish the
significance of observed effects to a non-significant result was estimated as the fail-safe N. A
fail-safe N+ represents the minimal number of additional null effects from multiple studies of
average sample size needed to reach a similar null conclusion.[15] The fail-safe N+ for the effect
of BCAA supplementation on DOMS using a random effects model estimated N+=551.7 effects.
A fail-safe N+ is often considered robust when the estimated value exceeds 5N+10, in which N
represents the number of original effects. Given the current fail-safe N+, publication bias can be
“safely ignored.”[16] A funnel plot for the effect of BCAA supplementation on DOMS was
created as an exploratory assessment to address potential publication bias related to study sample
size, and is presented in Figure 3. Potential publication bias was also addressed using Egger’s
test.[17] Inconsistent with the fail-safe N+ estimate, the results from Egger’s test indicated that
the mean effect of BCAA supplementation on DOMS was subject to potential bias
(F[1,24]=18.322 [P<0.001]).
Sensitivity Analysis
Two of the 26 effects (7.7%) outside of the 95% confidence interval were identified using
the funnel plot to identify potential outliers. Sensitivity analysis removing these two effects
decreased the mean effect of BCAA supplementation on DOMS (ES=0.8041, 95% CI 0.6172 to
0.9910, p<0.001) for the remaining 24 effects.
DISCUSSION
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The collective results of this analysis indicated that BCAA supplementation is an
effective method of reducing the exercise-induced DOMS, and appear consistent regardless of
sex and training status. The results of the current study add to the body of literature related to
BCAA supplementation and athletic performance. Collectively, BCAA supplementation appears
to have little ergogenic effect benefit when examining fatigue and exercise performance,
although there is some debate.[18, 19] Previous research indicated that BCAA supplementation
(50% leucine, 25% isoleucine, and 25% valine) prior to, and during exercise had little impact on
heart rate, core temperature, blood lactate concentration, or exercise performance during
prolonged cycling.[20] In addition, BCAA supplementation (30% leucine, 15% isoleucine, and
55% valine) did not appear to impact cognitive performance, mood, perceived exercise, comfort,
or exercise performance.[21] Although it appears that BCAA supplementation during exercise
may have little impact on performance per se, BCAA supplementation following training may
enhance recovery and reduce DOMS. The ergogenic benefits of enhanced recovery could
potentially allow for higher training frequency and greater volume accumulation, driving greater
long-term adaptations to training.
The mechanism by which BCAA’s reduce muscle tissue damage (thereby suppressing
DOMS) is understandable, though highly complex. It involves the interaction between leucine
and mechanistic target of rapamycin (mTOR) in the pathway of skeletal muscle protein synthesis
during the recovery phase, but is also mediated through the attenuation of muscle protein
breakdown during exercise. The increase in muscle soreness 24 to 48 hours following a bout of
resistance training, especially that with an emphasis on eccentric contraction, is typically
attributed to inflammation and myofibrillar damage.[22] Although all branch chain amino acids
are thought to play a role in skeletal muscle protein synthesis, leucine appears to have a greater
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effect in regards to DOMS.[23] Ingestion of leucine shortly after a resistance training bout may
help to signal mTOR pathways that are responsible for the regulation of protein synthesis and
cell growth.[24] An increase in mTOR activation may help to accelerate the recovery process,
thus reducing the severity and duration of DOMS.
Additionally, leucine supplementation is thought to reduce proteolysis within skeletal
muscle, causing less damage to the sarcolemma.[25] Reductions in blood creatine kinase levels
following supplementation indicate a reduced inflammatory response, and may indicate
decreased muscle damage and accelerated recovery. Furthermore, short-term amino acid
supplementation during resistance training, including BCAAs, has been shown to increase
testosterone, and decrease cortisol and creatine kinase levels during periods of high-intensity
training, potentially providing an additional hormonal mechanism by which soreness could be
reduced and performance could be enhanced.[26]
These results provide the basis for ingesting a BCAA supplement while undergoing an
exercise training program for the prevention or reduction of DOMS. However, little research has
examined the effect of BCAA supplementation on DOMS in older adults, a population that could
provide significant advancements in the field of rehabilitation, geriatric medicine, and the overall
promotion of a better quality of life. Evidence suggests BCAA supplementation improves muscle
protein synthesis in older adults, which may provide a potential avenue for future research in this
population.[27, 28]
LIMITATIONS
The results of the current study are not without limitation. It stands to reason that BCAA
supplementation would be most effective in suppressing DOMS and enhancing recovery in
untrained or minimally trained individuals. This is likely due to the fact that muscle performance
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is enhanced in highly trained participants, which reduces pain-inflicting damage to muscle tissue
while also speeding the rate of recovery.[29] However, due to the relatively small body of
literature and relatively homogeneous populations studied, determining the effect of BCAA
supplementation in specific populations was beyond the scope of the current study. Future
research should focus on BCAA supplementation in middle-aged to elderly individuals (that are
seen fit for physical activity) participating in an intensive endurance or resistance training
program, in order to provide a more thorough meta-regression analysis, with statistical power
sufficient enough to determine the nature of BCAA interaction with aged skeletal muscle tissue.
In addition, the subjective primary outcome measure is not a direct indicator of muscle
damage, and is not linked to an objective or functional endpoint (body composition, performance
outcome, etc.). Furthermore, although dietary supplement research may claim to be ostensibly
'blinded' experiments, treatments are nonetheless often distinguishable by taste (as can be the
case for BCAA). The placebo effect can account for over two-thirds of improvements in
muscular performance, and over half of improvements in psychosocial outcomes following
exercise training.[30, 31] Our results are consistent with previous results indicating BCAA
supplementation can alleviate muscle soreness,[32] however this previous review was also
limited to placebo-controlled trials. These previous results, and our current results, did not
compare BCAA supplementation to whole proteins or other dietary supplements. Even in light of
our current findings that indicated BCAA supplementation can reduce DOMS following
exercise, this study has only compared BCAAs to a placebo supplement or “nothing at all”
Furthermore, our results are limited to recovery following a single bout of strenuous exercise,
and should not be extended to imply that improvements in muscular strength, performance, or
body composition would occur following a structured exercise training program. Dietary
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supplements such as BCAA, are indeed just that, “supplements.” In that sense, BCAA
supplementation alone cannot support an increased rate of muscular protein synthesis,[33] and it
is our recommendation that dietary supplements should be used to “supplement” or compliment
a well-balanced diet that includes adequate amounts of dietary protein.[34] Finally, it is also
assumed that the magnitude of the effect should vary by time of ingestion, amount ingested, ratio
of specific amino acids, intensity of the exercise training program utilized, and many other
possible factors. Again, because of the relatively small body of literature and relatively
homogeneous populations studied, examining these potential moderators was not possible.
However, the results of this analysis strengthen the notion that some benefit will inherently be
seen, regardless of these factors, in untrained individuals.
CONCLUSION
Based on the cumulative results from peer-reviewed cross-over and randomized
controlled trials published between 2007 and 2013, it was determined that supplementation of
BCAA supplementation has a large effect on DOMS, as well as the rate of muscle tissue
recovery thereafter. Measurable improvements in DOMS will provide a considerable benefit to
athletes, as well as health and fitness professionals seeking to mitigate soreness and potentially
improve performance.
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Branched-chain amino acids and muscle soreness
Table 1. Study summary and quality assessment of branched-chain amino acid supplementation on delayed onset muscle soreness.
Items
Source Summary Randomization Blinding Withdrawal Total Score
Greer et al. 2007 Nine untrained male participants
(21.6±3.2 yrs., 26.3.2±4.3 kg/m2)
completed three 90 minute cycling
bouts at 55% of VO2max and ingested
a placebo, carbohydrate, or BCAA
supplement as part of the study
protocol using a cross-over design.
The 2.5 g BCAA supplement
contained 480 mg isoleucine, 1.22 g
leucine, and 730 mg valine. Self-
reported muscle soreness of the
quadriceps was assessed using a 1 to
10 scale at 24 and 48 hours after
exercise.
0 0 0 0
Howatson et al. 2012 Twelve resistance-trained male
participants (23±2 yrs.) were
randomly assigned to a placebo or
BCAA group and engaged in a
single bout of plyometric exercise
consisting of 100 drop jumps. The
10 g BCAA supplement consisted of
isoleucine, leucine, and valine in a
1:2:1 ratio.
Muscle soreness was assessed
using a 200 mm visual
analogue scale while
participants held a squatting
position (90°) at 24, 48, 72,
and 96 hours following
exercise.
1 2 0 3
Jackman et al. 2010 Twenty-four untrained male 0 0 0 0
369

Branched-chain amino acids and muscle soreness
participants were assigned to a
placebo or BCAA group and
engaged in a resistance training
protocol consisting of eccentric
unilateral knee extensions. The
BCAA supplement consisted of 2.1
g of isoleucine, 3.5 g of leucine, and
1.7 g of valine. Muscle soreness was
assessed using a 50 mm visual
analogue scale while the knee was
flexed and extended at 24, 48, and
72 hours following exercise.
Ra et al. 2013 Thirty-six untrained male
participants (22.5±3.8 yrs.)
were randomly assigned to
a placebo, BCAA, Taurine,
or BCAA+Taurine
supplement group and
engaged in a high-intensity
eccentric resistance
training exercise bout. The
3.2 g BCAA supplement
consisted of isoleucine,
leucine, and valine in a
1:2:1 ratio. Self-reported
muscle soreness of the
biceps brachii was assessed
using a 100 mm visual
analogue scale with
anchored with “no pain”
and “extreme pain” at
opposite poles at 24, 48,
72, and 96 hours following
exercise.
1 2 0 3

Branched-chain amino acids and muscle soreness
Shimomura et al. 2010 Twelve untrained female
participants (22.5±3.8 yrs.)
participated in a cross-over double-
blind experimental protocol
ingesting a placebo or BCAA
supplement and engaging in a lower-
body resistance training protocol.
The BCAA supplement consisted of
isoleucine, leucine, and valine in a
1:2.3:1.2 ratio. Participants were
asked to report muscle soreness of
the lower limbs while squatting
slowly using a 100 mm visual
analogue scale at 24, 48, 72, and 96
hours following exercise.
1 2 0 3
Note: Data are presented as mean±standard deviation. BCAA= branched-chain amino acid, VO2max=Aerobic capacity.

Branched-chain amino acids and muscle soreness
Table 2. Summary of subgroup analysis of the daily changes in DOMS following an acute bout
of exercise.
Effects (κ) Mean ES 95% CI p value Between
Group
Comparison
p value
Time Point
1 Day 9 0.7878 0.4865,
1.0892
<0.0001 0.1266
2 Days 7 1.1286 0.1886,
0.3754
<0.0001
3 Days 6 0.8458 0.4673,
1.2243
<0.0001
4 Days 4 0.6514 0.1726,
1.1303
0.0077
Note: ES=Effect size. CI= Confidence Interval.
370