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\begin{document}

\title{Effects of \selectlanguage{greek}β-\selectlanguage{english}hydroxy \selectlanguage{greek}β-\selectlanguage{english}methylbutryate (HMB) supplementation on
testosterone and cortisol concentration of athletes: A systematic review
and meta-analysis of randomized controlled trials\selectlanguage{english}}



\author[1]{Liu  Gang }%
\affil[1]{Hunan University of Technology}%


\vspace{-1em}



  
  \date{May 25, 2024}


\begingroup
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\selectlanguage{english}
\begin{abstract}
Background: \selectlanguage{greek}β-\selectlanguage{english}hydroxy \selectlanguage{greek}β-\selectlanguage{english}methylbutryate (HMB) is a metabolite of leucine
amino acid and it has several ergogenic benefits. Previous studies also
showed that it may affect beneficially the testosterone and cortisol
concentration in athletes. Due to the contradiction results between
studies, we aimed to conduct this meta-analysis to assess the HMB
supplementation effect on testosterone and cortisol in trained athletes.
Methods: Scopus, Medline and Google scholar were systematically searched
up to August 2020. The Cochrane Collaboration tool for evaluating the
risk of bias was applied for assessing the studies quality. Random
effects model, weighted mean difference (WMD), and 95\% confidence
interval (CI) were used for estimating the overall effect. Between-study
heterogeneity was evaluated applying the chi-squared and I2 statistic.
Results: Seven articles were included in the meta-analysis. Although,
the meta-analysis generally showed that HMB consumption did not have any
effect on the cortisol and testosterone concentration (P \textgreater{}
0.05), but subgroup analysis based on the exercise type, showed a
significant decrease in the cortisol concentration in resistance
training exercises (WMD= -3.30; 95\% CI: -5.50, -1.10; P= 0.003) and a
significant increase in the testosterone concentration in aerobic and
anaerobic combined sports (WMD= 1.56; 95\% CI: 0.07, 3.05; P= 0.040).
Conclusion: The results indicate that HMB supplementation in athletes
can reduce the concentration of cortisol in resistance exercises and
increase the concentration of testosterone in aerobic and anaerobic
combined exercises. Nevertheless, more studies are required to confirm
these results.%
\end{abstract}%



\sloppy


\textbf{1. Introduction}

In recent years, an enormous growth of interest has been placed on
nutritional supplements for enhancing training-induced adaptations. This
interest has been motivated by this theory that nutritional supplements
may improve performance by increasing anabolic and decreasing catabolic
effects, thereby improving body composition and decreasing
exercise-induced muscle damage (1-3).

One potential nutrient is the leucine metabolite \selectlanguage{greek}β-\selectlanguage{english}hydroxy
\selectlanguage{greek}β-\selectlanguage{english}methylbutryate (HMB)supplementation, that it may result in several
ergogenic advantages, including anti-catabolic (4), anabolic (5) and
lipolytic impacts (6). HMB a leucine and 2-ketoisocaproic acid
metabolite has been suggested to enhance recovery and improve skeletal
muscles during high-volume and high-intensity exercises (7-10). It has
been reported that HMB increased strength (11), power (12) and lean body
mass (5, 6) through muscle breakdown inhibition during exercise and
protein synthesis increase after exercise. Recent data suggested that
the advantages of HMB supplementation may be attributed to the some
mechanisms including; 1) upregulation of IGF-I (Insulin-like growth
factor 1) expression in skeletal muscle, 2) stimulating synthesis of
protein via the mammalian/mechanistic target of rapamycin complex 1
(mTOR), 3) membrane stabilization of muscle cells, 4) decreasing
proteolysis by inhibition of the ubiquitin-proteasome pathway (8, 13).

Previous studies also have found that supplementation with HMB resulted
in beneficial effects on performance by increasing anabolic hormones,
including IGF-1, growth hormone and testosterone and decreasing
catabolic stress hormones such as cortisol (7, 14). HMB also may
increase androgen concentration through increasing cholesterol, drawing
on this hypothesis that, HMB is metabolized to \selectlanguage{greek}β -\selectlanguage{english}hydroxy \selectlanguage{greek}β
-\selectlanguage{english}methylglutaryl CoA (HMG-CoA) which is a main source of cholesterol
synthesis and precursor of androgens such as testosterone (15).

While several studies have supported the HMB beneficial effect in
physical activity and clinical condition, some other studies have shown
conflicting results about the HMB supplementation effect on testosterone
and cortisol concentration in athletes (16-18). For example,
Durkalec-Michalski et al. reported an increase in testosterone after 12
weeks supplementation with HMB (3x1g HMB/ day) in 84 highly-trained
males (19). However, in another study, testosterone and cortisol did not
change in 28 male trained athletes after 6 weeks HMB supplementation
(3g/day) (20).

From our point of view, no systematic review and meta-analysis has been
conducted over the HMB supplementation effect on testosterone and
cortisol in trained athletes. Moreover, due to the contradiction results
between studies and common HMB consumption as an ergogenic aid,
particularly among athletes, we aimed to conduct this systematic review
and meta-analysis to assess the effects of HMB supplementation on
testosterone and cortisol in trained athletes.

\textbf{2. Methods}

2.1. Search Strategy

This systematic review and meta-analysis was reported according to the
guidelines of Preferred Reporting Items for Systematic Reviews and
Meta-Analyses (PRISMA) (21). A computerized search was coducted from
inception to August 2020 using various databases including PubMed, ISI
Web of Science, Scopus, and supplementary Google Scholar search. The
following terms and their combinations of MeSH and non-MeSH terms were
applied, including: ``beta hydroxy beta methylbutyrate'', ``hydroxy
methyl butyrate'', ``HMB'', ``exercise,'' ``sport supplements'',
``endocrine response'' ``cortisol'', and ``testosterone''. Reference
lists of all studies were checked for further eligible articles
identification.

2.2. Eligibility Criteria:

Studies were selected by applying the following
Population-Intervention-Comparator-Outcomes-Study design (PICOS)
criteria (21): 1) healthy subjects received oral HMB supplementation, as
a nutritional strategy before and after exercise; 2) original
randomized-controlled trial researches and 3) reporting at least one
outcome measure of hormones (cortisol and testosterone). Studies were
not conducted by using multiple supplementations, (HMB in conjunction
with other supplement like creatine (20), arginine, lysine (22) and
adenosine monophosphate (23)). There were restrictions on the performed
post-exercise and studies that assessed the acute effect of HMB on the
hormonal response (24, 25).

2.3. Selection strategy:

After computerized search, titles and received papers abstracts were
screened by the search strategy. Two authors (LG and M.M) selected
articles based on the inclusion criteria independently. Articles
including eligibility criteria in the title and abstract screening were
elected to be checked by full manuscript. Parallel clinical trials were
elected by applying a control group or crossover design in the
systematic review and meta-analysis. All classified trials were
retrieved by either of the authors. According to the data within the
full information, we used a form to elect the studies eligible for
inclusion in the meta-analysis. Contradictions between the authors were
solved by consensus or third researcher.

2.4. Data extraction:

M.M and LG extracted following needed information: first author's name,
year and publication country, design of studies, gender and age of
subjects, HMB dose and sample size, duration of intervention, and
training status. Also, we extracted mean and standard deviation (SD) of
plasma hormones' status (cortisol and testosterone) at baseline and
after the intervention.

2.5. Study quality:

Given that trial inclusion with a high risk of bias may distort the
outcomes of a meta-analysis (26, 27), the Cochrane Collaboration tool
was used for evaluating the risk of bias. The following items were
evaluated: randomization sequence generation; allocation concealment;
blinding of participants, personnel, investigator, and assessor;
attrition rates; and companies financial interest. These items were
given high, unclear, or low risk of bias rating. A study was categorized
as having low, medium, or high-risk according to the key areas of
allocation concealment, reporting of attrition rates, and participants
and assessor (high = all 4 factors rated high, medium = 2 or 3 factors
rated high or unclear, and low = all key areas rated low).

2.6. Analyses and measures of treatment effect:

For each trial, mean differences and standard deviation were calculated
for continuous variables. The differences of mean changes in cortisol
and testosterone concentration and their correspondence SD were
extracted as the effect size. In trials that the standard error (SE)
measure was reported, SE was converted to SD applying this formula: SD=
SE\selectlanguage{ngerman}×\selectlanguage{english}[?]n (n=number of subjects in each group). Between-study heterogeneity
was assessed using the chi-squared (\selectlanguage{greek}χ\selectlanguage{english}2) test and quantified applying the
I\textsuperscript{2} statistic, which shows the total variation
percentage across studies that is ascribable to heterogeneity rather
than to chance. Significant heterogeneity was defined with a P-value of
\textless{}0.05.

The random effects model was applied to calculate the weighted mean
differences (WMDs) with 95\% confidence intervals (CIs) for estimating
the overall effect. To evaluate whether the outcomes could have been
altered by a single study distinctly, a sensitivity analysis was
performed (28). Also, subgroup analysis was conducted, based on the
sports type (resistance training or aerobic and anaerobic combined
training) and duration of studies (over six weeks and 6 weeks or lower).
Publication bias was evaluated by Egger's regression asymmetry test and
Begg's rank correlation test. Funnel plots also depicted the effect
sizes against their corresponding standard errors. Statistical analyses
were conducted applying STATA 11.2 software (StataCorp, College Station,
Texas, USA).

\textbf{3. Results}

3.1. Search outcomes and overview of included studies

Our initial search led to 184 relevant studies. After removing
duplications, a wide range of screening of the titles and abstracts, the
careful assessment was performed on 142 related articles. Of these, 11
articles remained after considering the inclusion and exclusion criteria
for the eligibility. Eventually, 7 articles, including, 8 effect sizes,
which studied a total of 235 participants aged 16.1 --24.9 years, were
identified in the current systematic review and
meta-analysis.\textbf{Figure 1} represents the selection process and
reasons for excluding the studies. The data in \textbf{Table 1}
illustrates the main characteristics of the articles in our systematic
review and meta-analysis.

In brief, the studies (by 235 participants) were published between 2001
and 2017. The duration of these RCTs ranged between 1.5 to 12 weeks. 2
studies used a randomized crossover design (19, 29), one of them was
also single blind (30) and the other studies had the design of
double-blind. Two studies were conducted in Poland (19, 29), 1 in the
United States (30), 1 in Iran (31), 2 in Australia (20, 32) and 1 in
Israel (7). The effect of exercise on testosterone and cortisol
concentration was examined in 7 studies (7, 19, 20, 29-32); and 8 effect
sizes were extracted from these studies for testosterone and cortisol
concentration. The total number of subjects who completed the studies in
inclusion criteria was 121 subjects in the intervention and 107 in the
placebo groups. The dose of HMB supplementation was 3 g/day in all
studies.

3.2. Risk of bias

The quality of the studies is presented in \textbf{Table 2} . Briefly,
random sequencing generation was unclear in 3 studies (20, 30).
Participants and outcome blinding and incomplete outcome data were high
and unclear risk of bias in only two studies, respectively (20, 32). And
then ranked as low risk of bias for 5 studies (7, 19, 29-31), medium
risk of bias for 1 study (32), and high risk of bias for 1 study (20).
Most of studies had a low risk of bias for selective reporting and other
sources of bias except for one study (20).

3.3. Findings from the meta-analysis

3.3.1. Effects of HMB supplementation on serum cortisol concentration

Overall, HMB consumption had no significant effect on cortisol
concentration: WMD= -1.35 \selectlanguage{greek}μ\selectlanguage{english}g/dl; 95\% CI: -2.70, 0.002; P= 0.050. There
was no significant heterogeneity among the studies (Cochran's Q test =
14.05, P= 0.050, I\textsuperscript{2}=50.2\%). Subgroup analyses of
different types of exercise showed that cortisol concentration
significantly reduced after resistance exercises (WMD= -3.30 \selectlanguage{greek}μ\selectlanguage{english}g/dl; 95\%
CI: -5.50, -1.10; P= 0.003), whereas it had not significant effect on
cortisol concentration in aerobic and anaerobic combined activities
(WMD= -0.16; 95\% CI: -1.16, 0.84; P= 0.753). The results of subgroup
analysis are shown in \textbf{Table 3} and the forest plot is shown
in\textbf{Figure 2} .

3.3.2. Effects of HMB supplementation on testosterone concentration

As outlined in \textbf{Table 4} , our preliminary analysis indicated
that HMB consumption did not significantly improve serum testosterone
concentration (WMD= 0.75 nmol/L; 95\% CI: -0.09, 1.58; P= 0.079). Also,
no significant heterogeneity was observed among studies (Cochran's Q test
= 3.33, P= 0.853, I\textsuperscript{2} = 0.00\%). Subgroup analysis was
conducted to check as to how the effect of HMB supplementation on serum
testosterone is different according to type of exercise activities
(\textbf{Figure 3} ) or duration of the interventions (\textbf{Figure 4}
). This analysis revealed that the pooled effect of HMB supplementation
on testosterone concentration was influenced by the duration of the
supplementation (\textless{}6 weeks versus [?]6 weeks), in which a
significant increase in testosterone concentration was found in studies
that lasted longer than 6 weeks (WMD= 1.60 nmol/L; 95\% CI: 0.08, 3.12;
P= 0.039). Also, subgroup analysis based on the type of exercise
training indicated that the increasing effect of HMB supplementation on
serum testosterone is significant in aerobic and anaerobic combined
activities (WMD= 1.60 nmol/L; 95\% CI: 0.08, 3.12; P= 0.039). Subgroup
analysis didn't show any significant effect of HMB supplementation on
testosterone concentration in studies lasting lower than six weeks (WMD=
0.38; 95\% CI: -0.62, 1.38; P= 0.455) or on resistance training exercise
(WMD= 0.38 nmol/L; 95\% CI: -0.63, 1.38; P= 0.464).

3.3.3. Sensitivity analysis and publication bias

Sensitivity analysis showed that the omission of any of the studies from
the meta-analysis, create no change in the outcomes of the meta-analysis
on testosterone concentration whereas, the results on cortisol
concentration were sensitive to omitting 3 studies (7, 29, 30). Funnel
plots for cortisol and testosterone were visually symmetrical, and the
results of Egger's test did not determine any evidence of publication
bias in studies that examine the effect of HMB consumption on cortisol
(Egger's test, P = 0.337) and on testosterone (Egger's test, P = 0.140).

\textbf{4. Discussion}

The efficacy of HMB has not been distinctly established regarding
hormonal responses; thus, this systematic review and meta-analysis
provided comprehension into the potential benefits conferred by HMB
supplementation to help athletes to make aware decisions on its usage
and impact. In this systematic review and meta-analysis of 7 studies
(235 participants), we found that HMB consumption led to a significant
decrease in cortisol and increase in testosterone concentrations after
resistance exercises and aerobic and anaerobic combined activities,
respectively. Several probable mechanisms have been suggested for the
beneficial effects of HMB supplementation on testosterone and cortisol
concentration in athletes.

Our results support those of past investigations showing that amino acid
consumption may play a role in reducing exercise-induced increases in
cortisol (33). Cortisol, is a catabolic hormone and basic glucocorticoid
form in humans, secreted from the adrenal cortex in response to
psychological and physical stress (34). During cortisol elevates in
exercise, impacts of this hormone happen after exercise within the early
recovery. Elevation in plasma cortisol concentration, within the
physiological range in short-term, motivates proteolysis and augments
plasma leucine utilization and concentration (35). The study of Knitter
(36) showed that HMB operated as an anti-catabolic agent rather than an
anabolic agent. The mechanism for this reaction is not exactly obvious.
Some studies support the anti-catabolic hypothesis of HMB expressed by
reductions in the muscle damage indices such as creatine phosphokinase
and lactate dehydrogenase (15, 37) and subsequent lower cortisol levels.
The major characteristics of skeletal muscle damage without cell
necrosis is the muscle fibers disruption, exclusively the basal lamina
sheath. Regarding mechanical stimuli, especially in resistance exercise,
it is known that it can boost micro damage in muscle fibers imposed by
contractions or overload and, depending on the volume, duration and
intensity of training, the degree and severity of damage and discomfort
may be combined over time (38, 39). As such, HMB can affect muscle
damage and cortisol levels more efficiently after resistance exercise.
However, more studies should be conducted to reveal physiological and
molecular mechanisms by which muscle damage markers were decreased after
HMB supplementation.

Moreover, cortisol shows an anticipatory reaction to exercise and
physical activity (40), and Kraemer et al. previously suggested that
this reaction was reduced using a herbal supplement with specifically
designed (41). Because amino acids supplementation increases the
circulating amino acid concentrations (42), possibly less cortisol was
needed for gluconeogenesis before exercise to break down proteins into
amino acids.

Reduced cortisol at rest enhances the anabolic-to-catabolic hormone
ratio, that in theory, would increase testosterone chronically and
muscle tissue protein balance (12). Also, the primitive destination of
HMB is a conversion to HMG-CoA in the cytosol of liver and muscle, thus
HMB is a precursor of cholesterol (43, 44), and HMB supplementation
leads to an increase in synthesis of cholesterol and may act as a
structural component of cell membranes (45). Given that damaged muscle
cells after exercise (46) may lose their ability to make sufficient
HMG-CoA for the synthesis of cholesterol, HMB supplement for more than 6
weeks may be a suitable source of HMG-CoA to synthesize testosterone
(15, 47). The increment in testosterone concentration seems to be linked
with an increase in the endogenous cholesterol that is a substrate in
the steroidogenesis process. Additionally, our results in regard to the
HMB and aerobic and anaerobic exercise effects on changes in the
testosterone response propose that acute ingestion does not increase the
testosterone response to exercise. Townsend et al. study carried out 3
exercise protocols throughout the 12 weeks to assay the supplementation
acute response. At supplementation of weeks 6 and 9, the response of
testosterone was increased in the intervention group (24). Therefore,
chronic supplementation of HMB may lead to a more pronounced response of
testosterone. The increase of testosterone concentration could be
considered as a beneficial result and demonstrate a better anabolic
status in athletes, which plays a key roles in training adaptation and
recovery in well-trained athletes (48).

To the best of our knowledge, this study is the first systematic review
and meta-analysis that attempt to summarize the role of HMB
supplementation on hormonal changes (cortisol and testosterone) in
athletes. All included studies administered the same doses of HMB for
intervention and all participants were male (except in one study (49))
that resulted in a decrement in heterogeneity. Moreover, the absence of
heterogeneity among the included studies enhanced the power of our
outcomes. However, some limitations should be mentioned. Considering the
above items, it is not possible to evaluate the effect of the HMB
consumption in female athletes and dose-response relationship between
HMB supplementation and hormonal changes. Lack of information about data
on frequency and intensity of exercise, genetic background, lifestyle
factors and lack of complete baseline cortisol and testosterone data for
subgroup analysis make overall interpretation of the results difficult.
Eventually, the type of exercise was varied among the included studies,
which could affect the reported outcomes.

In conclusion, the current systematic review and meta-analysis outcomes
revealed that HMB supplementation may be linked with a decrease in
cortisol concentration after resistance exercise. In contrast to
cortisol, testosterone concentration significantly increased in aerobic
and anaerobic combined training. more investigations are recommended
with a variety of doses and exercises, longer time in periods and in
both sexes in athletes.

\textbf{Conflicts of interest} :

None

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al. The Cochrane Collaboration's tool for assessing risk of bias in
randomised trials. Bmj. 2011;343:d5928.

27. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis
JP, et al. The PRISMA statement for reporting systematic reviews and
meta-analyses of studies that evaluate health care interventions:
explanation and elaboration. PLoS medicine. 2009;6(7):e1000100.

28. Tobias A. Assessing the influence of a single study in the
meta-anyalysis estimate. Stata Technical Bulletin. 1999;8(47).

29. Durkalec-Michalski K, Jeszka J. The efficacy of a
beta-hydroxy-beta-methylbutyrate supplementation on physical capacity,
body composition and biochemical markers in elite rowers: a randomised,
double-blind, placebo-controlled crossover study. J Int Soc Sports Nutr.
2015;12:31.

30. Hoffman JR, Cooper J, Wendell M, Im J, Kang J. Effects of
beta-hydroxy beta-methylbutyrate on power performance and indices of
muscle damage and stress during high-intensity training. Journal of
strength and conditioning research. 2004;18(4):747-52.

31. Asadi A, Arazi H, Suzuki K. Effects of
\selectlanguage{greek}β-\selectlanguage{english}hydroxy-\selectlanguage{greek}β-\selectlanguage{english}methylbutyrate-free acid supplementation on strength, power
and hormonal adaptations following resistance training. Nutrients.
2017;9(12):1316.

32. Slater G, Jenkins D, Logan P, Lee H, Vukovich M, Rathmacher JA, et
al. \selectlanguage{greek}β-\selectlanguage{english}hydroxy-\selectlanguage{greek}β-\selectlanguage{english}methylbutyrate (HMB) supplementation does not affect
changes in strength or body composition during resistance training in
trained men. International journal of sport nutrition and exercise
metabolism. 2001;11(3):384-96.

33. Sharp CP, Pearson DR. Amino acid supplements and recovery from
high-intensity resistance training. The Journal of Strength \&
Conditioning Research. 2010;24(4):1125-30.

34. Brownlee KK, Moore AW, Hackney AC. Relationship between circulating
cortisol and testosterone: influence of physical exercise. Journal of
sports science \& medicine. 2005;4(1):76.

35. Tinsley GM, Givan AH, Graybeal AJ, Villarreal MI, Cross AG.
\selectlanguage{greek}β-\selectlanguage{english}Hydroxy \selectlanguage{greek}β-\selectlanguage{english}methylbutyrate free acid alters cortisol responses, but not
myofibrillar proteolysis, during a 24-h fast. British Journal of
Nutrition. 2018;119(5):517-26.

36. Knitter AE, Panton L, Rathmacher JA, Petersen A, Sharp R. Effects of
beta-hydroxy-beta-methylbutyrate on muscle damage after a prolonged run.
Journal of applied physiology (Bethesda, Md : 1985). 2000;89(4):1340-4.

37. Rahimi MH, Mohammadi H, Eshaghi H, Askari G, Miraghajani M. The
effects of beta-hydroxy-beta-methylbutyrate supplementation on recovery
following exercise-induced muscle damage: A systematic review and
meta-analysis. Journal of the American College of Nutrition.
2018;37(7):640-9.

38. Nakhostin-Roohi B, Nasirvand Moradlou A, Mahmoodi Hamidabad S,
Ghanivand B. The effect of curcumin supplementation on selected markers
of delayed onset muscle soreness (DOMS). Annals of Applied Sport
Science. 2016;4(2):25-31.

39. J\selectlanguage{ngerman}äger R, Purpura M, Kerksick CM. Eight weeks of a high dose of
curcumin supplementation may attenuate performance decrements following
muscle-damaging exercise. Nutrients. 2019;11(7):1692.

40. Suay F, Salvador A, González-Bono E, Sanch\selectlanguage{polish}ı\selectlanguage{english}s C, Mart\selectlanguage{polish}ı\selectlanguage{english}nez M,
Mart\selectlanguage{polish}ı\selectlanguage{english}nez-Sanchis S, et al. Effects of competition and its outcome on
serum testosterone, cortisol and prolactin. Psychoneuroendocrinology.
1999;24(5):551-66.

41. Kraemer WJ, French DN, Spiering BA, Volek JS, Sharman MJ, Ratamess
NA, et al. Cortitrol supplementation reduces serum cortisol responses to
physical stress. Metabolism. 2005;54(5):657-68.

42. Matsumoto K, Mizuno M, Mizuno T, Dilling-Hansen B, Lahoz A,
Bertelsen V, et al. Branched-chain amino acids and arginine
supplementation attenuates skeletal muscle proteolysis induced by
moderate exercise in young individuals. International journal of sports
medicine. 2007;28(06):531-8.

43. Rabinowitz JL. The Biosynthesis of Radioactive \selectlanguage{greek}β-\selectlanguage{english}Hydroxyisovaleric
Acid in Rat Liver1-3. Journal of the American Chemical Society.
1955;77(5):1295-6.

44. Rudney H. The biosynthesis of beta-hydroxy-beta-methylglutaric acid.
The Journal of biological chemistry. 1957;227(1):363-77.

45. Nissen S, Sharp R, Ray M, Rathmacher JA, Rice D, Fuller JC, Jr., et
al. Effect of leucine metabolite beta-hydroxy-beta-methylbutyrate on
muscle metabolism during resistance-exercise training. Journal of
applied physiology (Bethesda, Md : 1985). 1996;81(5):2095-104.

46. Evans WJ, Cannon JG. The metabolic effects of exercise-induced
muscle damage. Exercise and sport sciences reviews. 1991;19:99-125.

47. Holecek M, Muthny T, Kovarik M, Sispera L. Effect of
beta-hydroxy-beta-methylbutyrate (HMB) on protein metabolism in whole
body and in selected tissues. Food and chemical toxicology.
2009;47(1):255-9.

48. Koundourakis NE, Margioris AN. The complex and bidirectional
interaction between sex hormones and exercise performance in team sports
with emphasis on soccer. Hormones. 2019:1-22.

49. Portal S, Zadik Z, Rabinowitz J, Pilz-Burstein R, Adler-Portal D,
Meckel Y, et al. The effect of HMB supplementation on body composition,
fitness, hormonal and inflammatory mediators in elite adolescent
volleyball players: a prospective randomized, double-blind,
placebo-controlled study. Eur J Appl Physiol. 2011;111(9):2261-9.

\textbf{Figures:}

\textbf{Figure 1-} Flow diagram of the study selection process.

\textbf{Figure 2-} Forest plot representing the effect of HMB
supplementation on the cortisol concentration. The analysis was done
using a random-effects model, subgroup analysis performed based on the
type of exercise activities.

\textbf{Figure 3} - Forest plot representing the effect of HMB
supplementation on the testosterone concentration. The analysis was done
using a random-effects model, subgroup analysis performed based on the
type of exercise activities.

\textbf{Figure 4-} Forest plot representing the effect of HMB
supplementation on the testosterone concentration. The analysis was done
using a random-effects model, subgroup analysis performed based on the
duration of the interventions.

\textbf{Figure 1.} Flow diagram of the study selection process.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image1/image1}

\end{center}
\end{figure}

\textbf{Figure 2-} Forest plot representing the effect of HMB
supplementation on the cortisol concentration. The analysis was done
using a random-effects model, subgroup analysis performed based on the
type of exercise activities.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image2/image2}

\end{center}
\end{figure}

\textbf{Figure 3} - Forest plot representing the effect of HMB
supplementation on the testosterone concentration. The analysis was done
using a random-effects model, subgroup analysis performed based on the
type of exercise activities.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/image3/image3}

\end{center}
\end{figure}

\textbf{Figure 4-} Forest plot representing the effect of HMB
supplementation on the testosterone concentration. The analysis was done
using a random-effects model, subgroup analysis performed based on the
duration of the interventions.

\textbf{Table 1.} Characteristics of the Included Studies.\selectlanguage{english}
\begin{longtable}[]{@{}llllllllll@{}}
\toprule
\begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
Evaluated hormones\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
Sample Size\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
Sample Size\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
average age (y)\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
Study Design Characteristics\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
Study Design Characteristics\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
Study Design Characteristics\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
Study Design Characteristics\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
Study Design Characteristics\strut
\end{minipage} & \begin{minipage}[b]{0.07\columnwidth}\raggedright\strut
Author\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Control\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
HMB\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
gender\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Duration (w)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
HMB dose (gr)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
country\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
design\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
C, T\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
42\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
42\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
22.8\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
M\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
12\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
3\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Poland\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
C-O\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Durkalec-Michalski et al. (2017)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
C, T\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
8\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
8\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
21.4\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
M\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
3\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Iran\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
P\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Asadi et al. (2017)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
C, T\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
16\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
16\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
19.5\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
M\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
12\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
3\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Poland\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
C-O\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Durkalec-Michalski et al. (2015)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
C, T\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
14\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
14\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
16.1\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
M \& F\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
7\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
3\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Israel\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
P\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Portal et al. (2011)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
C, T\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
15\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
15\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
20.7\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
M\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
1.5\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
3\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
USA\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
P\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Hoffman et al. (2004)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
C, T\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
11\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
24.9\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
M\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
3\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Australia\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
P\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Crowe et al. (2003)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
C, T\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
7\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
7\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
24.6\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
M\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
3 (Standard)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Australia\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
P\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Slater et al. (2001)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
C, T\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
7\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
8\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
24.6\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
M\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
6\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
3 (Time Releasing)\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Australia\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
P\strut
\end{minipage} & \begin{minipage}[t]{0.07\columnwidth}\raggedright\strut
Slater et al. (2001)\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

C, Cortisol; T, Testosterone; HMB, \selectlanguage{greek}β -\selectlanguage{english}hydroxy- \selectlanguage{greek}β -\selectlanguage{english}methylbutyrate; P,
Parallel; C-O, cross-over studies; M, men; F, Female; W, weeks; Y,
years; t, trained; U, untrained

\textbf{Table 2.} Cochrane Risk of Bias Assessment\selectlanguage{english}
\begin{longtable}[]{@{}lllllllll@{}}
\toprule
\begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
Study\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
Random Sequence Generation\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
Allocation concealment\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
Blinding of participants and personnel\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
Blinding of outcome assessment\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
Incomplete outcome data\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
Selective outcome reporting\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
Other sources of bias\strut
\end{minipage} & \begin{minipage}[b]{0.11\columnwidth}\raggedright\strut
Overall Risk of Bias\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Durkalec-Michalski et al.(2017)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Asadi et al. (2017)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
H\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Durkalec-Michalski et al. (2015)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
H\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Portal et al. (2011)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Hoffman et al. (2004)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Crowe et al. (2003)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
H\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
H\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
H\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
H\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
H\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Slater et al. (2001)\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
U\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
L\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
M\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

L, low risk of bias; H, high risk of bias; M, medium risk of bias; U,
unclear risk of bias.

\textbf{Table 3.} Effect of HMB supplementation on cortisol
concentration in athletes, subgroup analyses based on study duration and
type of exercise activities (all analyses were conducted using random
effects model).\selectlanguage{english}
\begin{longtable}[]{@{}llllllll@{}}
\toprule
\begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Meta-analysis}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Meta-analysis}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Heterogeneity}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Heterogeneity}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Heterogeneity}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Heterogeneity}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{Study group}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{No. of} \textbf{effect sizes}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{Effect Mean difference (95\%CI)}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\emph{P} \textbf{effect}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\emph{Q} \textbf{statistic}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\emph{P} \textbf{within group}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\emph{I\textsuperscript{2}} \textbf{(\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\emph{P} \textbf{between group}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textgreater{} 6 weeks\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
3\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-0.25 (-1.42, 0.90)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.668\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.23\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.893\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.144\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
[?] 6 weeks\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-2.47 (-4.72, -0.21)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{0.032}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
10.96\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.027\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
63.50\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Aerobic and anaerobic combined\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-0.16 (-1.16, 0.84)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.753\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.32\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.956\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{0.003}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Resistance training\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-3.30 (-5.50, -1.10)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{0.003}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
4.93\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.177\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
39.1\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Overall}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
8\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-1.35 (-2.70, 0.002)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.050\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
14.05\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.050\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
50.20\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\textbf{Table 4.} Effect of HMB supplementation on testosteron
concentration in athletes, subgroup analyses based on study duration and
type of exercise activities (all analyses were conducted using random
effects model).\selectlanguage{english}
\begin{longtable}[]{@{}llllllll@{}}
\toprule
\begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Meta-analysis}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Meta-analysis}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Heterogeneity}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Heterogeneity}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Heterogeneity}\strut
\end{minipage} & \begin{minipage}[b]{0.10\columnwidth}\raggedright\strut
\textbf{Heterogeneity}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{Study group}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{No. of} \textbf{effect sizes}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\textbf{Effect Mean difference (95\%CI)}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\emph{P} \textbf{effect}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\emph{Q} \textbf{statistic}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\emph{P} \textbf{within group}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\emph{I\textsuperscript{2}} \textbf{(\%)}\strut
\end{minipage} & \begin{minipage}[t]{0.12\columnwidth}\raggedright\strut
\emph{P} \textbf{between group}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Duration}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textgreater{} 6 weeks\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
3\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.60 (0.08, 3.12)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{0.039}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.28\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.870\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.188\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
[?] 6 weeks\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
5\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.38 (-0.62, 1.38)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.455\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.32\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.858\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Type of exercise activities}\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
aaa\selectlanguage{english}Aerobic and anaerobic combined\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.56 (0.07, 3.05)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{0.040}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.34\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.952\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.196\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
Resistance training\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
4\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.38 (-0.63, 1.38)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.464\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
1.32\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.725\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
\textbf{Overall}\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
8\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.75 (-0.09, 1.58)\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.079\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
3.33\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.853\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
0.00\strut
\end{minipage} & \begin{minipage}[t]{0.10\columnwidth}\raggedright\strut
-\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

\selectlanguage{english}
\FloatBarrier
\end{document}

