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Does Branched-Chain Amino Acids (Bcaas) nutrients Review Does Branched-Chain Amino Acids (BCAAs) Supplementation Attenuate Muscle Damage Markers and Soreness after Resistance Exercise in Trained Males? A Meta-Analysis of Randomized Controlled Trials Chutimon Khemtong 1 , Chia-Hua Kuo 1 , Chih-Yen Chen 2,3, Salvador J. Jaime 4 and Giancarlo Condello 1,5,* 1 Institute of Sports Sciences, University of Taipei, 101 Zhongcheng Rd. Section 2, Shilin District, Taipei 111, Taiwan; [email protected] (C.K.); [email protected] (C.-H.K.) 2 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 112, Taiwan; [email protected] 3 Faculty of Medicine and Institute of Emergency and Critical Medicine, National Yang Ming Chiao Tung University College Medicine, Taipei 112, Taiwan 4 Department of Exercise and Sport Science, University of Wisconsin-La Crosse, La Crosse, WI 54601, USA; [email protected] 5 Graduate Institute of Sports Training, University of Taipei, 101 Zhongcheng Rd. Section 2, Shilin District, Taipei 111, Taiwan * Correspondence: [email protected] Abstract: Previous studies have reported the positive effects of branched-chain amino acids (BCAAs) supplementation on lowering plasma markers of muscle damage and subjective soreness after resistance exercise. However, a variety of factors can potentially moderate its efficacy. This meta- analysis aimed to summarize the evidence regarding the effect of BCAAs supplementation on plasma Citation: Khemtong, C.; Kuo, C.-H.; muscle damage markers and soreness after resistance exercise in only trained males, by considering Chen, C.-Y.; Jaime, S.J.; Condello, G. the plasma lactate dehydrogenase (LDH) and creatine kinase (CK). Randomized controlled trials were Does Branched-Chain Amino Acids (BCAAs) Supplementation Attenuate identified through a computerized literature search for the period 2010–2020. The pooled data were 2 Muscle Damage Markers and analyzed with the random-effects model and heterogeneity using I . Cochrane Collaboration tools Soreness after Resistance Exercise in was used for the assessment of risk of bias. Nine studies met the inclusion criteria. A positive effect Trained Males? A Meta-Analysis of was found for CK at <24, 24, and 48 h after exercise and for muscle soreness at <24 h only. However, Randomized Controlled Trials. the positive effect was not evident for plasma LDH at any follow-up time. Different outcomes for Nutrients 2021, 13, 1880. https:// post-exercise responses may suggest that BCAAs supplementation can attenuate muscle damage and doi.org/10.3390/nu13061880 ameliorate muscle soreness after resistance exercise in trained males. Received: 31 March 2021 Keywords: branched-chain amino acids; muscle damage; muscle soreness; creatine kinase; lactate Accepted: 28 May 2021 dehydrogenase; resistance exercise; inflammatory response; meta-analysis Published: 31 May 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in 1. Introduction published maps and institutional affil- iations. Resistance exercise is commonly used by general population and athletes to increase muscular strength, endurance, power, and muscle mass. It can be executed across the three muscle contractions, eccentric, concentric, and isometric, in isolation or combination. Eccentric muscle contraction has been postulated to induce a higher magnitude of muscle damage compared with concentric and isometric ones [1,2], in particular when unaccus- Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. tomed eccentric exercises with greater force production [3] and fast angular velocities [4] This article is an open access article are performed. The proposed model of exercise-induced muscle damage (EIMD) includes distributed under the terms and two phases, the primary damage resulting from the mechanical stress during the exercise conditions of the Creative Commons bout, and the subsequent secondary damage involving the loss of membrane integrity Attribution (CC BY) license (https:// at the sarcoplasmic reticulum and causing the leakage of intramuscular proteins from creativecommons.org/licenses/by/ the muscle sarcolemma into the blood for several days after exercise [5]. This secondary 4.0/). damage can be associated with the inflammatory responses, which are divided in early and Nutrients 2021, 13, 1880. https://doi.org/10.3390/nu13061880 https://www.mdpi.com/journal/nutrients Nutrients 2021, 13, 1880 2 of 14 late stages, encompassing satellite cells activation and proliferation and terminal differenti- ation and growth, respectively [6]. The possible consequences of EIMD are disruption of intracellular muscle structure, sarcolemma and extracellular matrix, prolonged impairment of muscle function, delayed-onset muscle soreness (DOMS), stiffness, and swelling lasting for several days [7]. The inflammation status can be identified by the indirect inflammatory biomarkers el- evated into the blood circulation, such as lactate dehydrogenase (LDH) and creatine kinase (CK) [8,9], myoglobin, and cytokines [1,10]. Plasma LDH elevation occurs immediately after exercise before CK increases. Differently, plasma CK may peak anywhere from 24 to 96 h [11,12]. The different response patterns of these two markers may correspond to different stages of inflammation (early and late stage) before resolution of inflammation [6]. Although exercise-induced inflammation is essential for adaptive remodeling [13], subse- quent exercise sessions could be compromised by residual muscle soreness, restriction of movement, and reduced capacity. Therefore, several strategies have been suggested to mit- igate these negative consequences from EIMD, including massage, cryotherapy, stretching, non-steroidal anti-inflammatory drugs, and nutritional strategies [5]. Considering the nutritional strategies, dietary protein provides amino acids to stim- ulate muscle protein synthesis in order to support the inflammatory process and muscle regeneration after exercise [14,15]. Due to the existence of several protein sources, the com- position of amino acids and bioavailability of each source may influence the understanding of protein quality and the capacity of the diet to support muscle protein synthesis [15,16]. In particular, dietary protein sources vary for the branched-chain amino acids (BCAAs) content, which ranges from 14% (potatoes) to 26% (milk) and is considered an impor- tant factor for stimulating muscle protein synthesis and promoting muscle growth [15]. Moreover, the three components of BCAAs (i.e., leucine, isoleucine, and valine) are pri- marily catabolized in the skeletal muscles, whereas other amino acids are catabolized in the liver [17]. Consequently, the protein turnover in the muscle cells can be directly regulated by BCAAs to counteract the catabolic and anti-anabolic effects produced by EIMD [18]. Specifically, leucine has been identified as a key regulator of mTOR signaling and translation initiation [15]. Therefore, among the possible protein sources, whey protein, BCAAs, and leucine-enriched essential amino acids are suggested for the supplementation strategy due to the high availability of amino acids (especially leucine) for the promotion of muscle protein synthesis [15,18,19]. However, BCAAs have the advantages to be lower in calories, omitting gluconeogenesis, and preventing augmented kidney workload compared with high protein diet, like dietary or whey protein [20]. Therefore, the use of BCAAs as supplementation strategy becomes popular among general population and athletes due to its ability in attenuating the negative symptoms of EIMD [21]. Recently, the effects of BCAAs on the EIMD mitigation and muscle soreness have been widely investigated under different exercise conditions and populations, even though heterogeneity exists among outcomes and methodological quality [22]. A summary of evidence is available from previous meta-analyses [23–25]. Evidence demonstrates the po- tential positive effect of BCAAs supplementation on muscle damage, muscle soreness and function [23], fatigue substances, energy metabolites and muscle soreness substances [24], and muscle damage [25]. The previous meta-analyses have been conducted with broad eligibility criteria in terms of gender (both male and female participants), training status (trained and untrained populations), type of exercise (endurance, resistance, or specific sports), and supplementation interventions (BCAAs combined with other amino acids and vitamins). Although this evidence can still be informative, the generalizability of the findings could be influenced by the effects of potential moderators, hence a refined selection of eligibility criteria could narrow the understanding of the effect of BCAAs supplementation. Therefore, the purpose of this article was to conduct a meta-analysis of studies investi- gating the effects of BCAAs supplementation on the plasma muscle damage markers and soreness after resistance exercise in trained males. The evaluation of markers LDH and CK Nutrients 2021, 13, 1880 3 of 14 may help to provide insight into the effects of BCAAs supplementation related to the early and late stages of the inflammation. Furthermore, female hormones are fluctuating with time and estrogen has been shown to influence the exercise-induced response in plasma muscle damage markers [26]. To avoid the potential influence of sex hormone, the present meta-analysis only included studies on trained males. 2. Materials and Methods 2.1. Study Protocol The systematic review with meta-analysis was conducted
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