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Effects and feasibility of exercise therapy combined with branched-chain amino acid supplementation on muscle strengthening in frail and pre-frail elderly people requiring long-term care: a crossover trial

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Applied Physiology Nutrition and Metabolism
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This study examined the effects and feasibility of a twice-weekly combined therapy of branched-chain amino acids (BCAAs) and exercise on physical function improvement in frail and pre-frail elderly people requiring long-term care. We used a crossover design in which the combination of exercise and nutritional interventions was carried out twice a week during cycles A (3 months) and B (3 months) and the exercise intervention alone was performed during the washout period. The exercise intervention entailed the following 5 training sets: 3 sets of muscle training at 30% of maximum voluntary contraction, 1 set of aerobic exercise, and 1 set of balance training. For the nutritional intervention, 6 g of BCAAs or 6 g of maltodextrin was consumed 10 min before starting the exercise. We determined upper and lower limb isometric strength, performance on the Functional Reach Test (FRT) and the Timed Up and Go test, and activity level. In the comparison between the BCAA group and the control group after crossover, the improvement rates in gross lower limb muscle strength (leg press, knee extension) and FRT performance were significantly greater (by approximately 10%) in the BCAA group. In the comparison between different orders of BCAA administration, significant effects were shown for the leg press in both groups only when BCAAs were given. The combination of BCAA intake and exercise therapy yielded significant improvements in gross lower limb muscle strength and dynamic balance ability.
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ARTICLE
Effects and feasibility of exercise therapy combined with
branched-chain amino acid supplementation on muscle
strengthening in frail and pre-frail elderly people requiring
long-term care: a crossover trial
Takashi Ikeda, Junya Aizawa, Hiroshi Nagasawa, Ikuko Gomi, Hiroyuki Kugota, Keigo Nanjo,
Tetsuya Jinno, Tadashi Masuda, and Sadao Morita
Abstract: This study examined the effects and feasibility of a twice-weekly combined therapy of branched-chain amino acids
(BCAAs) and exercise on physical function improvement in frail and pre-frail elderly people requiring long-term care. We used
a crossover design in which the combination of exercise and nutritional interventions was carried out twice a week during cycles
A (3 months) and B (3 months) and the exercise intervention alone was performed during the washout period. The exercise
intervention entailed the following 5 training sets: 3 sets of muscle training at 30% of maximum voluntary contraction, 1 set of
aerobic exercise, and 1 set of balance training. For the nutritional intervention,6gofBCAAs or6gofmaltodextrin was consumed
10 min before starting the exercise. We determined upper and lower limb isometric strength, performance on the Functional
Reach Test (FRT) and the Timed Up and Go test, and activity level. In the comparison between the BCAA group and the control
group after crossover, the improvement rates in gross lower limb muscle strength (leg press, knee extension) and FRT perfor-
mance were significantly greater (by approximately 10%) in the BCAA group. In the comparison between different orders of BCAA
administration, significant effects were shown for the leg press in both groups only when BCAAs were given. The combination
of BCAA intake and exercise therapy yielded significant improvements in gross lower limb muscle strength and dynamic balance
ability.
Key words: amino acid supplementation, low-intensity resistance exercise, aging, outpatient rehabilitation, combined therapy.
Résumé : Cette étude examine les effets et la faisabilité d’un traitement combiné incluant des acides aminés a
`chaîne ramifiée
(BCAA) et l’exercice physique a
`raison de deux fois par semaine sur l’amélioration des fonctions physiques chez des personnes
âgées au seuil ou en perte d’autonomie dans un cadre de soins prolongés. On applique les traitements kinésique et nutritionnel
selon un devis croisé a
`raison de deux fois par semaine durant les cycles A (3 mois) et B (3 mois) et on applique le traitement
kinésique seul au cours de la période d’élimination. Le traitement kinésique comprend cinq séances : trois séances de renforce-
ment musculaire avec une charge équivalente a
`30 % de la force de contraction maximale volontaire, une séance d’exercice
aérobie et une séance d’équilibre. Le traitement nutritionnel consiste en un apport de6gdeBCAA ou de maltodextrine avant le
début de l’exercice. On évalue la force isométrique des membres supérieurs et inférieurs, on administre le test de portée
fonctionnelle (FRT), le test TUG (Timed up and Go) et on détermine le niveau d’activité. La comparaison du groupe BCAA et du
groupe de contrôle après le croisement des traitements révèle une amélioration significative de la force musculaire brute des
membres inférieurs (développé des membres inférieurs : LP, extension des genoux) et du résultat au FRT dans le groupe BCAA par
rapport au groupe de contrôle; l’amélioration est d’environ 10 %. La comparaison des différents ordres d’administration de BCAA
révèle un effet significatif en ce qui concerne LP dans les deux groupes seulement quand le traitement au BCAA est appliqué. En
combinant la consommation de BCAA et les exercices, on observe des améliorations significatives de la force musculaire brute
des membres inférieurs et de l’équilibre dynamique. [Traduit par la Rédaction]
Mots-clés : supplémentation en acides aminés, exercice contre résistance de faible intensité, vieillissement, réadaptation en
consultation externe, traitement combiné.
Received 19 August 2015. Accepted 16 December 2015.
T. Ikeda. Tokyo Medical and Dental University Graduate School, Department of Rehabilitation Medicine, Tokyo 113-8510, Japan; Rehab-care Shonan
Kamakura, Japan.
J. Aizawa. Tokyo Medical and Dental University, Clinical Center for Sports Medicine & Sports Dentistry, Japan.
H. Nagasawa. Kanagawa University of Human Services, Department of Rehabilitation, Japan.
I. Gomi. Kanagawa University of Human Services, Department of Nutrition, Japan.
H. Kugota and K. Nanjo. Rehab-care Shonan Kamakura, Japan.
T. Jinno. Tokyo Medical and Dental University Graduate School, Department of Joint Surgery and Sports Medicine, Japan.
T. Masuda. Fukushima University, Faculty of Symbiotic Systems Science, Japan.
S. Morita. Tokyo Medical and Dental University Graduate School, Department of Rehabilitation Medicine, Tokyo 113-8510, Japan.
Corresponding author: Takashi Ikeda (email: ikereh@tmd.ac.jp).
438
Appl. Physiol. Nutr. Metab. 41: 438–445 (2016) dx.doi.org/10.1139/apnm-2015-0436 Published at www.nrcresearchpress.com/apnm on 5 January 2016.
... Primary outcomes. The primary outcomes will be skeletal muscle mass (e.g., using dual-energy X-ray absorptiometry, [5,14,[16][17][18] bioelectrical impedance method, [26,27] ultrasonic reflectoscope, [28,29] or circumference of the limbs [30,31] ) or muscle strength (e.g., knee extensor strength, [26,28,29,31,32] grip strength, [16,18,[28][29][30]32] and leg-press strength [27,32] ). If different assessment methods are adopted, standardization will be conducted as standardized mean difference. ...
... Primary outcomes. The primary outcomes will be skeletal muscle mass (e.g., using dual-energy X-ray absorptiometry, [5,14,[16][17][18] bioelectrical impedance method, [26,27] ultrasonic reflectoscope, [28,29] or circumference of the limbs [30,31] ) or muscle strength (e.g., knee extensor strength, [26,28,29,31,32] grip strength, [16,18,[28][29][30]32] and leg-press strength [27,32] ). If different assessment methods are adopted, standardization will be conducted as standardized mean difference. ...
... Primary outcomes. The primary outcomes will be skeletal muscle mass (e.g., using dual-energy X-ray absorptiometry, [5,14,[16][17][18] bioelectrical impedance method, [26,27] ultrasonic reflectoscope, [28,29] or circumference of the limbs [30,31] ) or muscle strength (e.g., knee extensor strength, [26,28,29,31,32] grip strength, [16,18,[28][29][30]32] and leg-press strength [27,32] ). If different assessment methods are adopted, standardization will be conducted as standardized mean difference. ...
Research Proposal
Background In recent years, prevention of sarcopenia and frailty is a matter of concern for community dwelling older persons. The recommended protein daily intake is not fulfilled by 10% of community-dwelling elderly and 35% of residents in aged-care facilities. Furthermore, the optimum time of protein consumption is unclear because of the varying combinations of intake timing and exercise. Although it is desirable to increase protein intake at breakfast and lunch without reducing intake at supper to maximize muscle protein synthesis, this is not clear for older people. Therefore, before considering whether protein consumption at breakfast is superior to other times of the day, its effectiveness needs to be clarified in older adults. Methods The inclusion criterion will be healthy or frail adults older than 60 years. This protocol of systematic review adhered to the PRISMA 2020 statement. A comprehensive study strategy is designed for PubMed, EMBASE, CENTRAL, and Clinical Trials.gov. Search strategies will be made using Boolean Search Logic by an experienced librarian in systematic review search formula design. Two authors will carry out independent screening of titles, abstracts, and data extraction for randomized controlled trials. Statistical heterogeneity will be assessed by meta-analysis. Assessment of the risk of bias will be conducted using the Risk-of-bias 2 tool. Integrated data will be analyzed using Review Manager software to create summary tables. Findings summary tables for primary and secondary outcomes will be produced in accordance with the procedures in the Cochrane Handbook. Results We believe that the effects of protein or BCAA intake at breakfast in older people analysed in this review will provide evidence that contributes to the establishment of treatment strategies to prevent frailty and sarcopenia. Conclusion The benefits of protein intake at breakfast for the elderly will be clarified. This will encourage hospitals and elderly care facilities to review the content of the diet and encourage the elderly to change their own behavior. This is expected to ultimately reduce healthcare costs.
... Open access exercise has the problem of low efficacy compared with high-load exercise. 4 Previous studies [5][6][7] have suggested that combining supplementation with branched chain amino acids (BCAAs) and exercise therapy offers an effective method for bridging this gap. However, patients with cardiac disease often have reduced renal function and are, thus, unable to benefit from this approach. ...
... 11 12 The combination of BCAAs and exercise therapy has been shown to be more useful in achieving muscle strengthening than either BCAA intake or exercise therapy alone. [5][6][7] Significantly greater increases in muscle strength and mass have been reported with a combined approach compared with the increases seen in older people receiving BCAAs alone. Beta-hydroxy beta-methyl butyrate (HMB) is a metabolite of leucine, a kind of BCAA. ...
... 28 In preliminary studies, the Pearson correlation for knee extensor strength was 0.83 between the preintervention period and 1 month after the intervention 29 and 0.82 between the preintervention period and 3 months after intervention. 7 Since the sample size required for hypothesis testing using a two-sided analysis of covariance model with alpha=0.05 and beta=0.2 will be 48, the number of cases to be enrolled is set at 52 subjects. ...
Research Proposal
Full-text available
Introduction The current treatment for heart disease consists of exercise therapy in addition to pharmacotherapy, nutritional support and lifestyle guidance. In general, nutritional support focuses on protein, salt and energy restrictions, with no active protein or amino acid intake in cases involving moderate or higher renal failure. From this perspective, patients with cardiac disease are at high risk of frailty. Beta-hydroxy beta-methyl butyrate (HMB) is a metabolite of leucine. HMB is widely used for muscle strengthening and can be safely ingested even by patients with renal failure. The proposed study protocol will investigate the effects of HMB-calcium (HMB-Ca) administered in combination with comprehensive cardiac rehabilitation for muscle strength, muscle mass and cardiac function in patients with cardiac disease during the convalescent period. The primary outcome will be knee extensor strength. Secondary outcomes will be gross isometric limb strength and skeletal muscle mass. Methods and analysis This study will be a single-blinded, randomised, controlled trial with parallel comparisons between two groups. The study period will be 60 days from the start of outpatient cardiac rehabilitation. Participants will be randomly divided into two groups: an HMB group consuming HMB-Ca one time per day for 60 days; and a Placebo group consuming reduced maltose once one time per day for 60 days. Exercise therapy will be performed by both groups. Ethics and dissemination The study protocol will be published in a peer-reviewed journal. Ethics approval was provided by the Showa University Clinical Research Review Board. Trial registration number jRCTs031220139; Japan Registry of Clinical Trails.
... When implementing interventions for this population, it is advisable to address not only nutritional aspects but also the broader context of eating, food, and other relevant psychosocial factors. Despite the importance of dietary and exercise factors for community-dwelling older adults, many studies [6,7,[9][10][11][12][13][14] have not emphasized the significance. However, there is a noticeable gap when it comes to investigating the efficacy of interventions that combine both food and exercise for the older adults. ...
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This systematic review and meta-analysis discusses the available data on the efficacy of diet, food intake, and exercise mixed interventions (DEMI) for community-dwelling older adults in Japan and assesses the evidence level. We searched the literature regarding the research questions using electronic and hand-searching methods. To ensure the reliability and quality of the evidence, we used the Cochrane risk of bias tool and GRADE system. All studies included DEMI; other interventions included group activities, health education, and community participation. All interventions were categorized into three classifications, namely “Diet and food intake”, “Exercise”, and “Other”. Programs included lectures, practical exercises, group activities, consulting, and programs that could be implemented at home. By comparing groups and measuring outcomes at various time points, most studies reported positive results regarding the impact of the interventions. Specifically, usual gait speed, Food Frequency Questionnaire Score, and Diet Variety Score demonstrated significant improvement. Additionally, three studies demonstrated improvement in frailty. This review suggests that DEMI resulted in improvements in some outcome variables. However, the efficacy of all variables was not fully examined. The results of the meta-analysis revealed positive outcomes for some variables, although the evidence level for these outcomes was considered moderate.
... 13 The combination of BCAA intake and exercise is known to have a superior effect than each administered alone. [13][14][15] Sarcopenia occurs widely among orthopedic patients 16 and those with stroke. 17 Besides, >40% of Japanese patients with degenerative scoliosis and hip fracture have had concomitant sarcopenia. ...
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Background and Aims This study examined the feasibility of nutritional support combined with exercise intervention for restoring muscle and physical functions in convalescent orthopedic patients. Methods We used a crossover design in which nutritional support combined with exercise intervention was administered daily during the early (1 month) and late (1 month) cycles with a 1‐week washout period. The exercise intervention was performed twice daily for 2 months in the early and late groups. The exercise intervention consisted of one set of muscle strength, stretching, and physical activity exercises for 20 min each. Nutritional interventions were administered immediately after the exercise. A 3.4 g of branched‐chain amino acid supplements (BCAAs) or 1.2 g of starch was ingested. We measured the skeletal muscle mass and isometric muscle strength of the limbs and performed balance tests. After the crossover, the BCAA and Placebo groups were compared. Results The ratio of improvement in the echo intensity of the rectus femoris (RF) was significantly higher in the BCAA group. A comparison of the order of nutritional intervention showed a significant effect on the RF echo intensity in both groups only when BCAAs were administered. Conclusion This study's results suggest that the proposed combined intervention improves muscle quality and mass in convalescent orthopedic patients.
... Amino acid intake can enhance the effects of exercise in older women with sarcopenia [3]. Moreover, amino acid intake in older adults with frailty or pre-frailty can improve the lower limb muscle strength and physical function [25]. Therefore, it is important to evaluate the nutritional status and nutritional guidance including detail intake to improve physical function and quality of life. ...
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... Помимо ОК изучаются добавки некоторых метаболитов, например никотинамидмононуклеотида (NMN) [36], как интервенционный подход против старения человека. Комбинация упражнений и добавок аминокислот с разветвлённой цепью укрепляет мышцы нижних конечностей при физической слабости [37]. ...
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Aging of a living organism is closely related to systemic metabolic changes. But due to the multilevel and network nature of metabolic pathways, it is difficult to understand these connections. Today, this problem is solved using one of the main approaches of metabolomics — untargeted metabolome profiling. The purpose of this publication is to systematize the results of metabolomic studies based on such profiling, both in animal models and in humans.
... Some epidemiological studies show that slightly overweight people live longer [39]. In addition to CR, supplementation of food with some metabolites, such as NMN [40], branched-chain amino acid (BCAA) [41], antioxidants, beta-carotene, vitamin A, or vitamin E [42], is being studied as an interventional approach against human aging. ...
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... However, our results revealed that patients with poor performance had increased urinary levels of alanine, valine, and lactate when compared to those with better performance. We can speculate that this difference could be linked to either (1) an increased β-alanine [50,51] and branched-chain amino acid supplementation [52,53] in more frail patients (however, our patients did not take supplements) or (2) a greater release of metabolites involved in the antioxidant and anti-inflammatory reactions. We also observed an increased urine level of trimethylamine N-oxide (TMAO), in patients with poor physical performance compared with those with better performance. ...
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Bed rest-induced muscle loss and impaired muscle recovery may contribute to age-related sarcopenia. It is unknown if there are age-related differences in muscle mass and muscle anabolic and catabolic responses to bed rest. A secondary objective was to determine if rehabilitation could reverse bed rest responses. Nine older and fourteen young adults participated in a 5-day bed rest challenge. This was followed by 8-weeks of high intensity resistance exercise (REHAB). Leg lean mass (DXA) and strength were determined. Muscle biopsies were collected during a constant stable isotope infusion in the postabsorptive state and after EAA ingestion on three occasions: before (PRE), after bed rest (BEDREST) and after REHAB. Samples were assessed for protein synthesis, mTORC1 signaling, REDD1/2 expression and molecular markers related to muscle proteolysis (MURF1, MAFBX, AMPKα, LC3II/I, Beclin1). We found that leg lean mass and strength decreased in older but not younger adults after BEDREST (P<0.05) and was restored after REHAB. EAA-induced mTORC1 signaling and protein synthesis increased at PRE in both age-groups (P<0.05). Although both groups had blunted mTORC1 signaling, increased REDD2 and MURF1 mRNA after BEDREST, only older adults had reduced EAA-induced protein synthesis rates and increased MAFBX mRNA, p-AMPKα and the LC3II/I ratio (P<0.05). We conclude that older adults are more susceptible than young persons to muscle loss after short-term bed rest. This may be partially explained by a combined suppression of protein synthesis and a marginal increase in proteolytic markers. Finally, rehabilitation restored bed rest-induced deficits in lean mass and strength in older adults. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
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We previously reported that low-intensity [50% of one repetition maximum (1RM)] resistance training with slow movement and tonic force generation (LST) causes muscle hypertrophy and strength gain in older participants. The aim of this study was to determine whether resistance training with slow movement and much more reduced intensity (30%1RM) increases muscle size and strength in older adults. Eighteen participants (60-77 years) were randomly assigned to two groups. One group performed very low-intensity (30% 1RM) knee extension exercise with continuous muscle contraction (LST: 3-s eccentric, 3-s concentric, and 1-s isometric actions with no rest between each repetition) twice a week for 12 weeks. The other group underwent intermitted muscle contraction (CON: 1-s concentric and 1-s eccentric actions with 1-s rest between each repetition) for the same time period. The 1RM, isometric and isokinetic strengths, and cross-sectional image of the mid-thigh obtained by magnetic resonance imaging were examined before and after the intervention. LST significantly increased the cross-sectional area of the quadriceps muscle (5·0%, P<0·001) and isometric and isokinetic knee extension strengths (P<0·05). CON failed to increase muscle size (1·1%, P = 0·12), but significantly improved its strength (P<0·05). These results indicate that even if the intensity is as low as 30% 1RM, LST can increase muscle size and strength in healthy older adults. The large total contraction time may be related to muscle hypertrophy and strength gain. LST would be useful for preventing sarcopenia in older individuals.
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Non-steroidal anti-inflammatory drugs (NSAIDs) are widely consumed among athletes worldwide, despite growing evidence for a negative influence on the adaptation of skeletal muscle to exercise, at least in young healthy individuals. This review focuses on the potential of NSAIDs to alter the activity of satellite cells, the muscle stem cell responsible for repair and maintenance of skeletal muscle. The signaling pathways that are potentially modified by NSAID exposure are also considered. Growth factors as well as inflammatory cells and connective tissue appear to be key factors in the response of muscle under conditions where cyclooxygenase and prostaglandin activity are blocked through NSAID ingestion or infusion. Discrepancies in the literature regarding the response of young and old individuals are addressed, where it appears that the elderly may benefit from NSAID ingestion, although this clearly requires further study. The long-term implications for the muscle of the apparent inhibitory effect of NSAIDs on satellite cells in younger individuals are not clear and it is possible these may first become apparent with chronic use in athletes training at a high level or with advancing age. Reports of the potential for NSAIDs to alter prostaglandin and growth factor signalling provide a basis for further study of the mechanism of NSAID action on satellite cells.
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SALEM, G. J., M-Y. WANG, J. T. YOUNG, M. MARION, and G. A. GREENDALE. Knee strength and lower- and higher-intensity functional performance in older adults. Med. Sci. Sports Exerc., Vol. 32, No. 10, pp. 1679-1684, 2000. Purpose: This study characterizes the linear relations among knee strength, work capacity, and lower- and higher-intensity measures of functional performance in ambulatory, high-functioning older adults. Methods: Sixty-two seniors (average age = 73.4 ± 7.3 yr) participated in the study. Isokinetic measures included the peak flexion/extension torque produced during five continuous repetitions and the total flexion/extension work performed during 20 repetitions (60°·s-1). Functional measures included lower-intensity tests (timed 8-foot and 50-foot walking tests at the participants' normal pace, and a standing reach task) and higher-intensity tests (a timed 50-foot brisk walk, timed chair stands, and a timed stair climb). Results: Isokinetic strength and work capacity measures explained between 41% and 54% of the variance in the higher-intensity functional models and only between 31% and 33% of the variance in the lower-intensity models. The strength of the associations, approximated by the beta coefficients of the strength and work terms, was also greater for the higher-intensity functional tasks. Conclusions: Further research is warranted to determine whether exercises that increase knee strength and work capacity, improve brisk walking, stair climbing, and chair standing capabilities in older adults.