Sarcopenia, skeletal muscle loss with advancing age, leads to muscular weakness and reduced physical functions. It was reported that the high-leucine essential amino acid mixture (HLEAA, 11 g twice...
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It is suggested that amino acids influence lipid and glucose metabolism, e.g., infusion of glutamine increases glucose uptake in muscle and liver in dogs (Borel M.J. et. al. 1998), dietary L-argini...
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Background Appropriate energy intake (EI) is essential to prevent frailty. Because self-reported EI is inaccurate and has systematic errors, adequate biomarker calibration is required. This study examined the association between doubly... more
Background Appropriate energy intake (EI) is essential to prevent frailty. Because self-reported EI is inaccurate and has systematic errors, adequate biomarker calibration is required. This study examined the association between doubly labeled water (DLW)-calibrated EI and the prevalence of frailty among community-dwelling older adults. Method A cross-sectional study was performed using baseline data of 7,022 older adults aged ≥65 years in the Kyoto-Kameoka Study. EI was evaluated using a validated food frequency questionnaire (FFQ), and calibrated EI was obtained from a previously established equation using the DLW method. Physical and comprehensive frailty were defined by the Fried phenotype (FP) model and the Kihon Checklist (KCL), respectively. We used multivariable-adjusted restricted cubic spline logistic regression analysis. Results The prevalence of physical frailty was 14.8% and 13.6% in women and men, respectively. The spline models showed significant reverse J-shaped or U...
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We aimed to investigate whether frequencies of protein-rich food intake were associated with frailty among older Japanese adults. A cross-sectional study was conducted in 2011 among 3843 men and 4331 women in a population-based cohort of... more
We aimed to investigate whether frequencies of protein-rich food intake were associated with frailty among older Japanese adults. A cross-sectional study was conducted in 2011 among 3843 men and 4331 women in a population-based cohort of Kameoka city, Kyoto Prefecture, Japan. Frailty was assessed by the weighted score based on the 25-item Kihon-Checklist. The frequency of protein-rich food intake was examined as "seafood", "meat", "dairy products", "eggs", and "soy products". The outcome of frailty was analyzed with a multiple logistic regression model using the frequency of protein-rich food intake. When compared to the first quartile, it was observed that there was a significant association between the lower adjusted prevalence ratio (PR) for frailty and the frequency of seafood intake in the fourth quartile among men (PR 0.64, 95% confidence interval (CI), 0.42, 0.99) and from the second quartile to the third quartile among women ...
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Dietary protein intake is inversely associated with physical frailty risk. However, it is unknown whether an association exists between dietary protein intake and comprehensive frailty. To evaluate the association between protein intake... more
Dietary protein intake is inversely associated with physical frailty risk. However, it is unknown whether an association exists between dietary protein intake and comprehensive frailty. To evaluate the association between protein intake and comprehensive frailty in older Japanese adults. This cross-sectional study included 5638 Japanese participants (2707 men and 2931 women) aged ≥65 years from Kameoka City, Kyoto, Japan. Dietary intake was estimated using a validated self-administered food frequency questionnaire. Comprehensive frailty was assessed using a 25-item Kihon Checklist (KCL), which comprised instrumental activities of daily living, mobility disability, malnutrition, oral or eating function, socialization and housebound, cognitive function, and depression domains. A KCL score of 4 to 6 was defined as prefrailty, and ≥7 as frailty. In women, but not in men, protein intake showed a lower prevalence for prefrailty (Q1-Q4, 40.2%, 34.3%, 34.3%, and 36.0%). Higher protein intak...
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To investigate the effects of exercise and/or nutritional supplementation on body composition, blood components, and physical function in community-dwelling elderly Japanese women with sarcopenic obesity. Randomized controlled trial.... more
To investigate the effects of exercise and/or nutritional supplementation on body composition, blood components, and physical function in community-dwelling elderly Japanese women with sarcopenic obesity. Randomized controlled trial. Urban community in Tokyo, Japan. Among 1213 community-dwelling elderly women over 70 years of age, 307 were defined with sarcopenic obesity, and 139 women participated in the study. Participants were randomly assigned to one of four intervention groups. The exercise and nutrition (Ex + N) and exercise only (Ex) groups attended 60-minute exercise classes twice a week for 3 months. The Ex + N and nutrition only (N) groups were provided with essential amino acid supplementation and tea fortified with catechins to be taken daily for 3 months. Health education classes were provided to the control (HE) group every 2 weeks. Bioelectric impedance analysis was used to measure body composition. Skeletal muscle mass index was calculated using measures of muscle ma...
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Branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, the enzyme catalyst for the second step of the BCAA catabolic pathway, plays a central role in the regulation of BCAA catabolism. The activity of the complex is regulated by a... more
Branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, the enzyme catalyst for the second step of the BCAA catabolic pathway, plays a central role in the regulation of BCAA catabolism. The activity of the complex is regulated by a covalent modification cycle in which phosphorylation by BCKDH kinase inactivates and dephosphorylation by BCKDH phosphatase activates the complex. Many studies suggest that control of the activity of the kinase is a primary determinant of the activity of the complex. The kinase exists at all times in the mitochondrial matrix space in two forms, with a large amount being free and a smaller amount bound rather tightly to the BCKDH complex. Only the bound form of the kinase appears to be catalytically active and, therefore, responsible for phosphorylation and inactivation of the complex. alpha-Ketoisocaproate, the transamination product of leucine and the most important known physiological inhibitor of BCKDH kinase, promotes release of the kinase from ...
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The intracellular concentrations of essential amino acids (EAA) in muscle are maintained relatively constant under a variety of conditions. However, the effect of a decrease in blood amino acid concentrations on intracellular... more
The intracellular concentrations of essential amino acids (EAA) in muscle are maintained relatively constant under a variety of conditions. However, the effect of a decrease in blood amino acid concentrations on intracellular concentrations is not clear. Similarly, the relation between intracellular and interstitial concentrations has not been determined in this circumstance. Thus the aim of this study was to determine the effect of hypoaminoacidemia on intracellular, interstitial, and plasma concentrations of EAA and the mechanisms responsible for the respective changes. Twelve normal pigs were investigated before and during 120 min of hemodialysis by use of stable-isotope tracer methodology, microdialysis technique, and muscle biopsies. During hemodialysis, there was a decrease in the interstitial fluid concentrations of phenylalanine, leucine, alanine, and lysine that corresponded to their decrease in plasma concentration. Nonetheless, the intracellular concentrations of these am...
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To determine the association between geriatric disorders and dietary intake, validation of a food frequency questionnaire (FFQ) for elderly individuals is needed. We compared energy and nutrient intakes derived from dietary records (DR)... more
To determine the association between geriatric disorders and dietary intake, validation of a food frequency questionnaire (FFQ) for elderly individuals is needed. We compared energy and nutrient intakes derived from dietary records (DR) and FFQ in an elderly population and compared the data against results from middle-aged individuals (30–68 years) from a previous study. Current participants included 65 women and 78 men (65–88 years) who completed FFQ and 7-day DR in a subpopulation of the Kyoto-Kameoka study. Our FFQ was created for middle-aged individuals. To validate the FFQ, we investigated equivalent precision by comparing the correlation coefficients between the present and previous study. Median correlations for energy and nutrient intake between the DR and FFQ in the current and previous studies were 0.24 and 0.30 (p = 0.329) in women and 0.24 and 0.28 (p = 0.399) in men, respectively. The median ratio of FFQ to DR for these intakes were also similar. The accuracy and precis...
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Dysregulated anabolic responses to nutrition/exercise may contribute to sarcopenia; however, these characteristics are poorly defined in female populations. We determined the effects of two-feeding regimes in older women (66±2.5y... more
Dysregulated anabolic responses to nutrition/exercise may contribute to sarcopenia; however, these characteristics are poorly defined in female populations. We determined the effects of two-feeding regimes in older women (66±2.5y N=8/group): bolus-whey protein (WP-20 g) or novel low-dose leucine-enriched essential amino acids (EAA) (LEAA-3g [40% leucine]). Using (13)C6-Phenylalanine infusions, we quantified muscle (MPS) and albumin (APS) protein synthesis at baseline and both in response to feeding (FED) and feeding-plus-exercise (FED-EX; RE: 6×8 knee-extensions at 75%-1RM). We also quantified plasma insulin/AA concentrations, whole-leg (LBF)/muscle microvascular blood-flow (MBF), and muscle anabolic signaling by phospho-immunoblotting. Plasma insulinemia and EAA-aemia were markedly greater after WP than LEAA (P<0.001). Neither LEAA nor WP modified LBF in response to FED or FED-EX, while MBF increased to a similar extent in both groups, only after FED-EX (P<0.05). In response ...
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The authors examined the effect of branched-chain amino acid (BCAA) supplementation on squat-exercise-induced delayed-onset muscle soreness (DOMS) using 12 young, healthy, untrained female participants. The experiment was conducted with a... more
The authors examined the effect of branched-chain amino acid (BCAA) supplementation on squat-exercise-induced delayed-onset muscle soreness (DOMS) using 12 young, healthy, untrained female participants. The experiment was conducted with a crossover double-blind design. In the morning on the exercise-session day, the participants ingested either BCAA (isoleucine:leucine:valine = 1:2.3:1.2) or dextrin at 100 mg/kg body weight before the squat exercise, which consisted of 7 sets of 20 squats/set with 3-min intervals between sets. DOMS showed a peak on Days 2 and 3 in both trials, but the level of soreness was significantly lower in the BCAA trial than in the placebo. Leg-muscle force during maximal voluntary isometric contractions was measured 2 d after exercise (Day 3), and the BCAA supplementation suppressed the muscle-force decrease (to ~80% of the value recorded under the control conditions) observed in the placebo trial. Plasma BCAA concentrations, which decreased after exercise in the placebo trial, were markedly elevated during the 2 hr postexercise in the BCAA trial. Serum myoglobin concentration was increased by exercise in the placebo but not in the BCAA trial. The concentration of plasma elastase as an index of neutrophil activation appeared to increase after the squat exercise in both trials, but the change in the elastase level was significant only in the placebo trial. These results suggest that muscle damage may be suppressed by BCAA supplementation.
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The authors examined the effect of branched-chain amino acid (BCAA) supplementation on squat-exercise-induced delayed-onset muscle soreness (DOMS) using 12 young, healthy, untrained female participants. The experiment was conducted with a... more
The authors examined the effect of branched-chain amino acid (BCAA) supplementation on squat-exercise-induced delayed-onset muscle soreness (DOMS) using 12 young, healthy, untrained female participants. The experiment was conducted with a crossover double-blind design. In the morning on the exercise-session day, the participants ingested either BCAA (isoleucine:leucine:valine = 1:2.3:1.2) or dextrin at 100 mg/kg body weight before the squat exercise, which consisted of 7 sets of 20 squats/set with 3-min intervals between sets. DOMS showed a peak on Days 2 and 3 in both trials, but the level of soreness was significantly lower in the BCAA trial than in the placebo. Leg-muscle force during maximal voluntary isometric contractions was measured 2 d after exercise (Day 3), and the BCAA supplementation suppressed the muscle-force decrease (to ~80% of the value recorded under the control conditions) observed in the placebo trial. Plasma BCAA concentrations, which decreased after exercise i...
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BCAA catabolism in skeletal muscle is regulated by the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, located at the second step in the BCAA catabolic pathway. The activity of the BCKDH complex is regulated by a... more
BCAA catabolism in skeletal muscle is regulated by the branched-chain alpha-keto acid dehydrogenase (BCKDH) complex, located at the second step in the BCAA catabolic pathway. The activity of the BCKDH complex is regulated by a phosphorylation/dephosphorylation cycle. Almost all of BCKDH complex in skeletal muscle under normal and resting conditions is in an inactive/phosphorylated state, which may contribute to muscle protein synthesis and muscle growth. Exercise activates the muscle BCKDH complex, resulting in enhanced BCAA catabolism. Therefore, exercise may increase the BCAA requirement. It has been reported that BCAA supplementation before exercise attenuates the breakdown of muscle proteins during exercise in humans and that leucine strongly promotes protein synthesis in skeletal muscle in humans and rats, suggesting that a BCAA supplement may attenuate muscle damage induced by exercise and promote recovery from the damage. We have examined the effects of BCAA supplementation o...
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We have examined the effect of a hemodialysis-induced 40% reduction in plasma amino acid concentrations on rates of muscle protein synthesis and breakdown in normal swine. Muscle protein kinetics were measured by tracer methodology using... more
We have examined the effect of a hemodialysis-induced 40% reduction in plasma amino acid concentrations on rates of muscle protein synthesis and breakdown in normal swine. Muscle protein kinetics were measured by tracer methodology using [(2)H(5)]phenylalanine and [1-(13)C]leucine and analysis of femoral arterial and venous samples and tissue biopsies. Net amino acid release by muscle was accelerated during dialysis. Phenylalanine utilization for muscle protein synthesis was reduced from the basal value of 45 +/- 8 to 25 +/- 6 nmol x min(-1) x 100 ml leg(-1) between 30 and 60 min after start of dialysis and was stimulated when amino acids were replaced while dialysis continued. Muscle protein breakdown was unchanged. The signal for changes in synthesis appeared to be changes in plasma amino acid concentrations, as intramuscular concentrations remained constant throughout. The changes in muscle protein synthesis were accompanied by a reduction or stimulation, respectively, in the gua...
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Carbohydrate supplementation is extremely important during prolonged exercise because it maintains blood glucose levels during later stages of exercise. In this study, we examined whether maintaining blood glucose levels by carbohydrate... more
Carbohydrate supplementation is extremely important during prolonged exercise because it maintains blood glucose levels during later stages of exercise. In this study, we examined whether maintaining blood glucose levels by carbohydrate supplementation could be enhanced during long-term exercise by combining this supplementation with alanine and proline, which are gluconeogenic amino acids, and whether such a combination would affect exercise endurance performance. Male C57BL/6J mice were orally administered either maltodextrin (1.25 g/kg) or maltodextrin (1.0 g/kg) with alanine (0.225 g/kg) and proline (0.025 g/kg) 15 min before running for 170 min. Combined supplementation of maltodextrin, alanine, and proline induced higher blood glucose levels than isocaloric maltodextrin alone during the late exercise phase (100-170 min). The hepatic glycogen content of mice administered maltodextrin, alanine, and proline was higher than that of mice ingesting maltodextrin alone 60 min after beginning exercise, but the glycogen content of the gastrocnemius muscle showed no difference. We conducted a treadmill running test to determine the effect of alanine and proline on endurance performance. The test showed that running time to exhaustion of mice that were supplemented with maltodextrin (2.0 g/kg) was longer than that of mice that were supplemented with water alone. Maltodextrin supplementation (1.0 g/kg) with alanine (0.9 g/kg) and proline (0.1 g/kg) further increased running time to exhaustion compared to maltodextrin alone (2.0 g/kg). These results indicate that combined supplementation of carbohydrate, alanine, and proline is effective for maintaining blood glucose and hepatic glycogen levels and increasing endurance performance during long-term exercise in mice.
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The present study was conducted to examine alterations in the concentrations of plasma free amino acids, glucose, insulin, free fatty acids (FFAs), and urea nitrogen induced by branched-chain amino acid (BCAA) supplementation in young... more
The present study was conducted to examine alterations in the concentrations of plasma free amino acids, glucose, insulin, free fatty acids (FFAs), and urea nitrogen induced by branched-chain amino acid (BCAA) supplementation in young men. Overnight-fasted subjects ingested drinks containing 1 or 5 g of a BCAA mixture (weight ratio of 1 : 2.3 : 1.2 for isoleucine : leucine : valine), and blood was intermittently collected for 3 h after ingestion. Ingestion of the BCAA mixture resulted in significant increases in the plasma concentrations of individual BCAAs, corresponding to the amounts of amino acids ingested. On the other hand, plasma concentrations of methionine and aromatic amino acids tended to decrease in the trial with 5 g BCAAs, suggesting that BCAA ingestion affects the metabolism of these amino acids. The ingestion of BCAAs temporarily increased plasma insulin levels and affected plasma concentrations of FFAs, but had almost no effect on glucose or urea nitrogen.
Research Interests: Nutrition and Dietetics, Energy, Concentration, Humans, Blood Glucose, and 8 moreInsulin, Male, Young Adult, Urea, Nitrogen, Adult, Methionine, and Substrate
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Skin collagen decreases in protein-malnourished states. Amino acids regulate protein metabolism, glutamine stimulates collagen synthesis through the conversion process to proline and provides 75 % of the intracellular free proline in... more
Skin collagen decreases in protein-malnourished states. Amino acids regulate protein metabolism, glutamine stimulates collagen synthesis through the conversion process to proline and provides 75 % of the intracellular free proline in fibroblasts. However, the impact of these amino acids on collagen synthesis under malnutrition has not been examined. We investigated the effect of amino acids on dermal tropocollagen synthesis in protein-malnourished rats. The fractional synthesis rate (FSR, %/h) of dermal tropocollagen was evaluated by the incorporation of L-[ring-(2)H(5)]-phenylalanine after 4 h infusion of each amino acid and the stable isotope. None of the infused 12 single amino acids (glutamine, proline, alanine, arginine, glutamate, glycine, aspartate, serine, histidine, lysine, phenylalanine and threonine) significantly increased the FSR (P = 0.343, one-way ANOVA). In contrast, amino acid mixtures of essential amino acids + glutamine + arginine (EAARQ) and branched-chain amino acids + glutamine (BCAAQ) significantly increased the FSR compared to saline, but the branched-chain amino acids (BCAAs) and amino acid mixture of collagen protein (AAC) did not alter the FSR (saline, 0.96 ± 0.24 %/h; EAARQ, 1.76 ± 0.89 %/h; BCAAQ 1.71 ± 0.36 %/h; BCAAs, 1.08 ± 0.20 %/h and AAC 1.39 ± 0.35 %/h, P &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05, Tukey&amp;amp;amp;amp;amp;amp;amp;amp;#39;s test). Proline conversion from glutamine represented only 3.9 % of the free proline in skin, as evaluated by the primed-constant infusion of L-d7-proline and L-α-15N-glutamine in rats. These results suggested that the combination of BCAAQ is a key factor for the enhancement of skin collagen synthesis in protein-malnourished rats. The contribution of extracellular free glutamine on de novo proline synthesis and collagen synthesis is very low in vivo compared to the contribution in vitro.
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Research Interests: Methodology, Skeletal muscle biology, DISTRIBUTION, Biopsy, Biological Sciences, and 19 moreHumans, Muscle, Carbon Isotopes, Female, Male, American, Threonine, Steady state, Amino Acids, Body water, Adult, Phenylalanine, Femoral Vein, Leg, Amino Acid Profile, Distribution, Blood Flow Velocity, Intracellular, and Femoral Artery
The present study was conducted to examine alterations in plasma free amino acid concentrations induced by squat exercise and branched-chain amino acid (BCAA) supplementation in young, untrained female subjects. In the morning on the... more
The present study was conducted to examine alterations in plasma free amino acid concentrations induced by squat exercise and branched-chain amino acid (BCAA) supplementation in young, untrained female subjects. In the morning on the exercise session day, participants ingested drinks containing either BCAA (isoleucine:leucine:valine=1:2.3:1.2) or dextrin (placebo) at 0.1 g/kg body weight 15 min before a squat exercise session, which consisted of 7 sets of 20 squats, with 3 min intervals between sets. In the placebo trial, plasma BCAA concentrations were decreased subsequent to exercise, whereas they were significantly increased in the BCAA trial until 2 h after exercise. Marked changes in other free amino acids in response to squat exercise and BCAA supplementation were observed. In particular, plasma concentrations of methionine and aromatic amino acids were temporarily decreased in the BCAA trial, being significantly lower than those in the placebo trial. These results suggest that BCAA intake before exercise affects methionine and aromatic amino acid metabolism.
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Skin collagen metabolism abnormalities induced by ultraviolet (UV) radiation are the major causes of skin photoaging. It has been shown that the one-time exposure of UV irradiation decreases procollagen mRNA expression in dermis and that... more
Skin collagen metabolism abnormalities induced by ultraviolet (UV) radiation are the major causes of skin photoaging. It has been shown that the one-time exposure of UV irradiation decreases procollagen mRNA expression in dermis and that chronic UV irradiation decreases collagen amounts and induces wrinkle formation. Amino acids are generally known to regulate protein metabolism. Therefore, we investigated the effects of UV irradiation and various orally administered amino acids on skin collagen synthesis rates. Groups of 4–5 male, 8-week-old HR-1 hairless mice were irradiated with UVB (66 mJ/cm2) twice every other day, then fasted for 16 h. The fractional synthesis rate (FSR; %/h) of skin tropocollagen was evaluated by incorporating l-[ring-2H5]-phenylalanine. We confirmed that the FSR of dermal tropocollagen decreased after UVB irradiation. The FSR of dermal tropocollagen was measured 30 min after a single oral administration of amino acids (1 g/kg) to groups of 5–16 UVB-irradiated mice. Branched-chain amino acids (BCAA, 1.34 ± 0.32), arginine (Arg, 1.66 ± 0.39), glutamine (Gln, 1.75 ± 0.60), and proline (Pro, 1.48 ± 0.26) did not increase the FSR of skin tropocollagen compared with distilled water, which was used as a control (1.56 ± 0.30). However, essential amino acids mixtures (BCAA + Arg + Gln, BCAA + Gln, and BCAA + Pro) significantly increased the FSR (2.07 ± 0.58, 2.04 ± 0.54, 2.01 ± 0.50 and 2.07 ± 0.59, respectively). This result suggests that combinations of BCAA and glutamine or proline are important for restoring dermal collagen protein synthesis impaired by UV irradiation.