Analysis of the Association between Protein Intake and Disability-Adjusted Life Year Rates for Alzheimer's Disease in Japanese Aged over 60.

With advancements in medical technology, the structure of disease is shifting from acute illnesses to chronic conditions, such as Alzheimer's disease (AD). Consequently, there is an escalating need for evaluations that discourse on the potential effects on healthy life years, as well as disease onset. We aimed to evaluate the associations with AD disability-adjusted life year (AD-DALY) rates and protein intake by sex and age group. For the analysis, we used representative values for males and females in their 60s and aged over 70, extracted from the public dataset of the Global Burden of Disease Study and the National Health and Nutrition Survey in Japan, covering the years 1990 to 2019. In order to evaluate the association between AD-DALY rates and protein intake, we analyzed correlations and stratified multiple regression models. Additionally, we simulated alterations in AD-DALY rates associated with changes in protein intake by utilizing stratified multiple regression models. AD-DALY rates and protein intake indicated significant negative correlations across all sex and age groups. In stratified multiple regression models, significant associations were found between higher protein intake and lower AD-DALY rates in females. In the simulation, when protein intake was increased to 1.5 g/kg/day, AD-DALY rates decreased by 5-9 percent compared with 2019. However, the association between intake of animal and plant protein and AD-DALY rates were found to vary based on sex and age group. The present study suggests the possibility to improve AD-DALY rates by increasing population average protein intake levels in a recommended range.

The additive effects of exercise and essential amino acid on muscle mass and strength in community-dwelling older Japanese women with muscle mass decline, but not weakness and slowness: a randomized controlled and placebo trial.

BACKGROUND: Exercise and essential amino acid supplementation have been separately shown to improve muscle mass in elderly people, however, the combined, added effects of both interventions have yielded inconsistent results on muscle mass, strength, and physical function improvement. AIMS: To investigate the additive effects of exercise and essential amino acid supplementation on muscle mass, strength, and walking ability in older Japanese women with muscle mass decline, but not weakness and slowness. METHODS: One hundred thirty women over 65 years of age were defined as having muscle decline and randomly assigned into two groups; exercise and amino acid supplementation (n = 65) or exercise and placebo supplementation (n = 65). The exercise group attended a 60-min comprehensive training program once a week and were encouraged to perform a home-based exercise program. The amino acid or placebo group ingested a 3 g supplement daily for 3-month. Body composition was determined by bioelectrical impedance analysis. Interview data and functional fitness measurements, such as muscle strength and walking ability were collected at baseline and after the 3-month intervention. RESULTS: There were no significant group × time interactions in primary outcomes such as muscle mass and strength. However, interactions were observed in the degree of low back discomfort (P = 0.014). Percent change of low back discomfort was significantly greater in exercise + amino acid group compared with exercise + placebo group. CONCLUSIONS: The combination of exercise and amino acid supplementation had a beneficial effect on low back discomfort. However, additional effects were not observed in primary outcomes including muscle mass and strength in this population.

Association Between the Prevalence of Frailty and Doubly Labeled Water-Calibrated Energy Intake Among Community-Dwelling Older Adults.

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-shaped relationships between the prevalence of physical or comprehensive frailty against the DLW-calibrated EI, respectively. The lowest prevalence of both types of frailty was found at 1,900-2,000 kcal/d in women and 2,400-2,500 kcal/d in men, which corresponded to approximately 40 kcal/d/kg IBW (ideal body weight = 22 × height2) with DLW-calibrated EI. Uncalibrated EI underestimated approximately 20% compared with calibrated EI; underestimated EI were attenuated by calibration approach. CONCLUSIONS: This study suggests that low EI has a greater detrimental effect compared with excessive EI, particularly on physical frailty. Using biomarkers to calibrate EI holds promise for providing accurate energy requirements to establish guidelines used in public health and clinical nutrition.

Genotoxicity and repeated-dose toxicity evaluation of dried Wolffia globosa Mankai.

Wolffia is a genus of protein-rich aquatic plants. Mankai, a cultivated strain of Wolffia globosa, contains more than 40 % protein based on dry matter evaluation. Furthermore, Mankai is nutritionally excellent as a food material, and is expected to be applicable to various products as a substitute for animal protein. A battery of toxicological studies was conducted on the dried product of Mankai (Dry Mankai), with the expectation to utilize it as a raw material for food applications. Dry Mankai was not genotoxic in a bacterial reverse mutation test and in vitro micronucleus assay. In the subchronic toxicity study, rats were provided Dry Mankai in the diet at levels of 0 %, 5 %, 10 %, or 20 % (w/w), equivalent to 0, 3.18, 6.49, and 13.16 g/kg/day for males and 0, 3.58, 7.42, and 15.03 g/kg/day for females, respectively. No adverse effects that could be attributable to treatment were observed in clinical observations, body weight, food consumption, ophthalmology, hematology and blood chemistry, urinalysis, and macroscopic and microscopic findings. According to the repeated-dose study in rats, the no observed adverse effect level of Dry Mankai was 20 % (w/w) for both sexes (13.16 and 15.03 g/kg/day for males and females, respectively).

Validation of Energy and Nutrition Intake in Japanese Elderly Individuals Estimated Based on a Short Food Frequency Questionnaire Compared against a 7-day Dietary Record: The Kyoto-Kameoka Study.

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 precision of the FFQ for energy and nutrient intake in elderly individuals did not differ compared with previous findings in a middle-aged population. A validation study evaluating energy and nutrient intake using recovery biomarkers is further needed.

[Amino Acid Nutrition in the Prevention and Treatment of Sarcopenia].

　Sarcopenia is the decrease in skeletal muscle mass and muscular function that occurs with aging. The underlying mechanisms of sarcopenia include anabolic resistance, which is defined as a poor muscle protein synthetic response to previously effective stimuli such as nutrients and exercise. Among the nutrients that humans ingest, amino acids directly trigger the synthesis of muscle proteins. The essential amino acid leucine, in particular, functions as a stimulatory signal. Leucine-enriched essential amino acids help overcome anabolic resistance in elderly individuals to effectively stimulate muscle protein synthesis. Long-term intake of leucine-enriched essential amino acids has a synergistic effect with exercise to increase skeletal muscle mass, strength, and walking speed in elderly individuals, and can be an effective countermeasure to sarcopenia.

Sex Difference in the Association Between Protein Intake and Frailty: Assessed Using the Kihon Checklist Indexes Among Older Adults.

BACKGROUND: 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. OBJECTIVE: To evaluate the association between protein intake and comprehensive frailty in older Japanese adults. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study included 5638 Japanese participants (2707 men and 2931 women) aged ≥65 years from Kameoka City, Kyoto, Japan. MEASUREMENTS: 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. RESULTS: 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 intake was associated with lower prevalence of frailty both in men (32.5%, 28.4%, 28.3%, and 27.3%) and women (35.7%, 31.4%, 27.6%, and 28.2%). Moreover, higher dietary protein intake decreased the odds ratio (OR) for frailty after adjustment for potential confounding factors in both men (OR for highest vs lowest quartile, 0.62; 95% CI, 0.43-0.89; P for trend = 0.016) and women (OR 0.64; 95% CI, 0.45-0.91; P for trend = 0.017). CONCLUSIONS/IMPLICATIONS: The higher dietary protein intake may be inversely associated with the prevalence of comprehensive frailty in Japanese men and women. Future studies are needed to examine associations of dietary protein intake within KCL domains.

Association between the Frequency of Protein-Rich Food Intakes and Kihon-Checklist Frailty Indices in Older Japanese Adults: The Kyoto-Kameoka Study.

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 (PR 0.61, 95% CI, 0.43, 0.85; PR 0.64, 95% CI, 0.46, 0.91). The frequency of dairy products intake in the third quartile among women was significantly associated with a lower PR for frailty (p-value = 0.013). Our findings suggest that the consumption of seafood and dairy products may help older adults in maintaining their independence.

Effects of leucine-enriched essential amino acid and whey protein bolus dosing upon skeletal muscle protein synthesis at rest and after exercise in older women.

BACKGROUND & AIMS: Impaired anabolic responses to nutrition and exercise contribute to loss of skeletal muscle mass with ageing (sarcopenia). Here, we tested responses of muscle protein synthesis (MPS), in the under represented group of older women, to leucine-enriched essential amino acids (EAA) in comparison to a large bolus of whey protein (WP). METHODS: Twenty-four older women (65 ± 1 y) received (N = 8/group) 1.5 g leucine-enriched EAA supplements (LEAA_1.5), 6 g LEAA (LEAA_6) in comparison to 40 g WP. A primed constant I.V infusion of 13C6-phenylalanine was used to determine MPS at baseline and in response to feeding (FED) and feeding-plus-exercise (FED-EX; 6 × 8 unilateral leg extensions; 75%1-RM). We quantified plasma insulin/AA concentrations, leg femoral blood flow (LBF)/muscle microvascular blood flow (MBF), and anabolic signalling via immunoblotting. RESULTS: Plasma insulineamia and EAAemia were greater and more prolonged with WP than LEAA, although LEAA_6 peaked at similar levels to WP. Neither LEAA or WP modified LBF or MBF. FED increased MPS similarly in the LEAA_1.5, LEAA_6 and WP (P < 0.05) groups over 0-2 h, with MPS significantly higher than basal in the LEAA_6 and WP groups only over 0-4 h. However, FED-EX increased MPS similarly across all the groups from 0 to 4 h (P < 0.05). Only p-p70S6K1 increased with WP at 2 h in FED (P < 0.05), and at 2/4 h in FED-EX (P < 0.05). CONCLUSIONS: In conclusion, LEAA_1.5, despite only providing 0.6 g of leucine, robustly (perhaps maximally) stimulated MPS, with negligible trophic advantage of greater doses of LEAA or even to 40 g WP. Highlighting that composition of EAA, in particular the presence of leucine rather than amount is most crucial for anabolism.

New Functions and Potential Applications of Amino Acids.

Currently, several types of amino acids are being produced and used worldwide. Nevertheless, several new functions of amino acids have been recently discovered that could result in other applications. For example, oral stimulation by glutamate triggers the cephalic phase response to prepare for food digestion. Further, the stomach and intestines have specific glutamate-recognizing systems in their epithelial mucosa. Regarding clinical applications, addition of monosodium glutamate to the medicinal diet has been shown to markedly enhance gastric secretion in a vagus-dependent manner. Branched-chain amino acids (BCAAs) are the major components of muscles, and ingestion of BCAAs has been found to be effective for decreasing muscle pain. BCAAs are expected to be a solution for the serious issue of aging. Further, ingestion of specific amino acids could be beneficial. Glycine can be ingested for good night's sleep: glycine ingestion before bedtime significantly improved subjective sleep quality. Ingestion of alanine and glutamine effectively accelerates alcohol metabolism, and ingestion of cystine and theanine effectively prevents colds. Finally, amino acids could be used in a novel clinical diagnostic method: the balance of amino acids in the blood could be an indicator of the risk of diseases such as cancer. These newly discovered functions of amino acids are expected to contribute to the resolution of various issues.

Co-ingestion of carbohydrate with leucine-enriched essential amino acids does not augment acute postexercise muscle protein synthesis in a strenuous exercise-induced hypoinsulinemic state.

Strenuous exercise following overnight fasting increases fat oxidation during exercise, which can modulate training adaptation. However, such exercise induces muscle protein catabolism by decreasing blood insulin concentrations and increasing amino acid oxidation during the exercise. Leucine-enriched essential amino acids (LEAAs) enhance muscle protein synthesis (MPS) at rest and after exercise. However, it remains to be clarified if the co-ingestion of carbohydrate with LEAAs induces an additional increase in MPS, particularly in a hypoinsulinemic state induced by strenuous exercise. Eight-week-old male Sprague-Dawley rats were made to perform strenuous jump exercise (height 35 cm, 200 jumps, 3-s intervals), after which they ingested distilled water and 1 g/kg LEAAs with or without 1 g/kg of glucose. The fractional synthesis rate was determined by measuring the incorporation of l-[ring-(2)H5]-phenylalanine into skeletal muscle protein. Immediately after the exercise, plasma insulin concentration was significantly lower than that at the basal level. Co-ingestion of glucose with LEAAs alleviated the reduction in plasma insulin concentration, while LEAA ingestion alone did not. LEAA administration with or without glucose led to a higher MPS compared with water administration (P < 0.05). However, the co-ingestion of glucose with LEAAs did not induce further increases in MPS compared with LEAA ingestion alone. Thus, the co-ingestion of glucose with LEAAs does not additionally increase MPS under a strenuous exercise-induced hypoinsulinemic state when glucose is co-ingested with a dose of LEAAs that maximally stimulates MPS.

Exercise and Nutritional Supplementation on Community-Dwelling Elderly Japanese Women With Sarcopenic Obesity: A Randomized Controlled Trial.

OBJECTIVES: 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. DESIGN: Randomized controlled trial. SETTING: Urban community in Tokyo, Japan. PARTICIPANTS: Among 1213 community-dwelling elderly women over 70 years of age, 307 were defined with sarcopenic obesity, and 139 women participated in the study. INTERVENTION: 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. MEASUREMENTS: Bioelectric impedance analysis was used to measure body composition. Skeletal muscle mass index was calculated using measures of muscle mass and height. Physical function measures included grip strength, knee extension strength, usual walking speed, and walking parameters (stride, step length, width, walking angles). Blood samples were obtained to analyze levels of albumin, triglycerides, cholesterol, hemoglobin A1c, leptin, cystatin C, vitamin D, interleukin-6, and high-sensitivity C-reactive protein. RESULTS: Significant between-group × time interactions were observed in usual walking speed (P = .012), stride (P = .004), right step length (P = .003), average number of steps (P = .029), and vitamin D (P < .001). Compared to the HE group, the Ex + N intervention significantly decreased total body fat mass (P = .036) and increased stride (P = .038) and vitamin D (P < .001). Significant reductions in trunk fat were observed in the Ex group compared with HE (P = .014). The Ex + N and Ex interventions were over four times as likely (odds ratio [95% confidence interval]) to reduce body fat mass than the HE group (4.42 [1.21-16.19]; 4.50 [1.13-17.9], respectively). Significant odds ratios of the Ex + N intervention improving walking speed (3.05 [1.01-9.19]), vitamin D (14.22 [1.64-123.02]), and leptin (3.86 [1.19-12.47]) were also observed. CONCLUSION: Although exercise and nutrition have beneficial effects on individual variables of body composition, blood components, and physical function, improvements in muscle mass and variable combinations such as percent fat + skeletal muscle mass index or percent fat + physical functions were not observed in this population. Further large-scale and long-term investigation is necessary.

Leucine-Enriched Essential Amino Acids Augment Mixed Protein Synthesis, But Not Collagen Protein Synthesis, in Rat Skeletal Muscle after Downhill Running.

Mixed and collagen protein synthesis is elevated for as many as 3 days following exercise. Immediately after exercise, enhanced amino acid availability increases synthesis of mixed muscle protein, but not muscle collagen protein. However, the potential for synergic effects of amino acid ingestion with exercise on both mixed and collagen protein synthesis remains unclear. We investigated muscle collagen protein synthesis in rats following post-exercise ingestion of leucine-enriched essential amino acids. We determined fractional protein synthesis rates (FSR) at different time points following exercise. Mixed protein and collagen protein FSRs in skeletal muscle were determined by measuring protein-bound enrichments of hydroxyproline and proline, and by measuring the intracellular enrichment of proline, using injections of flooding d3-proline doses. A leucine-enriched mixture of essential amino acids (or distilled water as a control) was administrated 30 min or 1 day post-exercise. The collagen protein synthesis in the vastus lateralis was elevated for 2 days after exercise. Although amino acid administration did not increase muscle collagen protein synthesis, it did lead to augmented mixed muscle protein synthesis 1 day following exercise. Thus, contrary to the regulation of mixed muscle protein synthesis, muscle collagen protein synthesis is not affected by amino acid availability after damage-inducing exercise.

Intake of low-dose leucine-rich essential amino acids stimulates muscle anabolism equivalently to bolus whey protein in older women at rest and after exercise.

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 ± 2.5 yr; n = 8/group): bolus whey protein (WP-20 g) or novel low-dose leucine-enriched essential amino acids (EAA) [LEAA; 3 g (40% leucine)]. Using [(13)C6]phenylalanine infusions, we quantified muscle (MPS) and albumin (APS) protein synthesis at baseline and in response to both feeding (FED) and feeding plus exercise (FED-EX; 6 × 8 knee extensions at 75% 1-repetition maximum). We also quantified plasma insulin/AA concentrations, whole leg (LBF)/muscle microvascular blood flow (MBF), and muscle anabolic signaling by phosphoimmunoblotting. 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, whereas MBF increased to a similar extent in both groups only after FED-EX (P < 0.05). In response to FED, both WP and LEAA equally stimulated MPS 0-2 h (P < 0.05), abating thereafter (0-4 h, P > 0.05). In contrast, after FED-EX, MPS increased at 0-2 h and remained elevated at 0-4 h (P < 0.05) with both WP and LEAA. No anabolic signals quantifiably increased after FED, but p70 S6K1 Thr(389) increased after FED-EX (2 h, P < 0.05). APS increased similarly after WP and LEAA. Older women remain subtly responsive to nutrition ± exercise. Intriguingly though, bolus WP offers no trophic advantage over LEAA.

Leucine-enriched essential amino acids attenuate muscle soreness and improve muscle protein synthesis after eccentric contractions in rats.

Eccentric exercise results in prolonged muscle weakness and muscle soreness, which are typical symptoms of muscle damage. Recovery from muscle damage is related to mammalian target of rapamycin (mTOR) activity. Leucine-enriched essential amino acids (LEAAs) stimulate muscle protein synthesis via activation of the mTOR pathway. Therefore, we investigated the effect of LEAAs on muscle protein synthesis and muscle soreness after eccentric contractions (EC). Male Sprague-Dawley rats (9-11 weeks old) were administered an LEAA solution (AminoL40; containing 40 % leucine and 60 % other essential amino acids) at 1 g/kg body weight or distilled water (control) 30 min before and 10 min after EC. Tibialis anterior (TA) muscle was exposed to 500 EC by electrical stimulation under anesthesia. The fractional synthesis rate (FSR; %/h) in the TA muscle was measured by incorporating L-[ring-(2)H5] phenylalanine into skeletal muscle protein. Muscle soreness was evaluated by the paw withdrawal threshold using the Randal-Selitto test with some modifications from 1 to 3 days after EC. The FSR in the EC-control group (0.147 ± 0.016 %/h) was significantly lower than in the sedentary group (0.188 ± 0.016 %/h, p < 0.05). AminoL40 administration significantly mitigated the EC-induced impairment of the FSR (0.172 ± 0.018 %/h). EC decreased the paw withdrawal threshold at 1 and 2 days after EC, which indicated that EC induced muscle soreness. Furthermore, AminoL40 administration alleviated the decreased paw withdrawal threshold. These findings suggest that LEAA supplementation improves the rate of muscle protein synthesis and ameliorates muscle soreness after eccentric exercise.

Combined supplementation of carbohydrate, alanine, and proline is effective in maintaining blood glucose and increasing endurance performance during long-term exercise in mice.

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.

Combination of BCAAs and glutamine enhances dermal collagen protein synthesis in protein-malnourished rats.

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 < 0.05, Tukey'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.

Importance of amino acid composition to improve skin collagen protein synthesis rates in UV-irradiated mice.

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.

Effects of exercise and amino acid supplementation on body composition and physical function in community-dwelling elderly Japanese sarcopenic women: a randomized controlled trial.

OBJECTIVES: To evaluate the effectiveness of exercise and amino acid supplementation in enhancing muscle mass and strength in community-dwelling elderly sarcopenic women. DESIGN: Randomized controlled trial. SETTING: Urban community in Tokyo, Japan. PARTICIPANTS: One hundred fifty-five women aged 75 and older were defined as sarcopenic and randomly assigned to one of four groups: exercise and amino acid supplementation (exercise + AAS; n = 38), exercise (n = 39), amino acid supplementation (AAS; n = 39), or health education (HE; n = 39). INTERVENTION: The exercise group attended a 60-minute comprehensive training program twice a week, and the AAS group ingested 3 g of a leucine-rich essential amino acid mixture twice a day for 3 months. MEASUREMENTS: Body composition was determined using bioelectrical impedance analysis. Data from interviews and functional fitness parameters such as muscle strength and walking ability were collected at baseline and after the 3-month intervention. RESULTS: A significant group × time interaction was seen in leg muscle mass (P = .007), usual walking speed (P = .007), and knee extension strength (P = .017). The within-group analysis showed that walking speed significantly increased in all three intervention groups, leg muscle mass in the exercise + AAS and exercise groups, and knee extension strength only in the exercise + AAS group (9.3% increase, P = .01). The odds ratio for leg muscle mass and knee extension strength improvement was more than four times as great in the exercise + AAS group (odds ratio = 4.89, 95% confidence interval = 1.89-11.27) as in the HE group. CONCLUSION: The data suggest that exercise and AAS together may be effective in enhancing not only muscle strength, but also combined variables of muscle mass and walking speed and of muscle mass and strength in sarcopenic women.