Leucine-enriched Essential Amino Acids Research Articles

The efficacy and safety of leucine-enriched essential amino acids in knee osteoarthritis patients: A randomized controlled trial.

Supplementation with leucine-enriched essential amino acids (LEAAs) has shown efficacy in the recovery of muscle injury and activation of muscle synthesis. Muscle function in knee osteoarthritis is a crucial factor for managing pain and preserving ambulatory function. However, the efficacy and safety of LEAAs supplementation in patients with knee osteoarthritis have not been evaluated. In this prospective analysis, we evaluated the efficacy and safety of supplementation with 12 g of LEAAs daily for 8 weeks in knee-symptomatic osteoarthritis patients. For assessing the efficacy, clinical pain, calf circumference, and disability were assessed using questionnaires (visual analog scale, Knee Society Score, and 36-item short form survey [SF-36]), laboratory analyses (total protein and albumin), and radiologic study (dual-energy X-ray absorptiometry [DEXA]) for muscle and bone density. To evaluate safety, generalized or localized protein allergic reactions, complete blood count, liver and kidney function, and serum glucose were measured. Sixty-five participants, categorized into the experimental (n = 32) and control (n = 33) groups, were included in this 8-week trial from March 2022 to July 2022. A significantly higher efficacy was observed in the experimental group than in the control group, as indicated by muscle density in the DEXA scan (P = .001) and SF-36 (P < .001). The safety evaluation revealed no related generalized or local protein allergy. Hematological findings, serum glucose, and kidney and liver toxicity were not significantly different between the groups. Supplementation with leucine-enriched proteins is safe and efficacious in the improvement of muscle density and quality of life.

The effects of resistance exercise and leucine-enriched essential amino acid supplementation on muscle mass and physical function in post-gastrectomy patients: a pilot randomized controlled trial.

[Purpose] In gastric cancer patients, low muscle mass decreases overall survival and quality of life (QOL). Resistance exercise with leucine-enriched essential amino acid (LEAA) supplementation may prevent muscle mass loss. This study was aimed at determining whether resistance exercise with LEAA supplementation prevents muscle mass loss in post-gastrectomy patients. [Participant and Methods] We conducted a single-center, open-label, randomized controlled pilot trial. Ten participants who underwent gastrectomy were divided into two groups. The intervention group underwent resistance exercise at 70% of one repetition maximum and received a supplement of 3 g of LEAA twice daily for 15 days, while the control group received standard care. We compared changes in muscle mass, physical function (muscle strength and continuous walking distance), and QOL between the groups. [Results] We found good adherence and participation rates in both groups. We failed to detect a significant difference in muscle mass between the groups. The intervention group showed significant improvements in muscle strength and QOL, while the control group showed no significant changes. [Conclusion] We failed to detect a significant difference in muscle mass due to resistance exercise with LEAA supplementation in post-gastrectomy patients. However, resistance exercise with LEAA supplementation might be beneficial for muscle strength recovery and QOL improvements.

Leucine-Enriched Essential Amino Acids Enhance the Antiseizure Effects of the Ketogenic Diet in Rats.

The classic ketogenic diet (KD) can be used successfully to treat medically refractory epilepsy. However, the KD reduces seizures in 50–70% of patients with medically refractory epilepsy, and its antiseizure effect is limited. In the current study, we developed a new modified KD containing leucine (Leu)-enriched essential amino acids. Compared with a normal KD, the Leu-enriched essential amino acid-supplemented KD did not change the levels of ketosis and glucose but enhanced the inhibition of bicuculline-induced seizure-like bursting in extracellular recordings of acute hippocampal slices from rats. The enhancement of antiseizure effects induced by the addition of Leu-enriched essential amino acids to the KD was almost completely suppressed by a selective antagonist of adenosine A1 receptors or a selective dose of pannexin channel blocker. The addition of Leu-enriched essential amino acids to a normal diet did not induce any antiseizure effects. These findings indicate that the enhancement of the antiseizure effects of the KD is mediated by the pannexin channel-adenosine A1 receptor pathway. We also analyzed amino acid profiles in the plasma and hippocampus. A normal KD altered the levels of many amino acids in both the plasma and hippocampus. The addition of Leu-enriched essential amino acids to a KD further increased and decreased the levels of several amino acids, such as threonine, histidine, and serine, suggesting that altered metabolism and utilization of amino acids may play a role in its antiseizure effects. A KD supplemented with Leu-enriched essential amino acids may be a new therapeutic option for patients with epilepsy, including medically refractory epilepsy.

The Effect of Leucine-Enriched Essential Amino Acid Supplementation on Anabolic and Catabolic Signaling in Human Skeletal Muscle after Acute Resistance Exercise: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Comparison Trial.

Resistance exercise transiently activates anabolic and catabolic systems in skeletal muscle. Leucine-enriched essential amino acids (LEAAs) are reported to stimulate the muscle anabolic response at a lower dose than whey protein. However, little is known regarding the effect of LEAA supplementation on the resistance exercise-induced responses of the anabolic and catabolic systems. Here, we conducted a randomized, double-blind, placebo-controlled, parallel-group comparison trial to investigate the effect of LEAA supplementation on mechanistic target of rapamycin complex 1 (mTORC1), the ubiquitin–proteasome system and inflammatory cytokines after a single bout of resistance exercise in young men. A total of 20 healthy young male subjects were supplemented with either 5 g of LEAA or placebo, and then they performed 10 reps in three sets of leg extensions and leg curls (70% one-repetition maximum). LEAA supplementation augmented the phosphorylation of mTORSer2448 (+77.1%, p < 0.05), p70S6KThr389 (+1067.4%, p < 0.05), rpS6Ser240/244 (+171.3%, p < 0.05) and 4EBP1Thr37/46 (+33.4%, p < 0.05) after resistance exercise. However, LEAA supplementation did not change the response of the ubiquitinated proteins, MuRF-1 and Atrogin-1 expression. Additionally, the mRNA expression of IL-1β and IL-6 did not change. These data indicated that LEAA supplementation augments the effect of resistance exercise by enhancing mTORC1 signal activation after exercise.

Novel Essential Amino Acid Supplements Following Resistance Exercise Induce Aminoacidemia and Enhance Anabolic Signaling Irrespective of Age: A Proof-of-Concept Trial.

We investigated the effects of ingesting a leucine-enriched essential amino acid (EAA) gel alone or combined with resistance exercise (RE) versus RE alone (control) on plasma aminoacidemia and intramyocellular anabolic signaling in healthy younger (28 ± 4 years) and older (71 ± 3 years) adults. Blood samples were obtained throughout the three trials, while muscle biopsies were collected in the postabsorptive state and 2 h following RE, following the consumption of two 50 mL EAA gels (40% leucine, 15 g total EAA), and following RE with EAA (combination (COM)). Protein content and the phosphorylation status of key anabolic signaling proteins were determined via immunoblotting. Irrespective of age, during EAA and COM peak leucinemia (younger: 454 ± 32 µM and 537 ± 111 µM; older: 417 ± 99 µM and 553 ± 136 µM) occurred ~60–120 min post-ingestion (younger: 66 ± 6 min and 120 ± 60 min; older: 90 ± 13 min and 78 ± 12 min). In the pooled sample, the area under the curve for plasma leucine and the sum of branched-chain amino acids was significantly greater in EAA and COM compared with RE. For intramyocellular signaling, significant main effects were found for condition (mTOR (Ser2481), rpS6 (Ser235/236)) and age (S6K1 (Thr421/Ser424), 4E-BP1 (Thr37/46)) in age group analyses. The phosphorylation of rpS6 was of similar magnitude (~8-fold) in pooled and age group data 2 h following COM. Our findings suggest that a gel-based, leucine-enriched EAA supplement is associated with aminoacidemia and a muscle anabolic signaling response, thus representing an effective means of stimulating muscle protein anabolism in younger and older adults following EAA and COM.

Effects of leucine-enriched essential amino acid supplementation on muscular fatigue and inflammatory cytokines in wheelchair basketball players.

[Purpose]This study aimed to investigate the effects of leucine-enriched essential amino acid (LEAA) supplementation on muscle fatigue and the level of inflammatory cytokines in wheelchair basketball players after a basketball game and interval training.[Methods]Of the ten recruited wheelchair basketball players (aged 34.5±8.9 years; lean body mass of 34.3±10.0 kg) who had spinal cord injury (SCI) and had undergone amputation, nine participated in the final test. These nine athletes received LEAA supplements (3 times 4.0 g/day) or placebo treatment in a double-blind, randomized, crossover study. We measured variables related to muscular fatigue and inflammatory response before the intense exercise and 4 days after recovery.[Results]The significant effect of LEAA supplementation was inhibition of circulating IL-6 levels in the LEAA-treated group compared with the placebo group (P < .05). However, no changes were observed in the TNF-α and creatinine kinase levels. Moreover, analysis of variance analysis showed no significant difference in the relative values of muscle soreness. However, the effect size analysis with Cohen’s d reported a significant improvement in the relative values of whole body and back muscle soreness.[Conclusion]Our results revealed that LEAA supplementation before and after intense exercise could help reduce muscle soreness and IL-6 levels in wheelchair basketball players.

Leucine-Enriched Essential Amino Acids Improve Recovery from Post-Exercise Muscle Damage Independent of Increases in Integrated Myofibrillar Protein Synthesis in Young Men.

Background: Leucine-enriched essential amino acids (LEAAs) acutely enhance post-exercise myofibrillar protein synthesis (MyoPS), which has been suggested to be important for muscle repair and recovery. However, the ability of LEAAs to concurrently enhance MyoPS and muscle damage recovery in free-living humans has not been studied. Methods: In a randomized, double-blind, placebo-controlled, parallel-group design, twenty recreationally active males consuming a controlled diet (1.2 g/kg/d of protein) were supplemented thrice daily with 4 g of LEAAs (containing 1.6 g leucine) or isocaloric placebo for four days following an acute bout of lower-body resistance exercise (RE). MyoPS at rest and integrated over 96 h of recovery was measured by D2O. Isometric and isokinetic torque, muscle soreness, Z-band streaming, muscle heat shock protein (HSP) 25 and 72, plasma creatine kinase (CK), and plasma interleukin-6 (IL-6) were measured over 96 h post-RE to assess various direct and indirect markers of muscle damage. Results: Integrated MyoPS increased ~72% over 96 h after RE (p < 0.05), with no differences between groups (p = 0.98). Isometric, isokinetic, and total peak torque decreased ~21% by 48 h after RE (p < 0.05), whereas total peak torque was ~10% greater overall during recovery in LEAAs compared to placebo (p < 0.05). There were moderate to large effects for peak torque in favour of LEAAs. Muscle soreness increased during recovery with no statistical differences between groups but small to moderate effects in favour of LEAAs that correlated with changes in peak torque. Plasma CK, plasma IL-6, and muscle HSP25 increased after RE (p < 0.05) but were not significantly different between groups (p ≥ 0.13). Consistent with a trend toward attenuated Z-band streaming in LEAAs (p = 0.07), muscle HSP72 expression was lower (p < 0.05) during recovery in LEAAs compared with placebo. There were no correlations between MyoPS and any measures of muscle damage (p ≥ 0.37). Conclusion: Collectively, our data suggest that LEAAs moderately attenuated muscle damage without concomitant increases in integrated MyoPS in the days following an acute bout of resistance exercise in free-living recreationally active men.

Leucine-enriched essential amino acid supplementation in mechanically ventilated trauma patients: a feasibility study

BackgroundCritically ill patients lose up to 2% of muscle mass per day. We assessed the feasibility of administering a leucine-enriched essential amino acid (L-EAA) supplement to mechanically ventilated trauma patients with the aim of assessing the effect on skeletal muscle mass and function.MethodsA randomised feasibility study was performed over six months in intensive care (ICU). Patients received 5 g L-EAA five times per day in addition to standard feed (L-EAA group) or standard feed only (control group) for up to 14 days. C-reactive protein, albumin, IL-6, IL-10, urinary 3-MH, nitrogen balance, protein turnover ([1-13C] leucine infusion), muscle depth change (ultrasound), functional change (Katz and Barthel indices) and muscle strength Medical Research Council (MRC) sum score to assess ICU Acquired Weakness were measured sequentially.ResultsEight patients (9.5% of screened patients) were recruited over six months. L-EAA doses were provided on 91/124 (73%) occasions. Inflammatory and urinary marker data were collected; serial muscle depth measurements were lacking due to short length of stay. Protein turnover studies were performed on five occasions. MRC sum score could not be performed as patients were not able to respond to the screening questions. The Katz and Barthel indices did not change. L-EAA delivery was achievable, but meaningful functional and muscle mass outcome measures require careful consideration in the design of a future randomised controlled trial.ConclusionL-EAA was practical to provide, but we found significant barriers to recruitment and measurement of the chosen outcomes which would need to be addressed in the design of a future, large randomised controlled trial.Trial registrationISRCTN Registry, ISRCTN79066838. Registered on 25 July 2012.

Effect of a leucine-enriched essential amino acids mixture on muscle recovery.

[Purpose] The aim of this study was to determine whether the consumption of a leucine-enriched essential amino acid mixture (LEAA), which is known to increase protein synthesis in muscles, alleviates muscle damage and accelerates recovery by ameliorating muscle damage. [Participants and Methods] A double-blind, randomized crossover trial was conducted over a 5-week period. Ten untrained males (age, 23.0 ± 1.6 years) were asked to repeatedly flex and extend their elbows for 10 counts/set × 5 sets at full power while using a dynamometer. The participants took 3.6-g supplements (LEAA mixture or placebo) 3 times daily on day 0 and for the next 7 days. Changes in serum creatine phosphokinase (CPK) activity and myoglobin concentration as markers of muscle tissue damage were evaluated prior to and after exercise and on days 1, 2, 3, 5, and 7. [Results] The relative ratio of the changes in peak serum CPK activity measured on day 5 was significantly lower after taking LEAA than after taking the placebo. [Conclusion] LEAA consumption suppressed exercise-induced elevation of muscle damage markers in blood, which suggests that LEAA could attenuate muscle damage and aid muscle recovery.

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.

Hormones and Sarcopenia.

Sarcopenia is defined as the loss of muscle mass associated with a loss of muscle function, e.g., walking speed. A number of consensus definitions exist for sarcopenia with cut-off points being ethnically specific. A rapid screen test (SARC-F) is available and does not require different ethnic cut-off points. Sarcopenia leads to the development of frailty, disability and mortality. The prevalence of sarcopenia varies from 1-29% in community- dwelling and 14 to 33% in long-term care populations. Hormones play a role in the development of muscle mass and in the regulation of muscle strength. Testosterone appears to be the central hormone involved in the development of sarcopenia; it increases both muscle mass and activates satellite cells leading to increased muscle function. Growth hormone deficiency leads to the loss of muscle mass but not muscle strength. Lack of insulin or insulin resistance leads to accelerated development of sarcopenia. Vitamin D deficiency plays a role in the loss of muscle strength. A variety of other hormones appear to play minor roles in age-related alterations in muscle mass and function. At present, the treatment of sarcopenia is resistance exercise, leucine enriched essential amino acids or hydroxymethylbutyrate and vitamin D replacement.

Leucine-Enriched Essential Amino Acids Augment Muscle Glycogen Content in Rats Seven Days after Eccentric Contraction.

Eccentric contractions induce muscle damage, which impairs recovery of glycogen and adenosine tri-phosphate (ATP) content over several days. Leucine-enriched essential amino acids (LEAAs) enhance the recovery in muscles that are damaged after eccentric contractions. However, the role of LEAAs in this process remains unclear. We evaluated the content in glycogen and high energy phosphates molecules (phosphocreatine (PCr), adenosine di-phosphate (ADP) and ATP) in rats that were following electrically stimulated eccentric contractions. Muscle glycogen content decreased immediately after the contraction and remained low for the first three days after the stimulation, but increased seven days after the eccentric contraction. LEAAs administration did not change muscle glycogen content during the first three days after the contraction. Interestingly, however, it induced a further increase in muscle glycogen seven days after the stimulation. Contrarily, ATP content decreased immediately after the eccentric contraction, and remained lower for up to seven days after. Additionally, LEAAs administration did not affect the ATP content over the experimental period. Finally, ADP and PCr levels did not significantly change after the contractions or LEAA administration. LEAAs modulate the recovery of glycogen content in muscle after damage-inducing exercise.

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

SummaryBackground & aimsImpaired 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).MethodsTwenty-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.ResultsPlasma 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).ConclusionsIn 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.

The impact of leucine enriched essential amino acid jelly on activities of daily living improvement in older people living in long-term health care facility

The impact of leucine enriched essential amino acid jelly on activities of daily living improvement in older people living in long-term health care facility

Frailty and sarcopenia in elderly.

Frailty is apre-disability syndrome where an older person can be identified as being at risk when exposed to stressors associated with high risk for disability or needing to be hospitalized. Two major frailty definitions exist. The physical phenotype of frailty and the multiple deficit model. Asimple frailty screening tool-FRAIL-has been validated. Treatment of frailty involves resistance exercise, optimization of nutrition, and treatment of fatigue (sleep apnea, depression), treatable causes of weight loss and adjustment of polypharmacy. Sarcopenia (decline in function with low muscle mass) is amajor cause of frailty. Asimple sarcopenia screening tool-SARC-F-has been validated. The multiple causes of sarcopenia are reviewed. Optimal treatment is resistance exercise, leucine-enriched essential amino acids and vitaminD replacement.

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-2H5]-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.

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.

Leucine-enriched essential amino acids attenuate inflammation in rat muscle and enhance muscle repair after eccentric contraction.

Eccentric exercise results in prolonged muscle damage that may lead to muscle dysfunction. Although inflammation is essential to recover from muscle damage, excessive inflammation may also induce secondary damage, and should thus be suppressed. In this study, we investigated the effect of leucine-enriched essential amino acids on muscle inflammation and recovery after eccentric contraction. These amino acids are known to stimulate muscle protein synthesis via mammalian target of rapamycin (mTOR), which, is also considered to alleviate inflammation. Five sets of 10 eccentric contractions were induced by electrical stimulation in the tibialis anterior muscle of male SpragueDawley rats (8–9 weeks old) under anesthesia. Animals received a 1 g/kg dose of a mixture containing 40 % leucine and 60 % other essential amino acids or distilled water once a day throughout the experiment. Muscle dysfunction was assessed based on isometric dorsiflexion torque, while inflammation was evaluated by histochemistry. Gene expression of inflammatory cytokines and myogenic regulatory factors was also measured. We found that leucine-enriched essential amino acids restored full muscle function within 14 days, at which point rats treated with distilled water had not fully recovered. Indeed, muscle function was stronger 3 days after eccentric contraction in rats treated with amino acids than in those treated with distilled water. The amino acid mix also alleviated expression of interleukin-6 and impeded infiltration of inflammatory cells into muscle, but did not suppress expression of myogenic regulatory factors. These results suggest that leucine-enriched amino acids accelerate recovery from muscle damage by preventing excessive inflammation.

The impact of leucine‐enriched essential amino acid and whey protein dosing upon skeletal muscle protein synthesis in older women at rest and after exercise

Loss of skeletal muscle mass with ageing (sarcopenia) is a problem for which anabolic neutraceutical interventions could hold therapeutic promise. Older women are understudied with recommendations based on studies in older men inappropriate given that women exhibit distinct protein metabolism (i.e. reduced responses to feeding).We previously showed that increases in muscle protein synthesis (MPS) were identical in older women fed 3 g of 40% leucine‐enriched essential amino acids (LEAA) vs. 20 g whey protein (WP). Here we tested whether lower or higher doses of LEAA and WP modified this response.We recruited 24 older women (64±0.7 y) who received (N=8/group) 1.5 g LEAA, 6 g LEAA or 40 g WP while undergoing a primed constant I.V infusion of 13C6 phenylalanine. Using a unilateral resistance exercise model (6×8 leg extensions; 75% 1‐RM) we determined the effects of feeding (FED) and feeding‐plus‐exercise (FED‐EX) over a 2 and 4 h period upon MPS, microvascular blood flow (MBF) and plasma insulin. Muscle biopsies were taken from the vastus lateralis at baseline, 2.5 h later (BASAL) and then at 2 and 4 h in both the rest and exercised legs. MPS was determined by mass spectrometry, MBF by contrast‐enhanced ultrasound (CEUS) and plasma insulin by ELISA. Data were analyzed by 2‐way repeated measures ANOVA with Bonferroni post‐hoc testing; a P‐value of &lt;0.05 was considered significant.We found that FED increased MPS similarly in response to 1.5 g LEAA (0.061±0.003 vs. 0.086±0.005 %/h, P&lt;0.05), 6 g LEAA (0.066±0.006 vs. 0.090±0.007 %/h, P&lt;0.05) and 40 g WP (0.056±0.004 vs. 0.084±0.011 %/h, P&lt;0.01) over 0–2 h, whereas at 2–4 h this was not significantly different to baseline under each condition. Only 40g WP maintained FED responses at 0–4 h.At 0–2 h FED‐EX increased MPS only in response to 40 g WP (0.056±0.004 vs. 0.089±0.017 %/h, P&lt;0.05), however over 0–4 h increases in MPS were similar across the groups (1.5 g, 0.061±0.003 vs. 0.091±0.007 %/h, P&lt;0.01; 6 g, 0.066±0.006 vs. 0.097±0.007 %/h, P&lt;0.01 and 40 g WP, 0.56±0.004 vs. 0.104±0.011 %/h, P&lt;0.001).No significant increases in MBF were evident in response to FED, whilst only WP elicited increases with FED‐EX (0.13±0.04 vs. 0.31±0.09 AU, P&lt;0.05). Plasma insulin increased in response to 1.5 g LEAA (peak: 11.50±1.83 uU/mL), 6 g LEAA (peak: 12.76±1.61 uU/mL) and 40 g WP (peak: 21.03±3.62 uU/mL, all P&lt;0.01). However, both the peak and area under the curve (AUC: 74.62±11.8 vs. 45.6±10.4 (1.5 g LEAA), 33.79±3.0 (6 g LEAA), P&lt;0.05) was markedly greater in response to WP.We conclude there does not exist a bona fide dose‐response of MPS to FED in older women as 1.5 g of LEAA (equating to 0.6 g leucine and 0.9 g other EAA) maximally stimulated MPS in relation to 40 g WP. Similar was true following FED‐EX. The lack of increase in MBF is consistent with reports in older men while the heightened insulin response to WP vs. LEAA would not be expected to modify MPS given the permissive role of insulin in MPS. We conclude LEAA strategies have anabolic potential in older women; nonetheless longer‐term studies are needed to determine how “one‐off” MPS responses reflect myo‐anabolic and functional outcomes.Support or Funding InformationThis work was funded by Ajinomoto Company Incorporation

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.