Mixed Muscle Fractional Synthetic Rate Research Articles

Native Whey Induces Similar Post Exercise Muscle Anabolic Responses as Regular Whey, Despite Greater Leucinemia, in Elderly Individuals

ObjectiveElderly muscle seems less sensitive to the anabolic stimulus of a meal. Changes in blood concentrations of leucine are suggested as one important trigger of the anabolic response in muscle. The aim of this study was to investigate whether native whey protein, containing high amounts of leucine, may be a more potent stimulator of muscle protein synthesis (MPS) in elderly than regular whey protein (WPC-80) or milk.DesignRandomized controlled partial crossover.SettingNorwegian School of Sport Sciences.Participants21 healthy elderly men and women (≥70 years).InterventionParticipants received either 20 g of WPC-80 and native whey (n = 11) on separate days in a crossover design, or milk (n = 10). Supplements were ingested immediately and two hours after a bout of lower body heavy-load resistance exercise.MeasurementsBlood samples and muscle biopsies were collected to measure blood concentrations of amino acids by gas-chromatography mass spectrometry (GCMS), phosphorylation of p70S6K, 4E-BP1 and eEF-2 by immunoblotting and mixed muscle fractional synthetic rate (FSR) by use of [2H5]phenylalanine-infusion, GCMS and isotope-ratio mass spectrometry.ResultsNative whey increased blood leucine concentrations more than WPC-80 (P < 0.05), but not p70S6K phosphorylation or mixed muscle FSR. Both whey supplements increased blood leucine concentrations (P < 0.01) and P70S6K phosphorylation more than milk (P = 0.014). Native whey reached higher mixed muscle FSR values than milk (P = 0.026) 1-3h after exercise.ConclusionsDespite greater increases in blood leucine concentrations than WPC-80 and milk, native whey was only superior to milk concerning increases in MPS and phosphorylation of P70S6K during a 5-hour post-exercise period in elderly individuals.

Whey Hydrolysate Supplementation Following Resistance Exercise Elicits Similar Anabolic Responses in Both Young and Older Adults

Skeletal muscle sensitivity to dietary protein and exercise typically declines during aging. However, previous data presented by our group indicates that whey protein hydrolysate (WH, di- and tri-peptide mixture) may be able to stimulate muscle anabolism at lower dosages than observed with intact whey protein in older adults. PURPOSE: To compare the effect of a minimal dose (10 g) of WH provided after resistance exercise (REx) on skeletal muscle anabolism in young and older adults. METHODS: Twenty healthy recreationally active adults (YOUNG: M=8, F=2; 25±4yr, 25±4 kg[BULLET OPERATOR]m2 | OLD: M=7, F=3; 65±4yr, 25±4 kg[BULLET OPERATOR]m2) were studied pre- and post-ingestion (PI) of 10 g of WH 1 h after high-intensity REx ([email protected]~70% 1RM, leg ext). We measured mixed-muscle protein fractional synthetic rate (FSR) and plasma BCAA concentrations by stable isotopic methods. Western-blotting was used to asses anabolic signaling and the presence of peptide transporters in muscle. Muscle biopsies from the vastus lateralis were collected at rest and during the early (0–2 h) and late (2–4 h) PI periods. Mixed muscle FSR and anabolic signaling was analyzed using a 2(group) x 3(time) mixed model ANOVA repeated across time. BCAA concentrations were modeled separately per time point using a 2 (group) x 2 (time) mixed-model ANOVA. Type I error for all analyses was set at α=0.05.Table: No title available.RESULTS: Compared with rest, increases in p-mTOR (Young: +2.0 fold, Old: +2.5 fold) and p-4E-BP1 (Young: +1.5 fold, Old: +1.4 fold) were observed in both groups at 4h PI (p<0.05). Increases in p-S6K1 were observed in both groups at 2h PI but to a greater extent in the OLD group (p <0.05). Peptide transporter-1 (PEPT1) expression was found in muscle samples from both groups. CONCLUSION: WH provided after Rex enhances muscle anabolism in older adults at a dose previously shown to be ineffective with intact whey isolate. Future studies will be required to determine if WH may aid in the long-term preservation of muscle in this population.

Resistance exercise-induced S6K1 kinase activity is not inhibited in human skeletal muscle despite prior activation of AMPK by high-intensity interval cycling.

Combining endurance and strength training in the same session has been reported to reduce the anabolic response to the latter form of exercise. The underlying mechanism, based primarily on results from rodent muscle, is proposed to involve AMPK-dependent inhibition of mTORC1 signaling. This hypothesis was tested in eight trained male subjects who in randomized order performed either resistance exercise only (R) or interval cycling followed by resistance exercise (ER). Biopsies taken from the vastus lateralis before and after endurance exercise and repeatedly after resistance exercise were assessed for glycogen content, kinase activity, protein phosphorylation, and gene expression. Mixed muscle fractional synthetic rate was measured at rest and during 3 h of recovery using the stable isotope technique. In ER, AMPK activity was elevated immediately after both endurance and resistance exercise (∼90%, P < 0.05) but was unchanged in R. Thr(389) phosphorylation of S6K1 was increased severalfold immediately after exercise (P < 0.05) in both trials and increased further throughout recovery. After 90 and 180 min recovery, S6K1 activity was elevated (∼55 and ∼110%, respectively, P < 0.05) and eukaryotic elongation factor 2 phosphorylation was reduced (∼55%, P < 0.05) with no difference between trials. In contrast, markers for protein catabolism were differently influenced by the two modes of exercise; ER induced a significant increase in gene and protein expression of MuRF1 (P < 0.05), which was not observed following R exercise only. In conclusion, cycling-induced elevation in AMPK activity does not inhibit mTOR complex 1 signaling after subsequent resistance exercise but may instead interfere with the hypertrophic response by influencing key components in protein breakdown.

Lipid-induced insulin resistance is associated with an impaired skeletal muscle protein synthetic response to amino acid ingestion in healthy young men.

The ability to maintain skeletal muscle mass appears to be impaired in insulin-resistant conditions, such as type 2 diabetes, that are characterized by muscle lipid accumulation. The current study investigated the effect of acutely increasing lipid availability on muscle protein synthesis. Seven healthy young male volunteers underwent a 7-h intravenous infusion of l-[ring-(2)H5]phenylalanine on two randomized occasions combined with 0.9% saline or 10% Intralipid at 100 mL/h. After a 4-h "basal" period, a 21-g bolus of amino acids was administered and a 3-h hyperinsulinemic-euglycemic clamp was commenced ("fed" period). Muscle biopsy specimens were obtained from the vastus lateralis at 1.5, 4, and 7 h. Lipid infusion reduced fed whole-body glucose disposal by 20%. Furthermore, whereas the mixed muscle fractional synthetic rate increased from the basal to the fed period during saline infusion by 2.2-fold, no change occurred during lipid infusion, despite similar circulating insulin and leucine concentrations. This "anabolic resistance" to insulin and amino acids with lipid infusion was associated with a complete suppression of muscle 4E-BP1 phosphorylation. We propose that increased muscle lipid availability may contribute to anabolic resistance in insulin-resistant conditions by impairing translation initiation.

Chocolate Milk and Endurance Exercise Recovery

This study examined effects of fat-free chocolate milk (MILK) consumption on kinetic and cellular markers of protein turnover, muscle glycogen, and performance during recovery from endurance exercise. Male runners participated in two trials separated by 1 wk and consumed either MILK or a nonnitrogenous isocaloric carbohydrate (CHO) control beverage (CON) after a 45-min run at 65% of V˙O(2peak). Postexercise muscle protein fractional synthetic rate (FSR) and whole-body protein turnover were determined during 3 h of recovery using muscle biopsies and primed constant infusions of L-[ring-²H₅]phenylalanine and L-[1-¹³C]leucine, respectively. Phosphorylation of translational signaling proteins and activity of proteolytic molecules were determined using Western blotting and enzymatic activity assays. Muscle glycogen was quantified, and treadmill time to exhaustion was determined after the recovery period. Consuming MILK after exercise resulted in higher mixed muscle FSR with lower whole-body proteolysis and synthesis compared with CON (P ≤ 0.05). Phosphorylation of eIF4E-BP1 and FOXO3a was higher for MILK (P < 0.01), whereas Akt phosphorylation was lower during recovery regardless of dietary treatment (P < 0.05). Enzymatic activity assays indicated lower caspase-3 activity during recovery for MILK (P < 0.01) and higher 26S proteasome activity for CON (P < 0.01). Muscle glycogen was not affected by either dietary treatment; however, time to exhaustion was greater for MILK than for CON (P < 0.05). The effects of consumption of MILK after endurance exercise on FSR, signaling molecules of skeletal muscle protein turnover, leucine kinetics, and performance measures suggest unique benefits of milk compared with a CHO-only beverage.

Endocrine Responses During Overnight Recovery From Exercise: Impact of Nutrition and Relationships With Muscle Protein Synthesis

Nocturnal endocrine responses to exercise performed in the evening and the potential role of nutrition are poorly understood. To gain novel insight, 10 healthy men ingested carbohydrate with (C+P) and without (C) protein in a randomized order and double-blind manner during 2 hr of interval cycling followed by resistance-type exercise and into early postexercise recovery. Blood samples were obtained hourly throughout 9 hr of postexercise overnight recovery for analysis of key hormones. Muscle samples were taken from the vastus lateralis before and after exercise and then again the next morning (7 a.m.) to calculate mixed-muscle protein fractional synthetic rate (FSR). Overnight plasma hormone concentrations were converted into overall responses (expressed as area under the concentration curve) and did not differ between treatments for either growth hormone (1,464 ± 257 vs. 1,432 ± 164 pg/ml · 540 min) or total testosterone (18.3 ± 1.2 vs. 17.9 ± 1.2 nmol/L · 540 min, C and C+P, respectively). In contrast, the overnight cortisol response was higher with C+P (102 ± 11 nmol/L · 540 min) than with C (81 ± 8 nmol/L · 540 min; p = .02). Mixed-muscle FSR did not differ between C and C+P during overnight recovery (0.062% ± 0.006% and 0.062% ± 0.009%/hr, respectively) and correlated significantly with the plasma total testosterone response (r = .7, p < .01). No correlations with FSR were apparent for the response of growth hormone (r = -.2, p = .4), cortisol (r = .1, p = .6), or the ratio of testosterone to cortisol (r = .2, p = .5). In conclusion, protein ingestion during and shortly after exercise does not modulate the endocrine response or muscle protein synthesis during overnight recovery.

Acute Energy Deprivation Affects Skeletal Muscle Protein Synthesis and Associated Intracellular Signaling Proteins in Physically Active Adults

To date, few studies have characterized the influence of energy deprivation on direct measures of skeletal muscle protein turnover. In this investigation, we characterized the effect of an acute, moderate energy deficit (10 d) on mixed muscle fractional synthetic rate (FSR) and associated intracellular signaling proteins in physically active adults. Eight men and 4 women participated in a 20-d, 2-phase diet intervention study: weight maintenance (WM) and energy deficient (ED; ∼80% of estimated energy requirements). Dietary protein (1.5 g · kg−1 · d−1) and fat (∼30% of total energy) were constant for WM and ED. FSR and intracellular signaling proteins were measured on d 10 of both interventions using a primed, constant infusion of [2H5]-phenylalanine and Western blotting techniques, respectively. Participants lost ∼1 kg body weight during ED (P < 0.0001). FSR was reduced ∼19% (P < 0.05) for ED (0.06 ± 0.01%/h) compared with WM (0.074 ± 0.01%/h). Protein kinase B and eukaryotic initiation factor 4E binding protein 1 phosphorylation were lower (P < 0.05) during ED compared with WM. AMP activated protein kinase phosphorylation decreased (P < 0.05) over time regardless of energy status. These findings show that FSR and associated synthetic intracellular signaling proteins are downregulated in response to an acute, moderate energy deficit in physically active adults and provide a basis for future studies assessing the impact of prolonged, and perhaps more severe, energy restriction on skeletal muscle protein turnover.

Coingestion of protein with carbohydrate during recovery from endurance exercise stimulates skeletal muscle protein synthesis in humans

Coingestion of protein with carbohydrate (CHO) during recovery from exercise can affect muscle glycogen synthesis, particularly if CHO intake is suboptimal. Another potential benefit of protein feeding is an increased synthesis rate of muscle proteins, as is well documented after resistance exercise. In contrast, the effect of nutrient manipulation on muscle protein kinetics after aerobic exercise remains largely unexplored. We tested the hypothesis that ingesting protein with CHO after a standardized 2-h bout of cycle exercise would increase mixed muscle fractional synthetic rate (FSR) and whole body net protein balance (WBNB) vs. trials matched for total CHO or total energy intake. We also examined whether postexercise glycogen synthesis could be enhanced by adding protein or additional CHO to a feeding protocol that provided 1.2 g CHO x kg(-1) x h(-1), which is the rate generally recommended to maximize this process. Six active men ingested drinks during the first 3 h of recovery that provided either 1.2 g CHO.kg(-1).h(-1) (L-CHO), 1.2 g CHO + 0.4 g protein x kg(-1) x h(-1) (PRO-CHO), or 1.6 g CHO x kg(-1) x h(-1) (H-CHO) in random order. Based on a primed constant infusion of l-[ring-(2)H(5)]phenylalanine, analysis of biopsies (vastus lateralis) obtained at 0 and 4 h of recovery showed that muscle FSR was higher (P < 0.05) in PRO-CHO (0.09 +/- 0.01%/h) vs. both L-CHO (0.07 +/- 0.01%/h) and H-CHO (0.06 +/- 0.01%/h). WBNB assessed using [1-(13)C]leucine was positive only during PRO-CHO, and this was mainly attributable to a reduced rate of protein breakdown. Glycogen synthesis rate was not different between trials. We conclude that ingesting protein with CHO during recovery from aerobic exercise increased muscle FSR and improved WBNB, compared with feeding strategies that provided CHO only and were matched for total CHO or total energy intake. However, adding protein or additional CHO to a feeding strategy that provided 1.2 g CHO x kg(-1) x h(-1) did not further enhance glycogen resynthesis during recovery.

Co-ingestion of leucine with protein does not further augment post-exercise muscle protein synthesis rates in elderly men

Leucine has been suggested to have the potential to modulate muscle protein metabolism by increasing muscle protein synthesis. The objective of this study was to investigate the surplus value of the co-ingestion of free leucine with protein hydrolysate and carbohydrate following physical activity in elderly men. Eight elderly men (mean age 73 +/- 1 years) were randomly assigned to two cross-over treatments consuming either carbohydrate and protein hydrolysate (CHO+PRO) or carbohydrate, protein hydrolysate with additional leucine (CHO+PRO+leu) after performing 30 min of standardized physical activity. Primed, continuous infusions with L-[ring-(13)C(6)]phenylalanine and L-[ring-(2)H(2)]tyrosine were applied, and blood and muscle samples were collected to assess whole-body protein turnover as well as protein fractional synthetic rate in the vastus lateralis muscle over a 6 h period. Whole-body protein breakdown and synthesis rates were not different between treatments. Phenylalanine oxidation rates were significantly lower in the CHO+PRO+leu v. CHO+PRO treatment. As a result, whole-body protein balance was significantly greater in the CHO+PRO+leu compared to the CHO+PRO treatment (23.8 (SEM 0.3) v. 23.2 (SEM 0.3) micromol/kg per h, respectively; P < 0.05). Mixed muscle fractional synthetic rate averaged 0.081 (SEM 0.003) and 0.082 (SEM 0.006) %/h in the CHO+PRO+leu and CHO+PRO treatment, respectively (NS). Co-ingestion of leucine with carbohydrate and protein following physical activity does not further elevate muscle protein fractional synthetic rate in elderly men when ample protein is ingested.

Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle

We recently showed that resistance exercise and ingestion of essential amino acids with carbohydrate (EAA+CHO) can independently stimulate mammalian target of rapamycin (mTOR) signaling and muscle protein synthesis in humans. Providing an EAA+CHO solution postexercise can further increase muscle protein synthesis. Therefore, we hypothesized that enhanced mTOR signaling might be responsible for the greater muscle protein synthesis when leucine-enriched EAA+CHOs are ingested during postexercise recovery. Sixteen male subjects were randomized to one of two groups (control or EAA+CHO). The EAA+CHO group ingested the nutrient solution 1 h after resistance exercise. mTOR signaling was assessed by immunoblotting from repeated muscle biopsy samples. Mixed muscle fractional synthetic rate (FSR) was measured using stable isotope techniques. Muscle protein synthesis and 4E-BP1 phosphorylation during exercise were significantly reduced (P < 0.05). Postexercise FSR was elevated above baseline in both groups at 1 h but was even further elevated in the EAA+CHO group at 2 h postexercise (P < 0.05). Increased FSR was associated with enhanced phosphorylation of mTOR and S6K1 (P < 0.05). Akt phosphorylation was elevated at 1 h and returned to baseline by 2 h in the control group, but it remained elevated in the EAA+CHO group (P < 0.05). 4E-BP1 phosphorylation returned to baseline during recovery in control but became elevated when EAA+CHO was ingested (P < 0.05). eEF2 phosphorylation decreased at 1 and 2 h postexercise to a similar extent in both groups (P < 0.05). Our data suggest that enhanced activation of the mTOR signaling pathway is playing a role in the greater synthesis of muscle proteins when resistance exercise is followed by EAA+CHO ingestion.

Co-ingestion Of Carbohydrate With Protein Does Not Stimulate Post-exercise Muscle Protein Synthesis Rates

Endurance athletes maximize post-exercise muscle glycogen synthesis by ingesting ample amounts of carbohydrate following exercise. In contrast, resistance athletes generally focus on protein intake during recovery to augment muscle protein anabolism. It has been suggested that both carbohydrate and protein should be ingested to maximize muscle protein synthesis rates. As many recreational athletes perform resistance type exercise for health and/or esthetic purposes, they generally prefer to restrict their caloric intake during recovery. Therefore, it is of importance to assess the need for co-ingestion of carbohydrate with protein on post-exercise muscle protein synthesis. PURPOSE: To determine the impact of the co-ingestion of different amounts of carbohydrate with protein on post-exercise muscle protein synthesis. METHODS: Ten healthy, untrained men were randomly assigned to 3 randomized cross-over trials. After 60 min of resistance exercise, subjects consumed 0.3 g·kg-1·h-1 protein hydrolysate with 0, 0.15 or 0.6 g·kg-1·h-1 carbohydrate during a 6 h recovery period (PRO, PRO+LCHO, and PRO+HCHO, respectively). Primed, continuous infusions of L-[ring-13C6]phenylalanine, L-[ring-2H2]tyrosine, and [6,6-2H2]glucose were applied, and blood and muscle samples were collected to assess whole-body protein turnover, glucose kinetics and fractional synthetic rate (FSR) in the vastus lateralis muscle over 6 h of recovery. RESULTS: Plasma insulin response was significantly higher in HCHO+PRO compared to LCHO+PRO and PRO (18.4±2.9 vs. 3.7±0.5 and 1.5±0.2 U·6h·L-1, respectively, P<0.001). Plasma glucose rate of appearance (Ra) and disappearance (Rd) increased over time in HCHO+PRO and LCHO+PRO but not in PRO. Plasma glucose Ra and Rd were substantially greater in HCHO+PRO vs. LCHO+PRO (P<0.01). Whole-body protein breakdown, synthesis and oxidation rates, as well as whole-body protein balance did not differ between trials. In accordance mixed muscle FSR did not differ between trials and averaged 0.114±0.010, 0.104±0.009% and 0.100±0.009%·h-1 in the HCHO+PRO, LCHO+PRO and PRO trial, respectively (NS). CONCLUSIONS: Co-ingestion of carbohydrate with an ample amount of protein hydrolysate (0.3 g·kg-1·h-1) does not further augment muscle protein synthesis rate during post-exercise recovery.

Androgen Therapy Induces Muscle Protein Anabolism in Older Women

Normal healthy men and women undergo a gradual loss of skeletal muscle mass and strength with advancing age. While androgens are protein anabolic in older men, the metabolic effects in older women are poorly understood. The objective of this study was to determine whether oral administration of a synthetic derivative of testosterone [oxandrolone, Oxandrin (OX)] (7.5 mg orally twice daily for 14 d) to five older women (age, 65 +/- 2 yr) would enhance skeletal muscle anabolic biomarkers including mixed muscle fractional synthetic rate (FSR), net phenylalanine balance, androgen receptor, and IGF-I protein expression at d 0, 5, and 14 of treatment. As a positive control, seven older men were examined after 14 d of OX (10 mg orally twice daily). The study was performed at the General Clinical Research Center. Fourteen days of OX significantly increased skeletal muscle FSR in older women (d 0, 0.073 +/- 0.006 vs. d 5, 0.092 +/- 0.006 vs. d 14, 0.115 +/- 0.007%/h) (P < 0.05, d 0 vs. d 14). Conversely, OX stimulated FSR in older men after only 5 d (d 0, 0.061 +/- 0.003 vs. d 5, 0.101 +/- 0.01 vs. d 14, 0.084 +/- 0.01%/h) (P < 0.05, d 0 vs. d 5). Androgen receptor expression was significantly increased in older men by d 14, but had not increased in older women. No change was noted in IGF-I expression in either group. We conclude that the skeletal muscle of older women and men responds to androgen administration, although the time course of anabolism appears to be gender specific.

Age Specific Changes in Protein Synthesis and Plasma Amino Acid Profiles Following Intact Protein Ingestion

Muscle protein synthesis is acutely stimulated by an increase in precursor availability. While young and elderly respond similarly to ingestion of a supplement containing essential amino acids, there are limited data quantifying the respective changes in plasma amino acid concentrations and protein synthesis following ingestion of a normal dietary protein source. PURPOSE: To compare changes in plasma amino acid concentrations and mixed muscle fractional synthesis rate (FSR) following ingestion of a 4 oz serving of lean beef in healthy young and elderly volunteers. METHODS: Peripheral venous blood samples and vastus lateralis muscle biopsy samples were obtained during a primed, constant infusion of L-ring- 13C6 phenylalanine phenylalanine. Plasma amino acid concentrations were measured using High Performance Liquid Chromatography (HPLC; Waters 2695 Separation Module, 2475 Multi wavelength Detector). Mixed muscle fractional synthetic rate (FSR) was calculated during the post-absorptive period and for 5 h following ingestion of a 4 oz serving of lean beef (90% lean; 30% fat) in young (n=10; 173±4 cm; 88.4±4.6yrs; 28.5±2.8 % body fat; 60.9±3.5 % lean muscle mass) and elderly (n=10; 169±3 cm; 69.9±3.8 yrs; 27.3±1.8 % body fat; 48.4±3.3 % lean muscle mass) volunteers. RESULTS: Beef ingestion increased mixed muscle FSR values in both groups by 27.9±7.5% (Young) and 29.1±9.3% (Elderly) respectively. Plasma amino acid concentrations (essential, non-essential and total) peaked approximately 100 minutes following nutrient ingestion in both young and elderly. The magnitude of the increase in plasma amino acid concentration was significantly greater in elderly individuals, reflecting a smaller plasma volume and lower lean muscle mass. CONCLUSIONS: Despite differences in precursor availability, a standard 4 oz serving of beef stimulates muscle protein synthesis in both young and elderly individuals. Further investigations are needed to examine the efficiency of muscle protein anabolism following ingestion of different amounts of dietary protein in young and elderly individuals. This project is funded (DPJ) by beef and veal producers and importers through their $1-per-head check off and was produced for the Cattlemen's Beef Board and State beef councils by the National Cattlemen's Beef Association. Support also provided by M01 RR 00073 from the National Center for Research Resources, NIH, USPHS.

Differential stimulation of muscle protein synthesis in elderly humans following isocaloric ingestion of amino acids or whey protein

To counteract the debilitating progression of sarcopenia, a protein supplement should provide an energetically efficient anabolic stimulus. We quantified net muscle protein synthesis in healthy elderly individuals (65–79 yrs) following ingestion of an isocaloric intact whey protein supplement (WY; n=8) or an essential amino acid supplement (EAA; n=7). Femoral arterio-venous blood samples and vastus lateralis muscle biopsy samples were obtained during a primed, constant infusion of L-[ring- 2H 5]phenylalanine. Net phenylalanine uptake and mixed muscle fractional synthetic rate (FSR) were calculated during the post-absorptive period and for 3.5 h following ingestion of 15 g EAA or 15 g whey. After accounting for the residual increase in the intracellular phenylalanine pool, net post-prandial phenylalanine uptake was 53.4±9.7 mg phe leg −1 (EAA) and 21.7±4.6 mg phe leg −1 (WY), ( P<0.05). Postabsorptive FSR values were 0.056±0.004% h −1 (EAA) and 0.049±0.006% h −1 (WY), ( P>0.05). Both supplements stimulated FSR ( P<0.05), but the increase was greatest in the EAA group with values of 0.088±0.011% h −1 (EAA) and 0.066±0.004% h −1 (WY), ( P<0.05). While both EAA and WY supplements stimulated muscle protein synthesis, EAAs may provide a more energetically efficient nutritional supplement for elderly individuals.

Amino Acids Stimulate Muscle Protein Synthesis In The Elderly More Effectively Than Intact Protein

PURPOSE To combat the debilitating progression of sarcopenia, a nutritional supplement should provide a calorically efficient anabolic stimulus that does not result in a compensatory reduction in voluntary food intake. We sought to quantify net muscle protein synthesis in healthy elderly individuals following bolus oral ingestion of an intact whey protein supplement (whey: n=5, 70 ± 6 yr) and an essential amino acid supplement (EAA: n= 7, 67 ± 2 yr). METHODS Femoral arterio-venous blood samples and vastus lateralis muscle biopsy samples were obtained during a primed, constant infusion of L-[ring-2H5]phenylalanine. Muscle protein kinetics and mixed muscle fractional synthetic rate (FSR) were calculated during the post-absorptive period and for 3 h following ingestion of 15g EAA or 15g whey. RESULTS EAA ingestion stimulated net phenylalanine uptake and FSR more than whey protein. Postabsorptive FSR values were 0.056 ± 0.004 %.hr−1 (EAA) and 0.053 ± 0.004 %.hr−1 (whey), p > 0.05), while postprandial FSR values increased to 0.088 ± 0.011 %.hr−1 (EAA) and 0.072 ± 0.04 %.hr−1 (whey), (p < 0.05). CONCLUSIONS Compared to an equivalent quantity of intact protein, EAAs may provide a more effective and energetically efficient anabolic nutritional supplement for elderly individuals.

The Catabolic Effects of Prolonged Inactivity and Acute Hypercortisolemia Are Offset by Dietary Supplementation

We compared the anabolic stimulus provided by an essential amino acid and carbohydrate (AA/CHO) supplement to a mixed clinical meal during bed rest (BR) and episodic hypercortisolemia ( approximately 24 microg.dl(-1)). In the experimental (EXP; n = 7) and control (CON; n = 6) groups, femoral arteriovenous blood samples and vastus lateralis biopsy samples were obtained during a primed constant infusion of l-[ring-(2)H(5)]phenylalanine and a 14-h infusion of hydrocortisone sodium succinate (60 microg.kg.h(-1)) before (pre-BR) and after (post-BR) 28 d of BR. Muscle protein kinetics were calculated during the postabsorptive state, for 2.5 h after ingestion of a meal and for 2.5 h after ingestion of an AA/CHO supplement (EXP) or placebo (CON). Postabsorptive net phenylalanine balance values were as follows: EXP, -35.14 +/- 2.93, and CON, -32.60 +/- 6.65 (pre-BR); and EXP, -32.91 +/- 5.67, and CON, -30.43 +/- 6.28 nmol phe.ml(-1).100 ml leg volume(-1) (post-BR). After AA/CHO supplementation, net phenylalanine balance improved to 33.51 +/- 8.06 (pre-BR) and 24.15 +/- 11.4 nmol phe.ml(-1).100 ml leg volume(-1) (post-BR), but remained negative after the meal. Cumulative 5.5-h mixed muscle fractional synthetic rate was greater in the EXP group pre-BR (EXP, 0.108 +/- 0.01, and CON, 0.073 +/- 0.04%.h(-1)) and post-BR (EXP, 0.111 +/- 0.015, and CON, 0.05 +/- 0.002%.h(-1)). Unlike a typical clinical meal, AA/CHO supplementation stimulated net muscle protein synthesis despite acute hypercortisolemia and prolonged inactivity.

Exogenous amino acids stimulate human muscle anabolism without interfering with the response to mixed meal ingestion

We sought to determine whether ingestion of a between-meal supplement containing 30 g of carbohydrate and 15 g of essential amino acids (CAA) altered the metabolic response to a nutritionally mixed meal in healthy, recreationally active male volunteers. A control group (CON; n = 6, 38 +/- 8 yr, 86 +/- 10 kg, 179 +/- 3 cm) received a liquid mixed meal [protein, 23.4 +/- 1.0 g (essential amino acids, 14.7 +/- 0.7 g); carbohydrate, 126.6 +/- 4.0 g; fat, 30.3 +/- 2.8 g] every 5 h (0830, 1330, 1830). The experimental group (SUP; n = 7, 36 +/- 10 yr, 87 +/- 12 kg, 180 +/- 3 cm) consumed the same meals but, in addition, were given CAA supplements (1100, 1600, 2100). Net phenylalanine balance (NB) and fractional synthetic rate (FSR) were calculated during a 16-h primed constant infusion of L-[ring-2H5]phenylalanine. Ingestion of a combination of CAA supplements and meals resulted in a greater mixed muscle FSR than ingestion of the meals alone (SUP, 0.099 +/- 0.008; CON, 0.076 +/- 0.005%/h; P < 0.05). Both groups experienced an improvement in NB after the morning (SUP, -2.2 +/- 3.3; CON, -1.5 +/- 3.5 nmol x min(-1) x 100 ml leg volume(-1)) and evening meals (SUP, -9.7 +/- 4.3; CON, -6.7 +/- 4.1 nmol x min(-1) x 100 ml leg volume(-1)). NB after CAA ingestion was significantly greater than after the meals, with values of 40.2 +/- 8.5 nmol x min(-1) x 100 ml leg volume(-1). These data indicate that CAA supplementation produces a greater anabolic effect than ingestion of intact protein but does not interfere with the normal metabolic response to a meal.

Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects

The present study was designed to determine postexercise muscle protein synthesis and whole body protein balance following the combined ingestion of carbohydrate with or without protein and/or free leucine. Eight male subjects were randomly assigned to three trials in which they consumed drinks containing either carbohydrate (CHO), carbohydrate and protein (CHO+PRO), or carbohydrate, protein, and free leucine (CHO+PRO+Leu) following 45 min of resistance exercise. A primed, continuous infusion of L-[ring-13C6]phenylalanine was applied, with blood samples and muscle biopsies collected to assess fractional synthetic rate (FSR) in the vastus lateralis muscle as well as whole body protein turnover during 6 h of postexercise recovery. Plasma insulin response was higher in the CHO+PRO+Leu compared with the CHO and CHO+PRO trials (+240 +/- 19% and +77 +/- 11%, respectively, P < 0.05). Whole body protein breakdown rates were lower, and whole body protein synthesis rates were higher, in the CHO+PRO and CHO+PRO+Leu trials compared with the CHO trial (P < 0.05). Addition of leucine in the CHO+PRO+Leu trial resulted in a lower protein oxidation rate compared with the CHO+PRO trial. Protein balance was negative during recovery in the CHO trial but positive in the CHO+PRO and CHO+PRO+Leu trials. In the CHO+PRO+Leu trial, whole body net protein balance was significantly greater compared with values observed in the CHO+PRO and CHO trials (P < 0.05). Mixed muscle FSR, measured over a 6-h period of postexercise recovery, was significantly greater in the CHO+PRO+Leu trial compared with the CHO trial (0.095 +/- 0.006 vs. 0.061 +/- 0.008%/h, respectively, P < 0.05), with intermediate values observed in the CHO+PRO trial (0.0820 +/- 0.0104%/h). We conclude that coingestion of protein and leucine stimulates muscle protein synthesis and optimizes whole body protein balance compared with the intake of carbohydrate only.

Acute response of net muscle protein balance reflects 24-h balance after exercise and amino acid ingestion.

The purpose of this study was to determine if the acute anabolic muscle response to resistance exercise and essential amino acids (EAA) reflects the response over 24 h. Seven subjects participated in the following two 24-h studies: 1) resting (REST) and 2) rest plus resistance exercise and consumption of EAA (ES). Net balance (NB) across the leg was determined for four amino acids. [(13)C(6)]phenylalanine was infused to determine mixed muscle fractional synthetic rate (FSR). Twenty-four-hour FSR was significantly greater for ES than for REST (P = 0.003). Exchange of phenylalanine across the leg was -194 +/- 74 (SE) mg for ES and -371 +/- 88 mg for REST (P = 0.07) over 24 h and 229 +/- 42 mg (ES) and 28 +/- 15 mg (REST; P < 0.01) over 3 h corresponding to exercise and EAA consumption for ES. The difference in phenylalanine exchange between REST and ES was not different for measurements over 24 and 3 h. Increases in NB during ES were primarily the result of increases in protein synthesis. Results for other amino acids were similar. The acute anabolic response of muscle to EAA intake and exercise is additive to the response at rest and thus reflects the 24-h response.