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Inactivity-mediated protein catabolism occurs in many circumstances ranging from catastrophic events such as severe illness or injury, to unique environments such as spaceflight/microgravity, to more insidious causes such as physical frailty and the progression of aging. Nevertheless, regardless of the etiology, the consequences of inactivity are readily observable and debilitating. Mechanistically, the loss of lean body mass during inactivity is the result of a chronic imbalance between muscle protein synthesis and breakdown. When inactivity is accompanied by the stress of trauma or disease, the rate of muscle protein catabolism can increase several fold. Bed rest studies in healthy volunteers provide a unique opportunity to examine the mechanisms contributing to muscle loss and evaluate strategies for intervention that may slow muscle catabolism and promote anabolism. The prerequisite for muscle protein synthesis and the most readily adaptable stimulus is dietary-derived amino acids. This review focuses on the role of amino acid supplementation in the maintenance of skeletal muscle mass during age-related and clinically mandated inactivity. [ABSTRACT FROM AUTHOR]

Abstract: 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-2H5]phenylalanine. Net phenylalanine uptake and mixed muscle fractional synthetic rate (FSR) were calculated during the post-absorptive period and for 3.5h following ingestion of 15g EAA or 15g whey. After accounting for the residual increase in the intracellular phenylalanine pool, net post-prandial phenylalanine uptake was 53.4±9.7mg pheleg−1 (EAA) and 21.7±4.6mgpheleg−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. [Copyright &y& Elsevier]

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·min-1·100 ml leg volume-1) and evening meals (SUP, -9.7 -+ 4.3; CON, -6.7 ± 4.1 nmol·min-1·100 ml leg volume-1). NB after CAA ingestion was significantly greater than after the meals, with values of 40.2 ± 8.5 nmol·min-1·100 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. [ABSTRACT FROM AUTHOR]

We recently demonstrated that muscle protein synthesis was stimulated to a similar extent in young and elderly subjects during a 3-h amino acid infusion. We sought to determine if a more practical bolus oral ingestion would also produce a similar response in young (34 ± 4 yr) and elderly (67 ± 2 yr) individuals. Arteriovenous blood samples and muscle biopsies were obtained during a primed (2.0 µmol/kg) constant infusion (0.05 µmol·kg-1·min-1 of L-[ring-²H5]phenylalanine. Muscle protein kinetics and mixed muscle fractional synthetic rate (FSR) were calculated before and after the bolus ingestion of 15 g of essential amino acids (EAA) in young (n = 6) and elderly (n = 7) subjects. After EAA ingestion, the rate of increase in femoral artery phenylalanine concentration was slower in elderly subjects but remained elevated for a longer period. EAA ingestion increased FSR in both age groups by ∼0.04%/h (P < 0.05). However, muscle intracellular (IC) phenylalanine concentration remained significantly higher in elderly subjects at the completion of the study (young: 115.6 ± 5.4 nmol/ml; elderly: 150.2 ± 19.4 nmol/ml). Correction for the free phenylalanine retained in the muscle IC pool resulted in similar net phenylalanine uptake values in the young and elderly. EAA ingestion increased plasma insulin levels in young (6.1 ± 1.2 to 21.3 ± 3.1 µIU/ml) but not in elderly subjects (3.0 ± 0.6 to 4.3 ± 0.4 µIU/ml). Despite differences in the time course of plasma phenylalanine kinetics and a greater residual IC phenylalanine concentration, amino acid supplementation acutely stimulated muscle protein synthesis in both young and elderly individuals. [ABSTRACT FROM AUTHOR]

Debilitating injury is accompanied by hypercortisolemia, muscle wasting, and disruption of the normal anabolic response to food. We sought to determine whether acute hypercortisolemia alters muscle protein metabolism following ingestion of a potent anabolic stimulus: essential amino acids (EAA). A 27-h infusion (80 µg·kg[sup -1]·h[sup -1]) of hydrocortisone sodium succinate mimicked cortisol (C) levels accompanying severe injury (>30 µg/dl), (C + AA; n = 6). The control group (AA) received intravenous saline (n = 6). Femoral arteriovenous blood samples and muscle biopsies were obtained during a primed (2.0 µmol/kg) constant infusion (0.05 µmol·kg[sup -1]·min[sup -1]) of L-[ring-²H[sub 5]]phenylalanine before and after ingestion of 15 g of EAA. Hypercortisolemia [36.5 ± 2.1 (C + AA) vs. 9.0 ± 1.0 µg/dl (AA)] increased postabsorptive arterial, venous, and muscle intracellular phenylalanine concentrations. Hypercortisolemia also increased postabsorptive and post-EAA insulin concentrations. Net protein balance was blunted (40% lower) following EAA ingestion but remained positive for a greater period of time (60 vs. 180 min) in the C + AA group. Thus, although differences in protein metabolism were evident, EAA ingestion improved muscle protein anabolism during acute hypercortisolemia and may help minimize muscle loss following debilitating injury. [ABSTRACT FROM AUTHOR]

Abstract: It is recognized that both whey protein (WY) and essential amino acids (EAA) are stimuli for muscle protein anabolism. The aim of the present study was to determine if the effects of WY ingestion on muscle protein accrual in elderly persons are due solely to its constituent EAA content. Fifteen elderly persons were randomly assigned to ingest a bolus of either 15 g of WY, 6.72 g of EAA, or 7.57 g of nonessential amino acids (NEAA). We used the leg arteriovenous model to measure the leg phenylalanine balance, which is an index of muscle protein accrual. Phenylalanine balance (nmol∙min−1∙kg lean leg mass−1) during the 3.5 hours after the bolus ingestion improved in the WY (−216 ± 14 vs −105 ± 19; P < .05) but not in the EAA (−203 ± 21 vs −172 ± 38; P > .05) or NEAA groups (−203 ± 19 vs −204 ± 21; P > .05). The insulin response (uIU∙mL−1∙210 min−1) during the same period was lower in both the NEAA (48 ± 40) and EAA (213 ± 127) when compared to the WY (1073 ± 229; P < .05). In conclusion, WY ingestion improves skeletal muscle protein accrual through mechanisms that are beyond those attributed to its EAA content. This finding may have practical implications for the formulation of nutritional supplements to enhance muscle anabolism in older individuals. [Copyright &y& Elsevier]

Physiological hyperglycemia with hyperinsulinemia reduces fat oxidation in skeletal muscle. The mechanism responsible for this decrease in fat oxidation in human muscle is not known and may contribute to the development of insulin resistance. We hypothesized that the transfer of long-chain fatty acids (LCFAs) into the mitochondria via carnitine palmitoyltransferase-1 (CPT-1) is inhibited by increased malonyl coenzyme A (malonyl-CoA) (a known potent inhibitor of CPT-1) in human muscle during hyperglycemia with hyperinsulinemia. We studied six healthy subjects after an overnight fast and during an induced 5-hour period of hyperglycemia with hyperinsulinemia. Muscle fatty acid oxidation was calculated using stable isotope methodology combined with blood sampling from the femoral artery and vein of one leg. Muscle functional CPT-1 activity was assessed by concurrently infusing an LCFA tracer and a CPT-independent medium-chain fatty acid tracer. Muscle biopsies were obtained from the vastus lateralis after the periods of fasting and hyperglycemia with hyperinsulinemia. Hyperglycemia with hyperinsulinemia decreased LCFA oxidation, but had no effect on LCFA uptake or medium-chain fatty acid oxidation across the leg. Malonyl-CoA concentration significantly increased from 0.13 +/- 0.01 to 0.35 +/- 0.07 nmol/g during hyperglycemia with hyperinsulinemia. We conclude that hyperglycemia with hyperinsulinemia increases malonyl-CoA, inhibits functional CPT-1 activity, and shunts LCFA away from oxidation and toward storage in human muscle. [ABSTRACT FROM AUTHOR]