Elderly Men Show a Diminished Sensitivity of the Dose Response of Muscle Protein Synthesis to Essential Amino Acids (EAA) Compared to Young Men

Plant-sourced proteins offer environmental and health benefits, and research increasingly includes them in study formulas. However, plant-based proteins have less of an anabolic effect than animal proteins due to their lower digestibility, lower essential amino acid content (especially leucine), and deficiency in other essential amino acids, such as sulfur amino acids or lysine. Thus, plant amino acids are directed toward oxidation rather than used for muscle protein synthesis. In this review, we evaluate the ability of plant- versus animal-based proteins to help maintain skeletal muscle mass in healthy and especially older people and examine different nutritional strategies for improving the anabolic properties of plant-based proteins. Among these strategies, increasing protein intake has led to a positive acute postprandial muscle protein synthesis response and even positive long-term improvement in lean mass. Increasing the quality of protein intake by improving amino acid composition could also compensate for the lower anabolic potential of plant-based proteins. We evaluated and discussed four nutritional strategies for improving the amino acid composition of plant-based proteins: fortifying plant-based proteins with specific essential amino acids, selective breeding, blending several plant protein sources, and blending plant with animal-based protein sources. These nutritional approaches need to be profoundly examined in older individuals in order to optimize protein intake for this population who require a high-quality food protein intake to mitigate age-related muscle loss.

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Postexercise net protein synthesis in human muscle from orally administered amino acids

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1999.276.4.e628 ◽

1999 ◽

Vol 276 (4) ◽

pp. E628-E634 ◽

Cited By ~ 124

Author(s):

Kevin D. Tipton ◽

Arny A. Ferrando ◽

Stuart M. Phillips ◽

David Doyle ◽

Robert R. Wolfe

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Amino Acid ◽

Resistance Exercise ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Random Order ◽

Essential Amino Acids ◽

Constant Infusion ◽

Protein Balance

We examined the response of net muscle protein synthesis to ingestion of amino acids after a bout of resistance exercise. A primed, constant infusion ofl-[ ring-2H5]phenylalanine was used to measure net muscle protein balance in three male and three female volunteers on three occasions. Subjects consumed in random order 1 liter of 1) a mixed amino acid (40 g) solution (MAA), 2) an essential amino acid (40 g) solution (EAA), and 3) a placebo solution (PLA). Arterial amino acid concentrations increased ∼150–640% above baseline during ingestion of MAA and EAA. Net muscle protein balance was significantly increased from negative during PLA ingestion (−50 ± 23 nmol ⋅ min−1 ⋅ 100 ml leg volume−1) to positive during MAA ingestion (17 ± 13 nmol ⋅ min−1 ⋅ 100 ml leg volume−1) and EAA (29 ± 14 nmol ⋅ min−1 ⋅ 100 ml leg volume−1; P < 0.05). Because net balance was similar for MAA and EAA, it does not appear necessary to include nonessential amino acids in a formulation designed to elicit an anabolic response from muscle after exercise. We concluded that ingestion of oral essential amino acids results in a change from net muscle protein degradation to net muscle protein synthesis after heavy resistance exercise in humans similar to that seen when the amino acids were infused.

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The impact of delivery profile of essential amino acids upon skeletal muscle protein synthesis in older men: clinical efficacy of pulse vs. bolus supply

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00112.2015 ◽

2015 ◽

Vol 309 (5) ◽

pp. E450-E457 ◽

Cited By ~ 26

Author(s):

W. Kyle Mitchell ◽

Bethan E. Phillips ◽

John P. Williams ◽

Debbie Rankin ◽

Jonathan N. Lund ◽

...

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Blood Flow ◽

Protein Synthesis ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Older Men ◽

Essential Amino Acids ◽

Low Amplitude ◽

The Impact

Essential amino acids (EAA) are responsible for skeletal muscle anabolic effects after nutrient intake. The pattern of appearance of EAA in blood, e.g., after intake of “slow” or “fast” protein sources or in response to grazing vs. bolus feeding patterns, may impact anabolism. However, the influence of this on muscle anabolism is poorly understood, particularly in older individuals. We determined the effects of divergent feeding profiles of EAA on blood flow, anabolic signaling, and muscle protein synthesis (MPS) in older men. Sixteen men (∼70 yr) consumed EAA either as a single dose (bolus, 15 g; n = 8) or as small repeated fractions (pulse, 4 × 3.75 g every 45 min; n = 8) during 13C6 phenylalanine infusion. Repeated blood samples and muscle biopsies permitted measurement of fasting and postprandial plasma EAA, insulin, anabolic signaling, and MPS. Muscle blood flow was assessed by contrast-enhanced ultrasound (Sonovue). Bolus achieved rapid insulinemia (12.7 μiU/ml 25-min postfeed), essential aminoacidemia (∼3,000 μM, 45–65 min postfeed), and mTORC1 activity; pulse achieved attenuated insulin responses, gradual low-amplitude aminoacidemia (∼1,800 μM 80–195 min after feeding), and undetectable mTORC1 signaling. Despite this, equivalent anabolic responses were observed: fasting FSRs of 0.051 and 0.047%/h (bolus and pulse, respectively) increased to 0.084 and 0.073%/h, respectively. Moreover, pulse led to sustainment of MPS beyond 180 min, when bolus MPS had returned to basal rates. We detected no benefit of rapid aminoacidemia in this older population despite enhanced anabolic signaling and greater overall EAA exposure. Rather, apparent delayed onset of the “muscle-full” effect permitted identical MPS following low-amplitude-sustained EAA exposure.

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Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling

Journal of Applied Physiology ◽

10.1152/japplphysiol.91397.2008 ◽

2009 ◽

Vol 106 (4) ◽

pp. 1374-1384 ◽

Cited By ~ 175

Author(s):

Micah J. Drummond ◽

Hans C. Dreyer ◽

Christopher S. Fry ◽

Erin L. Glynn ◽

Blake B. Rasmussen

Keyword(s):

Skeletal Muscle ◽

Amino Acids ◽

Protein Synthesis ◽

Resistance Exercise ◽

Human Skeletal Muscle ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Essential Amino Acids ◽

Skeletal Muscle Protein ◽

Mtorc1 Signaling

In this review we discuss current findings in the human skeletal muscle literature describing the acute influence of nutrients (leucine-enriched essential amino acids in particular) and resistance exercise on muscle protein synthesis and mammalian target of rapamycin complex 1 (mTORC1) signaling. We show that essential amino acids and an acute bout of resistance exercise independently stimulate human skeletal muscle protein synthesis. It also appears that ingestion of essential amino acids following resistance exercise leads to an even larger increase in the rate of muscle protein synthesis compared with the independent effects of nutrients or muscle contraction. Until recently the cellular mechanisms responsible for controlling the rate of muscle protein synthesis in humans were unknown. In this review, we highlight new studies in humans that have clearly shown the mTORC1 signaling pathway is playing an important regulatory role in controlling muscle protein synthesis in response to nutrients and/or muscle contraction. We propose that essential amino acid ingestion shortly following a bout of resistance exercise is beneficial in promoting skeletal muscle growth and may be useful in counteracting muscle wasting in a variety of conditions such as aging, cancer cachexia, physical inactivity, and perhaps during rehabilitation following trauma or surgery.

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Role of specific dietary amino acids in clinical conditions

British Journal Of Nutrition ◽

10.1017/s0007114512002358 ◽

2012 ◽

Vol 108 (S2) ◽

pp. S139-S148 ◽

Cited By ~ 34

Author(s):

Renate Jonker ◽

Mariëlle P. K. J. Engelen ◽

Nicolaas E. P. Deutz

Keyword(s):

Amino Acids ◽

Protein Synthesis ◽

Amino Acid ◽

Muscle Wasting ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Essential Amino Acids ◽

Dietary Proteins ◽

Disease States ◽

Stimulation Of

In a variety of chronic and acute disease states, alterations in protein synthesis, breakdown and protein turnover rates occur that are related to the loss of body protein and skeletal muscle wasting. A key observation is the stimulation of protein breakdown in muscle and the stimulation of protein synthesis in the splanchnic area; mainly liver. An altered splanchnic extraction of amino acids as well as an anabolic resistance to dietary protein, related to stress, disuse and aging play a key role in the pathogenesis of muscle wasting in these conditions. To overcome these factors, specific dietary protein and amino acid diets have been introduced. The main focus of these diets is the quantity and quality of dietary proteins and whether a balanced mixture or solely dietary essential amino acids are required with or without higher intake levels of specific amino acids. Specifically in cancer patients, stimulated muscle protein synthesis has been obtained by increasing the amount of protein in a meal and by providing additional leucine. Also in other chronic diseases such as chronic obstructive pulmonary disease and cystic fibrosis, meals with specific dietary proteins and specific combinations of dietary essential amino acids are able to stimulate anabolism. In acute diseases, a special role for the amino acid arginine and its precursor citrulline as anabolic drivers has been observed. Thus, there is growing evidence that modifying the dietary amino acid composition of a meal will positively influence the net balance between muscle protein synthesis and breakdown, leading to muscle protein anabolism in a variety of chronic and acute disease states. Specific amino acids with anabolic potential are leucine, arginine and citrulline.

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