Resistance exercise and nutrition to counteract muscle wasting.

Loss of muscle mass is an unfavourable consequence of aging and many chronic diseases. The debilitating effects of muscle loss include declines in physical function and quality of life and increases in morbidity and mortality. Loss of muscle mass is the result of a decrease in muscle protein synthesis, an increase in muscle protein degradation, or a combination of both. Much research on muscle wasting has tended to focus on preventing muscle protein breakdown, and less attention has been paid to providing adequate stimulation to increase muscle protein synthesis. In this review, we present evidence to suggest that interventions aimed at increasing muscle protein synthesis represent the most effective countermeasure for preventing, delaying, or reversing the loss of skeletal muscle mass experienced in various muscle wasting conditions. Based on results from acute and chronic studies in humans in a wide variety of wasting conditions, we propose that resistance exercise training combined with appropriately timed protein (likely leucine-rich) ingestion represents a highly effective means to promote muscle hypertrophy, and may represent a highly effective treatment strategy to counteract the muscle wasting tassociated with aging and chronic disease.

[1]  K. Tipton Nutrition for Acute Exercise-Induced Injuries , 2011, Annals of Nutrition and Metabolism.

[2]  Stuart M Phillips,et al.  Resistance exercise and appropriate nutrition to counteract muscle wasting and promote muscle hypertrophy , 2010, Current opinion in clinical nutrition and metabolic care.

[3]  B. Shenkman,et al.  Time course of ribosomal kinase activity during hindlimb unloading , 2010, Doklady Biochemistry and Biophysics.

[4]  I. Janssen Evolution of sarcopenia research. , 2010, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[5]  I. Chapman,et al.  Preventing sarcopaenia in older people. , 2010, Maturitas.

[6]  E. Volpi,et al.  Rapamycin administration in humans blocks the contraction‐induced increase in skeletal muscle protein synthesis , 2009, The Journal of physiology.

[7]  M. Rennie,et al.  Age‐related differences in the dose–response relationship of muscle protein synthesis to resistance exercise in young and old men , 2009, The Journal of physiology.

[8]  F. Nuttall,et al.  Leucine, when ingested with glucose, synergistically stimulates insulin secretion and lowers blood glucose. , 2008, Metabolism: clinical and experimental.

[9]  M. Tarnopolsky,et al.  Resistance exercise decreases eIF2Bepsilon phosphorylation and potentiates the feeding-induced stimulation of p70S6K1 and rpS6 in young men. , 2008, American journal of physiology. Regulatory, integrative and comparative physiology.

[10]  J. Layne,et al.  Resistance training and timed essential amino acids protect against the loss of muscle mass and strength during 28 days of bed rest and energy deficit. , 2008, Journal of applied physiology.

[11]  M. Sjöström,et al.  Neuromuscular training and the risk of leg injuries in female floorball players: cluster randomised controlled study , 2008, BMJ : British Medical Journal.

[12]  M. Rennie,et al.  Disassociation between the effects of amino acids and insulin on signaling, ubiquitin ligases, and protein turnover in human muscle , 2008, American journal of physiology. Endocrinology and metabolism.

[13]  M. Sheffield-Moore,et al.  Skeletal muscle protein anabolic response to resistance exercise and essential amino acids is delayed with aging. , 2008, Journal of applied physiology.

[14]  D. Chinkes,et al.  Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. , 2008, American journal of physiology. Endocrinology and metabolism.

[15]  A. Hayes,et al.  Effect of whey protein isolate on strength, body composition and muscle hypertrophy during resistance training , 2008, Current opinion in clinical nutrition and metabolic care.

[16]  Stuart M Phillips Resistance exercise: good for more than just Grandma and Grandpa's muscles. , 2007, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[17]  M. Tisdale,et al.  Effect of branched-chain amino acids on muscle atrophy in cancer cachexia. , 2007, The Biochemical journal.

[18]  I. Vogiatzis,et al.  Resistance exercise-induced increase in muscle mass correlates with p70S6 kinase phosphorylation in human subjects , 2007, European Journal of Applied Physiology.

[19]  S. B. Wilkinson,et al.  Consumption of fat-free fluid milk after resistance exercise promotes greater lean mass accretion than does consumption of soy or carbohydrate in young, novice, male weightlifters. , 2007, The American journal of clinical nutrition.

[20]  S. Fujita,et al.  Nutrient signalling in the regulation of human muscle protein synthesis , 2007, The Journal of physiology.

[21]  M. Schuster,et al.  Pharmacological treatment of geriatric cachexia: evidence and safety in perspective. , 2007, Journal of the American Medical Directors Association.

[22]  Paolo Capodaglio,et al.  Long-term strength training for community-dwelling people over 75: impact on muscle function, functional ability and life style , 2007, European Journal of Applied Physiology.

[23]  S. Fujita,et al.  Aerobic Exercise Overcomes the Age-Related Insulin Resistance of Muscle Protein Metabolism by Improving Endothelial Function and Akt/Mammalian Target of Rapamycin Signaling , 2007, Diabetes.

[24]  B. Miller Human Muscle Protein Synthesis After Physical Activity and Feeding , 2007, Exercise and sport sciences reviews.

[25]  M. Mello,et al.  Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats , 2007, BMC Cancer.

[26]  J. Schertzer,et al.  Therapeutic approaches for muscle wasting disorders. , 2007, Pharmacology & therapeutics.

[27]  Swarnali Acharyya,et al.  Cancer Cachexia Signaling Pathways Continue to Emerge Yet Much Still Points to the Proteasome , 2007, Clinical Cancer Research.

[28]  B. Nigg,et al.  Lower leg muscle atrophy in ankle osteoarthritis , 2006, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[29]  E. Blomstrand,et al.  Maximal lengthening contractions increase p70 S6 kinase phosphorylation in human skeletal muscle in the absence of nutritional supply. , 2006, American journal of physiology. Endocrinology and metabolism.

[30]  A. Hayes,et al.  Effects of supplement timing and resistance exercise on skeletal muscle hypertrophy. , 2006, Medicine and science in sports and exercise.

[31]  M. Kjaer,et al.  The effect of protein and carbohydrate supplementation on strength training outcome of rehabilitation in ACL patients , 2006, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[32]  S. Bodine mTOR signaling and the molecular adaptation to resistance exercise. , 2006, Medicine and science in sports and exercise.

[33]  D. Chinkes,et al.  Resistance exercise increases AMPK activity and reduces 4E‐BP1 phosphorylation and protein synthesis in human skeletal muscle , 2006, The Journal of physiology.

[34]  R. Wolfe The underappreciated role of muscle in health and disease. , 2006, The American journal of clinical nutrition.

[35]  I. Rieu,et al.  Leucine supplementation improves muscle protein synthesis in elderly men independently of hyperaminoacidaemia , 2006, The Journal of physiology.

[36]  R. Wolfe,et al.  A high proportion of leucine is required for optimal stimulation of the rate of muscle protein synthesis by essential amino acids in the elderly. , 2006, American journal of physiology. Endocrinology and metabolism.

[37]  M. Rennie,et al.  Protein synthesis a low priority for exercising muscle , 2006, Journal of Physiology.

[38]  F. Marino,et al.  Independent and combined effects of liquid carbohydrate/essential amino acid ingestion on hormonal and muscular adaptations following resistance training in untrained men , 2006, European Journal of Applied Physiology.

[39]  D. Layman,et al.  Leucine regulates translation initiation of protein synthesis in skeletal muscle after exercise. , 2006, The Journal of nutrition.

[40]  K. Yarasheski,et al.  Effects of progressive resistance training on body composition in frail older adults: results of a randomized, controlled trial. , 2005, The journals of gerontology. Series A, Biological sciences and medical sciences.

[41]  F. López‐Soriano,et al.  The pivotal role of cytokines in muscle wasting during cancer. , 2005, The international journal of biochemistry & cell biology.

[42]  Samuele M. Marcora,et al.  Dietary treatment of rheumatoid cachexia with β-hydroxy-β-methylbutyrate, glutamine and arginine: A randomised controlled trial , 2005 .

[43]  Paul Tempst,et al.  Phosphorylation and Functional Inactivation of TSC2 by Erk Implications for Tuberous Sclerosisand Cancer Pathogenesis , 2005, Cell.

[44]  A. Jatoi,et al.  Total parenteral nutrition in cancer patients: why and when? , 2005, Nutrition in clinical care : an official publication of Tufts University.

[45]  L. V. van Loon,et al.  Combined ingestion of protein and free leucine with carbohydrate increases postexercise muscle protein synthesis in vivo in male subjects. , 2005, American journal of physiology. Endocrinology and metabolism.

[46]  J. Babraj,et al.  Anabolic signaling deficits underlie amino acid resistance of wasting, aging muscle , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[47]  S. Kimball,et al.  Oral leucine administration stimulates protein synthesis in rat skeletal muscle. , 2005, The Journal of nutrition.

[48]  P. Delmas,et al.  Low Skeletal Muscle Mass Is Associated With Poor Structural Parameters of Bone and Impaired Balance in Elderly Men—The MINOS Study , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[49]  P. Gachon,et al.  Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[50]  R. Wolfe,et al.  Essential amino acid and carbohydrate supplementation ameliorates muscle protein loss in humans during 28 days bedrest. , 2004, The Journal of clinical endocrinology and metabolism.

[51]  N. LeBrasseur,et al.  Contraction-mediated mTOR, p70S6k, and ERK1/2 phosphorylation in aged skeletal muscle. , 2004, Journal of applied physiology.

[52]  Stuart M Phillips Protein requirements and supplementation in strength sports. , 2004, Nutrition.

[53]  P. Flakoll,et al.  Effect of β-hydroxy-β-methylbutyrate, arginine, and lysine supplementation on strength, functionality, body composition, and protein metabolism in elderly women , 2004 .

[54]  J. Wong,et al.  Long‐term oral branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma: a randomized trial , 2004, Alimentary pharmacology & therapeutics.

[55]  F. Booth,et al.  Control of the size of the human muscle mass. , 2004, Annual review of physiology.

[56]  C. Proud mTOR-mediated regulation of translation factors by amino acids. , 2004, Biochemical and biophysical research communications.

[57]  R. Wolfe,et al.  Human Muscle Protein Synthesis is Modulated by Extracellular, Not Intramuscular Amino Acid Availability: A Dose‐Response Study , 2003, The Journal of physiology.

[58]  M. Nelson,et al.  The benefits of strength training for older adults. , 2003, American journal of preventive medicine.

[59]  R. Wolfe,et al.  Essential amino acids are primarily responsible for the amino acid stimulation of muscle protein anabolism in healthy elderly adults. , 2003, The American journal of clinical nutrition.

[60]  P. Gallagher,et al.  Mitogen‐activated protein kinase (MAPK) pathway activation: effects of age and acute exercise on human skeletal muscle , 2003, The Journal of physiology.

[61]  D. Chinkes,et al.  Independent and combined effects of amino acids and glucose after resistance exercise. , 2003, Medicine and science in sports and exercise.

[62]  K. Yarasheski,et al.  Exercise treatment to counteract protein wasting of chronic diseases , 2003, Current opinion in clinical nutrition and metabolic care.

[63]  A. Kenny,et al.  Prevalence of sarcopenia and predictors of skeletal muscle mass in healthy, older men and women. , 2002, The journals of gerontology. Series A, Biological sciences and medical sciences.

[64]  C. Lang,et al.  Contribution of insulin to the translational control of protein synthesis in skeletal muscle by leucine. , 2002, American journal of physiology. Endocrinology and metabolism.

[65]  R. Wolfe,et al.  Essential amino acids and muscle protein recovery from resistance exercise. , 2002, American journal of physiology. Endocrinology and metabolism.

[66]  N. Abumrad,et al.  Reversal of cancer-related wasting using oral supplementation with a combination of β-hydroxy-β-methylbutyrate, arginine, and glutamine , 2002 .

[67]  K. Nair,et al.  Muscle protein synthesis in younger and older men. , 2002, JAMA.

[68]  S. Heymsfield,et al.  Effects of whey protein and resistance exercise on body cell mass, muscle strength, and quality of life in women with HIV , 2001, AIDS.

[69]  A. Levey,et al.  Resistance Training To Counteract the Catabolism of a Low-Protein Diet in Patients with Chronic Renal Insufficiency , 2001, Annals of Internal Medicine.

[70]  F. Maltais,et al.  Peripheral muscle wasting in chronic obstructive pulmonary disease. Clinical relevance and mechanisms. , 2001, American journal of respiratory and critical care medicine.

[71]  I. Wilson,et al.  Effect of resistance training on self-reported physical functioning in HIV infection. , 2001, Medicine and science in sports and exercise.

[72]  V. Baracos Management of muscle wasting in cancer‐associated cachexia , 2001, Cancer.

[73]  K. Kanegae,et al.  Oral supplementation of branched-chain amino acid improves nutritional status in elderly patients on chronic haemodialysis. , 2001, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[74]  R. Wolfe,et al.  Timing of amino acid-carbohydrate ingestion alters anabolic response of muscle to resistance exercise. , 2001, American journal of physiology. Endocrinology and metabolism.

[75]  M. Kjaer,et al.  Timing of postexercise protein intake is important for muscle hypertrophy with resistance training in elderly humans , 2001, The Journal of physiology.

[76]  Jeffrey M. Hausdorff,et al.  Randomized trial of progressive resistance training to counteract the myopathy of chronic heart failure. , 2001, Journal of applied physiology.

[77]  Liping Wei,et al.  Branched chain amino acids activate messenger ribonucleic acid translation regulatory proteins in human skeletal muscle, and glucocorticoids blunt this action. , 2001, The Journal of clinical endocrinology and metabolism.

[78]  R. Wolfe,et al.  The response of muscle protein anabolism to combined hyperaminoacidemia and glucose-induced hyperinsulinemia is impaired in the elderly. , 2000, The Journal of clinical endocrinology and metabolism.

[79]  K. Yarasheski,et al.  The utility of resistance exercise training and amino acid supplementation for reversing age-associated decrements in muscle protein mass and function , 2000, Current opinion in clinical nutrition and metabolic care.

[80]  S. Kimball,et al.  Leucine stimulates translation initiation in skeletal muscle of postabsorptive rats via a rapamycin-sensitive pathway. , 2000, The Journal of nutrition.

[81]  K. Häkkinen,et al.  Neuromuscular adaptation during prolonged strength training, detraining and re-strength-training in middle-aged and elderly people , 2000, European Journal of Applied Physiology.

[82]  F. Bozzetti,et al.  Effect of Total Parenteral Nutrition on the Protein Kinetics of Patients with Cancer Cachexia , 2000, Tumori.

[83]  R. Staron,et al.  Effects of high-intensity resistance training on untrained older men. I. Strength, cardiovascular, and metabolic responses. , 2000, The journals of gerontology. Series A, Biological sciences and medical sciences.

[84]  T. Yasmin,et al.  Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study. , 2000, JPEN. Journal of parenteral and enteral nutrition.

[85]  K. Yarasheski,et al.  Resistance exercise acutely increases MHC and mixed muscle protein synthesis rates in 78-84 and 23-32 yr olds. , 2000, American journal of physiology. Endocrinology and metabolism.

[86]  R. Wolfe,et al.  An oral essential amino acid-carbohydrate supplement enhances muscle protein anabolism after resistance exercise. , 2000, Journal of applied physiology.

[87]  K. Nair,et al.  Reduced synthesis of muscle proteins in chronic renal failure. , 2000, American journal of physiology. Endocrinology and metabolism.

[88]  G. Boden,et al.  Attenuation of the protein wasting associated with bed rest by branched-chain amino acids. , 1999, Nutrition.

[89]  K. Yarasheski,et al.  Resistance exercise training increases mixed muscle protein synthesis rate in frail women and men ≥76 yr old. , 1999, American journal of physiology. Endocrinology and metabolism.

[90]  R. Wolfe,et al.  Postexercise net protein synthesis in human muscle from orally administered amino acids. , 1999, American journal of physiology. Endocrinology and metabolism.

[91]  C. Lang,et al.  Regulation of protein synthesis after acute resistance exercise in diabetic rats. , 1999, American journal of physiology. Endocrinology and metabolism.

[92]  R. Wolfe,et al.  Nonessential amino acids are not necessary to stimulate net muscle protein synthesis in healthy volunteers. , 1999, The Journal of nutritional biochemistry.

[93]  J. Crowley,et al.  Increased plasma Gln and Leu Ra and inappropriately low muscle protein synthesis rate in AIDS wasting. , 1998, American journal of physiology. Endocrinology and metabolism.

[94]  C. Gibert,et al.  Weight loss as a predictor of survival and disease progression in HIV infection. Terry Beirn Community Programs for Clinical Research on AIDS. , 1998, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[95]  R. Wolfe,et al.  Exogenous amino acids stimulate net muscle protein synthesis in the elderly. , 1998, The Journal of clinical investigation.

[96]  K. Nair,et al.  Effects of aging on in vivo synthesis of skeletal muscle myosin heavy-chain and sarcoplasmic protein in humans. , 1997, American journal of physiology. Endocrinology and metabolism.

[97]  G. Biolo,et al.  An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein. , 1997, The American journal of physiology.

[98]  R. Wolfe,et al.  Mixed muscle protein synthesis and breakdown after resistance exercise in humans. , 1997, The American journal of physiology.

[99]  P. Ponikowski,et al.  Wasting as independent risk factor for mortality in chronic heart failure , 1997, The Lancet.

[100]  M. McNurlan,et al.  Whole-body protein turnover from leucine kinetics and the response to nutrition in human immunodeficiency virus infection. , 1995, The American journal of clinical nutrition.

[101]  A. Hicks,et al.  Long-term resistance training in the elderly: effects on dynamic strength, exercise capacity, muscle, and bone. , 1995, The journals of gerontology. Series A, Biological sciences and medical sciences.

[102]  Katelyn J. Smith,et al.  Changes in human muscle protein synthesis after resistance exercise. , 1992, Journal of applied physiology.

[103]  L. Lipsitz,et al.  High-intensity strength training in nonagenarians. Effects on skeletal muscle. , 1990, JAMA.

[104]  C. Scrimgeour,et al.  Increase in anterior tibialis muscle protein synthesis in healthy man during mixed amino acid infusion: studies of incorporation of [1-13C]leucine. , 1989, Clinical science.

[105]  C. Scrimgeour,et al.  Muscle wasting in emphysema. , 1988, Clinical science.

[106]  R. Souhami,et al.  Protein synthesis in muscle measured in vivo in cachectic patients with cancer. , 1984, British medical journal.

[107]  Joseph R. Bertino,et al.  Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. , 1980, The American journal of medicine.

[108]  A. Hicks,et al.  Weight training to activities of daily living: helping older adults make a connection. , 2006, Medicine and science in sports and exercise.

[109]  S. Kimball,et al.  Signaling pathways and molecular mechanisms through which branched-chain amino acids mediate translational control of protein synthesis. , 2006, The Journal of nutrition.

[110]  K. Yarasheski,et al.  Resistance exercise training reduces hypertriglyceridemia in HIV-infected men treated with antiviral therapy. , 2001, Journal of applied physiology.

[111]  S. Kimball,et al.  Orally administered leucine stimulates protein synthesis in skeletal muscle of postabsorptive rats in association with increased eIF4F formation. , 2000, The Journal of nutrition.

[112]  J. Kopple Pathophysiology of protein-energy wasting in chronic renal failure. , 1999, The Journal of nutrition.

[113]  R. Wolfe,et al.  Resistance training reduces the acute exercise-induced increase in muscle protein turnover. , 1999, American journal of physiology. Endocrinology and metabolism.

[114]  F. Bozzetti,et al.  Effects of cachexia due to cancer on whole body and skeletal muscle protein turnover , 1998, Cancer.

[115]  R. Marcus,et al.  Muscle strength and fiber adaptations to a year-long resistance training program in elderly men and women. , 1994, Journal of gerontology.