Essential amino acid supplementation in patients following total knee arthroplasty.

BACKGROUND By the year 2030, 3.48 million older U.S. adults are projected to undergo total knee arthroplasty (TKA). Following this surgery, considerable muscle atrophy occurs, resulting in decreased strength and impaired functional mobility. Essential amino acids (EAAs) have been shown to attenuate muscle loss during periods of reduced activity and may be beneficial for TKA patients. METHODS We used a double-blind, placebo-controlled, randomized clinical trial with 28 older adults undergoing TKA. Patients were randomized to ingest either 20 g of EAAs (n = 16) or placebo (n = 12) twice daily between meals for 1 week before and 2 weeks after TKA. At baseline, 2 weeks, and 6 weeks after TKA, an MRI was performed to determine mid-thigh muscle and adipose tissue volume. Muscle strength and functional mobility were also measured at these times. RESULTS TKA patients receiving placebo exhibited greater quadriceps muscle atrophy, with a -14.3 ± 3.6% change from baseline to 2 weeks after surgery compared with -3.4 ± 3.1% for the EAA group (F = 5.16, P = 0.036) and a -18.4 ± 2.3% change from baseline to 6 weeks after surgery for placebo versus -6.2 ± 2.2% for the EAA group (F = 14.14, P = 0.001). EAAs also attenuated atrophy in the nonoperated quadriceps and in the hamstring and adductor muscles of both extremities. The EAA group performed better at 2 and 6 weeks after surgery on functional mobility tests (all P < 0.05). Change in quadriceps muscle atrophy was significantly associated with change in functional mobility (F = 5.78, P = 0.021). CONCLUSION EAA treatment attenuated muscle atrophy and accelerated the return of functional mobility in older adults following TKA. TRIAL REGISTRATION Clinicaltrials.gov NCT00760383.

[1]  H. Donald,et al.  Mixed‐Effects Regression Models for Continuous Outcomes , 2006 .

[2]  J. Katz,et al.  Knee range of motion after total knee arthroplasty: how important is this as an outcome measure? , 2003, The Journal of arthroplasty.

[3]  R. Marcus,et al.  The Long‐Term Contribution of Muscle Activation and Muscle Size to Quadriceps Weakness Following Total Knee Arthroplasty , 2009, Journal of geriatric physical therapy.

[4]  D. Chinkes,et al.  Amino acid supplementation increases lean body mass, basal muscle protein synthesis, and insulin-like growth factor-I expression in older women. , 2009, The Journal of clinical endocrinology and metabolism.

[5]  M. Brown,et al.  The relationship of strength to function in the older adult. , 1995, The journals of gerontology. Series A, Biological sciences and medical sciences.

[6]  Lynn Snyder-Mackler,et al.  Early Postoperative Measures Predict 1- and 2-Year Outcomes After Unilateral Total Knee Arthroplasty: Importance of Contralateral Limb Strength , 2010, Physical Therapy.

[7]  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.

[8]  P. Dieppe,et al.  Total knee replacement: is it really an effective procedure for all? , 2007, The Knee.

[9]  Abbey C. Thomas,et al.  Importance of Attenuating Quadriceps Activation Deficits After Total Knee Arthroplasty , 2012, Exercise and sport sciences reviews.

[10]  L. Snyder-Mackler,et al.  Altered loading during walking and sit‐to‐stand is affected by quadriceps weakness after total knee arthroplasty , 2005, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[11]  L. Snyder-Mackler,et al.  Quadriceps strength and the time course of functional recovery after total knee arthroplasty. , 2005, The Journal of orthopaedic and sports physical therapy.

[12]  N. Cook,et al.  A prospective study of incident comprehensive medical home care use among the elderly. , 1988, American journal of public health.

[13]  R. Marcus,et al.  Intramuscular adipose tissue and central activation in older adults , 2012, Muscle & nerve.

[14]  J. Kalbfleisch,et al.  Between- and within-cluster covariate effects in the analysis of clustered data. , 1998, Biometrics.

[15]  E. Volpi,et al.  Role of Protein and Amino Acids in the Pathophysiology and Treatment of Sarcopenia , 2005, Journal of the American College of Nutrition.

[16]  M. Conditt,et al.  Does Total Knee Replacement Restore Normal Knee Function? , 2005, Clinical orthopaedics and related research.

[17]  R. Lawson,et al.  The effect of unselected post-operative nutritional supplementation on nutritional status and clinical outcome of orthopaedic patients. , 2003, Clinical nutrition.

[18]  M. Cesari,et al.  RECOMMENDATIONS FROM THE INTERNATIONAL WORKING GROUP ON SARCOPENIA , 2013 .

[19]  C. Brot,et al.  Early changes in muscle strength after total knee arthroplasty. A 6-month follow-up of 30 knees. , 1999, Acta orthopaedica Scandinavica.

[20]  S. Kurtz,et al.  Projections of primary and revision hip and knee arthroplasty in the United States from 2005 to 2030. , 2007, The Journal of bone and joint surgery. American volume.

[21]  S M Kurtz,et al.  Economic Burden of Revision Hip and Knee Arthroplasty in Medicare Enrollees , 2006, Clinical orthopaedics and related research.

[22]  Rebecca R. Miller Total , 2014, Definitions.

[23]  L. Ferrucci,et al.  International working group on Sarcopenia , 2011 .

[24]  S. Kritchevsky,et al.  The loss of skeletal muscle strength, mass, and quality in older adults: the health, aging and body composition study. , 2006, The journals of gerontology. Series A, Biological sciences and medical sciences.

[25]  A. Newman,et al.  Attenuation of skeletal muscle and strength in the elderly: The Health ABC Study. , 2001, Journal of applied physiology.

[26]  Steven Kurtz,et al.  Prevalence of primary and revision total hip and knee arthroplasty in the United States from 1990 through 2002. , 2005, The Journal of bone and joint surgery. American volume.

[27]  M. Nalls,et al.  Reduced physical activity increases intermuscular adipose tissue in healthy young adults. , 2007, The American journal of clinical nutrition.

[28]  Matthew J. McAuliffe,et al.  Medical Image Processing, Analysis and Visualization in clinical research , 2001, Proceedings 14th IEEE Symposium on Computer-Based Medical Systems. CBMS 2001.

[29]  S. Kurtz,et al.  International survey of primary and revision total knee replacement , 2011, International Orthopaedics.

[30]  Robert Ross,et al.  Low Relative Skeletal Muscle Mass (Sarcopenia) in Older Persons Is Associated with Functional Impairment and Physical Disability , 2002, Journal of the American Geriatrics Society.

[31]  F. Hartgens,et al.  Prolonged leucine supplementation does not augment muscle mass or affect glycemic control in elderly type 2 diabetic men. , 2011, The Journal of nutrition.

[32]  M. Rennie,et al.  Facts, noise and wishful thinking: muscle protein turnover in aging and human disuse atrophy , 2010, Scandinavian journal of medicine & science in sports.

[33]  P. Stratford,et al.  Modeling early recovery of physical function following hip and knee arthroplasty , 2006, BMC musculoskeletal disorders.

[34]  R. Marcus,et al.  Total knee arthroplasty: muscle impairments, functional limitations, and recommended rehabilitation approaches. , 2008, The Journal of orthopaedic and sports physical therapy.

[35]  R Ross,et al.  Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content. , 2000, Journal of applied physiology.

[36]  Ronenn Roubenoff,et al.  The Healthcare Costs of Sarcopenia in the United States , 2004, Journal of the American Geriatrics Society.

[37]  Lynn Snyder-Mackler,et al.  Improved function from progressive strengthening interventions after total knee arthroplasty: a randomized clinical trial with an imbedded prospective cohort. , 2009, Arthritis and rheumatism.

[38]  L. V. van Loon,et al.  Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men. , 2009, The American journal of clinical nutrition.

[39]  D. Matthews Observations of branched-chain amino acid administration in humans. , 2005, The Journal of nutrition.

[40]  R. J. Johnson,et al.  The risk of nursing home placement and subsequent death among older adults. , 1992, Journal of gerontology.

[41]  D E Krebs,et al.  Quadriceps muscle strength and dynamic stability in elderly persons. , 1999, Gait & posture.

[42]  Stuart M Phillips,et al.  Alterations of protein turnover underlying disuse atrophy in human skeletal muscle. , 2009, Journal of applied physiology.

[43]  R. Lawson,et al.  Compliance of orthopaedic patients with postoperative oral nutritional supplementation. , 2000, Clinical nutrition.

[44]  P. Fadel,et al.  Simvastatin impairs exercise training adaptations. , 2013, Journal of the American College of Cardiology.

[45]  Alan C. Evans,et al.  A nonparametric method for automatic correction of intensity nonuniformity in MRI data , 1998, IEEE Transactions on Medical Imaging.

[46]  Stuart M Phillips,et al.  Two weeks of reduced activity decreases leg lean mass and induces "anabolic resistance" of myofibrillar protein synthesis in healthy elderly. , 2013, The Journal of clinical endocrinology and metabolism.

[47]  Austin D Hocker,et al.  Proteins regulating cap-dependent translation are downregulated during total knee arthroplasty. , 2012, American journal of physiology. Regulatory, integrative and comparative physiology.

[48]  W. Frontera,et al.  Aging of skeletal muscle: a 12-yr longitudinal study. , 2000, Journal of applied physiology.

[49]  L. Woodhouse,et al.  Functional ability perceived by individuals following total knee arthroplasty compared to age-matched individuals without knee disability. , 1998, The Journal of orthopaedic and sports physical therapy.

[50]  Austin D Hocker,et al.  Endoplasmic reticulum stress activation during total knee arthroplasty , 2013, Physiological reports.

[51]  Lynn Snyder-Mackler,et al.  Quadriceps strength and volitional activation before and after total knee arthroplasty for osteoarthritis , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[52]  L. Snyder-Mackler,et al.  Early quadriceps strength loss after total knee arthroplasty. The contributions of muscle atrophy and failure of voluntary muscle activation. , 2005, The Journal of bone and joint surgery. American volume.

[53]  C. Goldsmith,et al.  Muscle Weakness and Falls in Older Adults: A Systematic Review and Meta‐Analysis , 2004, Journal of the American Geriatrics Society.

[54]  Dan K Ramsey,et al.  Examining outcomes from total knee arthroplasty and the relationship between quadriceps strength and knee function over time. , 2008, Clinical biomechanics.

[55]  Austin D Hocker,et al.  MAFbx, MuRF1, and the stress-activated protein kinases are upregulated in muscle cells during total knee arthroplasty. , 2012, American journal of physiology. Regulatory, integrative and comparative physiology.

[56]  C. Senesac,et al.  Relationships of thigh muscle contractile and non-contractile tissue with function, strength, and age in boys with Duchenne muscular dystrophy , 2012, Neuromuscular Disorders.

[57]  P. Thompson,et al.  Effect of Statins on Skeletal Muscle Function , 2012, Circulation.

[58]  R. Marcus,et al.  Intramuscular adipose tissue attenuates gains in muscle quality in older adults at high risk for falling. A brief report , 2013, The journal of nutrition, health & aging.

[59]  I. Rieu,et al.  A leucine‐supplemented diet restores the defective postprandial inhibition of proteasome‐dependent proteolysis in aged rat skeletal muscle , 2005, The Journal of physiology.

[60]  S. Fujita,et al.  Essential amino acid and carbohydrate ingestion before resistance exercise does not enhance postexercise muscle protein synthesis. , 2009, Journal of applied physiology.

[61]  L. Ferrucci,et al.  Hospital diagnoses, Medicare charges, and nursing home admissions in the year when older persons become severely disabled. , 1997, JAMA.

[62]  E. Melanson,et al.  Nitrogen balance in older individuals in energy balance depends on timing of protein intake. , 2010, The journals of gerontology. Series A, Biological sciences and medical sciences.

[63]  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.

[64]  Larry E. Davis,et al.  A Brief Report , 2002 .

[65]  P. Gachon,et al.  Whole body protein breakdown is less inhibited by insulin, but still responsive to amino acid, in nondiabetic elderly subjects. , 2004, The Journal of clinical endocrinology and metabolism.

[66]  Sandrine Andrieu,et al.  Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia. , 2011, Journal of the American Medical Directors Association.