SARCOPENIA FRAILTY AND PROTEINS ALFONSO J. CRUZ-JENTOFT SERVICIO DE GERIATRÍA HOSPITAL UNIVERSITARIO RAMÓN Y CAJAL (IRICYS) UNIVERSIDAD EUROPEA DE MADRID MADRID, SPAIN
THERE IS NO UNIVERSALLY AGREED DEFINITION OF SARCOPENIA THERE IS NOT UNIVERSALLY AGREED DEFINITION OF FRAILTY
THERE IS NO UNIVERSALLY AGREED DEFINITION OF ALZHEIMER S DISEASE 1907, Alois Alzheimer: A peculiar disease of the cerebral cortex 1984, NINCDS-ADRDA criteria 1994, DSM- IV Several versions of ICD 2010, IWG New Research Criteria for the Diagnosis of AD 2011, NIA-AA
DEFINITIONS OF FRAILTY AND SARCOPENIA Sarcopenia EWGSOP (2010): 5039 citations IWGS (2011): 1413 citations FNIH (2014): 403 citations Frailty Frieds definition (2001): 9853 citations Rockwoods definition (2005): 2038 citations NIA-AA (2012): 427 citations Source: Google Academics, accessed September 4th, 2018
SARCOPENIA Acute or chronic muscle failure
SARCOPENIA: FIRST STEPS Conference on Nutritional Status and Body Composition Oct 19-21, 1988 I noted then that no decline with age is as dramatic or potentially more significant than the decline in lean body mass. In fact, there may be no single feature of age-related decline more striking than the decline in lean body mass in affecting ambulation, mobility, energy intake, overall nutrient intake and status, independence and breathing. I suggested that if this phenomenon were to be taken seriously, we had to give it a name. Rosenberg IH. Sarcopenia: Origins and Clinical Relevance. J Nutrition, 1997; 127:990S-991S
LOW SKELETAL BODY MASS AND AGE Janssen I et al. Low Relative Skeletal Muscle Mass (Sarcopenia) in Older Persons Is Associated with Functional Impairment and Physical Disability. J Am Geriatr Soc 2002
The importance of muscle strength
April 2010 April 2010 May 2011 July 2011
EWGSOP DEFINITION OF SARCOPENIA Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength with a risk of adverse outcomes such as physical disability, poor quality of life and death. Low muscle mass Low muscle strenght Low physical performance Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis. Report of the European Working Group on Sarcopenia in Older People. Age Ageing. 2010
HUMAN MUSCLES 600 muscles in human body Skeletal muscles: 40-45% of total body mass 55% of skeletal muscle mass in lower limbs 50% of total body protein is in muscles Frontera WR et al. In: Physical Medicine&Rehabilitation. DeLisa JA (ed). LWW 2005
CONCEPTUAL ADVANCES IN SARCOPENIA Muscle function Syndromic approach Adverse outcomes Degrees of severity
A NEW UNDERSTANDING OF SARCOPENIA Acute and chronic muscle insufficiency Cruz-Jentoft AJ. Eur Geriatr Med 2016
CLASSIFICATION OF SARCOPENIA Secondary Activity related Bed rest Sedentary lifestyle Deconditioning Primary Age-related Nutrition related Inadequate diet Malabsortion Gastrointestinal disorders Drug induced anorexia Disease related Advanced organ failure Inflamatory diseases Malignancy Endocrine diseases
ADVERSE OUTCOMES Dodds RM, Sayer AA. Age Ageing. 2016 Sep;45(5):570-1.
FRAILTY Vulnerability to adverse outcomes
SPOT THE FRAIL identify pre-frail older people in the community an old, demented, dependent, very frailwoman a frail old lady still living on her own
THE CONCEPT OF FRAILTY my strengths, due to an advanced age, are no longer suited to an adequate exercise of the Petrine ministry. both strength of mind and body are necessary, strength which in the last few months, has deteriorated in me to the extent that I have had to recognize my incapacity to adequately fulfil the ministry entrusted to me.
THE CONCEPT OF FRAILTY We do not grow stronger as the years go on. The accumulation of sufferings and sorrows weakens our capacity to endure more sufferings and sorrows, and since sufferings and sorrows are inevitable, even a small setback late in life can resound with the same force as a major tragedy when we are young.
DEFINITION OF FRAILTY A biologic syndrome of decreased reserve and resistance to stressors, resulting from cumulative declines across multiple physiologic systems, and causing vulnerability to adverse outcomes. This concept distinguishes frailty from disability. Frailty: A concept linked to the personas a whole Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146-156.
THE PHENOTYPE OF PHYSICAL FRAILTY Unintentional weight loss Self-reported exhaustion Weakness Slow walking speed Low physical activity level Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146-156.
THE CYCLE OF FRAILTY AND SARCOPENIA
A LIFE COURSE MODEL OF SARCOPENIA AND DISABILITY Frailty Disability Sayer AA et al. The developmental origins of sarcopenia. J Nutr Health Aging. 2008 Aug-Sep;12(7):427-32.
SARCOPENIA AND PHYSICAL FRAILTY Rizzoli R, et al. Quality of life in sarcopenia and frailty. Calcif Tissue Int. 2013.
FRAILTY AND SARCOPENIA ARE REVERSIBLE Nutrition may have a role in reversibility of frailty and sarcopenia Gill TM et al. Transitions between frailty states among community-living older persons. Arch Intern Med. 2006
NUTRITION Proteins and other nutrients (and don t forget exercise)
PROTEIN INTAKE IS ASSOCIATED WITH LOSS OF MUSCLE MASS Proteins g/kg/d 0.7 0.7 0.8 0.9 1.1 Houston D K et al. Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the Health, Aging, and Body Composition (Health ABC) Study. Am J Clin Nutr 2008
REDUCED PROTEIN INTAKE PREDICTS INCIDENT FRAILTY Houston D K et al. Dietary protein intake is associated with lean mass change in older, community-dwelling adults: the Health, Aging, and Body Composition (Health ABC) Study. Am J Clin Nutr 2008
HEALTHY DIET IS INVERSELY ASSOCIATED WITH DEVELOPMENT OF FRAILTY Design: 690 community residents in Tuscany, Italy, 65 years, over 6-year period Results: Adherence to Mediterranean-style diet was associated with lower odds of developing frailty (OR=0.30; 95% CI, 0.14, 0.66). Adherence to Mediterranean diet at baseline was also associated with reduced risk of low physical activity (OR=0.62; 95% CI, 0.40, 0.96) and slow walking speed (OR=0.48; CI, 0.27, 0.86). No associations were observed for other frailty components like physical exhaustion or poor muscle strength. A Mediterranean-style diet may reduce the odds of developing frailty. Talegawkar SA, et al. J Nutr. 2012;142:2161-2166. 29
REVIEW OF EVIDENCE 1. Protein needs for older people in good health 2. Protein needs for older people with specific acute or chronic diseases 3. Role of exercise along with dietary protein for recovering and maintaining muscle strength and function in older people 4. Practical aspects of providing dietary protein (ie, source and quality of dietary proteins, timing of protein intake, and intake of protein-sparing energy) 5. Use of functional outcomes to assess the impact of age- and disease-related muscle l oss and the effects of interventions.
PROT-AGE RECOMMENDATIONS HEALTHY OLDER ADULTS Bauer J, et al. J Am Med Dir Assoc. 2013
PROT-AGE RECOMMENDATIONS GERIATRIC PATIENTS WITH ACUTE OR CHRONIC CONDITIONS PROT-AGE recommendations for protein levels in geriatric patients with specific acute or chronic diseases The amount of additional dietary protein or supplemental protein needed depends on the disease, its severity, the patient s nutritional status prior to disease, as well as the disease impact on the patient s nutritional status. Most older adults who have an acute or chronic disease need more dietary protein (ie, 1.2e1.5 g/kg BW/d); people with severe illness or injury or with marked malnutrition may need as much as 2.0 g/kg BW/d. Older people with severe kidney disease (ie, estimated glomerular filtration rate [GFR] < 30 ml/min/1.73m 2 ) who are not on dialysis are an exception to the high-protein rule; these individuals need to limit protein intake.
PROT-AGE RECOMMENDATIONS PROTEIN QUALITY PROT-AGE recommendations on dietary protein and amino acid quality for older people The list of indispensable amino acids is qualitatively identical for young and old adults. There is no evidence that protein digestion and absorption capacities change significantly with aging. Fast proteins may have some benefits over slow proteins in muscle protein metabolism. Dietary enrichment with leucine or a mixture of branched-chain amino acids may help enhance muscle mass and muscle function, but further studies are needed to support specific recommendations. b-hmb may attenuate muscle loss and increase muscle mass and strength in older people, but further studies are needed to support specific recommendations. Creatine supplementation may be justified for older people, especially those who are creatine-deficient or at high risk of deficiency.
PROT-AGE SUMMARY
ESPEN EXPERT GROUP PROTEIN INTAKE IN OLDER PEOPLE Fig. 1. Protein status: factors leading to lower protein intake in older persons.
ESPEN EXPERT GROUP PROTEIN NEEDS IN OLDER PEOPLE Fig. 2. Protein status: factors leading to higher protein needs in older persons.
ESPEN EXPERT GROUP MAINTAINING MUSCLE HEALTH Dietary protein intake Older adults have greater protein needs to compensate for anabolic resistance and hypermetabolic disease. Older adults may also have decreased intake due to age-related appe te loss, medical condi ons, financial limits. Op mal intake of at least 1.0 to 1.5 g protein/kg BW/day is recommended; individual needs depend upon the severity of malnutri on risk. Exercise Regular exercise helps maintain skeletal muscle strength and func on in older adults. Resistance training has limited but posi ve e ects on recovery of muscle in older people. A combina on of resistance training and adequate dietary protein/amino acid intake for healthy muscle aging is recommended.
PROTEIN INTAKE IN FUNCTIONALLY LIMITED ADULTS Design: RCT, 6 months, 2x2, 0.8 vs 1.3 g protein (+/- testosterone) 92 men with functional limitations Results: Protein intake exceeding the RDA did not increase LBM, muscle performance, physical function, or well-being measures Bhasin S, et al. JAMA Intern Med. 2018 39
SUPPLEMENTATION WITH ONS W/WO INCREASED PROTEINS AND HBM Design: A 10 Multicenter RCT, 24 weeks of usual ONS vs specific ONS Leg Strength (Nm) 7.5 5 2.5 0-2.5-5 (-2, 10)* Severe Sarcopenia (-4, 10)* (-1, 10) Sarcopenia Normal Gait (2, 10) p=0.032 (-2, 8)* (-4, 8) Sarcopenia Normal Grip 330 sarcopenic, malnourished older subjects Results: Both groups improved all measures of muscle strength and physical performance Cramer JT, et al. J Am Med Dir Assoc. 2016. Those with less severe sarcopenia benefited faster from a modified composition of ONS 40
SUPPLEMENTATION WITH VITAMIN D AND LEUCINE-ENRICHED WHEY PROTEIN Design: Fig. 2. Change (kg) in appendicular muscle mass from baseline to week 13 follow-up. *The raw mean change from baseline to week 13 and SE. The P value represents the time treatment interaction derived from a mixed model (MMRM) adjusting for age, sex, and baseline protein intake. Multicenter RCT, 24 weeks of vitd+leucine whey protein vs placebo 380 sarcopenic, malnourished older subjects Results: Both groups improved all measures of muscle strength and physical performance Supplement only better in chairstand tests and muscle mass Bauer JM, et al. J Am Med Dir Assoc. 2015. 41
Woo J. Nutritional interventions in sarcopenia: where do we stand? Curr Opin Clin Nutr Metab Care. 2017
Robinson SM et al. Does nutrition play a role in the prevention and management of sarcopenia? Clin Nutr 2017
45 Editor-in-Chief Alfonso J. Cruz-Jentoft Hospital Universitario Ramón y Cajal, Madrid, Spain Honorary Editor-in-Chief Jean-Pierre Michel Medical School, Geneva University, Switzerland Associate Editors Hidenori Arai, National Center for Geriatrics and Gerontology, Obu (Aichi), Japan Antonio Cherubini, IRCCS-INRCA Ancona, Italy Peter Crome, UCL Primary Care, London, UK Helen Roberts, University of Southampton, Southampton, UK Timo Strandberg, University of Helsinki, Helsinki, Finland
REVERSIBILITY OF SARCOPENIA & FRAILTY TO PREVENT DISABILITY needs proteins!