Elsevier

Clinical Nutrition

Volume 33, Issue 5, October 2014, Pages 737-748
Clinical Nutrition

ESPEN endorsed recommendation
Muscle contractile and metabolic dysfunction is a common feature of sarcopenia of aging and chronic diseases: From sarcopenic obesity to cachexia

https://doi.org/10.1016/j.clnu.2014.03.007Get rights and content

Summary

Skeletal muscle is the most abundant body tissue accounting for many physiological functions. However, muscle mass and functions are not routinely assessed. Sarcopenia is defined as skeletal muscle loss and dysfunction in aging and chronic diseases. Inactivity, inflammation, age-related factors, anorexia and unbalanced nutrition affect changes in skeletal muscle. Mechanisms are difficult to distinguish in individual subjects due to the multifactorial character of the condition. Sarcopenia includes both muscle loss and dysfunction which induce contractile impairment and metabolic and endocrine abnormalities, affecting whole-body metabolism and immune/inflammatory response. There are different metabolic trajectories for muscle loss versus fat changes in aging and chronic diseases. Appetite regulation and physical activity affect energy balance and changes in body fat mass. Appetite regulation by inflammatory mediators is poorly understood. In some patients, inflammation induces anorexia and fat loss in combination with sarcopenia. In others, appetite is maintained, despite activation of systemic inflammation, leading to sarcopenia with normal or increased BMI. Inactivity contributes to sarcopenia and increased fat tissue in aging and diseases. At the end of the metabolic trajectories, cachexia and sarcopenic obesity are paradigms of the two patient categories. Pre-cachexia and cachexia are observed in patients with cancer, chronic heart failure or liver cirrhosis. Sarcopenic obesity and sarcopenia with normal/increased BMI are observed in rheumatoid arthritis, breast cancer patients with adjuvant chemotherapy and in most of patients with COPD or chronic kidney disease. In these conditions, sarcopenia is a powerful prognostic factor for morbidity and mortality, independent of BMI.

Introduction

A great achievement of modern medicine is the ability to stabilize chronic diseases, leading to extended life expectancy of populations. The chronically ill patient journey, however, is often associated with metabolic abnormalities and alterations in body composition (i.e., muscle loss with changes in adipose tissue mass) which affect disease outcome and increase health care burden and cost. A physiological decline of skeletal muscle tissue is also an important feature of the aging process. There are strict relationships between muscle loss associated with aging and that due to chronic diseases. In addition, decreased physical activity and muscle unloading are key variables affecting skeletal muscle mass and body composition in aging and chronic disease.

The term sarcopenia was originally introduced to define age-related skeletal muscle decline, however it is now used to indicate any loss of muscle tissue and function due to aging, chronic diseases (including cancer), low protein-energy intake and physical inactivity.1, 2 Other definitions may be used to describe decreases in muscle mass and function. The term wasting describes disease- and cancer-related muscle loss.3 Dynapenia defines decreased contractility and loss of strength.4 Muscle loss secondary to inactivity and unloading is often referred to as disuse atrophy.5 More recently, Fearon et al. proposed the term of “myopenia” to indicate a clinically relevant degree of muscle loss that is also associated with impaired contractile function.6 In 2010 the Special Interest Groups (SIG) “Cachexia-Anorexia in Chronic Wasting Diseases” and “Nutrition in Geriatrics” of the European Society of Clinical Nutrition and Metabolism (ESPEN) defined sarcopenia as any loss of skeletal muscle mass and strength secondary to aging and chronic diseases including cancer.1 Subsequently, it was agreed to continue the common efforts aimed at improving the knowledge about sarcopenia, cachexia, pre-cachexia, sarcopenic obesity in aging and chronic diseases among the scientific community. The process for the production of the present document was started in September 2012 in Barcelona, during the joint meeting of the two ESPEN SIGs. The draft of the paper was elaborated during the first semester of 2013. The manuscript draft was then circulated among the participants to the two SIGs (listed in the acknowledgments section in this paper) and progressively improved and integrated based on the indications of the participants. The endorsement of the document by the two SIGs was obtained in September 2013 in Leipzig, during the annual joint meeting of the 2 SIGs. In agreement with our previous definition,1 in the present paper we will use the term sarcopenia to define any clinically relevant skeletal muscle loss and dysfunction associated with aging, chronic diseases, cancer, low protein-energy intake and physical inactivity. This definition is also in agreement with the European Working Group on Sarcopenia in Older People (EWGSOP) that in 2010 developed a consensus document on sarcopenia endorsed by the following organizations: European Geriatric Medicine Society (EUGMS), the European Society for Clinical Nutrition and Metabolism (ESPEN), the International Association of Gerontology and Geriatrics—European Region (IAGG-ER) and the International Academy of Nutrition and Aging (IANA).2 The EWGSOP made a distinction between aging-associated sarcopenia (primary sarcopenia) and disease-associated sarcopenia (secondary sarcopenia).2 However, it is difficult to distinguish primary from secondary sarcopenia because 90–95% of older adults have at least one chronic disease, and 70–75% have two or more comorbidities.7 Evidence indicates that chronic diseases prevalence is increasing over the last decades.7

In the present joint document elaborated by the ESPEN SIG “cachexia-anorexia in chronic wasting diseases” and “nutrition in geriatrics” we will try to highlight that:

  • (a)

    criteria for a clinical diagnosis of sarcopenia are required (see: Clinical diagnosis of sarcopenia);

  • (b)

    sarcopenia is a key feature of age- and disease-related malnutrition (see: Skeletal muscle as a marker of nutritional status);

  • (c)

    sarcopenia is a multifactorial disorder where specific mechanisms related to aging, chronic disease or inactivity are difficult to distinguish in individual subjects; in addition, sarcopenia includes both muscle loss and muscle dysfunction, the latter not only involves contractile impairment but also metabolic and endocrine abnormalities affecting whole-body metabolism, systemic inflammation and immune system regulation (see: Muscle dysfunction: impaired contractile, metabolic and endocrine functions);

  • (d)

    sarcopenia is a major determinant of disease outcome and longevity (see: Impact of sarcopenia on outcomes);

  • (e)

    there are different metabolic trajectories for muscle loss versus fat changes in aging and chronic diseases leading to the two different paradigms of sarcopenia, i.e., cachexia and sarcopenic obesity (see: Cachexia and sarcopenic obesity); and

  • (f)

    cost-effective control of chronic disease and optimal aging require sarcopenia prevention, diagnosis and treatment (see: Sarcopenia of aging and chronic diseases: towards a clinical definition and therapy).

Section snippets

Clinical diagnosis of sarcopenia

Currently proposed criteria for sarcopenia assessment in a clinical setting include determination of muscle mass, strength and physical performance (Table 1).2, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17 Muscle mass can be measured by anthropometry,8 bioimpedance analysis (BIA),2, 9, 13, 15 dual energy X-ray absorptiometry (DXA),11, 12 computed tomography (CT) scan10, 11 and magnetic resonance imaging (MRI). BIA cannot reliably assess skeletal muscle mass in patients with body fluid abnormalities, as

Skeletal muscle as a marker of nutritional status

The role of malnutrition in increasing morbidity and mortality in aging as well as in patients with chronic diseases and cancer has been long recognized.19, 20 The hallmark of disease-related malnutrition is the unintentional loss of body weight secondary to the variable combination of reduced food intake, impaired substrate utilization and increased needs. Indeed, in most observational studies or randomized controlled trials, the assessment of nutritional status was mainly based on changes in

Muscle dysfunction: impaired contractile, metabolic and endocrine functions

Skeletal muscle is the largest organ in the human body accounting for about 40–50% of total weight in physiological conditions. Muscle fiber contraction permits locomotion and other body movements, maintenance of posture, respiration (diaphragm and intercostal muscles) and communication (verbal and facial muscles). Skeletal muscle is also involved in a number of metabolic functions such as energy homeostasis, heat regulation, insulin sensitivity and amino acid metabolism. Skeletal muscle has

Impact of sarcopenia on outcomes

Recent epidemiological evidence suggests that the harmful effect of low BMI on outcomes is largely due to the deleterious effects of muscle loss and dysfunction (Table 4).14, 26, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117 A number of epidemiological evidence indicates muscle depletion as reliable marker of poor prognosis in chronic diseases. Muscle loss is frequently found in end-stage liver disease,118 in these patients sarcopenia increased

Cachexia and sarcopenic obesity

While impaired energy balance mainly affects adipose tissue and fat mass, inflammation, catabolic hormones, inactivity and insufficient protein intake are the main drivers of sarcopenia of aging and chronic diseases (Fig. 5).123 We have recently defined cachexia and pre-cachexia as conditions characterized by actual or potential unintentional weight loss associated with systemic inflammation.1, 124 In these conditions, systemic inflammation is associated with anorexia and low nutrient intake,

Sarcopenia of aging and chronic diseases: towards a clinical definition and therapy

It is becoming increasingly clear that the spectrum of body composition changes in chronic diseases and aging is extremely wide, ranging from the minimal or potential weight loss of pre-cachexia to the extreme loss of fat and muscle in refractory cancer cachexia,11 to the high BMI of sarcopenic obesity. Nonetheless, sarcopenia with muscle loss and dysfunction is a common feature of virtually all chronic diseases characterized by inactivity and systemic inflammation as well as of aging. Reliable

Conclusions

The spectrum of body composition changes in disease states is extremely wide, ranging from the minimal or potential weight loss of pre-cachexia to the extreme loss of fat and muscle in refractory cancer cachexia, to the high BMI of sarcopenic obesity. During the last few years, the progressive understanding of the pathophysiology and clinical impact of disease-related changes in body composition, has highlighted the central role played by skeletal muscle loss in negatively influencing morbidity

Conflict of interest

The Authors declare they have no conflict of interest.

Acknowledgments

We thank all members of the Special Interest Groups (SIG) “Cachexia-Anorexia in Chronic Wasting Diseases” and “Nutrition in Geriatrics” of the European Society of Clinical Nutrition and Metabolism (ESPEN). We acknowledge the contribution of the following SIG members for critical revision of the manuscript: Stefan Anker, Charité, Campus Virchow, Klinikum, Berlin, Germany; Didier Attaix, INRA de Theix, Ceyrat, France; Vickie Baracos, University of Alberta, Edmonton, Alberta, Canada; Juergen

References (145)

  • R. Caporali et al.

    Disease-related malnutrition in outpatients with systemic sclerosis

    Clin Nutr

    (2012)
  • V.E. Baracos et al.

    Body composition in patients with non-small cell lung cancer: a contemporary view of cancer cachexia with the use of computed tomography image analysis

    Am J Clin Nutr

    (2010)
  • M.A. van Bokhorst-de van der Schueren et al.

    Relevance of the new pre-cachexia and cachexia definitions for patients with rheumatoid arthritis

    Clin Nutr

    (2012)
  • G. Guarnieri et al.

    Mechanisms of malnutrition in uremia

    J Ren Nutr

    (2003)
  • L.B. Pupim et al.

    Accelerated lean body mass loss in incident chronic dialysis patients with diabetes mellitus

    Kidney Int

    (2005)
  • B.K. Pedersen

    Exercise-induced myokines and their role in chronic diseases

    Brain Behav Immun

    (2011)
  • L. Ji et al.

    Factors associated with poor nutritional status among the oldest-old

    Clin Nutr

    (2012)
  • L. Genton et al.

    Body composition changes over 9 years in healthy elderly subjects and impact of physical activity

    Clin Nutr

    (2011)
  • S.M. Pasiakos et al.

    Acute energy deprivation affects skeletal muscle protein synthesis and associated intracellular signaling proteins in physically active adults

    J Nutr

    (2010)
  • G. Biolo et al.

    Calorie restriction accelerates the catabolism of lean body mass during 2 wk of bed rest

    Am J Clin Nutr

    (2007)
  • M. Seelaender et al.

    Inflammation in cancer cachexia: to resolve or not to resolve (is that the question?)

    Clin Nutr

    (2012)
  • M. Shimizu-Fujiwara et al.

    Decreased resting energy expenditure in patients with Duchenne muscular dystrophy

    Brain Dev

    (2012)
  • J.A. Langius et al.

    Resting energy expenditure in head and neck cancer patients before and during radiotherapy

    Clin Nutr

    (2012)
  • G. Biolo et al.

    Positive energy balance is associated with accelerated muscle atrophy and increased erythrocyte glutathione turnover during 5 wk of bed rest

    Am J Clin Nutr

    (2008)
  • T.M. Manini

    Energy expenditure and aging

    Ageing Res Rev

    (2010)
  • L. Genton et al.

    Nutritional state, energy intakes and energy expenditure of amyotrophic lateral sclerosis (ALS) patients

    Clin Nutr

    (2011)
  • M.J. Müller et al.

    Hypermetabolism in clinically stable patients with liver cirrhosis

    Am J Clin Nutr

    (1999)
  • G. Sergi et al.

    Body composition and resting energy expenditure in elderly male patients with chronic obstructive pulmonary disease

    Respir Med

    (2006)
  • J. Rittweger et al.

    Bone loss in the lower leg during 35 days of bed rest is predominantly from the cortical compartment

    Bone

    (2009)
  • J. Zhou et al.

    Association between metabolic syndrome and osteoporosis: a meta-analysis

    Bone

    (2013)
  • V.T. Samuel et al.

    Mechanisms for insulin resistance: common threads and missing links

    Cell

    (2012)
  • P. Tessari et al.

    Insulin resistance of amino acid and protein metabolism in type 2 diabetes

    Clin Nutr

    (2011)
  • J. Bauer et al.

    Evidence-based recommendations for optimal dietary protein intake in older people: a position paper from the PROT-AGE Study Group

    J Am Med Dir Assoc

    (2013)
  • W.H. Hartl et al.

    The trophic effects of substrate, insulin, and the route of administration on protein synthesis and the preservation of small bowel mucosal mass in large mammals

    Clin Nutr

    (2011)
  • G. Biolo et al.

    Muscle glutamine depletion in the intensive care unit

    Int J Biochem Cell Biol

    (2005)
  • A. Bonetto et al.

    Are antioxidants useful for treating skeletal muscle atrophy?

    Free Radic Biol Med

    (2009)
  • T. Hofmann et al.

    Irisin as a muscle-derived hormone stimulating thermogenesis – a critical update

    Peptides

    (2014)
  • C. Martín-González et al.

    Prognostic value of changes in lean and fat mass in alcoholics

    Clin Nutr

    (2011)
  • A.J. Cruz-Jentoft et al.

    Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on Sarcopenia in Older People

    Age Ageing

    (2010)
  • W.E. Mitch et al.

    Mechanisms of muscle wasting. The role of the ubiquitin-proteasome pathway

    N Engl J Med

    (1996)
  • T.M. Manini et al.

    Dynapenia and aging: an update

    J Gerontol A Biol Sci Med Sci

    (2012)
  • K. Fearon et al.

    Myopenia – a new universal term for muscle wasting

    J Cachexia Sarcopenia Muscle

    (2011)
  • W.W. Hung et al.

    Recent trends in chronic disease, impairment and disability among older adults in the United States

    BMC Geriatr

    (2011)
  • M.D. Miller et al.

    Corrected arm muscle area: an independent predictor of long-term mortality in community-dwelling older adults?

    J Am Geriatr Soc

    (2002)
  • M. Mourtzakis et al.

    A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care

    Appl Physiol Nutr Metab

    (2008)
  • L. Martin et al.

    Cancer cachexia in the age of obesity: skeletal muscle depletion is a powerful prognostic factor, independent of body mass index

    J Clin Oncol

    (2013)
  • T.K. Malmstrom et al.

    Sarcopenia: the target population

    J Frailty Aging

    (2013)
  • S. Volpato et al.

    Prevalence and clinical correlates of sarcopenia in community-dwelling older people: application of the EWGSOP definition and diagnostic algorithm

    J Gerontol A Biol Sci Med Sci

    (2013)
  • G. Biolo et al.

    Does cachexia prevention improve outcome of chronic disease and cancer?

    Intern Emerg Med

    (2011)
  • E. Cereda et al.

    Nutritional care routines in Italy: results from the PIMAI (Project: Iatrogenic MAlnutrition in Italy) study

    Eur J Clin Nutr

    (2010)
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    Joint document endorsed by Special Interest Groups (SIG) “Cachexia-Anorexia in Chronic Wasting Diseases” and “Nutrition in Geriatrics” of the European Society of Clinical Nutrition and Metabolism (ESPEN).

    d

    ESPEN-SIG “Cachexia-Anorexia in Chronic Wasting Diseases”.

    e

    ESPEN-SIG “Nutrition in Geriatrics”.

    f

    These authors equally contributed to conception and writing of the paper.

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