SarcopheniaIntroduction
Definition
Prevalence
Who is at risk?
Sarcopenia symptoms and effects
Pathogenesis
Definition of sarcopenia for clinical and epidemiological studies
Measurement of sarcopenia in clinical practice
Increase overall dietary protein
Quality of protein and specific amino acids
Summary
References

 

Introduction

Sarcopenia is a common clinical condition in people over 50 years of age. Originally, it was considered only loss of muscle mass, but according to the new European Consensus definition the condition is associated with loss of muscle function as well. It predicts functional decline, hospitalisation, mortality in community dwelling elderly population. Recently, with its recognition as a disease and agreed expert consensus on diagnostic criteria, sarcopenia has emerged as a key topic in geriatric medicine and represents a rapidly expanding field of clinical research.

There is increasing appreciation of sarcopenia’s importance for an ageing population. This condition is closely linked to physical ‘frailty’ and detection and management of sarcopenia is beginning to be incorporated into clinical practice, and to undergo large clinical trials.

 

Definition

Sarcopenia (Greek “sarx” or flesh + “penia” or loss) was initially proposed by Rosenberg, representing age-related loss of muscle mass in its original concept.1 Sarcopenia is a physiological phenomenon that usually starts in the fifth decade. The European Working Group on Sarcopenia in Older People (EWGSOP) defined sarcopenia in 2010 as a syndrome characterised by progressive and generalised loss of skeletal muscle mass and strength with the risk of adverse outcome such as physical disability, poor quality of life, and death.2 The new definition of sarcopenia is based on both muscle mass and function rather than muscle mass alone.

 

Prevalence

The prevalence of sarcopenia in large populations aged 60–70 years ranged from 5–13%, but increased to 11–50% in subjects aged >80 years.3

Prevalence of sarcopenia was, with regional and age-related variations, 1–29% in community- dwelling populations, 14–33% in long-term care populations and 10% in the only acute hospital-care population examined.4 In the UK, the prevalence of sarcopenia in Hertfordshire community dwelling older men and women (mean age 67 years) was 4.6% and 7.9%, respectively.5

With the rising elderly population, the number of older population with sarcopenia is expected to increase worldwide, and it is becoming one of the important public health concerns and interests.

 

Who is at risk?

Age

Sarcopenia tends to start at the age of 40 and progresses more rapidly after the age of 75 years. Lean muscle mass generally contributes up to approximately 50% of total body weight in young adults, but declines with ageing to about 25% at 75–80 years old.6

 

Sedentary lifestyle

A sedentary lifestyle increases risk for a multitude of diseases. One in four adults either engage in a low level of activity (ie., moderately active during usual daily activities and completely inactive during leisure time) or are never active at all.7 People who are physically inactive can lose as much as 3–5% of their muscle mass per decade after age 30. Muscle inactivity reduces muscle mass, even in young healthy adults.

 

Malnutrition

Older adults are particularly prone to reduction in food intake, and as a result, malnutrition. For a sarcopenia sufferer, malnutrition can cause protein deficiency, with further loss of muscle.

An American survey indicates in adults aged 50 years and older, 32–41% of women, and 22–38% of men consume less than the recommended dietary allowance of protein.6

Diets rich in acid producing foods (meat and cereal grains) and low in non-acid producing foods (fruits and vegetables) can also have negative effects on muscle mass.

What should clinicians look for? Well recognised risk factors for sarcopenia include increasing age, low levels of physical activity, inadequate nutrition, and comorbidity, such as type 2 diabetes. Identifying high risk groups of older people is straightforward, but making a definite diagnosis is more difficult.

 

Sarcopenia symptoms and effects

The main symptoms of sarcopenia are decreased muscle mass and strength. As a result, other symptoms and effects of sarcopenia include frailty, problems with mobility, falls and fractures, decreased activity levels (which only makes sarcopenia worse), loss of independence, osteoporosis, and weight gain from lack of activity.

The metabolic effects of sarcopenia include a decrease in resting metabolic rate, which leads to a higher prevalence of insulin resistance, type 2 diabetes mellitus, dyslipidemia (an elevation of plasma cholesterol, triglycerides or both) and hypertension.

It is interesting that sarcopenia may not be necessarily related to weight loss and is associated with major comorbidities including obesity. A new term is emerging called: sarcopenic obesity.8

Sarcopenia is present in between 50–70% of persons with frailty and ‘frailty’ is considered as one of the most important new geriatric giants. More importantly, when sarcopenia is coupled with other diseases associated with ageing, its affects can be even more pronounced. When patients suffer from both sarcopenia and osteoporosis, the risk of falling and subsequent fracture incidence is higher. Therefore, treating sarcopenia will in turn help to lessen its burden on co-existing diseases.

Sarcopenia contributes significantly to the morbidity, decrease in quality of life and large healthcare costs amongst the elderly.9

 

Pathogenesis

In most elderly patients, sarcopenia is multifactorial. Muscle proteins are subjected to a constant process of synthesis and degradation just like all body tissues. In healthy adults (with an adequate protein intake) this turnover allows the maintenance of a positive nitrogen balance and a constant muscle mass.

In the elderly, one of the pathogenic mechanisms leading to sarcopenia is altered muscle protein metabolism: the proteolytic processes are not accompanied by an adequate protein synthesis within the physiological turnover, and muscle cells lose progressively the sensitivity to the anabolic stimulus induced from the essential leucine and IGF-1 (insulin-like growth factor), thereby manifesting the so-called “anabolic resistance.”10

This phenomenon is associated with other hormonal, functional, and nutritional factors, each of which contributes to a greater or lesser extent— depending on gender, age, and clinical condition of the patient—to the progression of disease, defined as secondary sarcopenia.

 

Definition of sarcopenia for clinical and epidemiological studies

The European Working Group on Sarcopenia in Older People (EWGSOP) in 2010, developed a diagnostic definition11 that measures muscle strength and physical performance using well-validated techniques.

Diagnosis of sarcopenia is based on documentation of criterion 1, plus criterion 2 and/or 3:

  • Low muscle mass
  • Low muscle strength
  • Low physical performance

It is expected that in the future, once an operational definition of sarcopenia is adopted and included in the mainstream of comprehensive geriatric assessment, the next steps are to develop and define effective treatment.

Figure 1. Range of functional capacity over life course 

Measurement of sarcopenia in clinical practice

  • Gait speed is readily assessed in the clinical setting by measuring the time taken to walk a set distance, such as 4 metre, at usual pace. For clinical purposes, a cut-off point of 0.8m/sec has been used in the EWGSOP definition for sarcopenia.11

  • Grip strength is recommended for measuring ‘muscle strength’ in the clinical setting. The Jamar dynamometer is the most commonly described device.

  • Muscle mass. Possible techniques for measuring muscle mass in the clinical setting include anthropometry, bioelectrical impedance (BIA) and dual energy X-ray absorptiometry (DXA). DXA measures lean body mass in reference to a normal population.

Incorporation of walking speed and grip strength into routine comprehensive geriatric assessment may be the direction forward in identifying patients who would need further diagnostic testing ie. with bioelectrical impedance or DXA to measure muscle mass.

 

New ICD classification of sarcopenia

Sarcopenia is a progressive loss and disease of skeletal muscle beyond normal ageing process because of inadequate lifestyle and other issues. It negatively results in decreasing muscle strength and/or physical performance, which brings critical risks on the quality of life, independence and even mortality. So far, it was considered as a part of ageing that cannot be managed. Since October 2016, the new ICD-10-CM (M62.84) code for sarcopenia represents a major step forward in recognising sarcopenia as a disease.12 This should lead to an increase in availability of diagnostic tools and the enthusiasm for pharmacological companies to develop drugs for sarcopenia.

There is a need to raise awareness of sarcopenia as a new disease. Since the National Institutes of Health publicised osteoporosis as a disease in 1984 and the US Food and Drug Administration approved the use of osteoporosis medication, there has been universal agreement about the importance of prevention and treatment of osteoporosis for past 30 years. The establishment of disease recognition and diagnostic criteria are the basis for the clinical efficacy of various treatments and prevention measures. In the future, the significance of sarcopenia is expected to be similar to that of osteoporosis. Sarcopenia is likely to become a new geriatric giant.

With the new recognition of sarcopenia as a medical condition with its own unique ICD-10- CM code, rapid increase in research publications is expected. A recent longitudinal analysis of consecutive 172 hospitalised patients (72% female) with a mean (SD) age of 85.2 (6.4) years showed that in hospitalised older adults, sarcopenia prevalence is high in 69 (40.1%) patients.13 Sarcopenia was associated with dependency in both Activities of Daily Living (ADLs) and Instrumental ADLs, and patients with sarcopenia were twice as likely to die in the 12-months post-hospitalisation.

 Figure 2. Relationship between sarcopenia and frailty

Treatment

There are currently no approved drug treatments for sarcopenia. Researchers face limitations in developing studies due to the lack of standardised primary outcomes because it is a new field and protocols and outcomes for drug-related sarcopenia studies are difficult to determine. Research is now focusing on the role of physical activity, nutrition, and potential future medications that may be used to treat or prevent sarcopenia. The more rational approach to delay the progression of sarcopenia is based on the combination of proper nutrition, possibly associated with the use of supplements and/ or foods, and a regular exercise programme.

 

Exercise intervention

No trials have recruited individuals based on their sarcopenic status. Most published exercise studies have involved limited participants and were mainly conducted within a single country. Exercise interventions appear to have a role in increasing muscle strength and improving physical performance, although they do not seem to consistently increase muscle mass, in frail, sedentary, community-dwelling older individuals. The four categories of exercises (aerobic exercise, progressive resistance exercise, flexibility and balance) could have potential benefits in improving independence in the elderly.14 Exercise has been shown to increase strength, aerobic capacity and muscle protein synthesis, as well as to increase muscle mitochondrial enzyme activity in both young and older people. Exercise is recommended on most days of the week, but a minimum of three times per week is recommended to slow muscle loss and prevent sarcopenia. The current challenge is to develop programmes and interventions to promote physical activity in our sedentary societies.

 

Nutrition

Although nutrition intervention is considered one of the mainstays of intervention in sarcopenia, much of the evidence is based on short-term studies, and large clinical trials are lacking.

 

Increase overall dietary protein

Protein is the most valuable food for repairing and building muscle fibers. Studies show that 12% of men and 24% of women over age of 70 eat significantly less than the recommended (Recommended Dietary Allowance) 0.8 gram of protein per kilogram of their body weight each day.15 The FAO and the WHO indicate that an intake of 0.75 grams of high quality protein per kilogram of body weight is safe and adequate; however, for elderly subjects, it has been proposed to increase this value to 1.25 g/kg/day in order to avoid sarcopenia.16

For example, a person who weighs 150 pounds or 67.5 kilograms should aim for about 81 grams of protein per day. Most meat, poultry and fish have about 7 grams of protein in an ounce. One cup of milk or one egg has about 8 grams of protein.

The majority of elderly patients who present an acute or chronic disease have an increased need for protein intake (1.2 to 1.5 g/kg body weight/ day), while patients with critical illnesses or severe malnutrition have a need of protein equal to 2 g/kg body weight/day.

 

Quality of protein and specific amino acids

Not all dietary proteins have the same kinetic properties. It has been suggested that leucine, which is an essential amino acid belonging to the category of the branched chain amino acids (BCAAs; valine, and together with the isoleucine, whose average requirement is 40mg/kg/day), is critical to maintaining a healthy muscle tissue and liver. The main sources of leucine are chicken and fish, cottage cheese, lentils, sesame, and peanuts. At rest, BCAAs, in particular leucine, have an anabolic effect by increasing protein synthesis and/or a reducing the rate of protein degradation, resulting in a positive net muscle protein balance.17 However, studies of leucine supplementation have not shown consistent results.

Whey protein ingestion results in greater postprandial protein retention than does casein ingestion. Moreover, whey has a considerably higher leucine content.18

When the total protein intake is adequate, the source of protein consumed (vegetal or animal) does not influence muscle strength and size.

Using dietary interventions with protein-rich food has several advantages over supplementation with products such as free-form amino acids. Many plant- and animal-based protein-containing foods are readily accessible, relatively inexpensive, and palatable. For the majority of older adults the most practical means of increasing skeletal muscle protein is to include a moderate serving of protein of high biological value during each meal. Good sources of protein to include in the diet are lean cuts of meat, fish, eggs and low fat dairy products. Beans, pulses and lentils are also good choices. Often breakfast/ snacks can be comparatively low in protein, so eggs and beans could be included in some breakfasts; porridge could be made with milk rather than water, and nut butters, hummus or oily fish pâté on toast can be good snack options.

 

Omega 3 fatty acids

A study found that dietary omega-3 fatty acid supplementation versus corn oil increases the rate of muscle protein synthesis in older adults.19 Supplementing with fish oil or flaxseed oil could increase the omega-3 acid intake.

 

Antioxidants

It is recommended to have a diet with high intake of fruits, vegetables whole grains, which are rich in antioxidant, and lower consumption of red meat and saturated fats, because it is associated with a reduced risk of inflammation correlated to oxidative damage.20

Diets rich in acid producing foods (meat and cereal grains) and low in non-acid producing foods (fruits and vegetables) have been shown to have negative effects on muscle mass. As mentioned above, protein is important, but a diet high in meat and cereal grains should be balanced with a diet high in fruits and vegetable (non-acid-producing foods) in order to be effective in treating sarcopenia. A study of cross-sectional Korean community- dwelling 823 men and 1,089 women aged ≥65 years showed that dietary intake of vegetables, fruits and both vegetables and fruits was associated with a significantly reduced risk of sarcopenia after controlling for covariates.21

All persons should quit excess alcohol and smoking as they cause muscle damage and wasting.

 

Inflammatory foods

Processed foods such as simple, refined sugars and carbohydrates eg. high fructose corn syrup and transaturated fats can cause inflammation, which contributes to sarcopenia. Processed foods are also likely to be higher in omega-6 fatty acids, which are necessary but only to an extent. In excess and without the balance of omega-3s, omega-6 fats can create inflammation in the body.22 The typical American diet tends to contain 14–25 times more omega-6 fatty acids than omega-3 fatty acids.

 

Vitamin D

Many studies have shown that low blood levels of vitamin D are associated with lower muscle strength, increased body instability, falls and disability in older subjects.23 Vitamin D deficiency is the most common nutritional deficiency for older adults regardless of race or ethnicity. Up to 90% of adults in the US are believed to have a vitamin D insufficiency or deficiency. Low vitamin D levels have been associated with sarcopenia and supplementation of vitamin D in individuals with low levels can help improve muscle function and muscle mass.23 Muir and Montero-Odasso performed a meta-analysis of randomised control trials of the effect of vitamin D supplementation without an exercise intervention amongst adults above 60 years and showed that vitamin D supplementation (800–1000 IU) daily was associated with improvements of muscle strength and balance.24

Another meta-analysis25 showed that Vitamin D supplementation has a small positive impact on muscle strength, especially amongst people with 25-hydroxyvitamin D level <30 nmol/L.

Supplementation seems also more effective on people aged 65 years or older compared to younger subjects. Hence, in vitamin D deficient sarcopenic subjects, dietary vitamin D supplementation (800–1000 IU daily) could be a promising treatment of sarcopenia.

 

Summary

Sarcopenia, defined as low muscle mass and low muscle function and/or reduced physical performance, occurs in at least one in 20 community-dwelling individuals, and prevalence may be as high as one in three in frail older people living in nursing homes. The new definition of sarcopenia is based on muscle mass and function rather than muscle mass alone. New classification of sarcopenia as a geriatric syndrome allows its recognition and to assess its multiple risk factors, to implement a clinical and public health approach to the management of sarcopenic patients and population at risk and to disentangle the links with frailty and disability. Owing to the consequences of sarcopenia on the quality of life, disability and mortality, physicians should consider screening for sarcopenia, both in community and geriatric settings.

An adequate intake of proteins (1.2/g/kg/ day) is essential to prevent sarcopenia especially amino acids supplementation, in particular branched chain amino acids. Vitamin D supplementation could potentially provide a safe, simple, and low-cost intervention to counteract anabolic resistance and sarcopenia. Research on management interventions is advancing quickly, but questions still remain. More and larger trials will be needed to demonstrate the efficacy and safety of combining exercise and protein as a strategy for prevention and treatment of muscle loss. In the meantime, for the general population, the impact of a simple exercise and protein intervention, without the expense of supplementation, could have a large impact upon the wellbeing of the older person.

 

Dr Abhaya Gupta, Consultant Physician, Glangwili Hospital, Carmarthen

Conflict of interest: none declared

 


References

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