Sarcopenia

Sarcopenia is a condition characterized by loss of muscle mass, strength, and function in older adults and it can affect both under- and overweight adults. Sarcopenia is a part of normal aging, and occurs even in master athletes, although it is clearly accelerated by physical inactivity ¹. Sarcopenia is distinct from muscle loss (cachexia) caused by inflammatory disease, or from the weight loss and attendant muscle wasting caused by starva-tion or advanced disease ². Sarcopenia is increasingly recognized as a correlate of ageing and is associated with increased likelihood of adverse outcomes including falls, fractures, frailty and mortality ³. Sarcopenia is universal with advanced age. That is, reduced muscle mass and strength are evident in all elderly persons compared to young, healthy, physically active young adults ¹. If the sarcopenia progresses beyond a threshold of functional requirements, it leads to disability and frailty, and this can occur independently of any disease-induced frailty. Superimposed illness will accelerate the loss of muscle mass, and thus increase the risk of disability, frailty, and death ¹.

Sarcopenia signs and symptoms include weakness, fatigue, loss of energy, balance problems, and trouble walking and standing. Muscle loss or weakness can lead to falls, broken bones, and other serious injuries and can affect a person’s ability to care for oneself. Older age, getting little or no exercise, and poor nutrition may increase the risk of sarcopenia. Sarcopenia may also occur in people with cancer.

The term, sarcopenia, was first coined in 1988 by Irwin Rosenberg at a meeting in Albuquerque, New Mexico, to refer to muscle wasting of the older people ⁴. Its etymological origins are two Greek words: sarx for flesh and penia for reduced or deficiency. Baumgartner et al. ⁵ proposed an operational definition of sarcopenia in 1998. Utilizing dual energy X‐ray absorptiometry (DXA) to measure lean soft tissue, the authors defined sarcopenia as being <2 standard deviations (SDs) of appendicular muscle mass (ASM, kg) per height squared (m²) below the mean of a young reference group. Using this criterion, Baumgartner et al. ⁵ showed that the prevalence and the severity of sarcopenia significantly increased with age and that it was associated with physical disability. In 2002, Janssen et al. ⁶, using bioelectrical impedance analysis (BIA), showed that in the Third National Health and Nutrition Examination Survey (NHANES III), functional impairment was three times as likely in persons with an estimated lean mass below 2 SDs of the mean. Baumgartner et al ⁷, found that in older persons with obesity, those who had lost muscle mass had worse outcomes than those who had maintained their muscle mass. They coined the term ‘sarcopenic obesity’ for this condition. By the early 2000s, it was recognized that there are numerous causes of age‐related sarcopenia, including malnutrition, loss of motor units innervating muscle (α-motor neuron input), systemic inflammation-driven erosion of muscle mass, oxidative stress, decline in anabolic hormones, increased body fat and the ‘anorexia of aging’ coupled with a decrease in physical activity and disease burden are likely to culminate in sarcopena (see Figure 3 below) ⁸. At this stage, it was recognized that there were both primary sarcopenia (age related) and secondary sarcopenia (disease related, as with diabetes mellitus, cancer, chronic obstructive pulmonary disease, or heart failure) ⁹.

However, there is no absolute level of lean mass, body cell mass, or muscle mass at which one can definitely say that sarcopenia is present ¹. Such a definition would be an important advance. In reaching such a definition, one should consider two important and generally agreed-upon concepts in relation to lean body mass. First, there is a direct structure ± function link between muscle mass and strength, in that more muscle generally equals greater strength and vice versa. However, the function defining the relationship between muscle loss and strength loss is not the same as that applying to muscle and strength gain ¹.

Making the clinical diagnosis of sarcopenia is difficult for the following reasons. There is no absolute level of lean mass, body cell mass, or muscle mass for comparison. There is no generally accepted clinical test to diagnose sarcopenia. Finally, there is no accepted threshold of functional decline at which sarcopenia is implied. Dual-energy x-ray absorptiometry (DXA) is a well-established, low-radiation technique used to assess body composition and provides reproducible estimates of appendicular skeletal lean mass ¹⁰. It is acknowledged that the accuracy of DXA for assessing muscle mass in people of different ages and different pathological conditions may vary. Moreover, DXA (in contrast to CT-scan and MRI) cannot assess intra-muscular fat, which turns out to be of increasing importance in terms of the quality of muscle and associations with clinical outcomes. Bearing these limitations in mind, DXA is still considered as the procedure of choice for routine clinical assessment ³. Using DXA, appendicular skeletal lean mass (ASM) is measured as the sum of the non-bone and non-fat mass of the four limbs. To adjust for body size, a skeletal muscle index (SMI) is derived as ASM/height². Thresholds of skeletal muscle index (SMI) at two standard deviations (SDs) below the mean skeletal muscle index (SMI) of young male and female reference groups have been proposed as gender-specific cut-off points for sarcopenia. This results in two thresholds, proposed by the European Working Group on Sarcopenia (EWGSOP) ¹¹, the first of 5.5 kg/m² for women and 7.26 kg/m² ¹² for men and the second of 5.67 kg/m² for women and 7.25 kg/m² for men ¹³, depending on the reference group on which these cut-off have been established. Using a different approach, the Function NIH sarcopenia project ¹⁴ has also recently defined cut-offs for appendicular lean mass adjusted for body mass index (BMI), giving values of < 0.512 for women and < 0.789 for men. However, it should be pointed that these cut-offs might also be modified according to ethnicity ¹⁵.

Bio-electrical impedance analysis (BIA) is a method which estimates the volume of fat and lean body mass based on the relationship between the volume of a conductor and its electrical resistance. The method is not expensive, requires no specialized staff and is relatively easy to use in clinical practice, both on ambulatory subjects or on hospitalized patients. Moreover, reference values have been established for older individuals ¹¹. Even if the method’s accuracy has been challenged and has been reported to overestimate muscle mass and underestimate fat mass ¹⁶, it is possible to use some adjustment equations to obtain valid measurements ¹⁷.

Possible therapeutic strategies include increased protein intake and aggressive resistance-based exercise programs, but long-term randomized controlled trials are needed to evaluate the efficacy of these modalities. Hormonal supplementation may help if levels are low. Countermeasures should have the goals of maintaining adequate total body mass and protein intake. Physical activity incorporating resistance training is probably the most effective countermeasure to sarcopenia.

Pharmacologic interventions such as growth hormone or testosterone, which increase lean mass (and evidently muscle mass as well) do not alter strength much, while progressive resistance training, which causes large increases in strength, can do so with little evident muscle hypertrophy, at least in the first few months of training ¹. For example, the strength and vastus lateralis area (measured by CT scan) lost over a 12 years follow-up period in seven healthy men, and the amount gained during a 12 week period of intensive resistance training ¹⁸. It is clear that there is hysteresis in this system: the decline and the regain occur at vastly different rates. Thus, defining sarcopenia solely on compositional terms may be useful and attractive for research purposes, but it may be simplistic in explaining functional changes caused by treatment of sarcopenia ¹.

Second, there is reasonable evidence that there is a limit on how much lean body mass can be lost before death supervenes. The available data, based on starvation ¹⁹, AIDS patients ²⁰, and critical illness ²¹, suggest that loss of more than about 40% of baseline lean mass is fatal. `Baseline’ is a slippery concept here, because again absolute mass is not explanatory – basketball players do not necessarily outlive jockeys, but rather the amount of loss as a function of the baseline mass that the individual started with. Reference Man and Woman are one benchmark, based on a few cadaver studies in generally healthy persons ²². Kehayias et al ²³ defined baseline as the mean for adults aged 20 ± 30 years; no healthy subjects were found below approximately 70% of that standard, and there was a steady decline in body cell mass for both men and women across age groups between 30 and 100 years (see Figure 1).

The latter point also raises the issue of the importance of sarcopenia as an indicator of reduced protein stores for times of stress ¹. It is well accepted that during illness, gluconeogenesis increases in importance, while ketogenesis is relatively suppressed, so that protein is burned for energy in excess of the levels seen in starvation adaptation  ¹. Given the anorexia caused by acute illness, and by the iatrogenic limitation on dietary intake that often obtains in hospitals, endogenous protein stores are crucial in determining the availability of metabolic substrate to cope with the illness, and thus the ability to survive it. Therefore, it is no wonder that elderly, sarcopenic patients fare worse than young, healthy adults for almost all diseases. Tellado et al ²¹ have shown that measurement of body cell mass was the only independent determinant of survival in intensive care unit patients in multivariate analysis, removing the significance of univariate predictors such as albumin, age, and even diagnosis. Thus, the metabolic significance of sarcopenia in illness should be considered independently of its functional impact during times of better health, as both are important to the survival and well-being of elderly persons.

Figure 1. Lean body mass

Footnote: Body cell mass or lean body mass, measured as total body potassium (TBK) per kg body weight, as a function of age in a cross-sectional study. Data are expressed as a percentage of the reference 20 ± 30-year-old groups for men (O) and women (x) separately.

[Source  ²³ ]

Primary sarcopenia (sarcopenia of aging)

In 2010, the European Working Group on Sarcopenia for Older Persons ²⁴ recommended a new operational definition of sarcopenia of aging, i.e. the presence of low muscle mass together with low muscle function (strength or performance). Over the last decade, numerous other consensus groups have agreed to this revision to the meaning of sarcopenia of aging ²⁵. However, these groups all used different cut‐offs to define sarcopenia of aging, highlighting the fact that different cut‐offs are necessary for different ethnic groups ²⁶.

Towards the end of last year, two consensus articles on sarcopenia of aging were published. One was an update by the European Working Group on Sarcopenia (EWGSOP2) ²⁷ and the other was on the management of sarcopenia of aging by the International Clinical Practice Guidelines for Sarcopenia (ICFSR) ²⁸. The European Working Group on Sarcopenia (EWGSOP2) requires low muscle strength as a key characteristic of low muscle quality and the presence of low muscle quantity to confirm the diagnosis. If a person also has functional impairment, confirmed with a physical performance measure ²⁹, this is characterized as severe sarcopenia. The authors recommended measuring muscle strength with either grip strength or the chair stand test. Muscle mass can be measured by DXA, magnetic resonance imaging, or computed tomography. Either gait speed, the Short Physical Performance Battery (SPPB), the Timed Up and Go test, or the 400‐m‐walk can be used for the assessment of physical performance. The Short Physical Performance Battery (SPPB) takes about 10 min to complete ³⁰. Participants presenting a score ≤8 points have been described as having a poor physical performance ¹¹.

Recognizing the limited time available during a typical visit to a health care professional, the European Working Group on Sarcopenia also suggested that case finding should be used to identify older persons at risk for sarcopenia. They recommended the use of clinical symptoms usually associated with sarcopenia or the SARC‐F (Figure 2), a questionnaire with five questions, which has high specificity, albeit low sensitivity, to identify persons with sarcopenia ³¹. The SARC‐F has been translated into multiple languages. The SARC‐F is also recommended by the International Clinical Practice Guidelines for Sarcopenia (ICFSR) for screening ²⁸. The specificity of the SARC‐F can be improved by measuring calf circumference as well ³². The Ishii screening test (age, grip strength, and calf circumference) is recommended as an alternative screening test ³³. However, this already includes grip strength, which is a core measure of sarcopenia.

While bioelectrical impedance analysis (BIA) was not strongly supported by the European Working Group on Sarcopenia, to measure muscle mass, they recognize that its portability, affordability, and availability make bioelectrical impedance analysis (BIA) a feasible tool to estimate muscle mass in many care settings. Ultrasound of muscle such as the quadriceps is emerging as a potential tool to measure muscle quantity and, because it excludes intermuscular adipose tissue from the measurement, also muscle quality ³⁴; a protocol for using ultrasounds in sarcopenia has recently been proposed by the European Geriatric Medicine Society ³⁵.

There is increasing evidence that creatine dilution, implemented by ingesting a dose of the deuterium labelled isotope, may also offer an accurate approach for measuring muscle mass ³⁶. Studies so far suggest creatine dilution estimates of muscle mass may have good correlations with functional outcomes ³⁷. Nonetheless, its relevance and practicality in clinical settings remain to be determined.

The International Clinical Practice Guidelines for Sarcopenia (ICFSR) consensus made similar conditional recommendations utilizing the SARC‐F for screening and applying either the original European Working Group on Sarcopenia or Foundation for NIH diagnostic criteria ²⁸.

Figure 2. Sarcopenia questionnaire (SARC‐F questionnaire includes scoring)

[Source ⁹ ]

Secondary sarcopenia

Malignant disease has been the most studied secondary sarcopenia, and international consensus definitions specific to cancer sarcopenia ³⁸ are predicated on disease specific outcomes: mortality, complications of cancer surgery, and chemotherapy toxicity. Whether this secondary sarcopenia should be considered early cachexia or sarcopenia remains controversial ³⁹, but it is becoming clearer that sarcopenia is only one of the different features of muscle changes during cancer cachexia. Owing to the prevalent use of computed tomography imaging in cancer diagnosis and follow‐up, secondary analysis of oncologic imaging for skeletal muscle cross‐sectional areas or volumes is the current standard for the quantification of muscle mass in this domain.

There are several points of relevance regarding age‐related and disease‐related loss of muscle mass. Loss of muscle mass with age occurs in a continuous fashion after reaching peak muscle mass in young adulthood (at about 30 years of age). A variety of longitudinal observational studies provide information on the rate of muscle loss per decade. The percentage loss of appendicular muscle mass per 10 years is of the order of ~5% in men and is usually reported to be somewhat lower in women. Chronic illness‐related muscle loss is also progressive; however, these are non‐linear and of a considerably greater magnitude than the values seen in aging. For example, cancers of advanced stage induce muscle loss over time that take an exponential course ⁴⁰ with increasing intensity according to the disease progression, varying from 2% per 100 days to 15% per 100 days. Total cumulative loss in 12 months in colon cancer patients was 15.6%, equivalent to circa 30 years of aging ⁴⁰; this is partially disease‐related but also in part a consequence of cancer surgery or systemic antineoplastic therapies which induce punctate short‐term losses. Acute illness requiring hospitalization is associated with even higher intensity of muscle loss than in cancer. In elective hip replacement surgery during an average of 5.6 ± 0.3 days of hospitalization, associated with significant decline in quadriceps (−3.4 ± 1.0%) and thigh muscle cross‐sectional area (CSA) (−4.2 ± 1.1%) in the non‐operated leg aging ⁴¹. This could be in part due to bed rest as 5 days of one‐legged knee immobilization using a full leg cast resulted in decline of quadriceps muscle cross‐sectional area from baseline of 3.5 ± 0.5%. Acute sarcopenia secondary to hospitalization or chronic disease exacerbations may be partially recoverable or may lead to heightened risk of developing sarcopenia at a young age ⁴².

Sarcopenia causes

The biological mechanism of sarcopenia appears to be in the decreased ability of satellite cells to propagate themselves. Satellite cells are required to fuse into skeletal muscle fibers, and help in settings where repair and regeneration are required. Therefore aging muscle loses its ability to respond to anabolic stimuli, such as insulin, growth hormone, and amino acids. Catabolic stimuli may also play a role: the inflammatory IL-6, IL1-Ra, and TNF-alpha are elevated in elderly people with significant sarcopenia. Many anabolic stimuli are withdrawn in the elderly population. Decreased protein intake in the elderly plays a role: 1/3 of men over the age of 60 eat less than the recommended dietary allowance (RDA) of 0.8 g/kg. A decline in exercise, a potent stimulus to protein synthesis, also contributes. Hormonal factors may be involved, such as decreased levels of sex hormones, growth hormones, and decreased insulin.

Depleted muscles atrophy and are replaced by connective tissue, though the mechanism in sarcopenia may be different than that seen in other settings of “muscle atrophy”, since in younger individuals there is not an obvious problem with the satellite cells. Type II muscle fibers atrophy more so than type I.

Katherine Tucker, professor and chair of the Department of Health Sciences at Northeastern University, explained that individuals’ dietary needs change with aging ⁴³. Older adults may require less energy, experience less efficient absorption and utilization of many nutrients, and have different nutrient requirements due to chronic conditions and medications. These changes result in older adults needing a nutrient-dense diet. Unfortunately, it can be challenging for this population to obtain such a nutrient-dense diet because it involves overcoming barriers such as loss of appetite, changes in taste and smell, oral health decline, mobility constraints, and lower incomes.

Tucker concluded her presentation by recommending some dietary changes based on the available data. Older adults should be encouraged to eat:

• more fruits and vegetables, especially orange and dark green vegetables, to increase intakes of vitamin C, carotenoids, folate, vitamin B6, magnesium, potassium, and dietary fiber;
• more low-fat dairy to improve intakes of magnesium, calcium, potassium, and vitamins B12 and D;
• more whole grains, including more fortified breakfast cereals, to increase intakes of vitamin B6, crystalline vitamin B12, magnesium, and dietary fiber;
• fewer foods high in sugar, solid fats, sodium; and
• fewer refined grains.

Figure 3. Sarcopenia causes

Inadequate Intake

Data from the 2003–2004 the National Health and Nutrition Examination Survey (NHANES) were used by the Institute of Medicine Committee to Review Child and Adult Care Food Program Meal Requirements to identify the prevalence of inadequacy of protein and select nutrients among adults 60 years and older (see Table 1) ⁴⁴. Using NHANES data for adults 70 years and older, Lichtenstein and colleagues ⁴⁵ reported calcium, potassium, fiber, and vitamins D, E, and K as shortfall nutrients. In addition to those nutrients, Tucker emphasized the importance of adequate protein intake for prevention of sarcopenia and noted the controversy regarding the current recommendation for protein intake among older adults; should it be the same as the recommendation for younger adults or should it be higher?

Table 1. Estimated Prevalence of Inadequacy (%) of Protein and Selected Vitamins and Minerals Among Adults ≥ 60 Years Based on Usual Nutrient Intakes from NHANES 2003–2004

Nutrient	Males	Females
Protein	12	20
Vitamin A	54	43
Vitamin C	49	40
Vitamin E	92	98
Thiamin	6.0	12
Riboflavin	2.8	3.7
Niacin	1.8	4.6
Vitamin B6	19	39
Folate	11	24
Vitamin B12	2.4	9.0
Phosphorus	1.2	4.8
Magnesium	78	73
Iron	1.0	1.5
Zinc	26	21

Footnote: All nutrients in this table have an Estimated Average Requirement (EAR).

[Source ⁴⁴  ]

Tucker highlighted several nutrients of concern in the older adult population.

• Protein. The current Estimated Average Requirement for protein for all adults 19 years and older is 0.66 g/kg/day; however, Tucker indicated that a moderately higher protein intake (1.0–1.3 g/kg/day) may be required for older adults to maintain nitrogen balance due to decreased efficiency of protein synthesis and impaired insulin action. Need for increased protein intake is further supported by the Health, Aging, and Body Composition Study, which found that older adults with the highest intake of protein lost less lean body mass than those with lower protein intakes ⁴⁶. However, there is some concern that higher protein intake may increase risk of toxicity or impaired renal function ⁴⁷.
• Vitamin E. Vitamin E is important because of its role as an antioxidant and in immune function. There is some controversy over whether the current Recommended Daily Allowance (RDA), 15 mg of α-tocopherol, is too high, as very few individuals are able to meet this recommendation from diet alone. Vitamin E supplements increase α-tocopherol levels while reducing γ-tocopherol, so supplements may not be the healthiest option for increasing intake. Some literature suggests that other tocopherols (found in nuts, seeds, and plant oils) are also important ⁴⁸; however, there are no current nutrient recommendations for other forms of vitamin E.
• Vitamin B12. Although the daily intake of total vitamin B12 does not appear to be low for most older adults, dietary intake data may underestimate the number of people who are vitamin B12 deficient given that atrophic gastritis and loss of stomach acid prevent some older adults from absorbing it. As a result, the Institute of Medicine ⁴⁴ recommended that older adults get their vitamin B12 in crystalline form such as from fortified foods or supplements. The Framingham Offspring Study found that nonsupplement users had a higher prevalence of low B12 (less than 250 μmol/L) than those who were taking a supplement containing vitamin B12 ⁴⁹. Vitamin B12 deficiency can lead to peripheral neuropathy, balance disturbances, cognitive disturbances, physical disability, and increased risk of heart disease from high homocysteine. Tucker stated, “It’s critical that more attention be given to this important nutrient as many of these symptoms are nonspecific and not always diagnosed correctly” ⁴⁹.
• Vitamin B6. Vitamin B6 is important for numerous metabolic reactions and health outcomes. Inadequacy may lead to high homocysteine and impaired immune function and has been associated with impaired cognitive function and depression. Data from the Massachusetts Hispanic Elders Study showed that 30 percent of Hispanics and 28 percent of non-Hispanic whites had plasma pyridoxal 5′-phosphate (the active form of vitamin B6 used as a biomarker for vitamin B6 status) concentrations less than 30 nmol/L (indicator of inadequate status), and 11 percent of Hispanics and 16 percent of nonwhite Hispanics had concentrations less than 20 nmol/L (clinical cutoff level indicating deficient concentrations). Furthermore, pyridoxal 5′-phosphate was associated with depressive symptomatology in this population-based study of older adults ⁵⁰.
• Omega-3 fatty acids. Among adults 60 years and older, the median intake of α-linolenic acid by women was above the Adequate Intake (AI), whereas the median intake by men was not ⁴⁴. Omega-3 fatty acids are associated with protection against heart disease, diabetes, and cognitive decline. Low intake may be partially due to the limited sources in the diet (e.g., fatty fish, flax seeds, and walnuts).
• Dietary fiber. Fiber is important for intestinal health and protection against heart disease and metabolic syndrome; however, the median intakes of neither men nor women 60 years and older meet the AI ⁴⁴.
• Vitamin D. Tucker reported that older adults’ poor vitamin D intake and status may be due to low intakes of fortified dairy foods and fatty fish, low sun exposure, reduced dermal synthesis of vitamin D3 ⁵¹, and decreased capacity of kidneys to convert 25OHD into 1,25-OH2-D. A study of homebound older adults found that about 65 percent had suboptimal concentrations of 25OHD in their blood (less than 50 nmol/L) and 48 percent had intakes below 400 International Units ⁵². In addition to its importance to bone status, vitamin D deficiency has been associated with neurological conditions, diabetes, and other metabolic conditions. Increasingly, more nutritionists are recommending that older adults take a vitamin D supplement.

Excessive intakes

Excessive intake of some nutrients is also a concern among older adults as it is for the general population.

• Sodium. The Tolerable Upper Intake Level for sodium is 2.3 g/day; however, the 2015 Dietary Guidelines Advisory Committee recommended it should be lowered to 1.5 g/day ⁵³ to reduce the risk of hypertension and heart disease. Men and women over the age of 70 years are exceeding both recommendations; the usual daily mean intake for men and women is 3.0 and 2.4 g, respectively ⁵⁴.
• Saturated fat. The Dietary Guidelines for American’s recommendation for saturated fat intake is less than 10 percent of energy intake, with the goal of reducing that recommendation to 7 percent ⁵³. However, most adults have intakes greater than 10 percent of their energy intake ⁵⁵.
• Folic acid. Whereas some adults do not meet the recommended intake levels of folic acid (400 μg), research shows that others are at risk of exceeding the upper level of 1,000 μg per day due to intake of fortified flour and breakfast cereals, and supplement use. More research is needed but high folic acid may contribute to the progression of neurological diseases associated with vitamin B12 deficiency ⁵⁶ and lead to increased risk of some cancers ⁵⁷.

Food intakes

In order to determine why older adults’ nutrient intakes are inadequate, one must review their food intake patterns. The 2011 IOM report Child and Adult Care Food Programs: Aligning Dietary Guidance for All presented the mean daily food group intakes by adults ages 60 years and older as compared to the 2,000-calorie MyPyramid food group pattern. It showed that older adults are not meeting any of the MyPyramid food group recommendations and are exceeding the recommendations for daily intake of solid fats and added sugar (see Table 2).

Table 2. 52,000-Calorie MyPyramid Food Group Pattern and Mean Daily Amounts Consumed by Adults ≥ 60 Years of Age

Food Group or Component	≥ 19 Years	≥ 60 Years
	2,000-kcal Pattern58	Mean Intake 55
Total fruit (cup eq)	2.0	1.1
Total vegetables (cup eq)	2.5	1.7
Whole grains (oz eq)	3.0	0.86
Total milk group (8 fl oz eq)	3.0	1.3
SoFAS (kcal)	267	570

Abbreviations: eq = equivalent; fl = fluid; kcal = calories; oz = ounce; SoFAS = solid fats and and sugar.

[Source ⁴⁴ ]

Sarcopenia treatment

For the management of sarcopenia, there is a strong recommendation that individuals with sarcopenia should be enrolled in a resistance exercise programme ⁹. There is a reasonable amount of evidence that resistance exercise will increase both muscle mass and strength ⁵⁹. The use of a protein rich diet (1 to 1.5 g/day) or protein supplementation received a conditional recommendation based on a small amount of evidence and a previous consensus conference ⁶⁰. Higher doses of protein (up to 2 g/day) may be appropriate in persons with severe illness or injury or when there is evidence of a pro‐inflammatory/catabolic state ⁶¹. β‐hydroxy β‐methylbutyrate (HMB) has been shown to improve muscle mass and to preserve muscle strength and function in older people with sarcopenia or frailty ⁶². Vitamin D supplementation specifically for sarcopenia was found to have insufficient evidence, though there is evidence that persons with low vitamin D levels may improve their strength with vitamin D supplementation ⁶³. Similarly, while testosterone can increase muscle mass and strength in older individuals and a meta‐analysis has confirmed its safety ⁶⁴, the lack of evidence in persons with sarcopenia did not lead to its integration into these recommendations. Preliminary data with anamorelin, a growth hormone secretagogue receptor type 1 (ghrelin receptor) agonist that increases muscle mass but not strength ⁶⁵ and anti‐myostatin antibodies ⁶⁶ were considered insufficient to make recommendations in favour of their use.

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