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EFFECT OF β-HYDROXY-β-METHYLBUTYRATE (HMB) ON MUSCLE STRENGTH IN OLDER ADULTS WITH LOW PHYSICAL FUNCTION

 

K. Kinoshita1, S. Satake1,2, Y. Matsui3, S. Kawashima2, H. Arai1,2,4

 

1. Section of Frailty Prevention, Department of Frailty Research, Center for Gerontology and Social Science, National Center for Geriatrics and Gerontology, Obu, Japan; 2. Department of Geriatric Medicine, Hospital, National Center for Geriatrics and Gerontology, Obu, Japan; 3. Department of Orthopedics, Hospital, National Center for Geriatrics and Gerontology, Obu, Japan; 4. Director, Hospital, National Center for Geriatrics and Gerontology, Obu, Japan

Corresponding Author: Kaori Kinoshita, R.D., M.S. National Center for Geriatrics and Gerontology, 7-430 Morioka, Obu, Aichi, Japan 474-8511, TEL: +81-562-46-2311, FAX: +81-562-44-8518, E-mail address: kino4ta@ncgg.go.jp

J Aging Res Clin Practice 2019;8:1-6
Published online January 2, 2019, http://dx.doi.org/10.14283/jarcp.2019.1

 

 


Abstract

Objectives: To evaluate the effects of β-hydroxy-β-methylbutyrate (HMB) on muscle strength, physical performance, and muscle mass without additional exercise training in older adults with low physical function. Design: Randomized, controlled trial (Open-label study). Setting: Outpatients. Participants: 34 senior outpatients with low physical function who do not exercise regularly. Intervention: 2.4 g of HMB (3.0 g of calcium β-hydroxy-β-methylbutyrate [CaHMB]) per day was given for 60 days, and subjects in the control group were asked to engage in daily activities as normal. Measurements: Weakness or low function was defined by the Asian Working Group for Sarcopenia criteria, then the participants were assigned to the HMB group or the control group. All participants underwent several evaluations such as grip strength, the timed up and go test, the 5-times chair stand test (5CS), and skeletal muscle mass index by the bioimpedance method at baseline and at the end of intervention or control period. Results: An intragroup comparison of pre- to post-treatment values showed significant improvement in grip strength and the 5CS in the HMB group (grip strength: HMB, 16.6±6.1 kg to 18.2±6.4 kg, P=.001; control, 16.5±4.3 kg to 16.7±4.7 kg, P=.729; 5CS: HMB, 11.0 [8.8-13.0] s to 10.1 [8.5-12.6] s, P=.011; control, 11.1 [8.6-13.8] s to 10.0 [8.8-11.3] s, P=.246). Two-way repeated measures analysis of variance (ANOVA) used to compare the HMB and control groups showed a significant improvement in grip strength in the HMB group compared with the control group (P=.029). Conclusion: A supplementation of HMB without additional exercise may improve muscle strength in older patients with low muscle strength.

Key words: Randomized controlled trial, elderly, Asian Working Group for Sarcopenia, dynapenia, low muscle strength.


 

 

Introduction

One of the important cause of disability in the later lives is thought to be frailty. Frailty, characterized primarily by malnutrition and sarcopenia (a condition featuring loss of muscle mass with either muscular weakness or low physical performance) (1), is reversible (2), meaning that proper evaluation and intervention could bring improvement.
Maintaining skeletal muscle mass by consuming sufficient caloric content and protein and maintaining muscle strength through adequate exercise are effective ways to prevent malnutrition and sarcopenia. Food consumption generally induces protein synthesis and reduces protein catabolism in the skeletal muscles (3), but muscle synthesis in the skeletal muscles of older people appears to be less responsive to amino acids (4), which is called as anabolic resistance. To overcome such a condition, enough consumption of protein or essential amino acids is required, with leucine particularly playing a central role in protein synthesis in the body (5, 6).
The β-hydroxy-β-methylbutyrate (HMB) is a natural metabolic product of leucine (7), but only 5% of the leucine consumed is reportedly converted in the body to HMB. The HMB stimulates body protein synthesis (8) with anabolic effects more powerful than those of leucine (9) and may therefore have a potential effect on muscle growth and performance (10). These findings suggest that HMB may be effective in sarcopenia and dynapenia (11), but research in people with sarcopenia or poor physical performance is currently lacking. The findings of systematic reviews suggest that HMB consumption plus exercise may increase muscular strength in older persons, however there are no firm conclusions on the effects of HMB alone (12, 13). No randomized, controlled trial of HMB in sarcopenia or low physical function has been conducted under the Asian Working Group for Sarcopenia (AWGS) criteria (14).
To address this deficit, we decided to evaluate the effects of HMB consumption without additional exercise and within activities of daily living on physical performance of older people with low physical function.

 

Methods

Participants and informed consent

The participants were independent men and women aged 65 years and over who regularly visited the outpatient clinic of the department of geriatrics of the National Center for Geriatrics and Gerontology of Japan on an outpatient basis and were found to have weakness or low physical function according to the criteria of the AWGS (14) (Figure 1). Candidate participants were those who did not regularly exercise or undergo rehabilitation and had to be available for 2 months of the intervention/control period (the study period).

 

Figure 1 A flow chart of participants

Figure 1
A flow chart of participants

 

Candidates were excluded if they had experienced unintentional weight loss of 3 kg or more over the past 3 months, had an acute medical condition, had renal impairment requiring protein restriction, had moderate or greater cognitive impairment as shown by a Mini-Mental State Evaluation (MMSE) score of 18 or less, were certified as requiring assistance under Japan’s Long-term Care Insurance System, had a cardiac pacemaker, or were unsuited to physical performance evaluation because of visual or auditory impairment, quadriplegia, or a similar condition.
This study, which was grounded in the principles of the Declaration of Helsinki, was approved by the Ethics Committee of the National Center for Geriatrics and Gerontology of Japan. All participants were provided information about the purpose and procedures of the study and expected risks and benefits. Those who acknowledged the information and signed the informed consent form were enrolled.

Evaluation of low physical function

Weakness or low physical function was evaluated using the AWGS criteria (14). Grip strength and usual gait speed were first measured, and then muscle mass was evaluated. Men with a grip strength of less than 26 kg and women with a grip strength of less than 18 kg were considered to have muscular weakness. Participants with a gait speed of 0.8 m/s or below in a 5-m usual gait speed test (the middle 5 meters over an 11-meter walk) were considered to have decreased physical performance. A bioimpedance method was used to determine skeletal muscle mass. Men with a skeletal muscle mass index (SMI) of less than 7.0 kg/m² and women with an SMI of less than 5.7 kg/m² were considered to have low skeletal muscle mass. Sarcopenia was defined as low skeletal muscle mass and either muscle weakness or decreased physical performance. The low physical function was defined as either muscular weakness or decreased physical performance.

Randomization and intervention

Candidate participants who satisfied the criteria were examined by a physician and then informed about the study. Nutritional status was assessed with the Mini-Nutritional Assessment-Short Form (MNA®-SF) at the start of study period to confirm that none of the participants was malnourished. Those participants consenting to participate in the study were randomized by lottery to the intervention or control group.
The participants assigned to the interventional group were given 2 packets per day of a supplement containing 1.5 g of calcium HMB (1.2 g of HMB) (7 g of L-glutamine, 7 g of L-arginine, 1.5 g of calcium HMB; Abound™; Abbott Japan Co., Ltd., Tokyo) for 60 days. The participants were instructed to dissolve this powdered supplement in cold water before taking it because dissolving the supplement in hot water could have degraded its ingredients. The participants were given a calendar to use to record the amount consumed each day for 60 days.
The participants assigned to the control group were asked to conduct daily activities as normal for 60 days.
All participants underwent evaluations at baseline and at the end of study period (i.e., after 60 days). These evaluations were performed by a single trained nurse in the present study (Figure 1).
Participants were considered to have dropped out on becoming unable to undergo physical performance evaluations because of an acute illness, hospitalization, or injury during the study or when HMB compliance was less than 60%. This study was conducted in the full analysis set.

Outcome measures

All outcome measures were evaluated at baseline and at the end of study period. Grip strength was measured with a Smedley handgrip dynamometer (Matsumiya Ikaseiki Seisakusho Co., Ltd., Tokyo, Japan) facing outwards and the grip distance adjusted so that the second knuckle of the index finger was bent at a 90° angle. The participants were instructed to stand with their feet normally spaced and squeeze the dynamometer with their arm hanging so that the dynamometer did not touch their body or clothes. The grip strength of each hand was measured twice, with the highest measurement recorded.
The 5-times chair stand test (5CS) was used to evaluate leg strength. The participants, seated in a chair, were asked to stand and sit 5 times as quickly as possible with their arms folded in front of them. The time required was measured.
Skeletal muscle mass was measured with the Inbody 720 precision body composition analyzer (Inbody Japan Inc. Tokyo). Limb skeletal muscle mass (in kilograms) determined using the bioimpedance method was divided by the square of body height (in meters) to determine the SMI.
Functional mobility was evaluated with the timed up and go (TUG) test. The TUG test comprehensively evaluates functional mobility in terms of walking ability, dynamic balance, and agility. The time required for the participants to stand from a seated position, walk around a pylon 3 meters from the chair, return, and touch their pelvis to the chair was measured. The participants walked around the left and right sides of the pylon once. The shorter time was recorded. A time of 10 s or less is considered normal. Those with a time of 20 s or more are considered to require assistance in daily life (15).
Blood samples were taken to measure serum levels of IGF-1, DHEA-S, and 25(OH)D at baseline and at the end of the study period.

Sample size and statistical analyses

The required sample size was determined according to the calculations of a statistician. Based on the results of previous research (16), 2 groups of 17 participants each for a total of 34 participants were found to be necessary for a level of significance of 5% and power of 80% in statistical testing to evaluate the difference in the mean change in the primary outcome measure of grip strength.
SPSS 23.0 (IBM Japan, Tokyo, Japan) was used for all statistical analyses. A paired t-test was used to compare the pre- and post-treatment values in each group. Two-way repeated measures analysis of variance (ANOVA) was used to compare the changes between the groups. A t-test was used to compare mean differences from before to after treatment when a non-normal distribution was present. P-values less than .05 constituted a significant difference.

 

Results

The participants were sequentially randomized to the HMB group (n=19) and the control group (n=17). Two of the 19 participants in the HMB group were considered to have dropped out because they consumed less than the required amount of HMB (participant A: 54.2%, participant B: 50.0%). In the HMB group, 15 participants had sarcopenia. In the control group, 13 participants had sarcopenia.
The baseline characteristics of the participants are shown in Table 1. Their mean age was 80.4±5.9 years. According to the AWGS criteria, 15 participants in the HMB group and 13 participants in the control group had decreased grip strength, and 4 participants in the HMB group and 6 participants in the control group had decreased gait speed. MNA®-SF scores were 11.7±1.3 in the HMB group and 11.4±1.6 in the control group. No participant in either group was malnourished.

Table 1 Baseline characteristics

Table 1
Baseline characteristics

Average intake of HMB in subjects: 2.21 g/day (2.76 g/day CaHMB); GS: grip strength, WS: walking speed, SMI: skeletal muscle mass index, AWGS: Asian Working Group for Sarcopenia, MMSE: Mini Mental State Examination, MNA®-SF: Mini Nutritional Assessment-Short Form

 

Mean HMB consumption was 2.21 g/day (7.6 g/day as CaHMB). Compliance was 92.1%.
Changes in physical performance during the study period in each group are shown in Table 2. The HMB group achieved significant improvements in grip strength (P=.001) and 5CS (P=.011) with 60 days of intervention. SMI, however, did not change from before to after intervention. Gait speed and TUG scores as indicators of leg performance also showed no significant changes. No measure in the control group changed from before to after follow-up.
Intergroup comparisons of the changes using two-way repeated measures ANOVA showed a significant difference only in grip strength (P=.029).
Changes in blood test values during the follow-up period in each group are shown in Table 3. The only significant difference from before to after treatment was seen in serum 25(OH)D levels, which were significantly lower after 60 days in the HMB group.
Any adverse events on HMB supplement intervention were not observed in this study.

Table 2 Changes in physical functions before and after HMB supplementation

Table 2
Changes in physical functions before and after HMB supplementation

Average intake of HMB in subjects: 2.21 g/day (2.76 g/day CaHMB); Difference within group : * Wilcoxon Signed-rank test, otherwise paired t-test; Difference between groups: * t-test, otherwise two-way repeated measures ANOVA; SMI: skeletal muscle mass index, GS: grip strength, WS: walking speed; 5CS: 5 times Chair Stand test, TUG: Timed Up and Go test

 

 

Table 3 Changes in serum biomarkers before and after HMB supplementation

Table 3
Changes in serum biomarkers before and after HMB supplementation

Average intake of HMB in subjects: 2.21 g/day (2.76 g/day CaHMB); Difference within group: Paired t-test; Difference between groups: Two-way repeated measures ANOVA

 

Discussion

This study evaluated the effects of intervention with 60 days of 2.4 g of HMB (3.0 g of CaHMB) consumption without additional exercise in older people with low physical function. Grip strength improved significantly in the HMB group compared with the control group.
This finding supports the findings of a previous study conducted by Flakoll and colleagues (16). In their study, free- and assisted-living older women (mean age: 76.7 years) who were assigned to the intervention group were given 2.0 g of HMB daily for 12 weeks. Grip strength improved significantly in the present study, which featured intervention for 60 days (about 8 weeks). The duration of intervention in the present study, however, may have been too short to capture the effects of intervention on physical performance and muscle mass. Flakoll and colleagues (16) observed significant improvements in grip strength and leg strength, as well as a tendency of improvement in lean mass, after 12 weeks of intervention. Another study of the effects of consuming 2.0 g of CaHMB daily for 1 year found a significant increase in skeletal muscle mass, and in participants whose blood 25(OH)D level was at least 30 ng/mL, a significant improvement was found in leg strength (17). In the present study, 5CS in the HMB group was significantly shorter after 60 days of follow-up, but it did not differ significantly compared with the control group. Physical performance of the legs depends not only on muscular strength, but also pain caused by motor disorders. Such effects were not considered when selecting the participants, which means that the effects of HMB consumption on leg strength may not have been accurately assessed.
Recent studies have found plasma HMB levels in older people to be positively correlated with grip strength and percent appendicular lean mass (18). Although HMB levels in the blood were not measured, increased blood levels of HMB resulting from regular HMB consumption of a certain amount may have contributed to the increase in grip strength that was observed, given that 82.4% of the participants had low skeletal muscle mass (sarcopenia).
Poor grip strength has been associated with negative outcomes in older people. A survey of hospitalized patients found higher hospitalization costs among patients with poor grip strength (19). Separately, grip strength was found to be significantly predictive of quality of life and the condition requiring assistance after 1 year (20). Known to be associated with several measures of muscular strength, grip strength was recently found to be associated with tongue strength, which contributes to chewing and swallowing function (21, 22). Poor chewing and swallowing function contributes to nutritional imbalance and low food consumption, which in turn contribute to sarcopenia and malnutrition. People whose decline in chewing and swallowing function has progressed such that they can no longer eat regular meals require the support of a caregiver to prepare special meals that they can chew and swallow. When further progression of malnutrition and sarcopenia is present, physical performance also decreases to a level at which further assistance is required. Under the assumption that the improvement in grip strength following HMB consumption that was observed is associated with improved tongue strength, consuming HMB may help prevent declines in chewing and swallowing function.
In this study, blood 25(OH)D levels were significantly lower in the HMB group after 60 days than in the control group. Vitamin D, which binds to receptors in the skeletal muscle, may play a central role in regulating the growth, differentiation, and myotube size of skeletal muscle cells (23). Fuller and colleagues (17) observed a significant improvement in leg strength associated with HMB consumption only in participants with a blood 25(OH)D level of 30 ng/mL or greater. This finding, taken together with the findings of the present study, suggests that synergy between HMB and vitamin D may have certain effects on skeletal muscle synthesis and muscular strength enhancement, but further analysis is required because no studies have considered this speculation.
Nevertheless, there is a limitation regarding the blood vitamin D levels measured in this study. Vitamin D is normally synthesized in the body through the action of ultraviolet light, but the effects of ultraviolet light in the present study are unknown, because the participants’ exposure to sunlight was not measured. Other study limitations include the facts that the control group was not given a placebo, leg strength may not have been accurately assessed because the effects of leg pain and other conditions were not considered when selecting the participants, and the 60-day period of intervention was short. Further research that addresses these limitations is needed to better characterize the effects of HMB on low physical function.

 

Conclusions

The findings of the present study suggest that daily consumption of 2.4 g of HMB (3.0 g of CaHMB) for 60 days (about 8 weeks) without additional exercise may improve muscular strength in older people with low physical function. Although the present study identified no gain in skeletal muscle mass or improvement in physical performance, and no association with blood vitamin D levels was found, it indicated that HMB may be a viable treatment for older adults with low physical function.

 

Acknowledgments: Satomi Furuzono and Yayoi Sakuraba kindly assisted with participant measurements and visit scheduling throughout the study, and the authors would like to express their gratitude to them. The authors also deeply appreciate the kind help of our managerial dietician colleagues Noriko Kojima, Kayoko Hattori, and Saki Tomita for working with the participants and supporting this work.

Author Contributions: Study concept and design: Kaori Kinoshita, Shosuke Satake, and Hidenori Arai. Acquisition of data: Kaori Kinoshita, Shosuke Satake, Yasumoto matsui, Shuji Kawashima, and Hidenori Arai. Analysis and interpretation of data: Kaori Kinoshita, Shosuke Satake, and Hidenori Arai. Drafting of the manuscript: Kaori Kinoshita. Critical revision of the manuscript for important intellectual content: Shosuke Satake, Yasumoto Matsui, Shuji Kawashima, and Hidenori Arai.

Conflicts of interest: This work was supported by grants from the Honjo International Scholarship Foundation and the Chukyo Longevity Foundation, and with funds from Abbott Japan Co., Ltd. The funders had no role in study design, data collection, analysis and interpretation, decision to publish, or preparation of the manuscript. Furthermore, none of the authors have any commercial or financial involvement in connection with this study that represent or appear to represent any conflicts of interest.

Ethical standards: This study has been approved by the research ethics committee of National Center for Geriatrics and Gerontology, Japan.

Funding Sources: Abbott Japan, Honjo International Scholarship Foundation, and Chukyo Longevity Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

 

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SARCOPENIA VERSUS DYNAPENIA: FUNCTIONAL PERFORMANCE AND PHYSICAL DISABILITY IN CROSS SECTIONAL STUDY

 

T. Neves1,3, M. Bomfim Martin Lopes2, M.G. Crespilho Souza3, E. Ferriolli4, C.A. Fett3, W.C. Rezende Fett3

 

1. Department of Physical Education, University of the State of Mato Grosso, Diamantino, MT, Brazil; 2. Department of Physical Education, Physical Education College, IPE Faculty of Technology, Cuiabá, MT, Brazil; 3Department of Physical Education, Nucleus of Studies in Physical Fitness, Computers, Metabolism, and Sports and Health, Federal University of Mato Grosso, Cuiabá, MT, Brazil; 4. Department of Internal Medicine, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

Corresponding Author: Thiago Neves, Department of Physical Education, University of the State of Mato Grosso, 166, Rui Barbosa Street, Eldorado Garden, ZIP Code 78.400-000, Diamantino, MT, Brazil, E-mail address: thiago.alimt@gmail.com. Telephone: +5565-99957-9709. Fax: +55653336-1446.

J Aging Res Clin Practice 2018;7:60-68
Published online April 5, 2018, http://dx.doi.org/10.14283/jarcp.2018.12

 


Abstract

Background: The magnitude of “Sarcopenia” and “Dynapenia” as a public health problem is not well established, nor is the relationship of declines strength and muscle mass to physical disability and/or loss of mobility. Objectives: Test the hypothesis that the elderly with sarcopenia are more likely to physical disability than are those with dynapenia. Design: Cross-sectional study. Setting/Participants: A total of 387 older adults (≥65 years old) from the FIBRA Study in Cuiabá, Mato Grosso, Brazil. Measurements: Sarcopenia was diagnosed according to the European Working Group on Sarcopenia in Older People (EWGSOP), which includes the presence of low muscle mass, plus low muscle strength or low physical performance. Dynapenia was defined as handgrip strength <30kgf (men) and <20kgf (women). Data relating to socio-demographic, behavioral, health conditions, physical disability, the level of physical activity, body composition, hand grip strength and the Short Physical Performance Battery were collected. Results: Regarding the loss of mobility, sarcopenia was associated with age ≥75 years, female, sedentary lifestyle, stroke, arthritis, and falls (OR = 2.95, 95% CI: 1.07 – 8.09); with no association for physical disability in BADL and IADL. Dynapenia had no association with loss of mobility; however, for disability in BADL and IADL, it was associated with the elderly aged ≥80 years old and arthritis (OR = 2.35, 95% CI: 1.42 – 3.88). Conclusion: Dynapenia is more sensitive to the prevention of future self-reported physical disability, in comparison to sarcopenia which can be used in clinical practice as a screening tool for the early decline in mobility..

Key words: Physical disability, mobility, activities of daily living, sarcopenia, dynapenia.


 

Introduction

Physical disability usually occurs in older adults, and it is estimated that 20% to 30% of individuals over 70 years old have difficulties in performing basic and instrumental activities of daily living that require mobility and locomotion. Sarcopenia, which is defined as the loss of muscle mass associated with the presence of low muscle function (strength or physical performance), is one of the main causes of mobility loss and disability related to aging (1–4).
Sarcopenia is a syndrome characterized by the progressive and widespread loss of skeletal muscle mass and strength related to the age, leading to the risk of adverse outcomes, such as physical disability, poor quality of life and death (1). Complementary to the definition of sarcopenia, the recent discussion is that the decline in muscle strength can be given to a combination of muscular and neural factors and not only to reduced muscle mass, so recent questions about the inclusion of muscle mass and strength in the same concept (1, 5, 6).
Recently, results from some studies that analyzed muscle strength and muscle mass and their effect in physical disability, finding that muscle strength is a better predictor of disability (5). Dynapenia is the age-associated loss of muscle strength (5) and premature death (7,8). Thus, the term “dynapenia” was created to describe the functional impairment of the entire neuromuscular apparatus, and it was also claimed that sarcopenia has its original definition limited to the decline in age-related skeletal muscle mass (9). There is no evidence that the definition of sarcopenia has clinical importance (6), but this term attempts to achieve its widespread use. The proposal of the term dynapenia focuses on the aspect of performance seeking to overcome this dichotomy. However, some authors do not agree with the distinction between the terms “dynapenia” and “sarcopenia”, due to the risk of confusion between the nomenclatures (1).
The Fragility in Brazilian Elderly Research Network (FIBRA Network) was designed and developed to investigate and survey data on the prevalence, characteristics, and risk profiles for the biological fragility syndrome, among other syndromes in Brazilian elderly population. This study was performed with urban residents in localities with different levels of human development, in different geographic regions, considering socio-demographic, anthropometric, physical health, physical and mental functionality, and psychological variables (10).
Therefore, this study aimed to test the hypothesis that the elderly with sarcopenia (loss of physical performance and muscle mass) are more likely to physical disability and comorbidities than those with dynapenia (loss of physical performance).

 

Materials and methods

Participants

This research is a subproject of the Fragility in Brazilian Elderly Research Network (FIBRA Network) and consists of an exploratory cross-sectional multidisciplinary and multicentric population-based study, conducted in the period between 2009 and 2010 in 17 Brazilian regions selected by the criterion of quota sampling, with different indices of human development.
Regarding the present study, 513 elderly residents in the urban area of Cuiabá (Mato Grosso State, Brazil) were interviewed through registration forms from the census database of the IBGE, which registered 17,329 older adults. Participants aged under 65 years, or with severe mental retardation, severe or unstable Parkinson’s disease, terminal stage; amputations, and severe orthopedic limitations were not considered in this study.
Thus, only 387 older adults met all the inclusion criteria and completed all the evaluation stages of this study. All participants were previously informed about the study proposal and procedures they would be submitted to. Then they were asked to sign a consent form, approved by the Research Ethics Committee (protocol No. 196/96 CNS, approval number 632/09) of the Hospital Universitário Júlio Müller of the Federal University of Mato Grosso (HUJM-UFMT).

Anthropometric measurements

The body mass of the volunteers was determined using an electronic platform scale (ID 1500, Filizola®, Brazil) with a capacity of 200 kg and a precision of 0.1 kg. The elderly stood up in the middle of the platform scale, with their feet joined and arms along the body. Their height was measured with their body in an upright position, in bare feet, joined and close to the scale, using a portable stadiometer (Sanny®, Profissional model, Brazil) with a precision of 0.1 cm.
The body mass index was calculated by dividing the weight (in kilograms) by the squared height (in meters) (kg/m2). The reference values adopted for the body mass index were those suggested and suitable for the elderly, who are categorized in: <22.0 kg/m² = low weight, from 22.0 kg/m² to 27.0 kg/m² = eutrophic, and >27.0 kg/m² = excess weight (11). The circumferences of the abdomen (AC), waist (WC), calf (CC) and hip (HC) were measured using a flexible and inextensible plastic metric tape (Sanny®, Brazil) with a precision of 0.1 cm. The reference values for AC were ≥94.0 cm for men and ≥80.0 cm for women (12). The CC was used to verify the nutritional status, considering well-nourished those elderly who presented values ≥31 cm, for both genders (13).

Diagnosis and Classification of Sarcopenia

Sarcopenia was diagnosed according to consensus of the European Working Group on Sarcopenia in Older People (EWGSOP), which recommends the use of low muscle mass accompanied by low muscle function (strength or physical performance) for the diagnosis of sarcopenia (1). Thus, the diagnosis of sarcopenia in the present study sample required the confirmation of low muscle mass, in addition to the reduced muscle strength or poor physical performance (Figure 1).

 

Profile of the study using the consensus of the European Working Group on Sarcopenia in Older People (EWGSOP), suggested in case you find sarcopenia in older individuals. SMI = skeletal muscle mass index obtained by the absolute mass of the skeletal muscles divided by squared height in meters (kg/m²)

Profile of the study using the consensus of the European Working Group on Sarcopenia in Older People (EWGSOP), suggested in case you find sarcopenia in older individuals. SMI = skeletal muscle mass index obtained by the absolute mass of the skeletal muscles divided by squared height in meters (kg/m²)

 

Skeletal Muscle Mass Measurement

Muscle mass was estimated by skeletal muscle mass (SMM), using the mathematical equation of Lee (14).

SMM (kg) = 0.244 x body mass + 7.8 x height + 6.6 x gender – 0.098 x age + ethnicity – 3.3
The body mass was determined in kilograms and the height measured in meters. The age (years), gender (1 for men and 0 for women), race (-1.2 for Asians, 1.4 for Afro-descendants, and 0 for Caucasians) were also considered.
This equation was validated in the Brazilian population using the dual energy X-ray (DXA) method, and there was a high correlation between the methods (r = 0.86 for men and r = 0.90 for women, p<0.05). Moreover, there was a strong correlation between DXA and the predictive equation to determine the prevalence of sarcopenia (k = 0.74, p<0.001), with a high specificity (89%) and sensitivity (86%) (15).
The absolute skeletal muscle mass was converted to a skeletal muscle mass index (SMI), divided by squared height (kg/m2). The SMI was used to adjust the height and mass of non-skeletal muscle tissues, being used in several epidemiological studies (16, 17). The low muscle mass was defined by the SMI, with the cut-off point based on 20% of the lowest percentile of the population distribution, representing an SMI of ≤6.47 kg/m2 for women and ≤9.33 kg/m2 for men (16).

Muscle Strength Measurement

Muscle strength was evaluated by the hand grip strength, using a manual hydraulic dynamometer (Saehan Corporation®, Model SH5001, 973, Yangdeok-Dong, Masan 630-728, Korea). For this measurement, the elderly sat on an armless chair, and were positioned with the elbow flexed at 90°; shoulder adducted, forearm in a neutral position, and the wrist between 0° and 30° of extension. Three successive measurements were performed (at about 15 seconds between each one), and the best score of three trials was recorded for analysis. Cut-off values with a hand grip strength less than 30 kgf in men and 20 kgf in women  were considered to represent low muscle strength (1, 4).

Four-Meter Walking Test

The gait speed (meters/second) was determined by assessing the low physical performance of the lower limbs by the 4-meter walking test (4mWT) of the Short Physical Performance Battery (SPPB) (18). The average walking speed of the elderly was calculated by dividing the walking distance by the time spent in the test. The cut-off point of ≤0.8 m/s was used to identify low physical performance (1,4).

Loss of mobility

Loss of mobility was evaluated through the Short Physical Performance Battery (SPPB) (18), which is an instrument composed of three tests that evaluate, in sequence, the standing static balance, gait speed in usual step (measured in two times in a certain round-trip route of 4 meters) and the muscle strength of the lower limbs by the movement of standing up from and sitting down on a chair five consecutive times. The SPPB test is scored on a 0–12 scale, with higher scores indicating a higher functional level. The elderly who scored ≤7 points were considered at risk for mobility loss, because of their clinical relevance was associated with the triage of the elderly at risk of developing future disabilities, in addition to being objective, standardized and multidimensional. The variable of risk for loss of final mobility was dichotomous. A score of 0 indicates a higher functional level (>7 points in the SPPB) and 1 indicates a risk for mobility loss (≤7 points in the SPPB) (19).

Diagnosis and Classification of Dynapenia

Measures of upper extremity muscle strength were isometric shoulder adduction and handgrip. We selected the handgrip for the present analysis because the assessment of handgrip is easy, reliable, and inexpensive. Using the cut-off points indicated the Dynapenia was defined using the criteria with a hand grip strength less than 30 kgf in men and 20 kgf in women, considering with dynapenia those who exclusively lost only muscular strength (1, 4). Included in the classification individuals who had only loss of muscle strength (Figure 1).

Functional capacity

The functional capacity of the elderly for the basic activities of daily living (BADL) and instrumental activities of daily living (IADL) was evaluated by the Katz scale (20) and Lawton & Brody scale (21), respectively. Interviewees were asked if they had difficulties in performing the BADL (transfer, go to the bathroom, take a bath, urinary continence, get dressed, and eat) and the IADL (use a telephone, use mean of transportation, do/go shopping, cook, do light housework, do heavy housework, take medicines, and manage their money). The respondents who indicated difficulty or deficiency in performing one or more of the tasks were classified as having physical disability both in BADL and IADL. The final physical disability variable was dichotomous. A score of 0 indicates no limitation in BADL and IADL, whereas 1 indicates any limitation in BADL and/or IADL.

Physical Activity Level

The assessment of physical activity level was defined using self-report on weekly frequency and the daily duration of physical exercises, active sports, and domestic activities carried out in the week prior to the evaluation, based on items from the Minnesota Leisure Time Activity Questionnaire (22), validated for Brazil (23). For this research, the content, statements, and sequence of the questionnaire items were adapted to the study conducted by the FIBRA Network. Items describing common activities among the Brazilian elderly were kept, and questions on frequency and duration were included, intending to enrich the information on the regularity of the activity practices (if they had been practiced in the last 14 days).
The questionnaire was composed of 42 closed yes or no questions. Each dichotomous answer was followed by other questions about the continuity of activities during the evaluated period (if the elderly had performed each activity in the last two weeks), weekly frequency (how many days in a week) and duration (how many minutes a day).
The elderly who performed at least 150 minutes of weekly moderate-intensity physical activity, or 120 minutes of vigorous-intensity physical activities, following the recommendations of the American College of Sports Medicine (ACSM) and American Heart Association (AHA) (24), were considered active.

Geriatric Depression Scale (GDS)

The depressive symptoms were evaluated using the short version (15 items) of the Geriatric Depression Scale (GDS) (25). These items, together, showed a good diagnostic accuracy, with adequate sensitivity, specificity, and reliability, and can be an alternative for triage mood disorders in the elderly population. Participants with a score of ≥6 in the GDS were considered as having depressive symptoms.

Statistical analysis

The data were analyzed by using the Statistical Package for Social Sciences (SPSS for Windows, version 20.0). The Kolmogorov-Smirnov test was used to verify the normality of the independent variables. The descriptive statistics were presented as mean, standard deviation, median, and minimum – maximum; sample distribution was described, and the prevalence of sarcopenia and dynapenia of the population sample was calculated. For the independent samples, the T-student test was used if the data were parametric and the Mann-Whitney test if the data were non-parametric, and the chi-square test was used to examine the differences in the basic characteristics between the two groups. Values of p≤0.05 were considered significant.
Multiple logistic regression analysis was used to evaluate the effect of sarcopenia and dynapenia on physical disability and loss of mobility. For the degree of mobility, the dummy variables were created and coded, as follows: normal mobility = 0, loss of mobility = 1, whereas for physical disability, the dummy variables were created and coded, as follows: without physical disability = 0, with physical disability = 1, and Odds Ratio (OR) were subsequently computed for these factors. Associations with p≤0.20 in the univariate analysis were selected for logistic regression, for which the step-by-step advance method was used. Model 1 includes sarcopenia as an independent variable and model 2 includes dynapenia.

 

Results

The general characteristics of the sample of elderly are summarized in Table 1. The participants’ mean age was 72 years, most of them weren’t married, white, but had on mean 4 years of schooling, and received less than R$510,00 monthly. Regarding the occurrence of health problems, there was a prevalence of hypertension, diabetes, arthritis/rheumatism, and osteoporosis, with a high cardiovascular risk since the waist circumference was higher than the reference value: 94.0 cm for women and 105.0 cm for men. Sarcopenia and dynapenia were in 15% and 38% of the elderly, respectively, and were higher in women than in men (Table 1).

Table 1 The general characteristics of the sample of elderly by genders, Cuiabá, Mato Grosso, Brazil (2010)

Table 1
The general characteristics of the sample of elderly by genders, Cuiabá, Mato Grosso, Brazil (2010)

 

The majority were women; among them, there was a higher percentage of older people, with an income lower than R$ 510.00 monthly, excess weight, and a higher percentage of fat, arterial hypertension, arthritis, osteoporosis, and occurrence of falls, compared to men (Table 1).
The elderly with sarcopenia and dynapenia had functional and physical performance significantly lower in comparison to those classified as normal, and were slower and reported more dependencies in ADL (Table 2).

Table 2 Functional performance and physical dependence on 387 seniors living in Cuiabá, Mato Grosso, Brazil (2010)

Table 2
Functional performance and physical dependence on 387 seniors living in Cuiabá, Mato Grosso, Brazil (2010)

Different letters show significant statistical difference between the groups (p ≤ 0.05). Mann-Whitney test with data expressed as median (minimum-maximum). SPPB – Short Physical Performance Battery. BADL – basic activities of daily living. IADL – instrumental activities of daily living.

 

The logistic regression analysis for loss of mobility and disability in BADL and IADL is shown in Table 3. In model 1, the odds ratio (OR) and 95% CI for the factors statistically associated with loss of mobility were: being 75 years old or older, woman, sedentary, have had a stroke, arthritis, falls, and sarcopenia. The factors associated with disability in BADL and IADL were: being 80 years old or older, have had arthritis, and being a woman.

The logistic regression analysis for loss of mobility and disability in BADL and IADL is shown in Table 3. In model 1, the odds ratio (OR) and 95% CI for the factors statistically associated with loss of mobility were: being 75 years old or older, woman, sedentary, have had a stroke, arthritis, falls, and sarcopenia. The factors associated with disability in BADL and IADL were: being 80 years old or older, have had arthritis, and being a woman. In model 2, the OR and 95% CI for factors statistically associated with loss of mobility were the same as those found in model 1, but dynapenia was not associated with loss of mobility. The factors associated with disability in BADL and IADL were being 80 years old or older, have had arthritis and dynapenia.

Table 3 Multiple logistic regression models to test the association of physical dependence or loss of mobility with sarcopenia and dynapenia in the study in 387 seniors living in Cuiabá, Mato Grosso, Brazil (2010)

Table 3
Multiple logistic regression models to test the association of physical dependence or loss of mobility with sarcopenia and dynapenia in the study in 387 seniors living in Cuiabá, Mato Grosso, Brazil (2010)

OR – Odds ratio. CI – Confidence interval. SPPB – Short Physical Performance Battery. BADL – basic activities of daily living. IADL – instrumental activities of daily living.

 

Discussion

Perhaps the most relevant aspect of the present study is the observation that both classifications (sarcopenia and dynapenia) were significantly associated with physical disability and comorbidities, with a prevalence of 15% and 38%, respectively. Therefore, a division of these classifications is necessary because only the classification as sarcopenia, as proposed by some authors (1), would underestimate an important percentage of individuals with high risk for health and physical disability. Few studies involving elderly individuals have carried out these associations separately. Loss of mobility was only associated with sarcopenia; however, there was an association of self-reported physical disability in BADL and IADL only with dynapenia. Our results suggest that the association between sarcopenia and loss of mobility could be explained by the present comorbidities, the sedentary lifestyle, and the occurrence of falls.
The prevalence of sarcopenia varies among different populations, due to differences relating to age, gender, diagnostic method, and evaluation instruments (26–29). Different instruments used to define sarcopenia, as well as the age group and incompatible living habits of the study population may cause different diagnoses of its prevalence. Because of this variability, it is necessary to emphasize the importance of adopting a standardized and operational definition of sarcopenia for multidimensional geriatric assessment, similarly to the one adopted in the present study.
It is believed that the evaluation of muscle strength by the isolated hand grip strength is useful only in the triage phase of dynapenia, because it explains about 40% of the variation in the strength of the lower limbs, suggesting, for the diagnosis, the evaluation of the muscular strength by the extension of the Knee due to its association with gait speed and physical function (5). Other researchers observed that hand grip strength was a strong predictor of gait speed reduction and self-reported physical disability (in BADL and IADL) (30). These researchers found, in the elderly with low hand grip strength, a higher incidence of physical disability in IADL, and this correlation was higher in women (2.28, 95% CI = 1.59 – 3.27) than in men (1.90, 95% CI = 1.13 – 3.17) (31).
However, in this study, the hand grip strength was used as a method to define the dynapenia, since it is a good indicator of the strength of the whole body, given that a low hand grip strength is strongly associated with a high probability of mortality, the risk of complications and development of physical disability (8,32). Moreover this method makes easier the strength measurement, and it is significantly less expensive and accessible to developing countries, such as Brazil.
Sarcopenia was associated with an increase in loss of mobility, with advancing age, especially in sedentary women, with arthritis or stroke, and with a history of falls. These results together suggest that reductions in skeletal muscle mass accompanied by a decline in strength or physical performance with the aging, as suggested in the EWGSOP document, cause loss of mobility, and if these declines reach a critical point, the physical function can be compromised (33,34).
Data used from the longitudinal Health Aging and Body Composition Study, which observed 3,075 elderly Americans, showed that the lowest quintile of muscle mass was associated with a poor performance of the lower limbs in both genders (35), and they also showed an association with loss of mobility, similar to the results found in our study (34).
The Health, Welfare and Aging (SABE in Portuguese) study, conducted in Brazil with 478 elderly individuals aged 60 years or over, compared the association of sarcopenia and dynapenia with the incidence of deficiency in mobility or IADL, and with disability in basic and instrumental activities of daily living. The authors observed that sarcopenia was associated with a deficiency in mobility or IADL (2.38, 95% CI 1.10 – 5.17), whereas dynapenia was neither associated with physical disability nor with the loss of mobility (33), corroborating, in part, our findings since the dynapenia was associated with self-reported physical disability. Melton et al. (36) reported an association of sarcopenia with walking difficulty in older men and women.
Several studies have shown a relationship between sarcopenia and self-reported physical disability, using scales of basic and instrumental activities of daily living (16,17,37,38), evidencing that women and men with sarcopenia were 3.6 and 4.1 times, respectively, more likely to physical disability in comparison to individuals without sarcopenia (16). On the other hand, some authors reported that only severe sarcopenia was independently associated with an increase in the probability of functional damage and physical disability in the elderly, after adjustments for potential variables of confusion, such as age, race, health behaviors, and comorbidities (37), in addition, they showed that the effect of sarcopenia on physical disability was considerably lower (38,39). However, in our study, the self-reported physical disability was not associated with sarcopenia.
Another study carried out in Australia with 1,705 elderly men, aimed to determine the association among loss of strength, mass and muscle quality, functional limitation, and physical disability, concluded that the muscle strength measurement is the best one to measure age-related muscle change and that it is associated with the deficiency in instrumental activities of daily living and functional limitation (3), corroborating our results. In a sample of 1,030 elderly Italians, some researchers concluded that isometric hand grip strength is strongly related to muscle power of the lower extremities, knee extensor torque, and calf cross-sectional muscle area, and that the decrease in hand grip strength is a clinical marker of mobility loss (walking speed <0.8m/s) better than the decline in muscle mass (4). In other words, conversely to our findings, these researchers evidenced that low values of muscle strength can predict, regardless of other risk factors, the incidence of physical disability (31).
However, in our study, we did not find this association with sarcopenia, perhaps because the elderly participants did not have a high degree of disability in ADL, which could lead to a poor functional performance, explaining this dissociation, besides the fact that these activities are related to works that do not require strength, muscular endurance, and walking speed (40). The differences may be related to diversities in outcome measurements and characteristics of the studied populations, in addition to the fact that physical disability is self-reported, which can hide the true relationship between sarcopenia and physical disability in these elderly. In this sense, a battery of physical tests may be adequately sensitive to support the diagnosis of present and future dependencies and comorbidities (41).
Also, our study indicated that dynapenia was associated with disability in ADL, agreeing with some studies that reported the relationship between dynapenia (measured through hand grip strength) and ADL (31,32). Furthermore, these studies indicated that strength and body mass index (BMI) were positively and negatively associated with the disability in ADL, respectively (39). In this study, the occurrence of falls and sedentary lifestyle were other factors associated with loss of mobility. As found in other studies, older men and women, who are less physically active, have less skeletal muscle mass, which can increase the prevalence of physical disability (42). Thus, the effects of physical exercise, including a simple walk, can protect against the loss of mobility in older adults. Falls and their related injuries are a major health problem in the elderly population and are associated with an increase in morbidity and physical disability (16).
From the results presented here, the following limitation can be considered: 1) The fact this is a cross-sectional study, so the cause-and-effect relationships could not be established. 2) The use of regression equations to estimate muscle mass can underestimate or overestimate the prevalence of sarcopenia. However, few studies have used the DEXA to estimate muscle mass in elderly populations and epidemiological studies because of the high cost. Therefore, simple and feasible options that have the same function without causing population risk are indicated. Furthermore, the equation used in the present study was validated in American and Brazilian populations, presenting a high correlation with magnetic resonance and DXA (14,15). 3) The use of the sarcopenia equation (equation that assists in the diagnosis of sarcopenia by estimating skeletal muscle mass) does not include BMI, it only includes the weight and height in its logistic regression analysis. However, it is known that 50% of the variance of muscle mass is explained by BMI, preventing the identification of other factors related to muscle mass. 4) The FIBRA Study aimed to evaluate the population of elderly residents in the community and did not include the elderly from asylums and hospitals. Thus, the relationship between sarcopenia and physical disability and between dynapenia and physical disability cannot be considered for all elderly population.
Finally, regarding the dynapenia, few population studies were found, as it is a recent issue (32,43). However, the prevalence of dynapenia, as reported for sarcopenia, shows differences among the previous studies (32,43). Probably, the discrepancies among the results can be related to the lack of sufficient evidence in the literature to identify specific cut-off points, complete assessment of risk factors, and the lack of consensus relating to methods and instruments used to define the final diagnostic algorithm. Nevertheless, it is observed in the present study that, among the used methods, the one used to classify dynapenia was more sensitive to associate a higher percentage of the studied population with the factors related to self-reported physical disability.

 

Conclusions

In summary, this study is relevant because it focused on a large sample of elderly residents in the community, which represents the elderly population in a large Latin American city, in addition to comparing dynapenia with sarcopenia, using the EWGSOP criteria as factors of risk for the loss of mobility and physical disability in ADL.
It also evidenced that individuals who lost strength in addition to muscle mass were more likely to the loss of mobility than those who only lost muscle strength. However, the elderly with dynapenia showed a high disability in self-reported ADL. These associations were measured by the presence of comorbidities, sedentary lifestyle, and occurrence of falls.
The classification of dynapenia differs from the classification of sarcopenia (according to the EWGSOP) in qualitative and quantitative aspects, and we found a higher percentage of individuals classified as having dynapenia. This fact demonstrates that, at least in this population, the classification as dynapenia is more sensitive to prevent future physical dependencies in comparison to the classification as sarcopenia, and can be used in clinical practice as a screening tool for the early decline of mobility. Thus, we emphasize the need for an active lifestyle and the inclusion of physical exercise programs to protect old people against the loss of mobility.

 

Author affiliations: Center for Physical Fitness, Informatics, Metabolism, Sports and Health, Faculty of Physical Education, Federal University of Mato Grosso, Cuiabá, Mato Grosso State, Brazil (Thiago Neves, Marcela Bomfim Martin Lopes, Milene Giovana Crespilho Souza, Carlos Alexandre Fett, Waléria Christiane Rezende Fett). We thank the members of the Fragility in Brazilian Elderly Research Network (FIBRA Network) who assisted with the scientific and data collection team, in particular the general coordinator of this study, Eduardo Ferriolli, professor at the University of São Paulo, Medical School of Ribeirão Preto , Department of Clinical Medicine, Division of General Medical Clinic and Geriatrics. This research was supported by the National Council of Scientific and Technological Development – CNPq (nº 17/2006) and by the Foundation for Research Support of the State of Mato Grosso – FAPEMAT (002.017/2007). The funding body had no role in the design, data collection, data analysis and interpretation of the study, article writing, or in the decision to submit the manuscript.

Role of the Funding Source: This research was supported by the National Council of Scientific and Technological Development – CNPq (nº 17/2006) and by the Foundation for Research Support of the State of Mato Grosso – FAPEMAT (002.017/2007).

Conflict of interest: None declared.

Ethical standard: The experiments described in this manuscript comply with the current of laws of Brazil.

 

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