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M.J. Benton, A.L. Silva-Smith, J.M. Spicher

University of Colorado Colorado Springs, Colorado Springs, CO, USA.
Corresponding author: Melissa J. Benton, PhD, RN, Helen & Arthur E. Johnson Beth-El College of Nursing & Health Sciences, University of Colorado Colorado Springs, 1420 Austin Bluffs Parkway, Colorado Springs, CO 80918, phone: +1-719-255-4140, email: mbenton@uccs.edu

J Frailty Aging 2020;in press
Published online December 23, 2020, http://dx.doi.org/10.14283/jfa.2020.72


Background: Muscle provides a reservoir for water to maintain fluid volume and blood pressure, so older adults may be at risk for orthostatic hypotension due to muscle loss with age. Objectives: To evaluate the association between muscle loss with age and postural blood pressure. Design: Longitudinal comparison of overnight changes in hydration, postural blood pressure, and strength. Setting: Community field study. Participants: Sixty-nine men and women (76.0 ± 0.8 years) with low (Low) or normal (Normal) muscle based on the Lean Mass Index. Measurements: Body composition was measured with bioelectrical impedance analysis. Postural blood pressure was measured sequentially (lying, sitting, standing). Strength was measured with a handgrip dynamometer, Arm Curl test, and Chair Stand test. Results: On Day 1, Low had less hydration and a significant drop in postural systolic blood pressure compared to Normal (lying to standing: -11.06 ± 2.36 vs. +1.14 ± 2.20 mmHg, p < 0.001). Overnight, both groups lost significant total body water, while fluid volume was unchanged. On Day 2, both groups experienced significant drops in postural systolic blood pressure, although the drop in Low was more profound and significantly greater than Normal (lying to standing: -16.85 ± 2.50 vs. -3.89 ± 2.52 mmHg, p = 0.001). On both days, Normal compensated for postural changes with increases in postural diastolic blood pressure not observed in Low. Only Low experienced significant overnight decreases in all strength measures. Conclusions: In older men and women, muscle loss with age is accompanied by loss of hydration and less stable early morning postural systolic blood pressure that increase risk for orthostatic hypotension and can also increase risk for falls.

Key words: Orthostatic hypotension, postural blood pressure, lean mass index, hydration, strength.



Orthostatic hypotension (OH) increases risk for cognitive impairment, disability, and mortality (1-4). Generally, among older adults, the prevalence of OH is greater than 20% (5). However, among those with a history of falls, prevalence can exceed 50% (6). Finally, frailty and OH are associated, and among frail older adults, prevalence can be as high as 66% (4).
The criteria for OH are a decrease in postural systolic blood pressure of ≥ 20 mmHg or a decrease in postural diastolic blood pressure of ≥ 10 mmHg within three minutes of standing (7). Older adults who meet this criteria have been found to be weaker, slower, and have diminished physical function compared to those without OH (8). Notably, these characteristics are diagnostic of frailty (9), and related to sarcopenia or muscle loss with age (10).
Muscle provides a reservoir for water to maintain fluid volume and blood pressure (11), so older adults with low muscle mass may be at risk for OH, especially when oral intake is diminished, such as the overnight period. We previously demonstrated that older women with less muscle mass also have less total body water and intramuscular water compared to those with greater muscle mass, and these differences are reflected by more unstable systolic and diastolic postural blood pressure that meets the criteria for OH (12). By comparison, men have greater muscle mass, experience less loss with age, and have a lower prevalence of OH (2, 13). Nonetheless, men are at risk for OH and to our knowledge, the association between muscle, hydration, and postural blood pressure has not yet been evaluated among older men. Therefore, the objective of this study was to answer the question: Is muscle loss with age associated with risk of OH in both older men and women? To do so, we compared overnight changes in hydration, postural blood pressure, and strength in community-dwelling older men and women.




Men and women were recruited who were age 65 years or older, non-smokers, able to stand up independently, and able to ambulate independently or with an assistive device such as a cane or walker. Because our variable of interest was hydration, participants were excluded if they were currently using diuretic medications, or had any condition that could influence hydration including fever, nausea, vomiting or diarrhea; hemodialysis or peritoneal dialysis; or had been hospitalized within the last month.


The university Institutional Review Board approved the study and all participants gave written informed consent prior to enrollment.


Participants completed two identical measurement sessions in their own homes on consecutive days. Baseline (Day 1) measurements were completed in a euhydrated state (normal food and fluid intake) between 10:00 am – 4:00 pm when older adults are most well hydrated based on their 24-hour fluid consumption patterns (14). The second (Day 2) measurement session was completed the next morning, within 30 minutes of waking with participants in a fasted state (no food or fluids for at least 8 hours). All data were collected by the same researcher.


Lean mass and hydration were measured using multifrequency bioelectrical impedance analysis (Quadscan 4000, Bodystat, UK). Participants remained supine for at least 5 minutes prior to measurement. Bioelectrical impedance analysis is valid, reliable, and accurate despite hydration status (15).
Postural blood pressure was measured using a digital blood pressure monitor (Omron Healthcare, Japan). Three sequential measurements were taken (lying, sitting, standing). The initial (lying) measurement was taken after completion of lean mass and hydration measurement, so participants had been resting for at least 5 minutes. The second (sitting) measurement was taken 1 minute after sitting upright with both feet flat on the floor. The third (standing) measurement was taken 1 minute after standing erect.
Handgrip strength was measured to the nearest 0.1 kg using a digital grip dynamometer (Takei Scientific Instruments, Japan). Participants sat with the device in their dominant hand, their arm supported on a stable surface, their wrist in a neutral position, and their elbow at a 90° angle. They squeezed the device one time as hard as possible for 3 seconds. Handgrip strength has been validated using manual upper extremity muscle strength testing as the criterion measure (16), and reliability has been established in multiple studies with intra-class correlation coefficients exceeding 0.80 (17). Moreover, handgrip dynamometry has strong predictive validity for cognitive, physical, and functional decline in older adults (18).
Upper and lower body strength was measured using the Arm Curl and Chair Stand tests. For the Arm Curl, participants sat with a 5-lb (women) or 8-lb (men) dumbbell in their dominant hand. They repeatedly raised and lowered it through a full range of motion for 30 seconds. For the Chair Stand test, participants remained seated with both arms folded across their chest. They repeatedly stood up to a fully erect position and sat down again for 30 seconds. Criterion validity for the 30-second Arm Curl and Chair Stand tests has been determined using laboratory measurement of maximal upper and lower body strength (chest and leg press), and test-retest reliability has been well established with intra-class correlation coefficients exceeding 0.80 (19-21).

Grouping for Analysis

Participants were grouped by lean mass relative to height (kg/m2) using the Lean Mass Index (LMI). Low muscle mass (Low) was defined as women <15.0 kg/m2 and men <19.0 kg/m2, and normal muscle mass (Normal) was defined as women ≥15.0 kg/m2 and men ≥19.0 kg/m2, 22).

Statistical Analysis

Data were analyzed using SPSS version 25 (IBM, USA). Analysis of variance (ANOVA) was used to identify individual between-group differences, and repeated measures ANOVA was used to evaluate between and within-group differences over time (Day 1 vs. Day 2 measurements). An additional multivariate analysis using age as a covariate was conducted to assess the influence of age on postural blood pressure changes. Chi-square analysis was used to evaluate between-group differences in gender, and Spearman correlation analysis was used to evaluate the influence of gender on postural blood pressure changes. Significance was determined as p < 0.05 and data were reported as mean ± standard error with 95% confidence intervals. Effect sizes were calculated as eta squared (η2) and interpreted as small (≥ 0.01), medium (≥ 0.06), and large (≥ 0.14) effects. Sample size calculation determined that 64 participants were adequate for a two-group ANOVA with a significance level of 0.05, 80% power, and a medium effect size.



Sixty-nine men (n = 37) and women (n = 32) completed the study. Overall, they were 76 ± 0.8 years of age with an average body mass index (BMI) of 26.0 ± 0.5 kg/m2 (Table 1). There were no differences between genders for age, BMI, or resting (lying) blood pressure, and correlation analysis identified no influence of gender on postural blood pressure changes, so men and women were combined for analysis based on LMI. In total, 34 participants met the criteria for Low muscle mass. Nineteen (55%) were males and 15 (45%) were females.

Table 1
Participant characteristics at baseline (Day 1)

Note: Data reported as Mean ± SE, [95% CI], (η2) = effect size (eta squared); Low = Low muscle group; Normal = Normal muscle group; M = Male; F = Female; *Between-group differences in co-morbidities calculated using Fisher’s Exact Test.

At baseline (Day 1), participants in the Low group were significantly older, with lower body mass and BMI. They also had less lean mass that was accompanied by significantly less total body water, fluid volume, and intramuscular water. Although resting systolic blood pressure did not differ between groups, those in the Low group had significantly lower resting diastolic blood pressure, as well as significantly lower systolic and diastolic blood pressure when repositioned to sitting and standing postures (Table 1). In addition, during postural changes the Low group experienced a significant decrease in systolic blood pressure compared to the Normal group, which remained relatively stable (lying to standing: -11.06 ± 2.36 vs. +1.14 ± 2.20 mmHg, p < 0.001, η2 = 0.18) (Figure 1A). At the same time, a difference in diastolic blood pressure was observed. Specifically, the Normal group compensated for postural changes by increasing diastolic blood pressure, while the Low group did not (lying to standing: +5.14 ± 1.38 mmHg vs. +0.56 ± 1.49 mmHg; p = 0.027, η2 = 0.07). When age was included as a covariate, between-group differences in postural systolic blood pressure were somewhat attenuated (adjusted p = 0.003), while between-group differences in postural diastolic blood pressure were no longer significant.

Figure 1
Postural blood pressure changes on Day 1 (A) when participants were normally hydrated and Day 2 (B) when participants had fasted overnight. On both days, participants with low muscle had significant drops in systolic BP (Day 1: -11.06 ± 2.36 mmHg, p < 0.001; Day 2: -16.85 ± 2.50 mmHg, p < 0.001) that were not observed in those with normal muscle (Day1: +1.14 ± 2.20 mmHg; Day 2: -3.89 ± 2.52 mmHg). In contrast, participants in the normal muscle group compensated for postural changes with increases in diastolic BP (Day 1: +5.14 ± 1.38 mmHg, p = 0.027; Day 2: +5.37 ± 1.17 mmHg, p = 0.009) that were not observed in the low muscle group (Day 1: +0.56 ± 1.49 mmHg; Day 2: -0.03 ± 1.67 mmHg)


Overnight, both groups lost significant but similar amounts of total body water (p < 0.001), although only the Normal group lost significant amounts of intramuscular water (p = 0.038). Fluid volume remained stable in both groups (Table 2, Figure 2). This change in hydration was manifested as significant (p < 0.001) overnight decreases in both body mass (Low: -0.85 ± 0.07 kg; Normal: -0.97 ± 0.26 kg) and lean mass (Low: -1.08 ± 0.13 kg; Normal: -1.09 ± 0.16 kg). However, there were no between-group differences in any of these overnight changes. By comparison, significant between and within-group differences were observed in postural blood pressure (Figure 1B). On Day 2, systolic blood pressure decreased significantly (p < 0.001) during postural changes from lying to standing in both groups. However, the decrease in the Low group was even more profound than on Day 1 and significantly greater than that observed in the Normal group (lying to standing: -16.85 ± 2.50 vs. -3.89 ± 2.52 mmHg, p = 0.001, η2 = 0.18). Furthermore, as was observed on Day 1, the Normal group again compensated for postural changes with an increase in diastolic blood pressure that was significantly greater than the Low group that again remained stable (lying to standing: +5.37 ± 1.17 vs. -0.03 ± 1.67 mmHg, p = 0.009, η2 = 0.17). When age was included as a covariate, between-group differences in postural blood pressure were again somewhat attenuated (systolic blood pressure: adjusted p = 0.004; diastolic blood pressure: adjusted p = 0.040). Overall, on Day 2, 44.1% (n = 15) of the Low group met the criteria for OH (decrease in postural systolic blood pressure of ≥ 20 mmHg or decrease in postural diastolic blood pressure of ≥ 10 mmHg) compared to only 8.6% (n = 3) of the Normal group (p = 0.001).

Table 2
Overnight changes in mass, hydration, and strength in participants with Low and Normal muscle

Note: Data reported as Mean ± SE, [95% CI], (η2) = effect size (eta squared); Low = Low muscle group; Normal = Normal muscle group

Significant overnight changes in strength that favored older adults in the Normal group also occurred. On Day 1, handgrip strength was similar between groups (Low: 24.5 ± 1.6 kg; Normal: 22.5 ± 1.6 kg) (Table 1). Overnight, a significant between-group difference was observed (Table 2). Participants in the Low group experienced a significant decrease in handgrip strength (-2.42 ± 0.48 kg; p = 0.001) that was not observed in the Normal group (-0.76 ± 0.77 kg). A similar pattern was also observed in lower body strength. For lower body strength measured as the Chair Stand test, both groups were initially similar (Low: 11.6 ± 0.8 repetitions; Normal: 10.6 ± 0.7 repetitions). Overnight, a significant decrease in lower body strength was observed in the Low group (-1.42 ± 0.41 repetitions, p = 0.001) that was not observed in the Normal group (-0.43 ± 0.22 repetitions), and that resulted in a statistically significant difference between groups (p = 0.034). Finally, Arm Curl scores were initially similar between groups (Low: 14.5 ± 0.5 repetitions; Normal: 14.8 ± 0.8 repetitions). Overnight, a significant decrease was observed in both groups (Low: -2.67 ± 0.40 repetitions; p < 0.001; Normal: -0.91 ± 0.37 repetitions, p = 0.017), although the decrease in the Low group was statistically greater than that observed in the Normal group (p = 0.002).

Figure 2
Overnight changes in hydration between participants with Low and Normal muscle. Both groups lost similar and significant amounts of total body waster (p < 0.001), while only the Normal group lost significant amounts of intramuscular water (p = 0.038). Fluid volume remained stable in both groups



To our knowledge, this is the first study to evaluate postural blood pressure changes in men and women using muscle as the criterion for evaluation. Based on our findings, muscle loss with age is associated with risk for OH in both men and women. Although the average drop in postural systolic blood pressure of 17 mmHg that we observed in participants with low muscle mass was less than the ≥ 20 mmHg decrease needed to meet the definition of OH, the differences between older men and women with low compared to normal muscle mass were statistically significant with large effect sizes. Hence, we believe our findings reflect a clear association with muscle loss, especially as we found a statistically greater prevalence of participants that met the diagnostic criteria for OH among participants with low muscle mass (44.1%) compared to those with normal muscle mass (8.6%). Furthermore, we found no relationship with gender, indicating that both men and women are equally susceptible despite differences in absolute and relative lean mass.
Poor nutrition, which increases the risk for muscle loss and frailty in older adults, has previously been found to be associated with OH (23). This is consistent with the differences in body composition observed among our participants, in which those with low muscle were also observed to have significantly less fat and an overall lower BMI compared to those with normal muscle. Some previous research has demonstrated a negative association between BMI and OH, such that older adults with OH had lower BMI levels than those without OH (4, 24). However, average BMI values were in the overweight category and in one study, differences were not statistically significant (4). The association between OH and BMI is not clear. In other previous reports of normal (25) and overweight (2) older adults with and without OH, there were no differences based on BMI. Furthermore, in a comparison of OH prevalence among robust, pre-frail, and frail older adults, the prevalence of OH and participant age increased significantly with level of frailty, but there was no difference in BMI, which was in the overweight category for all participants (26). We believe the link between frailty and OH may lie in the influence of lean (muscle) mass. This is a gap in the literature and should be explored.
In addition to greater instability in postural blood pressure, participants with low muscle experienced greater overnight losses of strength compared to those with normal muscle. When loss of strength, especially in the lower body, is accompanied by severe early morning drops in postural blood pressure, this increases risk for falls in the early morning when between 30 to 50% of falls are reported to occur (27). Falls are of concern among older adults with OH, who have a greater than 50% higher risk of a first fall than older adults without OH (28). Treatment of OH is frequently driven by concerns regarding potential injuries due to falls. Unfortunately, first line treatment often focuses on medication reduction, including cardiovascular medications such as antihypertensives (29). This creates a burden for patients who must choose between the risks associated with OH and potential risks associated with discontinuance of medications. Cardiovascular medications optimize blood pressure control and reduce the risk of stroke, myocardial infarction, renal dysfunction, and complications of diabetes (30). Furthermore, abrupt discontinuation of blood pressure-lowering medications, can place patients at risk for an acute stroke or cardiovascular event (31). Non-pharmacological strategies for management of OH are available, but evidence indicates that they are minimally effective (32), and not generally acceptable to older adults with OH (33).
Increasing muscle mass may represent a novel strategy for OH that has not previously been considered. Although frailty is associated with OH (4), we can find no studies in which body composition has been included in the assessment of older adults with OH. Nonetheless, decreased fluid volume and deconditioning are recognized factors in the etiology of OH (34). Muscle, as a repository for body fluids, enhances fluid volume. As observed in our participants, those with greater muscle had significantly greater reserves of water. Furthermore, there was a non-selective loss of fluid overnight of approximately one liter that did not differ between those with low and normal muscle mass. This non-selective fluid loss is consistent with what we previously observed in older women (12). Our interpretation is that individuals with limited fluid reserves due to reduced amounts of muscle cannot compensate for fluids losses during periods of low intake. Hence, in our study, when muscle tissue apparently “donated” intramuscular water to maintain overall fluid volume during the overnight period, those with low muscle mass were seen to be at greater risk for unstable postural blood pressure and loss of strength compared to those with greater muscle mass and the fluid reserves that accompany it.
Resistance training may represent a feasible non-pharmacologic approach to blood pressure management in the context of OH. However, evidence is limited. We identified only one resistance training program for patients with OH by Zion and colleagues (35), and it did not successfully improve blood pressure. However, the duration was only 8 weeks and elastic bands were used for training. While elastic bands can provide adequate resistance to stimulate muscle hypertrophy, their use in research has been limited. Krause and colleagues reported use of elastic bands to increase muscle mass in healthy older adults, but the training program was 12 weeks long and all training was supervised (36). Unfortunately, Zion and colleagues did not measure body composition (35), but it seems likely that their shorter, unsupervised program was not sufficient to increase muscle mass and therefore had no effect on blood pressure. Evidently, more research is needed.
We recognize that the fact that we did not control for medications other than diuretics may be considered a study weakness. However, we also recognize that use of medications is increasing, especially use of multiple medications. In the United States, approximately 90% of older adults report use of at least one medication, while approximately 40% report polypharmacy (use of 5 or more medications) (37, 38). For the current study, we used a pragmatic approach with the intent of evaluating older adults under real-world conditions in their own homes, and those conditions include use of regularly prescribed medications. Furthermore, previous research demonstrates that medications do not have a significant influence on OH (39, 40). In older men and women no association has been found between OH and either the number or type of medications, including antihypertensives, diuretics, antipsychotics, antidepressants, and drugs for Parkinson’s disease (39, 40). Nonetheless, there are numerous other types of medications that may influence OH that have not been evaluated.
In conclusion, our findings support a role for muscle in maintaining stable postural blood pressure and decreasing risk for OH. Although more research is evidently needed, in these older adults, muscle loss with age was accompanied by loss of hydration and less stable early morning systolic blood pressure that may increase risk for falls. Resistance exercise to increase muscle mass may provide a novel therapeutic strategy that should be explored.

Acknowledgements: The authors thank Andrew Quinonez for assistance with graphic design to format the figures for publication.
Funding: No funding was received for this study.
Conflicts of Interest: All authors declare no conflict of interest.


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N.W. Bray1, G.J. Jones1, K.L. Rush2, C.A. Jones3, J.M. Jakobi1

1. School of Health and Exercise Sciences, Faculty of Health and Social Development, University of British Columbia Okanagan, Kelowna, British Columbia, Canada; 2. School of Nursing, Faculty of Health and Social Development, University of British Columbia Okanagan, Kelowna, British Columbia, Canada; 3. Southern Medical Program, Faculty of Medicine, University of British Columbia Okanagan, Kelowna, British Columbia, Canada.
Corresponding author: Jennifer M. Jakobi, School of Health and Exercise Sciences, Faculty of Health and Social Development, University of British Columbia Okanagan, Kelowna, British Columbia, Canada, V1V 1V7, jennifer.jakobi@ubc.ca

J Frailty Aging 2020;9(2)118-121
Published online March 30, 2020, http://dx.doi.org/10.14283/jfa.2020.15



Approaches to and benefits from resistance training for non-compromised older adults are well known. Less is understood about resistance training with pre-frail older adults, and even less information is available on the practical approaches to delivery. Herein, we describe an approach in pre-frail females who undertook a multi-component exercise intervention, inclusive of high-intensity, free-weight, functional resistance training. Capitalizing on the principle of overload is possible and safe for pre-frail females through constant reassurance of ability and adjustments in technique. Making exercise functionally relevant, for example, a squat is the ability to get on and off a toilet, resonates meaning. Older pre-frail females are affected by outside (clinical) influences. The exercise participant, and extraneous persons need to be educated on exercise approaches, to increase awareness, debunk myths, and enhance support for participation. Identification of individuality in a group session offers ability to navigate barriers for successful implementation.

Key words: Multi-component exercise, females, aging, strength, muscle.



This Research Note supplements the original research article, “Multi-component exercise with high-intensity, free-weight, functional resistance training in pre-frail females: A quasi-experimental, pilot study” (1). The primary aim of this study was to examine the feasibility and safety of multi-component exercise (MCE), inclusive of resistance training that is high in intensity, uses free-weights, and is based upon functional movement. Previous exercise interventions in pre-frail females have primarily used low-intensity, single-joint resistance training exercises (2), likely because of the commonly held, yet unsupported belief that the alternative is unsafe (3). Researchers and clinicians working with frail older adults can apply principles of our training program to exercise interventions.
Older adults are challenged with chronic health conditions and functional deficits that can render them frail (4). The incidence of frailty increases with age and is more prevalent in females (5); however, this syndrome can be positively influenced by interventions (6), especially exercise (7,8). Current recommendations to reverse frailty provide evidence to support an exercise strategy based upon the individual’s level of frailty (9). However, few studies report on the practical applications of effective delivery. Hence, we openly describe our experience administering a MCE intervention, inclusive of resistance training utilizing free-weight functional movements at high intensities, in a group of pre-frail older females.


Main text

Progression – Resistance exercise programs benefit muscle strength, power, and endurance when there is a progressive increase in work, balanced with appropriate recovery (10). During the early stages of resistance training, progression for pre-frail females may involve increasing the range of motion (ROM), as opposed to a traditional model of increasing the weight lifted. It is likely advantageous to first increase ROM as it has greater application to everyday tasks. We used a combination of custom built, stackable, “plyo-boxes” and free-weight plates to adjust the ROM when performing the squat and deadlift (Figure 1-2). The squat and deadlift are rarely implemented to train older adults yet, when boxes 12-24ˮ are used to adjust the ROM, these exercises can be safely undertaken.

Figure 1
A. Box heights (12-24ˮ) used to progressively and safely increase range of motion (ROM) for the squat and deadlift exercises.
1B and 1C highlight individuality, as it shows each participant squatting to a ~20ˮ and 12ˮ box, respectively. The participant squatting to the 20” box was working to achieve full ROM, while the participant squatting to the 12ˮ box is holding a dumbbell because they had progressed to the maximal ROM required of the training program, and this was the next level of progression


The squat exercise was initiated by squatting to a 24ˮ box. Progressive overload was applied by having the participant complete squats through a greater ROM (deeper squat) until the full-squat (~90 degree flexed knee bend/12ˮ box) was completed. Progression then involved the traditional approach of adding weight (dumbbell held in goblet position). The squat exercise should not be overlooked in designing programs for older females as it simulates functional activities, such as rising from a toilet.
Deadlifts, using a 35lb barbell, followed an identical progression. However, once participants reached the 12ˮ box, a 10lb bumper plate was added to each side of the barbell (total = 55lbs) instead of progressing to the ground, as the latter would likely represent a greater challenge. Once participants performed the prescribed sets and repetitions from the 12ˮ box, with the additional weight (total = 55lbs), they were then progressed to the ground. Exercise progression then included increasing the barbell load (Figure 2). The deadlift exercise should also not be overlooked as it simulates functional activities, such as picking up grandchildren.


For both the squat and deadlift, when a 6ˮ difference in box height represented too great of an increase in ROM, weight-plates (Virgin Rubber Grip Olympic Plates, Element Fitness; Latvia) ~2ˮ in width were used to safely progress (Figure 1B).
Overload – Refers to the gradual increase in stress that is placed upon the body during training, and is likely of particular importance to combatting the natural deterioration that occurs with aging. Exercise leaders, inclusive of Clinical Exercise Physiologists, were responsible for prescribing overload by increasing the weight/ROM and/or repetitions for each exercise over the course of the intervention. For example, if a participant performed three sets of eight repetitions during block one (weeks 1-4), they were then encouraged to complete nine repetitions on the next visit. The number of repetitions were increased until the participant reached 12, at which point resistance was increased and repetitions reduced back to eight. Not all participants willingly accepted the recommended progressive overload, and the exercise leaders needed to regularly build confidence for the participants to undertake this training principle.
Individuality – All exercises were modified based upon individual need (limited ROM, joint problems), as well as self-perceived ability. For example, during the early stages of the program, participants were instructed to lower the incline leg press sled (60lbs) to a point that they felt strong enough to still return it to the starting position (leg press guard ensured safety). Eventually, ROM was increased and then weight added to the sled. Continual monitoring assists in ensuring that resistance is added when participants can complete the full ROM safely.
Self-perceived Intensity – After the final set of every exercise, the OMNI Resistance Exercise Scale (OMNI-RES) was used to quantify Rating of Perceived Exertion (RPE; 11). RPE is a subjective indicator of how hard an individual is working. The OMNI-RES permits exercisers to report a measure from 0(extremely easy)-10(extremely hard). Participants often found it difficult to distinguish levels 3-8; frequently reporting a rating of 1-2 or 9-10, indicating that they could only perceive their level of exertion as very easy or very hard. The incongruity between completing more of the exercise and self-perceived scoring resulted in the decision to switch to the RPE method proposed by Zourdos (12), which has the exerciser rate their exertion based upon the number of repetitions they believe they could have executed before muscle failure. This type of RPE scale was more easily understood, potentially because of the objectivity, and thus, appeared to be more accurate in self-assessment.
Group Dynamics – Groups often adopt a ‘team’ approach, encouraging each other to improve and recognizing milestones. Positive group exercise dynamics can also foster social activities, further enhancing quality of life for older adults. The opposite situation may occur in random group assignment. Participants who question the exercise intervention and the necessity of progressive overload can minimize the development of positive group dynamics. Group settings bring together different personalities and it is not realistic to believe that they will consistently exist in harmony. The role of group dynamics should be considered in future frailty exercise interventions/programs (13).
Outside Clinician Influence – Pre-frail older females have co-morbidities that require clinical monitoring. Some participants made clear, to the certified exercise leaders, that their clinicians held negative, preconceived notions towards older females performing high-intensity, free-weight, functional resistance training. This negative influence phenomenon is quite common, despite evidence that exercise is beneficial in mitigating frailty. We observed that participants who relied on clinical suggestions were more apprehensive in the exercise program and tenuous in overloading. Importantly, our exercise intervention did not have any adverse events. Progressively overloading exercises for pre-frail older females is challenging, but it is feasible, safe, and beneficial.
Prior to the start of the intervention, researchers should hold a mandatory information session. During this session, participants should be educated about the intervention and granted the opportunity to pose concerns, as well as understand the qualifications of those administering the program. The participants primary clinician should be offered educational material (i.e. brochure) outlining the program as it could help address concerns and prevent contradictory recommendations.


This research note offers guidance to those undertaking exercise with frail older adults. However, the applicability might be limited to females. Researchers were aware that the OMNI-RES can be poorly understood given that new trainees often report less accurate perception of their exertion than more advanced exercisers (14). Therefore, careful explanation was undertaken prior to beginning and during the exercise session. Switching to an adapted RPE might have slowed exercise progression and influenced confidence in the exercise leaders. Across frailty scales, there is considerable confusion in classification, therefore, observations may vary with the level and scale used to identify frailty (15). This progressive exercise program was successful in inducing positive adaptations, yet, the approach needs to be applied in a large randomized controlled trial.



Trainers should create options for participants to work in a functional ROM, and to teach the squat and deadlift. Boxes of varying heights supported the prescription of the squat and deadlift exercise. When there was an improvement in strength, the boxes were lowered/ROM was increased. However, the height of boxes used for progression should be limited to ≤ 3″. Overall, this approach offers flexibility in exercise prescription for those with joint limitations. The following fitness equipment is also beneficial in creating progressive resistance: 1) a barbell weighing < 35lbs; 2) dumbbells increasing in 2.5lbs increments; and 3) an inclined leg press with a starting weight < 60lbs. Across all elements, pre-frail older females benefit from understanding the functional application of exercises.
Frailty is often an unfortunate reality for an aging population, its characteristics are all synonymous with lack of fitness. Strength and conditioning specialists are well suited to address frailty. To be most effective, exercise specialists need to tailor the exercise intervention, and constantly use monitoring approaches to create small progressions that promote meaningful strength gains and in-turn, enhance functional ability.


Funding: Partial funding for this study through the Canadian Institutes for Health Research (CIHR) Grant # 385692. The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; in the preparation of the manuscript; or in the review or approval of the manuscript.
Acknowledgments: We wish to acknowledge the support from Flaman Fitness™ and the Okanagan Men’s Shed Club for generously donating the exercise equipment, graduate students (Rowan Smart and Sam Kuzyk) and senior undergraduate students (Anup Dhaliwal, Brett Yungen, Savannah Frederick, Paul Cotton and Cydney Richardson), and all the participants involved in this study.
Ethics approval and consent: All participants read and signed a letter of informed consent. Ethical approval was granted by the institutional Research Ethics Board (H16-00712).
Availability of the data and materials: The original data and materials are available through the institutions open access graduate thesis repository https://open.library.ubc.ca/cIRcle/collections/ubctheses/24/items/1.0353165
Competing interests: None
Trial Registration: This study was prospectively registered with ClincalTrials.gov (NCT02952443) on October 31, 2016.



1. Bray NW, Jones GR, Rush KL, Jones CA, Jakobi JM. Multi-component exercise with high-intensity, free-weight, functional resistance-training in pre-frail females: A quasi-experimental, pilot study. J Frailty Aging 2019;In Press.
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B.C. Clark


Ohio Musculoskeletal and Neurological Institute (OMNI), Department of Biomedical Sciences, and the Division of Geriatric Medicine at Ohio University, Athens, Ohio, USA
Corresponding author: Brian C. Clark, Ph.D. Ohio University, Ohio Musculoskeletal & Neurological Institute (OMNI), 250 Irvine Hall, Athens, OH 45701, USA, Phone: 740.593.2354, Email: clarkb2@ohio.edu

J Frailty Aging 2018;in press
Published online October 22, 2018, http://dx.doi.org/10.14283/jfa.2018.35



Abstract: Sarcopenia was originally conceptualized as the age-related loss of skeletal muscle mass. Over the ensuing decades, the conceptual definition of sarcopenia has changed to represent a condition in older adults that is characterized by declining muscle mass and function, with “function” most commonly conceived as muscle weakness and/or impaired physical performance (e.g., slow gait speed). Findings over the past 15-years, however, have demonstrated that changes in grip and leg extensor strength are not primarily due to muscle atrophy per se, and that to a large extent, are reflective of declines in the integrity of the nervous system. This article briefly summarizes findings relating to the complex neuromuscular mechanisms that contribute to reductions in muscle function associated with advancing age, and the implications of these findings on the development of effective therapies.

Key words: Sarcopenia, dynapenia, aging, muscle, strength, weakness.



Sarcopenia was originally conceptualized, thirty years ago, as the age-related loss of skeletal muscle mass (1). Over the ensuing decades, sarcopenia has come to be conceptually defined as a condition in older adults that is characterized by declining muscle mass and function, with “function” most commonly conceived as muscle weakness and/or impaired physical performance (e.g., slow gait speed) (2, 3).
The central tenet for the evolution of the definition of sarcopenia is based on the premise that the loss of muscle mass leads to the loss of muscle function (e.g., weakness) and that this contributes to limitations in physical function and mobility. Two critical arguments, however, strongly question the scientific premise of this tenet:
1. Longitudinal data indicate that the age-related changes in strength are not due to muscle wasting (4, 5), and that strength, but not mass, is associated with negative health outcomes (6, 7). For instance, using data from the Health ABC study, Delmonico and colleagues (2009) assessed changes in thigh muscle size using computed tomography and isokinetic leg extensor strength serially over a 5-year period in a cohort of older adults that were between 70-79 years at baseline (4). They reported that annualized decreases in muscle strength were 2-5 times greater than the loss of muscle size in those who lost or maintained weight over the five-year period. Moreover, individuals that gained weight actually exhibited a small increase in muscle size, but this increase in muscle size did not prevent a loss of strength. Findings of this nature clearly indicate that the loss of muscle strength (and presumably power) in older adults is modestly associated with the loss of muscle mass or size, and suggest that neurological and non-muscle mass related factors are critical in the development of age-related muscle weakness. It should be noted that muscle atrophy should not be regarded as a negligible corollary of aging. Low muscle mass is associated with negative outcomes in a variety of disease conditions, and its importance to overall health should not be diminished (8).
2. Impairments in neural activation of skeletal muscle is (9) a key contributor to muscle weakness in older adults. Grip strength, due to widespread availability of grip dynamometers and ease of assessment, is by far the most common index of muscle strength in the field of aging systems and geriatrics. Loss of grip strength with advancing age has been shown to have predictive power in relation to a range of health-related conditions (6, 7, 10, 11). Grip strength is generally interpreted as a simple measure of skeletal muscle function, which is why it has largely been used in the recent conceptual definitions of sarcopenia. The interpretation of grip strength as a measure of skeletal muscle function is, however, arguably incorrect (9). Rather, a strong case can be made that grip strength, and age-related changes in grip strength in particular, is neither simple nor a measure skeletal muscle function per se (see reference (9) for a more detailed discussion) . Instead, evidence suggests that the force generated during a maximum voluntary grip force task is around half of what would be expected if the skeletal musculature itself were fully activated by the nervous system (Figure 1) (12-14), due to reduced neural drive to the muscles (15). Specifically, the maximum force that can be produced by each finger decreases in proportion to the number of other fingers that are engaged simultaneously, such that when four fingers contribute to the grip task, the maximum force that can be generated by each digit is typically less than half that produced when it is engaged in isolation (i.e., there is a force deficit) (14, 16). Moreover, this grip strength ‘force deficit’ is larger in older adults in comparison to young adults (14, 17). In agreement with the above-mentioned notion of impairments in neural activation being a key contributor to age-related changes in muscle strength, we have reported that weaker older adults exhibit a 20% deficit in voluntary (neural) activation of the wrist flexor muscles (18). In this study, the motor nerve was electrically stimulated during a maximal voluntary wrist flexion contraction and any increment in force evoked by a stimulus indicates that voluntary activation is less than 100%. Thus, voluntary activation represents the proportion of maximal possible force that is produced voluntarily, and impairment indicates some motor units are not recruited or are not firing fast enough to produce fused contractions (19). Accordingly, these findings indicate that impairments in neural activation, broadly speaking, is a key contributor to muscle weakness in older adults.

Figure 1 The force that can be generated during a maximum voluntary grip force task is around half of what would be expected if the skeletal musculature itself were fully activated. This data, which was recreated from data presented in Shinohara et al. (14), was obtained from 12 young (filled bars) and 12 older adults (unfilled bars). Subjects performed single-finger maximal voluntary contractions (MVC) as well as a four finger MVC by pressing on individual force transducers. Note the dramatic drop in the force of individual fingers during four-finger MVC tasks compared with single-finger MVC tasks (i.e., a force deficit). Further note that this force deficit was larger in older adults than young adults. Findings of this nature suggest that grip strength is heavily reflective of nervous system function, and not skeletal muscle function per se

Figure 1
The force that can be generated during a maximum voluntary grip force task is around half of what would be expected if the skeletal musculature itself were fully activated. This data, which was recreated from data presented in Shinohara et al. (14), was obtained from 12 young (filled bars) and 12 older adults (unfilled bars). Subjects performed single-finger maximal voluntary contractions (MVC) as well as a four finger MVC by pressing on individual force transducers. Note the dramatic drop in the force of individual fingers during four-finger MVC tasks compared with single-finger MVC tasks (i.e., a force deficit). Further note that this force deficit was larger in older adults than young adults. Findings of this nature suggest that grip strength is heavily reflective of nervous system function, and not skeletal muscle function per se

Significant differences for men vs. women, *P<0.05 and for elderly vs. young, +P<0.05.


Collectively, findings of this nature question the notion that 1) the loss of muscle mass is a critical mechanism leading to loss of muscle strength, and 2) that age-related muscle weakness is solely due to declining skeletal muscle function per se. Rather, these findings suggest that the nervous system, and specifically the neural control of skeletal muscle, is a key contributor to declining muscle and physical function commonly observed with advancing age. There is strong proof-of-concept evidence that aging results in a plethora of changes in the neuromuscular system that could theoretically effect neuromuscular function. These include changes in the nervous system, such as reductions in corticospinal excitability, degeneration as well as altered biophysical and behavioral characteristics of motor neurons, among others (for review see (19-22)). It should also be noted there are a number of non-mass dependent age-related changes in skeletal muscle properties that may also contribute to impaired neuromuscular function (e.g., excitation-contraction uncoupling and alterations in musculotendinous properties that lead to reductions in intrinsic muscle quality) (for review see (23, 24)). There has been much discussion in the literature about the relationship between fat infiltration in muscle and dynapenia. While it’s contribution to weakness is not fully understood, there is strong evidence that questions the contributing role of intermuscular fat. Specifically, a study that tracked 1,678 older adults over a 5-year period and examined the relationship between changes in muscle size, muscle fat infiltration and muscle strength, it was observed that the change in intermuscular fat explained less than 1% of the between subject variance in the change in muscle strength (4). Nevertheless, the salient point is that strong consideration needs to be given to the multiple mechanisms contributing to age-related reductions in neuromuscular function in the development of an operational definition of sarcopenia (or dynapenia, which we have previously recommended for consideration as an alternative to the term “sarcopenia”, in order to distinguish between the age-related loss of muscle strength (dynapenia) and the age-related loss of muscle mass (sarcopenia) for the reasons stated above (20, 21)).
Are We Barking Up the Wrong Tree? Sarcopenia is commonly conceptualized as a condition of the muscular system based on the rationale that the muscular system is responsible for the function of mobility (2, 3). However, this conceptualization does not give sufficient consideration to “muscle function” being a subset of “motor function”. Accordingly, one must raise the question of whether the sarcopenia field is at a critical junction in need of a major paradigm shift away from the traditional “skeletal muscle centric” focus that the field has largely pursued. For instance, the “graying of the nation” has resulted in a large number of pharmaceutical companies pursuing compounds to enhance muscle and physical function in older adults (25). To date, they have focused on compounds designed to target skeletal muscle, such as those designed to promote muscle growth, or— at a minimum— attenuate atrophy (e.g., myostatin-inhibitors) or those designed to increase skeletal muscle calcium sensitivity. These trials have, generally speaking, reported modest, if not disappointing effects, for enhancing muscle strength and physical function. Is it possible that these disappointing results are due to these compounds targeting the entirely wrong system— skeletal muscle— as opposed to the nervous system? There has certainly been an increased interest in the role of the nervous system in muscle weakness and mobility limitations in older adults in recent years, and in the coming years this answer to this question should become clearer.


Grant Support: This work was supported, in part, by a grant from the National Institute on Aging (R01AG044424).
Conflict of Interest Statement: Brian Clark has received research funding from the National Institutes of Health, Regeneron Pharmaceuticals, Astellas Pharma Global Development, Inc., RTI Health Solutions, Ohio Department of Higher Education, and the Osteopathic Heritage Foundations. In the past 5-years Brian Clark has received consulting fees from Regeneron Pharmaceuticals, Abbott Laboratories, and the Gerson Lehrman Group. Additionally, Brian Clark is co-founder with equity and scientific director of AEIOU Scientific, LLC.
Acknowledgements: The author wishes to thank Leatha A. Clark, DPT, MS and David W. Russ, PT, PhD for providing critical comments on an initial draft of the manuscript.
Open Access: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made.



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Department of Physical Therapy, College of Pharmacy and Health Sciences, Campbell University, Lillington, North Carolina, USA
Corresponding author: Richard W Bohannon, Department of Physical Therapy, College of Pharmacy and Health Sciences, Campbell University, 4150 US421 South, Lillington, North Carolina, 27546, USA  Phone: +1 (910) 814-4951; Fax: +1 (910) 814-4951; e-mail: bohannon@campbell.edu

J Frailty Aging 2017;in press
Published online August 30, 2017, http://dx.doi.org/10.14283/jfa.2017.32



Normative reference values for knee extension strength obtained by hand-held dynamometry from adults 60 to 79 years were derived using summary data from 3 studies. The studies, which were identified through PubMed and a hand-search, contributed data from between 3 and 29 individuals for each age, gender, and side stratum. Meta-analysis was employed to consolidate knee extension strength data. Strength, normalized against body weight, ranged 35.6% for the nondominant side of 70 to 79 year old women to 48.8% for the nondominant side of 60 to 69 year old men.  These values are more informative than those previously published in individual studies. However, reference values derived from a large population-based sample are needed.

Key words: Older adults, strength, reference values, dynamometry.



Muscle weakness is a principal component of both frailty (1) and sarcopenia (2). Although numerous different measures have been used to characterize muscle weakness, hand grip dynamometry has probably been the most commonly advocated for use with older adults (1,2). Alternatives to hand-grip dynamometry have been proposed; chiefly, the measurement of knee extension force using isokinetic, fixed, or hand-held dynamometers (2). Of these alternatives, hand-held dynamometry (HHD) is a particularly compelling option because of its relative affordability and portability. So long as the tester wielding the dynamometer possesses adequate strength, measurements of knee extension force obtained by HHD have been shown to be reliable (3) and valid relative to isokinetic dynamometry (4). Measurements of knee extension strength obtained by HHD have also been validated by their correlation with mobility measures obtained from older adults (5,6). Reference values have been published for measurements of knee extension strength obtained by HHD (7). Unfortunately most published reference values cannot be recommended for one reason or another. Among such reasons are their having been obtained using break tests, dynamometers with low force measurement ceilings, and samples of individuals that were insufficiently stratified and small (7).
The problem of small samples can be ameliorated through the consolidation of values from multiple studies. That was the purpose of this review- to use meta-analysis to provide reference values for knee extension strength obtained by HHD from apparently healthy adults aged 60 to 79 years.



Relevant literature was sought via a search of PubMed on May 10, 2017. The search string was: (hand held dynamomet*) AND (norms OR normative OR reference). The search was limited to age 65+ years. A hand-search was also conducted. To be considered for inclusion, an article had to provide summary statistics for knee extension strength normalized against body weight and stratified according to gender, age, and side. Articles were excluded if measurements were obtained using break tests or a dynamometer with a measurement ceiling of less than 500 Newtons. The rationale for these exclusions were that it is often not possible to break the knee extension effort of healthy adults and that some healthy older adults generate knee extension forces as high as 500 Newtons.
Normative reference values for knee extension strength were determined using summary data from included studies. Those data were delineated into age, gender, and side strata (eg, 60 69 year old men- dominant side). The sample size, mean, and standard deviation for each stratum were entered into the Comprehensive Meta-analysis (3.0) program (8) which generated weighted means and standard errors using a random effects model. Homogeneity was characterized using I squared.



The PubMed search identified 13 potentially relevant articles. Of these, all but 2 (9,10) were eliminated based on inclusion and exclusion criteria. A hand search produced one additional study (a thesis) (11). The 3 studies contributed data from 3 to 29 older adults per stratum.  All studies were conducted in the United States and involved make tests in which participants were seated, the knee was flexed 90 degrees, and a digital hand-held dynamometer was applied to the anterior leg just proximal to the malleoli.
Table 1 summarizes the results of the meta-analysis. The total number of individuals contributing data ranged from 44 to 51 depending on the stratum. Body weight normalized knee extension strength reference values ranged from 35.6% for the nondominant side of 70 to 79 year old women to 48.8% for the nondominant side of 60 to 69 year old men. The I-squared values (0-24.4) support the homogeneity of the stratified knee extension strength values.


Table 1 Reference Values for Knee Extension Force Normalized Against Body Weight

Table 1
Reference Values for Knee Extension Force Normalized Against Body Weight

Derived From Data of Three Studies Incorporating Hand-held Dynamometry



Grip strength has proven to be a practical and robust indicator of overall muscle strength in older adults, particularly those who are frail or sarcopenic (1, 2). Nevertheless, alternative measures of strength have been proffered. Knee extension strength, which is critical to activities such as sit-to-stand (6), is one such alternative. The value of a measurement, knee extension strength included, is dependent in part on the availability of reference values to which the measurements obtained from a patient can be compared (12). Reference values have been published for measurements of knee extension strength obtained by hand-held dynamometry, but until now reference values have been derived from samples that are quite small (9-11).  By using meta-analysis to consolidate data from 3 studies, reference values were generated that may be more representative of the population than those previously published. By normalizing knee extension strength to body weight, a major explanator of strength not captured within age, gender, and side strata is accommodated. These reference values may also be more informative than absolute measurements of strength (eg, kg of knee extension force) as they beter explain function. As an example, the combined knee extension strength threshold identified as necessary if patients are to rise from a chair independently without hands is 40% of body weight (6).   Not surprisingly, the reference values consolidated from studies of apparently healthy older adults in this review (combined > 70%) are higher than the 40% threshold.
This review had several limitations. First, the individuals whose strength values were consolidated were part of convenience samples. Therefore, they are probably not as representative as a population based sample. Second, while the number of individuals contributing to the reference values was larger than for any one contributing study, it was still rather small. Finally, the reference values only extend to individuals in their sixties or seventies. Values for older adults are needed.
In conclusion, reference values provided herein can serve as a standard to which the normalized knee extension strength of men and women in their sixties and seventies can be compared. Nevertheless, reference values from a larger, more representative, and older population are needed.


Conflict of interest: None



1.     Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med 2001; 56: M146-156.
2.    Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis. Age Ageing 2010; 39: 412-423.
3.    Bohannon RW, Wikholm J. Measurements of knee extension force obtained by two examiners of substantially different experience with a hand-held dynamometer. Isokinet Exerc Sci 1992; 2: 5-8.
4.    Bohannon RW. Hand-held versus isokinetic dynamometer for measurement of static knee extension torques. Clin Physics Physiol Meas 1990; 71: 123-128.
5.    Bohannon RW. Gait performance of hemiparetic stroke patients: selected variables. Arch Phys Med Rehabil 1987; 68: 777-781.
6.    Eriksrud O, Bohannon RW. Relationship of knee extension force to independence in sit-to-stand performance in patients receiving acute rehabilitation. Phys Ther 2003; 83: 544-551.
7.    Bohannon RW. Literature reporting normative data for muscle strength measured by hand-held dynamometry: A systematic review. Isokinet Exerc Sci 2011; 19: 143-147.
8.    Comprehensive Meta Analysis (3.0) 2014 Englewood NJ: Biostat Available from http://www.Meta-Analysis.com.
9.    Andrews AW, Thomas MW, Bohannon RW. Normative values for muscle strength obtained by hand-held dynamometry. Phys Ther 1996; 76: 248-259.
10.    Bohannon RW. Reference values for extremity muscle strength obtained by hand-held dynamometry from Adults aged 20 to 79 years. Arch Phys Med Rehabil 1997; 78: 26-32.
11.    DiPasquale C. Comparability of Reference Values for Extremity Muscle Strength Obtained by Hand-held Dynamometry and Fixed Force Strain Gauge Dynamometry from Adults 20 to 79 Years [thesis]. Storrs: University of Connecticut, 1998.
12.    Fraser CG. Inherent biological variation and reference values. Clin Chem Lab Med 2004; 42: 758-764.





Department of Physical Therapy, College of Pharmacy and Health Sciences, Campbell University, Lillington, North Carolina, USA.
Corresponding author: Richard W Bohannon, Department of Physical Therapy, College of Pharmacy and Health Sciences, Campbell University, 4150 US421 South, Lillington, North Carolina, 27546, USA. Phone: +1 (910) 814-4098; Fax: +1 (910) 814-4951; e-mail: bohannon@campbell.edu


J Frailty Aging 2017;6(2):83-87
Published online March 15, 2017, http://dx.doi.org/10.14283/jfa.2017.8



A systematic review was performed to summarize literature describing the test-retest reliability of grip strength measures obtained from older adults. Relevant literature was identified via a PubMed search. Seventeen articles were deemed appropriate based on inclusion and exclusion criteria.  The relative test-retest reliability of grip strength measures obtained by dynamometry was good to excellent (intra-class correlation coefficients > 0.80) in all but 3 studies, which involved older adults with severe dementia. Absolute reliability, as indicated by summary statistics such as the minimum detectable change (95%), was more variable. As a percentage, that change ranged from 14.5% to 98.5%. Consequently, clinicians can be confident in the relative reliability of grip strength measures obtained from at risk older adults. However, relatively large percentage changes in grip strength may be necessary to conclude with confidence that a real change has occurred over time in some populations.

Key words: Aging, grip, strength, reliability.




Muscle strength must be sufficient if individuals are to function independently in the community. With increased age and the onset of various pathologies muscle strength declines. There are numerous options for documenting this decline in older adults, but handgrip dynamometry is one of the most common, probably because of its simplicity and ability to provide information on overall muscle strength (1). This ability has led to the use of grip dynamometry for identifying older adults who are malnourished (2), sarcopenic (3), frail (4) or at risk of untoward outcomes such as premature mortality (5).
These uses notwithstanding, measurements of grip strength obtained by dynamometry must possess good test-retest reliability if the procedure is to be recommended and sound judgments as to changes in strength are to be made. The purpose of this review, therefore, was to summarize the findings of research addressing the test-retest reliability of measurements of grip strength obtained by dynamometry from older adults. Both relative and absolute reliability (6) were of interest.



Relevant literature was identified through a search of PubMed on October 18, 2016. The search string was: (hand OR grip) AND (strength) AND (reliable OR reliability). The search was limited to humans, English language publications, and adults 65+. Article inclusion required that the mean age of individuals tested was at least 60 years of age, that strength testing was performed with a commercially available dynamometer, that the test-retest interval was at least 1 day, and that the intra-class correlation coefficient (ICC) was used to indicate relative reliability. Articles describing use of a device that measures pressure rather than force (eg, Vigorimeter) were excluded.
Once established as appropriate in regard to inclusion and exclusion criteria, each article was extracted for information on the participants tested (basic description, number, mean age, and country of residence), measurement procedures (dynamometer, criterion measurement, number of test sessions, and intersession test interval), and findings addressing reliability. These findings included ICCs for relative reliability and one or more indicators of absolute reliability. The indicators of absolute reliability reported by authors included standard error of measurement (SEM), minimal detectable change (MDC), minimal detectable difference (MDD), smallest real difference (SRD), technical error of measurement (TEM), least significant change (LSC), and smallest real difference (SRD).
The quality of each article was rated using a custom 7-component, 14-point scale derived in part from criteria recommended by Terwee et al for rating the quality of studies focused on measurement properties (7). Other components were added to address the specifics of studies measuring grip strength.



The PubMed search identified 347 potentially relevant articles. Of these 17 were ultimately determined to be appropriate based on inclusion and exclusion criteria. The most common reasons an article was deemed inappropriate were that it did not report test- retest reliability, test-retest reliability was established within a single session or day, or a statistic other than an ICC (eg, coefficient of variation) was used to characterize relative reliability.
Table 1 summarizes the information extracted from articles incorporated in this review.  All studies involved older adults (mean age 60.2 to 83.9 years), but many had a more specific focus. Patients with dementia were the focus of 4 articles (8,11,18,23); patients with diabetes (9), critical illness (10), post-polio syndrome (13), stroke (15), neuropathy (16), myositis (17), intellectual disability (19), and frailty (21) were the focus of a single article. Studies included between 10 and 101 participants residing in 8 countries, with the United States being the most common country of residence (5 studies). Five different grip dynamometers were used in the studies; the Jamar was employed in 12. The criterion measurement reported in the studies varied greatly. It involved either the first, best, or mean of 2 or more efforts and either, 1 (eg, dominant), or both hands. All but 1 study involved 2 test sessions; the exception involved 3. The interval between tests ranged from 2 days to 3 months.

Table 1 Summary of articles identified as appropriate for review

Table 1
Summary of articles identified as appropriate for review

* ICC= intra-class correlation coefficient, SEM= standard error of measurement, MDC= minimum detectable change, SRD= smallest real difference, MDD= minimal detectable difference, TEM= technical error of measurement, LSC= least significant change

Aging, grip, strength, reliability.

The ICCs reported in the studies ranged from 0.415 to 0.996. However, the magnitude of all but 3 of 31 reported ICCs was 0.80 or greater. The exceptions were from studies of patients with dementia (8,23). Ten studies reported 1 or more measures of absolute reliability, most commonly the SEM. The SEMs ranged from 1.4 to 4.5 kg and from 5.2 to 35.5%. Expressed in kg, absolute differences at the 95% confidence level ranged from 2.9 kg for a SRD95% for patients with stroke (15) to 12.5 kg for a MDD95% for patients with critical illness (10).  Expressed as a percentage, absolute differences at the 95% confidence level ranged from 14.5% for a MDC95% for patients with post-polio weakness (13) to 98.5% for a MDD95% for patients with critical illness (10).
Table 2 summarizes the quality ratings for the selected articles. The scores ranged from 6 to 13 out of 14. The most common quality shortcomings were a failure to describe the type of sample (eg, convenience), a failure to indicate that retest measures were obtained while blinded to measurements obtained during the initial test, and a failure to include summary statistics test and retest strength measurements.

Table 2 Summary of articles identified as appropriate for review*

Table 2
Summary of articles identified as appropriate for review*

* Summary stats (mean [SD]) for each test, ICC= intra-class correlation coefficient, SEM= standard error of measurement, MDC= minimum detectable change, SRD= smallest real difference, MDD= minimal detectable difference, TEM= technical error of measurement, LSC= least significant change



This systematic review was undertaken to summarize what has been published regarding the test-retest reliability of measures of grip strength obtained dynamometrically from older adults. Based on the findings reported in 17 peer-reviewed journal articles, such measurements can be considered to demonstrate good to excellent relative test-retest reliability unless obtained from patients with severe dementia or dementia severe enough to warrant adult day care (8,23). Notably, grip forces obtained across sessions from patients with borderline or mild dementia demonstrated high relative reliability (8,11,18).  The absolute reliability of measurements obtained from older adults was not so uniform. While this might stem in part from the samples studied and procedural variations, there is also some diversity in indicators of absolute reliability reported and the model of ICC used in their calculation. Some indicators are fundamentally different (eg, TEM and MDC95%) while others are the same in all but name (eg, MDC95%, MDD95%, SRD). In any case, information on the absolute reliability of grip strength measures suggests that in some populations (eg, patients with critical illness), grip strength will have to change substantially before testers can be confident that a real change has occurred. Among the  studies reporting absolute reliability at the 95% confidence level as a percentage, the percentage change exceeded 20% in most cases. Some clinicians might find changes of 20% or more as unacceptable.
This review has several limitations. First, relevant articles were identified using a single bibliographic database. The use of additional databases such as Scopus may have revealed further relevant articles. Second, only a single author was involved in selecting articles and extracting relevant information from them. Thus, there was no confirmation of his choices. Third, there were quality issues with some of the reviewed articles. Based on the information of interest and a limited number of relevant articles, a decision was made to retain all articles regardless of quality.
In conclusion, the predictive value of grip strength and its relative test-retest reliability support the use of handgrip dynamometry to identify strength deficits among older adults at risk of malnutrition, frailty, and sarcopenia.  The absolute test-retest reliability of the measures, however, suggests that substantial changes in grip strength may sometimes be required to confidently conclude that a real change in strength has occurred over time.


Funding: None
Conflict of interest: None



1.     Bohannon RW, Magasi SR, Bubela DJ, Wang Y-C, Gershon RC. Grip and knee extension muscle strength reflect a common construct among adults. Muscle Nerve 2012;46:555-8.
2.    Norman K, Stobäus N, Gonzalez MC, Schulzke JD, Pirlich M. Hand grip strength: outcome predictor and marker of nutritional status. Clin Nutr 2011;30:135-42.
3.    Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis. Age Ageing 2010;39:412-23.
4.    Fried LP, Tangen CM, Walston J, et al. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med 2001;56:M146-56.
5.    Bohannon RW. Muscle strength: clinical and prognostic value of handgrip dynamometry. Curr Opin Clin Nutr Metab Care 2015;18:465-70.
6.    Bruton A, Conway JH, Holgate ST. Reliability: What is it, and how is it measured? Physiotherapy 2000;86:94-9.
7.    Terwee CB, Bot SDM, de Boer MR, et al. Quality criteria were proposed for measurement properties of health status questionnaires. J Clin Epidemiol 2007;60:34-42
8.    Alencar MA, Dias JMD, Figueiredo LC, Dias RC. Handgrip strength in elderly with dementia: study of reliability. Rev Bras Fisioter 2012;16:510-4.
9.    Alfonso-Rosa RM, del Pozo-Cruz B, del Pozo-Cruz J, Sañudo B, Rogers ME. Test-retest reliability and minimal detectable change scores for fitness assessment in older adults with type 2 diabetes. Rehabil Nurs 2014;39:260-8.
10.    Baldwin CE, Paratz JD, Bersten AD. Muscle strength assessment in critically ill patients with handheld dynamometry: an investigation of reliability, minimal detectable change, and time to peak force generation. J Clin Care 2013;28:77-86.
11.    Blankevoort CG, van Heuvelen MJG, Scherder EJA. Reliability of six physical performance tests in older people with dementia. Phys Ther 2013;93:69-78.
12.    Bohannon RW, Schaubert KL. Test-retest reliability of grip-strength measures obtained over a 12-week interval from community-dwelling elders. J Hand Ther 2005;18:426-7.
13.    Brogårdh C, Flansbjer U-B, Carlsson H, Lexell J. Intra-rater reliability of arm and hand muscle strength measurements in persons with late effects of polio. PM R 2015;7:1035-41.
14.    Buehring B, Krueger D, Fidler E, Gangnon R, Heiderscheit B, Binkley N. Reproducibility of jumping mechanography and traditional measures of physical and muscle function in older adults. Osteoporos Int 2015;26:819-25
15.    Chen H-M, Chen CC, Hsueh I-P, Huang S-L, Hsieh C-L. Test-retest reproducibility and smallest real difference of 5 hand function tests in patients with stroke. Neurorehab Neural Repair 2009;23:435-40.
16.    Draak THP, Pruppers MHJ, van Nes SI, et al. Grip strength comparisons in immune-mediated neuropathies: Vigorimeter vs Jamar. J Periph Nerv Syst 2015;20:269-76.
17.    Eriksson M, Lindberg C. Hand function in 45 patients with sporadic inclusion body myositis. Occup Ther Int 2012;19:108-16.
18.    Fox B, Henwood T, Neville C, Keogh J. Relative and absolute reliability of functional performance measures for adults with dementia living in residential aged care. Int Psychogeriatr 2014;26:1659-67.
19.    Hilgenkamp TIM, van Wijck R, Evenhuis HM. Feasibility and reliability of physical fitness tests in older adults with intellectual disability: A pilot study. J Intellect Dev Disabil 2012;37:158-62.
20.    Jenkins NDM, Buckner SL, Bergstrom HC, et al. Reliability and relationships among handgrip strength, leg extensor strength and power, and balance in older men. Exp Gerontol 2014;58:47-50.
21.    Payette H, Hanusaik N, Boutier V, Morais JA, Gray-Donald K. Muscle strength and functional mobility in relation to lean body mass in free-living frail elderly women. Eur J Clin Nutr 1998;52:45-53.
22.    Schaubert KL, Bohannon RW. Reliability and validity of three strength measures obtained from community-dwelling elderly persons. J Strength Cond Res 2005;19:717-20.
23.    Thomas VS, Hageman PA. A preliminary study on the reliability of physical performance measures in older day-care center clients with dementia. Int Psychogeriatr 2002;14:17-23.
24.    Wang C-Y, Chen L-Y. Grip strength in older adults: Test-retest reliability and cutoff for subjective weakness of using the hands in heavy tasks. Arch Phys Med Rehabil 2010;91:1747-51.




1. Waikato Institute of Technology, Centre for Sport Science and Human Performance, Hamilton, New Zealand; 2. School of Medicine, Division of Rheumatology – University of Sao Paulo, Sao Paulo, Brazil; 3. School of Physical Education and Sport, University of Sao Paulo, Sao Paulo, Brazil 

Corresponding author: Professor Bruno Gualano, Escola de Educação Física e Esporte; Departamento de Biodinâmica do Movimento Humano, Av. Mello de Moraes, 65, São Paulo, SP – Brazil, Postal code: 05508-030, Phone: + 55 11 30918783 / + 55 11 30913096, email: gualano@usp.br



Background: Studies assessing the effects co-supplementation with creatine and protein, along with resistance training, in older individuals with frailty are lacking. Objectives: This is an exploratory trial from the Pro-Elderly study (“Protein Intake and Resistance Training in Aging”) aimed at gathering knowledge on the feasibility, safety, and efficacy of co-supplementation with creatine and protein supplementation, combined with resistance training, in older individuals with frailty. Design: A 14-week, double-blind, randomized, parallel-group, placebo controlled exploratory trial. Setting, participants: The subjects were randomly assigned to whey protein and creatine co-supplementation (WHEY+CR) or whey protein supplementation (WHEY) group. All subjects undertook a supervised exercise training program and were assessed at baseline and after 14 weeks. Measurements: Muscle function, body composition, blood parameters, and self-reported adverse events were assessed. Results: No interaction effects (between-group differences) were observed for any dependent variables (p > 0.05 for all). However, there were main time-effects in handgrip (WHEY+CR = 26.65 ± 31.29; WHEY = 13.84 ± 14.93 Kg; p = 0.0005), timed-up-and-go (WHEY+CR = -11.20 ± 9.37; WHEY = -17.76 ± 21.74 sec; p = 0.006), and timed-stands test (WHEY+CR = 47.50 ± 35.54; WHEY = 46.87 ± 24.23 reps; p = 0.0001), suggesting that WHEY+CR and WHEY were similarly effective in improving muscle function. All of the subjects showed improvements in at least two of the three functional tests, regardless of their treatments. Body composition and blood parameters were not changed (p > 0.05). No severe adverse effects were observed. Conclusions: Co-supplementation with creatine and whey protein was well-tolerable and free of adverse events in older subjects with frailty undertaking resistance training. Creatine supplementation did not augment the adaptive effects of resistance training along with whey protein on body composition or muscle function in this population. Clinicaltrials.gov: NCT01890382.


 Key words: Whey protein, strength, lean mass, aging. 



Resistance training has been established as an important cornerstone in the prevention and treatment of disabilities and co-morbidities secondary to aging, increasing muscle function and lean mass (1 ,2). Moreover, there is evidence suggesting that some dietary interventions, including creatine and whey protein supplementation, can act synergistically to resistance training by enhancing its beneficial effects in elderly individuals (3-6).  

Creatine plays an important role in rapid energy provision during muscle contraction, functioning as both a temporal and a spatial energy buffer, shuttling high-energy phosphates between mitochondria and cellular adenosine triphosphate (ATP) utilization sites (7). Creatine supplementation has been consistently shown to increase muscle creatine and phosphylcreatine content, leading to improvements in training volume, which, in turn, could translate into greater adaptations to resistance exercise (8). In fact, there is growing evidence demonstrating creatine supplementation and resistance training seem to act synergistically in improving lean mass, fatigue resistance, muscle strength, performance of activities of daily living largely than resistance training alone (9-11). However, most studies have primarily focused on healthy elderly individuals. Recently, we showed that creatine supplementation was able to enhance the effects of resistance training on appendicular lean mass and muscle function in vulnerable older individuals (i.e., those who commonly complain of being ‘‘slowed up’’ or have disease symptoms) (5). Nonetheless, the number of studies involving older frailer individuals being supplemented with creatine is very limited. 

Another dietary intervention potentially able to improve lean mass and muscle function in the aging population is protein supplementation. Indeed, recent evidence has shown that higher dietary protein ingestion is beneficial to support good health, promote recovery from illness, and maintain functionality in older adults (12). According to recent review papers, the need for more dietary protein is in part because of a declining anabolic response to protein intake in older people; more protein is also needed to offset inflammatory and catabolic conditions associated with chronic and acute diseases that occur commonly with aging (2 ,3 ,12 ,13). Moreover, older individuals usually eat less protein compared to younger adults (14). Importantly, an imbalance between protein supply and protein need can result in loss of skeletal muscle mass because of a chronic disruption in the balance between muscle protein synthesis and degradation (2, 3). On the other hand, dietary protein supplementation promotes protein synthesis and can enhance recovery of physical function in older individuals (2 ,3 , 12, 13). Interestingly, a recent meta-analysis provided evidence that protein supplementation can augment the adaptive response of skeletal muscle to resistance training in the aging population (15). However, caution should be exercised because longer-term studies investigating the possible synergistic effects of protein supplementation and resistance training in older individuals remain scarce. 

Even scarcer are the studies exploring the potential beneficial effects of co-supplementation with protein and creatine in resistance trained older individuals. Three studies failed to show any additional benefit of combining whey protein (35g/day) with creatine (~5g/day) in older to elderly individuals (42-80 years of age) undergoing resistance training (16). In contrast, it was showed that creatine (0.1 g/kg/d) combined with protein supplementation (0.3 g/Kg/d) during a 10-week resistance training program increased lean tissue mass and bench press strength (but not leg press strength), as well as reduced muscle protein degradation and bone resorption in older individuals (59-77 yr) (10). These findings are hard to reconcile due to the heterogeneous characteristics of samples, training protocols, supplementation regimens, and research outcomes. Furthermore, these studies evaluated apparently heathy subjects; to our knowledge, no study has assessed the effects of co-supplementation with creatine and protein, along with resistance training, in older individuals with frailties. 

This is an exploratory trial from the Pro-Elderly study (“Protein Intake and Resistance Training in Aging”) aimed at gathering knowledge on the feasibility, efficacy and safety of co-supplementation with creatine and protein supplementation, in conjunction with resistance training, in older individuals with frailty.         


Materials and methods 

Experimental Design

A 14-week, double-blind, randomized, parallel-group, placebo controlled exploratory trial was conducted between January 2013 and December 2014 in Hamilton (New Zealand). This study is part of a larger clinical trial aimed at investigating the role of proteins, amino acids and derivatives along with resistance training in pre-frail and frail older subjects (“The Pro-Elderly Study”, registered at clinicaltrials.gov as NCT01472393). This small-scale exploratory study will be followed by a larger-sample confirmatory study to be conducted in Sao Paulo (Brazil). This two-stage analysis consents flexibility in analyses, while allowing further planning on how to confirm the findings herein (17).  

The subjects were randomly assigned (1:1) to compose either one of the following groups: 1) whey protein and creatine co-supplementation (WHEY+CR) or 2) whey protein supplementation (WHEY). All the subjects undertook a supervised exercise training program for 14 weeks. The subjects were assessed at baseline and after 14 weeks. The main dependent variables were muscle function (handgrip, timed-stands and timed-up-and go tests) and body composition. Self-reported adverse events were recorded throughout the trial and blood parameters (i.e., urea, creatinine, sodium, potassium, bilirubin, alkaline phosphatase, gamma glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, glucose, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triacylglycerides, and creatine kinase) were assessed before and after the intervention. Subjects were required to keep a food diary daily for 7 days prior to and after the trial.  


The subjects were recruited into the study by advertising at newspapers, newsletters, rest homes, retirement villages, local health centres, and agencies. The sample was comprised by postmenopausal women and men aged ≥ 65 years physically inactive. The exclusion criteria were cancer, uncontrolled cardiovascular diseases and/or musculoskeletal disturbances that could preclude exercise participation, and any difficulties to consume the supplements. 

All the participants were classified into one of the following categories:  “3 – well, with treated comorbid disease” (i.e., those whose disease symptoms are well controlled compared with those in category 4); “4 – apparently vulnerable» (i.e., those who commonly complain of being ‘‘slowed up’’ or have disease symptoms); or “5 – mildly frail”  (those with limited dependence on others for instrumental activities of daily living), according to the Canadian Study of Health and Aging (CSHA) clinical frailty scale, which varies from 1 («very fit») to 7 («severely ill») (18).  

The study was approved by the local ethical committee and all of the subjects signed the informed consent. All of the procedures were in accordance with the Helsinki Declaration revised in 2008. 

Supplementation protocols and blinding procedure

The subjects from WHEY+CR received a mixed powder containing 2.5 g of creatine monohydrate (Creapure, Alzchem, Germany) and 10 g of whey protein (Fonterra, New Zealand) to be consumed twice a day (totalizing 5 g/d and 20g/d of creatine and whey protein, respectively) after breakfast and dinner. The subjects from WHEY were given the same supplementation regimen, with dextrose in place of creatine. The supplement packages were coded so that neither the investigators nor the participants were aware of the contents until completion of the analyses. The supplements were provided by a staff member of our research team who did not have any participation in the data acquisition, analyses, and interpretation. 

Exercise training 

All the subjects engaged in a 12-week supervised resistance training program. Exercise sessions occurred twice-a-week and were monitored by fitness professionals. The exercise program was performed in a university gymnasium (Waikato University, Hamilton, New Zealand). Resistance training program was comprised of step-ups, chest press, squats, seated row, leg press, biceps curl, triceps extension, calf rise, sit-ups, and leg extension. The subjects were required to perform three sets of 8-12 repetition maximum. Two-min rest intervals were allowed between sets. Progression in the absolute exercise load was implemented when the subject could perform more than 12 repetitions on a given exercise set. 

Muscle function assessments

Prior to muscle function assessments, two familiarisation tests were conducted on two separate days with at least 48 hours between trials. Muscle function was measured by handgrip, timed-stands and timed-up-and-go tests. 

Handgrip test assesses the isometric strength. Subject stands in an upright position holding a dynamometer (Jamar Hydraulic Hand Dynamometer, model 5030J1) with the dominant hand. Three maximal attempts (with 1-min interval between them) are performed, and the best score is recorded. Timed-up-go test assesses the time that a subject requires to rise from a standard arm chair, walk to a line on the floor three meters away, turn, return, and sit down again (19), whereas timed-stands test evaluates the number of stand-ups that a subject can perform from a standard armless chair for 30 seconds (20). 

Bone mineral density and body composition

Bone mineral density and body composition (fat mass and fat free mass) were measured by dual energy x-ray absorptiometry (DXA), using a GE Lunar DPX MD+ densitometer (software enCore 2013 version 15 SP 2). Bone mineral density was determined at the following sites: lumbar spine, femur, and total body. The precision errors for bone mineral density measurements were determined based on the standard protocols from The International Society for Clinical Densitometry (ISCD) (21). The least significant change is considered to be 0.033 g/cm2, 0.039 g/cm2, and 0.010 g/cm2 for spine, femur, and total body, respectively (22).   

Statistical analysis

Data were tested by mixed-model analysis for repeated measures with Kenward-Roger correction for unequal samples. Tukey post-hoc was used when necessary. In addition, absolute delta changes were compared between groups using unpaired two-tailed T-tests. Effect sizes were calculated for the main dependent variables, according to Cohen (23). Fisher’s test was applied to assess possible between-groups differences in the incidence of chronic diseases and use of supplements and medications. Data are presented as mean ± standard deviation, delta scores, and individual responses. The significance level was previously set at p < 0.05.




The flowchart of participants is shown in Figure 1. A total of 47 subjects were screened for participation and 18 met the inclusion criteria. These patients were randomly assigned into WHEY+CR (n = 9) and WHEY (n = 9). Two subjects from WHEY withdrew due to personal reasons (n = 1) and medical conditions (n = 1). Thus, 16 subjects completed the trial and were analyzed (n = 9 and n = 7 in WHEY+CR and WHEY, respectively). Subjects’ main characteristics are expressed in Table 1. Groups were comparable regarding age, body composition, diseases, morbidities and frailty incidence, and use of medications (p > 0.05 for all).  


Figure 1 Flowchart of subjects



Table 1 Subjects’ main characteristics

No significant differences between groups were noted (p > 0.05); BMI = body mass index; BMD = bone mineral density; Data are reported as mean ± SD or number of subjects per group. 


Adherence the dietary interventions, exercise program and food intake

All participants reported a 100% compliance with the supplementation regimes. The adherence to the exercise program was comparable between groups (WHEY+CR: 95.53%; WHEY: 97.95%). Total energy and macronutrient intake did not significantly differ between groups at baseline or after the intervention (p > 0.05) (Table 2). However, as expected (due to whey protein supplementation in both groups) there was main time-effects for total energy intake (p = 0.001) and protein intake (increased absolute values, percentage values, and relative values per body weight; all p < 0.0001). Also, main time-effects were observed for carbohydrate (increased absolute values; p = 0.0006) and lipid intake (decreased percentage values; p = 0.03).


Table 2 Blood variables before and after supplementation with creatine and protein (CR+WHEY) or whey supplementation alone (WHEY) in older subjects undertaking resistance training

No significant differences within or between groups were noted (p > 0.05). Abbreviations: ALP = alkaline phosphatase; GGT = gamma glutamyltransferase; ALT = alanine aminotransferase; AST = aspartate aminotransferase; TAG = triacylglycerides, and CK = creatine kinase. Data are reported as mean ± SD.


Muscle function

Figure 2 shows muscle function data. We found a main time-effect in handgrip (WHEY+CR = 26.65 ± 31.29; WHEY = 13.84 ± 14.93 in the last at that time, i had been taking pliva and was switched to northstar . everyone here  Kg; p = 0.0005), timed-up-and-go (WHEY+CR = -11.20 ± 9.37; WHEY = -17.76 ± 21.74; p = 0.006 s), and timed-stands-test (WHEY+CR = 47.50 ± 35.54; WHEY = 46.87 ± 24.23 reps; p = 0.0001), suggesting that WHEY+CR and WHEY were similarly effective in improving these variables.


Figure 2 Muscle function variables before and after supplementation with creatine and protein (CR+WHEY) or whey supplementation alone (WHEY) in older subjects undertaking resistance training. Data are reported as mean ± SD. * denotes mean time-effects (p < 0.05)


Body composition

Figure 3 shows body composition data. Neither within- nor between-group differences were detected in any of the body composition variables (all p > 0.05). Also, relative changes were comparable across groups in all parameters (Fat free mass: WHEY+CR = 1.72 ± 5.07 and WHEY = 1.97 ± 2.36%); Fat mass: WHEY+CR = -2.66 ± 5.07 and WHEY = 0.59 ± 6.97%; Bone mineral content: WHEY+CR = -2.125 ± 5.82 and WHEY = -0.27 ± 8.23%; Total body bone mineral density: WHEY+CR = 0.08 ± 3.00 and WHEY = 1.97 ± 2.81%; Spine bone mineral density: WHEY+CR = -0.23 ± 5.74 and WHEY = -2.85 ± 6.44%; Femur bone mineral density: WHEY+CR = -0.64 ± 0.85 and WHEY = 0.56 ± 3.43%).


Figure 3 Body composition variables before and after supplementation with whey protein and creatine (WHEY+CR) or whey protein alone (WHEY) in older subjects undertaking resistance training. Data are reported as mean ± SD. No statistically significant effects were observed


Adverse effects

There were no self-reported side effects throughout the study, except for one single episode of mild upset stomach reported by a subject from WHEY, which did not cause the subject exclusion from the study. Clinical examinations did not reveal adverse events potentially associated with creatine/protein supplementation or resistance training. Moreover, blood parameters (i.e., urea, creatinine, sodium, potassium, bilirubin, alkaline phosphatase, gamma glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, glucose, cholesterol, HDL, LDL, triacylglycerides, and creatine kinase) remained within normal range and did not change across time (all p > 0.05 and changes ) (Table 3).


Table 3 Food intake variables before and after supplementation with creatine and protein (CR+WHEY) or whey supplementation alone (WHEY) in older subjects undertaking resistance training

* denotes main time-effects (p < 0.05). No significant differences between groups were observed. Data reported as mean ± SD.


Further exploratory analysis  

Table 4 shows individual data for both muscle function and body composition data at Pre and Post as well as absolute change values (i.e., delta), ES, and specific p values for between-group comparisons. Muscle function parameters (i.e., handgrip, timed-stands test, and timed-up-and-go test) were beneficially affected in both groups alike, with improvements in all muscle function tests (considering any improvement above zero). In addition, all of the subjects showed improvements in at least two of the three tests, regardless of their treatments. 


Table 4 Individual response before and after supplementation with creatine and protein (CR+WHEY) or whey supplementation alone (WHEY) in older subjects undertaking resistance training


In contrast, our analyses revealed that body composition variables (i.e., fat mass, fat free mass and bone mass) were neither clinically nor statistically changed on average in both groups, despite the high individual variability observed. 

Collectively, individual analysis, ES and delta changes along with inferential statistics suggested that the interventions (i.e., creatine plus whey protein vs. whey protein alone) were not consistently different from each other for any variable. The high individual variability found in this study seems to have occurred in both groups alike.  



This study showed that co-supplementation with creatine and whey protein was well-tolerable and free of severe adverse effects in older subjects with frailty. In addition, creatine supplementation did not enhance the effects of resistance training combined with whey protein on body composition or muscle function parameters in this population. 

Frailty represents one of the most significant public issues currently. It gives rise to muscle dysfunction and body composition disturbances (e.g., loss of bone and muscle mass), thereby resulting in vulnerability (18, 24). To date, the first-choice interventions to manage this syndrome consist of resistance training and a few dietary interventions (2, 13). In fact, a sufficient body of literature has evidenced the beneficial role of resistance exercise in counteracting muscle dysfunction and loss of fat free mass in older individuals (for a comprehensive review, see (2)). Furthermore, growing evidence has indicated that additional high-quality protein intake can also be supportive for muscle anabolism in elderly, particularly when combined with resistance training (for a meta-analysis, see (15)). More recently, a few studies have shown that creatine supplementation along with resistance training can improve muscle function, bone, and muscle mass in older subjects with frailty (5 ,25), although confirmatory studies remain necessary. Co-supplementation with creatine and protein might be expected to promote synergistic effects based on their differential mechanisms of actions. Protein supplementation has been shown to positively modulate muscle protein balance, stimulating protein synthesis in elderly subjects (26). Interestingly, it has been suggested that proper doses and types of protein supplementation (e.g., 30-40 g per meal or 1.2 g/Kg/day of high-quality proteins) can partially offset the so-called “anabolic resistance”, a condition characterized by a blunted-response to anabolic stimulus (i.e., exercise and protein intake) in the elderly (2, 3, 12, 13). Creatine supplementation, in turn, appears not to directly affect muscle protein balance, at least in young subjects (27, 28); the positive effect of this amine upon muscle mass seems to be a result of its bioenergetics role in enhancing ATP resynthesis, which could lead to increased training volume and, hence, muscle mass gains (8, 29, 30). Thus, we hypothesized that creatine could add to whey protein in improving muscle function and body composition parameters in older subjects undergoing a resistance training program. Our findings, however, failed to support any beneficial effect of creatine.

These findings seem to be in agreement with those of previous studies showing no synergistic effects of creatine and protein in elderly subjects engaged in resistance training (16-18). Bemben et al., (16) showed that a resistance-training program for 14 weeks in middle-aged and older men (48-72 yr) was able to increase muscular strength and muscle mass with no additional benefits from creatine (5 g/day) and/or whey protein supplementation (35 g/day). Similarly, Villanueva et al., (31) demonstrated that creatine (0.3 g/kg/day for 5 days followed by 0.07 g/kg/day) and whey protein (35g/day) supplementation did not provide additional benefits in older adults (60-80 yr) performing 12 weeks of periodized resistance training to augment muscular and functional performance. Finally, Eliot et al., (32) failed to show any effect of supplementation with creatine (5g/day) and whey protein (35 g/day), alone or combined, in middle-aged men (48-72) undergoing 14 weeks of resistance training. 

It is possible to speculate that the effects of creatine supplementation on muscle function and body composition parameters were too small to be detected by small-scale trials. In addition, there are subjects unresponsive to creatine supplementation, which might have further precluded us to find positive effects associated with this dietary supplement. In fact, previous studies investigating the possible additive effects of creatine and protein supplements have small samples too, which may partially explain the lack of positive outcomes. Certainly, additional studies with larger sample sizes are necessary to verify as to whether creatine supplementation adds to protein supplementation in promoting positive adaptations in older subjects undergoing resistance training. Moreover, further studies should determine muscle creatine/phosphoryilcreatine in order to provide a better link between changes in functional and morphological variables and possible increases in muscle high-energy phosphagens.  

Another interesting data from this study was the beneficial effect of resistance training and whey protein supplementation (regardless of creatine) in increasing muscle function, but not fat free mass, in older subjects with frailty. There are meta-analytic data suggesting that protein supplementation additively to prolonged resistance training can augment both free fat mass and muscle function (15). The lack of increases in fat free mass in this study may be a result of a too short follow-up period (i.e., 14 weeks in the current study vs. 24 weeks in the meta-analysis). Also, average protein intake was significantly increased in this study from 19% to 23% of total energy intake; however, the relative increase in protein intake per body weight did not reach the recent recommendations for optimum muscle mass gain in elderly individuals (0.9 to 1.1 g/Kg/day in the current study vs. ≥ 1.2 g/Kg/day in recent guidelines (2, 3, 12, 13), which may partially explain the absence of improvement in lean mass in this study. Importantly, it is worth noting that our experimental design did not allow us to distinguish the effects of resistance training from those of protein supplementation, nor the effects of training and supplementation from those of no intervention at all. Further studies with more comprehensive designs allowing full comparisons between creatine and whey protein supplementation, combined or alone, and placebo will be elucidative. 

It is important to highlight that co-supplementation with creatine and protein was safe and well-tolerable among older subjects with frailty in this study. All of them adhered to supplementation protocols. No adverse effects, except for a single episode of mild stomach upset, were reported. Blood parameters also revealed no abnormalities in muscle, kidneys or liver metabolism. Finally, the compliance with the resistance training protocol was highly satisfactory, with no incidence of injuries or any other training-related adverse events. Taking together, these observations allow concluding that our intervention is feasible and safe and, as such, merits further investigation. 

The main limitations of this study involve the low sample size, the lack of a non-trained group and a placebo group not receiving protein supplementation), and the lack of assessment of intramuscular creatine content. However, important lessons were learned from this exploratory trial. Firstly, based on the effect sizes found in this trial, larger sample sizes seem to be necessary to show any additive effect of creatine and protein. Secondly, longer-term follow-ups appear to be particularly important to show any beneficial effects of creatine and/or protein supplementation in resistance-trained elderly subjects. Thirdly, resistance training along with whey protein seem to be a well-tolerable, safe and effective strategy in improving muscle function in the elderly with frailty. The separate role of each intervention applied in this trial requires further investigation. All of these gaps will be taken into consideration in a larger comprehensive ongoing study to confirm or refute these preliminary data. 

Co-supplementation with creatine and whey protein was tolerable and free of adverse events in older subjects with frailty undertaking resistance training. Moreover, creatine supplementation did not augment the adaptive effects of resistance training along with whey protein on body composition or muscle function in this population.


Acknowledgments: We would like to thank Fonterra (New Zealand) and Alzchem (Germany) which donated the supplements for this study. Bruno Gualano and Hamilton Roschel are supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). 

Conflict of Interest: The authors declare that they do not have conflict of interests.



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Exercise Metabolism Research Group, Department of Kinesiology, McMaster University, Hamilton, ON, Canada

Corresponding author: Stuart M. Phillips, Ph.D. Department of Kinesiology, McMaster University, 1280 Main St. West, Hamilton, ON, L8S 4K1, Canada, Phone: +1-905-525-9140 x24465, Fax: +1-905-523-6011, Email: phillis@mcmaster.ca



An age-associated loss of muscle mass and strength – sarcopenia – begins at around the fifth decade of life, with mass being lost at ~0.5-1.2% per year and strength at ~3% per year.  Sarcopenia can contribute to a variety of negative health outcomes, including an increased risk for falls and fractures, the development of metabolic diseases like type 2 diabetes mellitus, and increase the chance of requiring assisted living. Linear sarcopenic declines in muscle mass and strength are, however, punctuated by transient periods of muscle disuse that can accelerate losses of muscle and strength, which could result in increased risk for the aforementioned conditions. Muscle disuse is recognizable with bed rest or immobilization (for example, due to surgery or acute illness requiring hospitalization); however, recent work has shown that even a relative reduction in ambulation (reduced daily steps) results in significant reductions in muscle mass, strength and possibly an increase in disease risk. Although reduced ambulation is a seemingly “benign” form of disuse, compared to bed rest and immobilization, reports have documented that 2-3 weeks of reduced daily steps may induce: negative changes in body composition, reductions in muscle strength and quality, anabolic resistance, and decrements in glycemic control in older adults.  Importantly, periods of reduced ambulation likely occur fairly frequently and appear more difficult to fully recover from, in older adults. Here we explore the consequences of muscle disuse due to reduced ambulatory activity in older adults, with frequent comparisons to established models of disuse: bed rest and immobilization.


Key words: Atrophy, strength, function, disability, diabetes. 



Sarcopenia, the age-associated loss of muscle mass and strength, begins to develop in or around the fifth decade of life (1) and contributes to an increased risk of falls and fractures in older individuals, as well as to the incidence of metabolic disorders like type 2 diabetes mellitus (T2DM).  Based on population estimates, the average person loses ~0.5-1.2% of their muscle mass per year (dependent on site of measurement; see Figure 1).  The loss of strength with age is greater at ~3% per year (2). Advancing age can be punctuated, likely more frequently than in younger persons, by periods of physical inactivity and muscle disuse, which result in atrophy and accelerate age-related sarcopenia. There are numerous situations common to advancing age that can result in inactivity and muscle disuse. For example, individuals who require orthopedic and other surgeries, hospitalization due to illness, or who experience falls will undergo transient muscle disuse and oftentimes marked reductions in muscle mass, strength, and mobility as a result. Bed rest and limb immobilization studies have confirmed that in addition to accelerated losses of strength (3) and muscle mass (4) during these periods of muscle disuse, metabolic health (in particular regulation of blood glucose) is also negatively affected (5). 


Figure 1 A representation of normal and disuse-accompanied sarcopenic loss of muscle mass and function in arbitrary units, for adults after the age of 50. We also add lines showing relative risk for disability, which we propose would have different trajectories based on the number of disuse events a person experiences. Normal: Muscle mass/function decline based upon population estimates of average sarcopenic muscle mass loss experienced by large cohorts of older adults – solid thin line. Relative risk for disability is based on a usual decline in muscle mass and function – solid thick line. Disuse-accompanied: Proposed accelerated muscle mass/function decline punctuated by repeated periods of physical inactivity – dashed thin line. Relative risk for disability is based on an accelerated decline in muscle mass and function – dashed thick line


Recently, studies of reduced ambulation (i.e., reduced daily steps) have shown effects on muscle strength, muscle mass and glucoregulation (6–14).  Reducing daily step count (usually from ~6-10k steps per day to less than ~1-1.5k steps per day) may appear to be a relatively benign intervention when compared to bed rest or immobilization. However, the negative impact that step-reduction has on overall muscle health simply represents, in our view, a milder version of what happens in complete disuse models. We also propose that acute periods of step-reduction may occur with far greater frequency in older persons than overt bed rest and muscle immobilization. Thus, we view step-reduction as a valuable model for examining moderate muscle disuse that can affect older adults. Periods of reduced ambulation mimic what an older person might experience when they contract an acute illness that does not require hospitalization, or during stretches of inclement weather (i.e., a cold winter).

The purpose of this review is to summarize the effects of reduced ambulation on strength, physical function and muscle mass in older adults, as well as to examine how reductions in muscle protein synthesis and insulin sensitivity may contribute to these outcomes.  We use the term “moderate muscle disuse” to differentiate step-reduction from overt muscle disuse (bed rest or limb immobilization); however, the reader should bear in mind that step-reduction is not a benign process, and it is responsible for a number deleterious health consequences.  While bed rest and immobilization will be discussed in short, the focus of this review will be on recent work investigating the effects of step-reduction and its consequences for older adults.  For a recent and more detailed review of more overt muscle disuse in older adults, please refer to Wall et al. (15). 


Strength and Physical Function 

With aging, muscle strength is lost at a greater rate than muscle mass (~3% versus ~1% per year, respectively) (16, 17). This simple fact is indicative of a decrease in muscle quality (force generated per muscle area) and neuromuscular changes involving motor unit dropout. As a result of the decrease in muscle strength and quality, a significant number of older adults have poor mobility and some are unable to complete basic activities of daily living (ADL) (18, 19). Due to reductions in strength, older persons are at an increasing risk of falls and often report a diminishing quality of life (QOL) (20). Furthermore, low muscle strength, but not low muscle mass, is an independent risk factor for mortality in both men and women (21). Despite recognition of the importance of muscle strength to the health of older adults, the impact of reduced ambulation (not to be confused with reduced gait speed) on muscle strength and function has not been extensively studied. Nonetheless, we do know that more overt forms of muscle disuse (immobilization, bed rest) result in significant decreases in muscle strength in both young and older adults (3, 4, 22–24).

In older adults, short-term periods of bed rest (10-14 days) result in reductions in leg strength that are 2-3 times greater than the amount of muscle mass lost in the same limbs (3, 4). Furthermore, given that muscle strength declines at a rate of ~2-4% per year (2, 17) short-term disuse-induced declines in muscle strength and mass are equivalent or greater than annual reductions in aging persons. While we know that overt disuse results in strength losses in both young and older adults, specific comparisons between young and older individuals in response to disuse have indicated that older adults may be at a greater risk for strength loss (22, 25, 26), while other studies have reported no age-related differences in disuse-induced declines in strength (23, 27). It appears as if the differential response between trials with respect to the effect of age on disuse-induced muscle strength losses may pertain to differences in the methods used to assess strength. Specifically, changes in muscle torque/strength are similar between young and older adults when strength is assessed with isometric (~10-28% and 7-23% in young and old, respectively) or lower velocity isokinetic (~10-11% and 12-15% in young and old, respectively) contractions (23, 25–27). In contrast, isokinetic torque assessed at higher velocities, shows greater disuse-mediated declines in older (~6-14%) versus younger (~0-4%) adults (25, 26). Furthermore, the effect of disuse on the rate of force development (RFD) and isokinetic “power” also appear to be affected to a greater extent in older adults (22, 25, 26). These findings are of importance given that velocity and power are crucial for typical ADL (28). For example, the ability to generate velocity and power in the lower extremity muscles is required in order to rise from a chair (28). Whether these differential declines in muscle strength between young and older adults impact functional performance was not determined in the aforementioned studies. However, 10 days of bed rest in older adults decreased isotonic (1RM) knee extensor strength by 13%, isometric peak torque by 11% and isokinetic strength at various speeds by 12-13%, with a corresponding decrease in stair climbing power by 14%. Although no effect on performance as assessed by short physical performance battery (SPBB) or 5-item physical performance tests (29) was observed, the decrease in stair climbing power indicates that participants may have developed some limitations in the ability to perform ADL. Furthermore, studies have shown that hospital patients typically take ~500-700 steps per day (30, 31), and this low step-count has been associated with a diminished ability to complete ADL and other functional tasks, as well as being associated an increased risk of mortality even after controlling for comorbities (32). These observations highlight the negative impact of disuse and reduced ambulation on functional capabilities.

Only ten step-reductions studies have been performed to date, and their results are summarized in Table 1. Of these ten studies only two have examined the effect of reduced ambulation on muscle torque or isotonic strength (6, 7). In both studies, 14 days of step-reduction (< 1500 steps per day) had no effect on muscle strength in older adults, although these studies used isometric (6, 7), and isotonic methodologies (7) to assess strength. And as previously discussed, findings from overt disuse studies show that older adults appear to experience a greater decline in the RFD and isokinetic torque (which were not assessed in the step-reduction studies), compared to other strength measurements. As such, isometric torque and isotonic strength measurements may not be the ideal methodology to employ when investigating the impact of disuse on muscle strength. Conversely, while not statistically significant, Devries et al (7) found a 7% decrease in isometric knee extensor peak torque in older adults in response to a step-reduction intervention, indicating that maximal force-generating capacity is impacted to a certain degree during moderate disuse. Future studies should consider assessing strength using more robust methodologies (single fibre peak toque, twitch-interpolated maximal toque, and/or measuring dynamic fatigue) as well as using higher velocity isokinetic measurements to confirm whether step-reduction impacts various aspects of muscle function in older adults. It would also be important to assess muscle groups other than the knee extensors such as the ankle dorsiflexors, for example, which play an important role in balance (33).


Table 1 Summary of available studies involving step-reduction protocols

All values based on presented averages from published studies. ND: no difference; NS: not significant; PPG: postprandial glucose; AUC: area under curve; OGTT: oral glucose tolerance test; CGMS: continuous glucose monitor; OFTT: oral fat tolerance test; ISI: insulin sensitivity index; HOMA-IR: homeostatic model assessment of insulin resistance; IAFM: intra-abdominal fat mas; VAT: visceral adipose tissue; FM: fat mass; MPS: muscle protein synthesis.  1 Sub-study 1; 2 Sub-study 2.  * Study involved hypercaloric diet; † values taken from unpublished, grouped raw data.


Breen and colleagues (6) investigated the effect of reduced ambulation in both older men and women, although with only five participants per sex, sex-based dimorphisms could not be examined. To the best of our knowledge only one study to date has examined the impact of sex on changes in strength in response to any sort of disuse (overt or more moderate) (24). In this study, young men and women underwent two weeks of unilateral leg immobilization. While both sexes demonstrated similar reductions in quadriceps cross-sectional area (CSA), leg lean mass and muscle fibre size, greater decreases in specific strength for isometric and slow concentric contractions were observed in women compared to men. This study suggests that strength may be lost a higher rate in women compared to men; nonetheless, more studies examining the influence of sex on muscle strength following both overt and more moderate forms of muscle disuse are required verify these findings. 

The ability to recover from muscle disuse also seems to be impaired in older adults (3, 25). Specifically, upon 7 days of recovery from 4 days of disuse, while dynamic strength, isometric strength and RFD were restored in young individuals, isometric and dynamic strength  (which decreased significantly due to disuse) did not return to baseline in older adults (25). Similarly, older adults who undertook a resistance training program for 4 weeks (i.e., a much more intensive program than standard rehabilitation) upon remobilization after 2 weeks of immobilization showed an attenuation in muscle RFD compared to younger subjects (22). If older adults are unable to fully recover their muscle function following periods of disuse, their ability to perform ADL and maintain a good quality of life may be compromised. As well, the risk of falls and fractures and more serious negative health outcomes could also increase.   


Muscle atrophy and muscle protein synthesis (MPS) 

Bed rest and limb immobilization, models of overt muscle disuse, result in muscle atrophy in young (3, 15, 34, 35) and older individuals (4, 5, 36, 37), with the most substantial losses observed in the lower limbs (15).  In the young, 20-35 days bed rest has been shown to decrease quadriceps CSA, assessed using magnetic resonance imaging (MRI), by 4-11% (34, 35, 38).  Similar reductions in quadriceps CSA have been reported with two weeks of single limb immobilization by means of casting, knee bracing or suspension. Fewer bed rest and immobilization studies have been performed in older adults, but it appears that periods of overt muscle disuse result in muscle losses of a similar magnitude compared to the young (4, 5, 36, 39).  Since older individuals typically enter periods of disuse with less muscle mass than their younger counterparts (18), losses of 4-11% represent 2-7 fold greater losses of muscle in a 3-5 week period, compared to what is seen annually. The decrease in whole muscle CSA with two weeks of single limb immobilization is paralleled by a ~5-10% decrease in type I, IIa and IIx fibre CSA (40).  D’Antona et al. (41) reported type I, IIa and IIx fibre CSAs that were 51%, 26% and 24% smaller, respectively, in older individuals who had undergone 3.5mo of limb immobilization compared to mobile elderly. In another study, Suetta and colleagues (3) documented that older subjects’ muscle RFD was not fully recovered following immobilization and subsequent resistance training compared to younger adults and, importantly, that quadriceps muscle volume did not return to baseline in the older subjects. While strength and RFD may be more important functional outcomes for older adults, the maintenance of muscle mass is still important.  Skeletal muscle is the largest sink for postprandial glucose (PPG) disposal and thus it is a large determinant of glycemic control. Since age is a bona fide risk factor for the development of T2DM the maintenance of muscle mass is important for metabolic health in aging.

Reduced ambulation, despite its seemingly benign nature, may contribute to significant decreases in lean tissue. The effects of reduced ambulation on lean tissue in younger individuals are equivocal, with two studies reporting reductions in whole body (9) and leg lean mass (11), one study reporting a gain in lean tissue (13) and yet another study reporting no change (14).  The inconsistency observed is likely due to the lack of sensitivity of dual-energy x-ray absorptiometry (DXA), which was used in all four studies (9, 11, 13, 14), to detect smaller changes in lean tissue.  Short periods of reduced activity can transiently accelerate the gradual loss of muscle mass with age.  Breen et al. (6) observed a 3.9% (~400g) decrease in leg lean mass in older adults after just two weeks of reduced ambulation, which equates to a rate of muscle loss that is nearly double the amount of muscle mass they would have been projected to lose in a year in only two weeks. Despite this, the researchers noted no change in body mass, although trunk fat mass increased significantly which is suggestive of increased visceral adiposity, a finding that has been observed in other step-reduction trials (9). In the only other step-reduction study conducted in older adults, Devries et al. (7) reported a 1.4% (~126g) decrease in unilateral leg lean mass.  While this was significant, it is a less substantial loss than was observed in our previous work from Breen et al. (6); however, the unilateral resistance training undertaken in this trial (7) may have tempered the loss in lean tissue mass observed in the step-reduced leg (42). 

The loss of lean tissue during periods of muscle disuse, whether overt or moderate, appears to be primarily driven by a blunting of the muscle protein synthetic (MPS) response to the anabolic stimulation induced by hyperaminoacidemia after ingestion of dietary protein.  The dynamic equilibrium that exists between MPS and muscle protein breakdown (MPB) is responsible for the maintenance of muscle mass. Reductions in MPS can result in net negative muscle protein balance, and chronically, are thought to contribute to muscle atrophy.  In the young, 14-21 days of bed rest depressed mixed-muscle protein synthesis by 46-48% in the postabsorptive state (43, 44).  Immobilization studies have also reported drastic reductions in postabsorptive (~30-50%) (45, 46) and postprandial (~30%) [15, 46] MPS in the young.  Bed rest studies in older individuals have observed a ~40-50% reduction in the mixed-muscle protein synthesis response to a dose of essential amino acids (EAA), however, no changes in postabsorptive MPS have been reported, possibly because of the shorter duration of the bed rest intervention (5-7 days vs. 14-21 days) (5, 39).  No studies to date have examined the MPS response to immobilization in the old, or to step-reduction in the young.

Breen et al. (6) observed a 26% decrease (p=0.028) in postprandial but no change in postabsorptive myofibrillar protein synthetic rate after two weeks of step-reduction in older adults. Devries et al. (7) observed that both postabsorptive and postprandial myofibrillar fractional synthetic rate (FSR) were lower in a step reduced leg compared to a leg that underwent low load resistance training on top of step-reduction. It is thought that over time, muscular disuse results in reduced sensitivity of skeletal muscle to the anabolic effects of insulin and aminoacidemia, which can contribute to muscle atrophy due lack of stimulation of MPS. This reduction in muscle sensitivity to normally anabolic stimuli may translate into deleterious changes in muscle strength and functionality if not counteracted. Importantly, studies have shown that older women may experience a greater degree of anabolic resistance compared to men (47, 48), which suggests that they may be more susceptible to the consequences of muscle disuse. It is possible that, like younger women, older women may lose strength at a greater rate than men following a period of disuse (24). The possible combined decrements in strength and anabolic sensitivity with muscle disuse may mean that, due to reduced muscle quality, older women are at an increased risk of falls, fractures and metabolic perturbations as a result of muscle disuse.  Future studies investigating these potential sex-based differences are warranted. 


Insulin sensitivity

Skeletal muscle serves an important metabolic purpose beyond its role in locomotion, as a site of substantial lipid oxidation, a major contributor to basal metabolic rate, as well as the primary organ responsible for PPG disposal. It is therefore understandable that aging itself is a primary risk factor for the development of insulin resistance and T2DM (49), potentially underpinned by sarcopenic declines in muscle mass. Estimates are that ~22% of men and 15% of women over 65 years of age in Canada are diabetic (50) and in general older adults exhibit reduced whole-body insulin sensitivity compared with younger adults (51). While sarcopenia is a contributing factor to the morbidity risk of T2DM (19), it is increasingly likely that regardless of age, physical inactivity is a primary cause of insulin resistance and the development of T2DM for older adults (52).

The growing body of data from step-reduction studies (Table 1) lends evidence to the potency of physical inactivity in the development of insulin resistance. Although the variability in step-reduction protocols (participants’ age, measurement techniques, length of intervention, and the relative reduction in steps) limits direct comparisons, all step-reduction protocols lead to a degree of detectable insulin resistance or impaired glycemic control. In younger adults, as little as one day of no daily ambulation while sitting and laying supine causes a decline of at least 18% in the rate of glucose disappearance (53). Short-term, less drastic reductions in daily steps, modelled through three to five days of fewer than 5000 steps in young men and women, led to a ~30% decrease in Matsuda insulin sensitivity index (ISI) during an oral glucose tolerance test (OGTT), as well as increases in PPG concentration following a mixed-macronutrient meal (8, 12). A greater and protracted reduction (<4000 steps per day for seven days) in a similar population of young men led to a ~48% decrease in Matsuda ISI and nearly a two-fold increase in whole-body, fasted insulin resistance from the homeostatic model assessment of insulin resistance (HOMA-IR) (13). Multiple studies have used the two-week, <1500 steps per day model of step-reduction to show as much as a ~61% increase in insulin area under the curve (AUC) during an OGTT (9), and a 17% reduction in glucose infusion rate during a hyperinsulinemic euglycemic clamp (11). Furthermore, the consequences of this inactivity model are augmented with overfeeding (44% reduction in glucose infusion rate) and manifest as impairments in free-living glycemic control in young men (14). Although the consequences of “longer” periods of step-reduction are highlighted by these studies (9, 11, 14), the effects of step-reduction on insulin sensitivity seem to taper after seven days, at least in younger men (9). 

By comparison, only one study (6) has investigated glycemic control and insulin sensitivity during step-reduction in older adults. Breen et al. found that two weeks of fewer than 1500 steps per day caused Matsuda ISI to decrease by ~43%, glucose and insulin AUC during an OGTT to increase by ~9% and ~12%, respectively, as well as a ~12% increase in HOMA-IR. While insulin resistance increased to a lesser degree in this study compared to step-reduction studies on younger adults, it is important to note that, on average, the older adults in this study were mildly insulin resistant prior to beginning the study, in contrast to the habitually insulin sensitive younger adults evaluated in comparable studies (9, 11). Therefore, while greater relative insulin resistance can develop in shorter periods of time with a lesser reduction in steps for younger adults (12, 13), the somewhat attenuated effects of step-reduction on insulin resistance in older adults may have greater negative health consequences as this population is already metabolically impaired at baseline. Since insulin resistance and impaired PPG precede the progression to T2DM and are risk factors for the development of T2DM and cardiovascular disease, a comprehensive understanding of their aetiology is of primary clinical importance to the well-being of older adults.

Impaired peripheral (i.e., skeletal muscle) insulin sensitivity, rather than impaired hepatic insulin sensitivity, is likely the primary cause of insulin resistance that develops as a result of physical inactivity. Evidence to support this notion stems from step-reduction studies in younger adults in which euglycemic clamp techniques demonstrate decreases in glucose infusion rates and rates of glucose delivery after two weeks of physical inactivity, without alterations in endogenous glucose output (11, 14). These findings suggest that the primary effects of step-reduction are found at skeletal muscle rather than the liver. There are several potential explanations for impaired glucose uptake and its storage/oxidation in skeletal muscle that may represent logical, multifactorial causes for the development of inactivity-mediated insulin resistance. Since skeletal muscle represents the largest site for postprandial blood glucose disposal, the loss of muscle mass associated with step-reduction may be a likely contributor to the development of insulin resistance, as it is postulated to occur with sarcopenia (54). However, while impairments in insulin sensitivity and glycemic control are seen in concert with losses of skeletal muscle in both young and old (6, 9, 11), they are also seen when no significant changes or even increases in lean tissue mass are detected (10, 13, 14). In fact, during a period of partial step-reduction, insulin resistance develops rapidly in younger men and precedes any measurable decreases in lean mass or increases in adipose tissue mass (14). In line with this finding, the effects of physical inactivity still manifest themselves regardless of caloric intake during moderate muscular disuse. Whether energy intake remains at habitual levels (6–9, 11, 12) or is increased above pre-intervention levels (10, 13, 14), step-reduction leads to insulin resistance. Nonetheless, even when energy intake is reduced to maintain energy balance during 24 hours of inactivity, insulin resistance still develops (53). 

The molecular mechanisms underlying insulin resistance with physical inactivity remain largely unknown. Signalling cascades at the skeletal muscle level are important for both insulin and contraction mediated glucose transporter type 4 (GLUT4) translocation and subsequent glucose uptake at the sarcolemma, but these pathways can be inhibited by intramyocellular lipid deposits, circulating inflammatory cytokines and free fatty acids (FFA), and lipid metabolites such as diacylglyceride and ceramides (55, 56). A reduction in the ratio of insulin-stimulated pAktThr308/total Akt was observed after step-reduction in young men, alluding to one mechanism of decreased glucose uptake via decreased GLUT4 translocation to the sarcolemma, yet there was no observed increase in inflammatory markers or FFA (11). In contrast, increased C-reactive protein, interleukin-6, and tumour necrosis factor-α were seen after step-reduction in older adults (6). In order to better understand the cellular mechanisms that drive inactivity-mediated insulin resistance and impairments in glycemic control more research is necessary. The use of glucose tracers to examine potential changes in peripheral glucose oxidation with inactivity and metabolomics will be an important consideration for future studies aiming to gain insight into how step-reduction affects the metabolic health of older adults.

Of greater significance to inactivity-associated insulin resistance for older adults is the potential for a lack of complete recovery with return to normal ambulation, much like that of strength and muscle mass with disuse (3). Younger adults are able to regain insulin sensitivity by simply returning to normal activities and daily steps for two weeks (14); however, it is unknown whether older adults would regain glycemic control and insulin sensitivity after an acute period of reduced daily ambulation. If not, it is possible that these periods of reduced physical activity, which become increasingly frequent with age, could underpin the increasing prevalence of T2DM in older adults by causing repeated, irrevocable periods of insulin resistance. Important factors such as sex-differences in insulin resistance with age, the effects of ‘sarcopenic obesity’ and the time-course of metabolic recovery are instrumental in the understanding of how the consequences of reduced physical activity manifest with step-reduction.



The negative effects of muscle disuse on strength, muscle mass and metabolism can be attenuated with loading (resistance and endurance training) and nutrition interventions.  In the young, studies have shown that when resistance exercise and/or aerobic-type exercises are performed by the immobilized limb during periods of overt disuse, deleterious changes in muscle mass, strength and muscle architecture are attenuated or ablated (34, 38, 57–59).  Furthermore, there is evidence to suggest that resistance exercise performed by a contralateral non-immobilized limb can even offset losses in strength and muscle mass in the ipsilateral limb (42, 60), possibly due to neural cross-education.  Broadly speaking, it appears that loading the muscle during periods of disuse preserves nutritional sensitivity of muscle protein synthesis (7), whether this loading occurs via traditional resistance exercise or even as ‘artificial gravity’ (43) or electrical stimulation (61).  Only one study to date has examined the effect of a resistance exercise intervention during a period of muscle disuse in an older population, however the results of Devries et al. support what has been reported thus far in younger individuals. Specifically, unilateral low load resistance training during two weeks of step-reduction augmented leg lean mass and the anabolic MPS response to a protein load in a group of older men (7). While these results are encouraging, intensive exercise rehabilitation following a period of muscle disuse does not appear to recover muscle mass (assessed by quadriceps CSA) or RFD in older adults (3, 23).  Given that the full recovery of muscle mass and some aspects of muscle function, such as RFD (25), following periods of disuse is much more difficult in older adults, the ability to attenuate or ablate these losses in muscle mass and strength during periods of reduced ambulation or immobilization is of the utmost importance.  Further studies are needed to fully characterize the response of older muscle to disuse in combination with an exercise intervention, as well as to determine whether this countermeasure would allow for a full recovery of muscle mass and strength during exercise rehabilitation. 



Although it is a less drastic model of muscle disuse than bed rest or immobilization, reduced ambulation has been shown to result in muscular atrophy and insulin sensitivity. While decrements in strength are smaller with reduced ambulation versus overt muscle disuse this is not unsurprising as participants are still exposed to a loading stimulus. Nonetheless, experimentally induced reduced ambulation has only extended, to date, to only two weeks in duration. When considered in the context of what an older person might experience in later life, the periods of reduced ambulation might extend for far longer periods than what has been evaluated in step-reduction studies thus far.  For example, older persons may reduce their day-to-day steps as a result of acute illness or inclement weather, and we propose that such periods transiently accelerate the development of sarcopenia and related disorders. More importantly, it appears older persons are impaired in their ability to recover lost muscle mass, and possibly muscle function, with reambulation after disuse. Resistance exercise training (loading) may prevent losses in muscle mass and reductions in anabolic sensitivity during periods of muscle disuse, but future research is needed to determine the optimal strategy for preserving muscle mass and function during transient reductions in physical activity.


Acknowledgements: KEB and MTvA were supported by Canadian Institutes for Health Research CGS-D and CGS-M awards. SMP is supported by grants from The Canadian Institutes for Health Research (MOP 123296), The National Science and Engineering Research Council (RGPIN-2015-04613), and the Canadian Diabetes Association (OG-3-14-4489) and gratefully acknowledges all of these sources of funding.

Conflict of Interest: None.



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